Datasets:

kenza-ily

/

JAMA_Chen2024

like 0

https://jamanetwork.com/journals/jamasurgery/fullarticle/2470898

A previously healthy, African American man in his mid-60s with a history of hepatitis C cirrhosis (compensated) presented to the emergency department after collapsing at work with sudden-onset back and abdominal pain. He was hypotensive (blood pressure, 87/55 mm Hg) on arrival to the emergency department. The patient’s condition was rapidly stabilized and computed tomography with contrast demonstrated a large (12.4 × 10.2-cm) right hepatic mass with heterogeneous enhancement on arterial phase and intrahepatic and intraperitoneal hemorrhage (Figure 1A). Emergency angiography was performed by interventional radiology, demonstrating active contrast extravasation originating from the right hepatic artery. Embolization was performed with Gelfoam and microparticles, resulting in hemodynamic stability and a quick recovery. Delayed liver resection was subsequently performed (Figure 1B).A, Large hepatic mass seen on computed tomography, with evidence of intrahepatic and intraperitoneal hemorrhage. B, Pathologic specimen after delayed surgical treatment of the underlying mass. What Is Your Diagnosis?

Ruptured giant cavernous hemangioma

Ruptured complex cystic liver mass

Ruptured hepatocellular carcinoma

Spontaneous liver bleeding

C. Ruptured hepatocellular carcinoma

C

Ruptured hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant neoplasm and the fastest-growing cause of cancer-related mortality.1,2 Spontaneous rupture of HCC is rare, with incidences ranging between 3% and 26%.3 Rupture is related to rapid growth of the tumor, vessel erosion, or coagulopathy,3,4 and it is associated with increasing tumor diameter and Child-Pugh score.5 In the setting of acute bleeding, contrast-enhanced computed tomography findings of bleeding from a large mass that is not cystic, with early arterial enhancement in the context of the patient’s history and presentation, support the diagnosis of ruptured HCC while essentially ruling out alternative processes. Short-term mortality of ruptured HCC is high (25%-100%).3 The goals of therapy during initial presentation are stabilization and hemostasis. Previously, treatments included surgical resection or packing; currently, the treatment of choice is transarterial embolization, which is associated with better outcomes than emergency surgery.3,6Median overall survival for ruptured HCC is short, ranging between 2 and 8 months.4,5,7 However, rupture of HCC does not preclude curative treatment. Delayed surgical resection should be considered in select patients with preserved liver function and no evidence of intraperitoneal dissemination and/or metastatic disease.6 Although delayed resection is associated with lower overall survival compared with resection of nonruptured HCC,4 it leads to improved 5-year overall survival when compared with other treatment strategies (0% for conservative treatment vs 6% for transarterial chemoembolization vs 34% for resection),5 and is recommended for well-selected patients.4,5,7For large right-sided HCC, an anterior approach during hepatectomy can improve survival.8 The “hanging maneuver” facilitates such an approach9; careful blunt dissection is performed in the retrohepatic avascular plane (tunnel) along the anterior surface of the inferior vena cava, and a Penrose drain is used to elevate the liver away from the cava. After inflow control, parenchymal transection is performed along this plane until the inferior vena cava is exposed. The right lobe can then be safely mobilized and the right hepatic vein transected to complete the resection.For this patient, rapid stabilization and embolization were accomplished at presentation. After recovery from the acute rupture, workup demonstrated a large resectable tumor. Owing to the patient’s cirrhosis, embolization of the portal vein was performed, which allowed growth of the future liver remnant and evaluation of the biological behavior of the tumor. Within 3 months of presentation, after appropriate regeneration of the left lobe with no evidence of progression or metastasis, the patient underwent a right hepatectomy using an anterior approach and hanging maneuver (Figure 2). Pathologic examination demonstrated a 14-cm moderately differentiated HCC with no evidence of vascular invasion and negative margins. The patient remains disease free 13 months after diagnosis.Intraoperative image demonstrating liver transection completed using an anterior approach and the “hanging maneuver.” Note the right lobe has not been mobilized and the inferior vena cava (IVC) is exposed between the right and left side of the liver at the transection plane.

Surgery

A previously healthy, African American man in his mid-60s with a history of hepatitis C cirrhosis (compensated) presented to the emergency department after collapsing at work with sudden-onset back and abdominal pain. He was hypotensive (blood pressure, 87/55 mm Hg) on arrival to the emergency department. The patient’s condition was rapidly stabilized and computed tomography with contrast demonstrated a large (12.4 × 10.2-cm) right hepatic mass with heterogeneous enhancement on arterial phase and intrahepatic and intraperitoneal hemorrhage (Figure 1A). Emergency angiography was performed by interventional radiology, demonstrating active contrast extravasation originating from the right hepatic artery. Embolization was performed with Gelfoam and microparticles, resulting in hemodynamic stability and a quick recovery. Delayed liver resection was subsequently performed (Figure 1B).A, Large hepatic mass seen on computed tomography, with evidence of intrahepatic and intraperitoneal hemorrhage. B, Pathologic specimen after delayed surgical treatment of the underlying mass.

what is your diagnosis?

What is your diagnosis?

Ruptured hepatocellular carcinoma

Spontaneous liver bleeding

Ruptured giant cavernous hemangioma

Ruptured complex cystic liver mass

a

male

61-70

African American

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2445343

A 64-year-old man was diagnosed with chronic lymphocytic leukemia (CLL). He presented with progressive inguinal lymphadenopathy and a leukocytosis of 144 000/µL with 97% lymphocytes (intermediate modified Rai stage). Bone marrow cytogenetics and fluorescence in situ hybridization demonstrated 11q and 13q deletions. He received fludarabine, cyclophosphamide, and rituximab, achieving a complete remission. Six months later, he experienced disease recurrence. He received bendamustine plus rituximab, with resolution of lymphadenopathy and lymphocytosis. Prolonged cytopenias precluded continuation of therapy, and lymphadenopathy and lymphocytosis again recurred. A next-generation sequencing (NGS) panel was ordered on peripheral blood to evaluate for potentially targetable genomic alterations (Table).CARD11 mutation is associated with ibrutinib resistance, therefore ibrutinib should not be used.CARD11 mutation is found only in a subclonal population and thus ibrutinib should be avoided.The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib may be considered.The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib should not be considered. How Do You Interpret These Test Results?

CARD11 mutation is associated with ibrutinib resistance, therefore ibrutinib should not be used.

CARD11 mutation is found only in a subclonal population and thus ibrutinib should be avoided.

The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib may be considered.

The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib should not be considered.

C

The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib may be considered.

Next-generation sequencing provides an unprecedented amount of molecular profiling data. This technique entails a parallel sequencing approach, creating millions of snippets of sequenced DNA that are recomposed by computerized algorithms.1 In this case, the selected NGS panel provided analysis of the coding sequences of 405 cancer-related genes, introns from 31 genes, and RNA sequencing of 265 genes for detection of gene fusions.Of the 5 identified genetic alterations in this case (Table), only the CARD11 mutation had a specific treatment implication listed—ibrutinib resistance. Card11 is a downstream target of the B-cell receptor (BCR).2 In activated B cell diffuse large B-cell lymphoma,3,4 oncogenic CARD11 mutations have been identified in the coiled-coil domains 1 and 2 (amino acid residues 123 to 250 and 294 to 442).3,4 These alterations lead to resistance to ibrutinib,3 an inhibitor of the Bruton tyrosine kinase that was US Food and Drug Administration–approved for the treatment of resistant or refractory CLL in July 2014.5However, these observations have limited applicability to our patient. Card11 mutations have been characterized only in the activated B-cell subtype of diffuse large B-cell lymphoma and not in CLL. Additionally, our patient’s identified mutation occurred in amino acid residue 626, not within a region of functionally characterized CARD11 mutations. Amino acid residue 626 lies within the C-terminal end of the CARD11 linker domain. No implications for ibrutinib efficacy have been described for this domain.Ibrutinib is the standard-of-care recommended treatment for relapsed or refractory CLL with 11q deletion, with overall survival of 75% at 26 months in a heavily pretreated, high-risk population.5,6 Although the clinical NGS report suggested that the identified CARD11 mutation was associated with ibrutinib resistance, our independent review of the available literature suggested that it was not relevant to Bruton’s tyrosine kinase inhibition resistance. We therefore prescribed ibrutinib.The advent of clinically available NGS panels in hematology-oncology has ushered in a new era of molecularly based individualized therapy. As uptake by clinicians increases, this technology has led to numerous questions, including costs, reproducibility, and the handling and interpretation of vast amounts of data. With over 95% of the genome lying outside the exons of known protein-coding genes, the selection and interpretation of gene panels in clinical practice requires careful consideration.Even for long-established and extensively studied cancer-related genes such as BRCA1, BRCA2, and p53, occasionally mutations must be classified as “variations of unknown significance.” Compare the knowledge base for these tumor suppressors, which includes decades of research on individual mutations, to the relatively scant reports on CARD11. With hundreds of genes now included in clinical NGS reports, it is critical to recognize the limitations of our collective knowledge base. Efforts to standardize and disseminate this knowledge, such as the catalog of somatic mutations in cancer, provide a valuable scientific resource. However, practicing clinicians may not have the time or scientific background to capitalize on these available databases.Although cytogenetics, fluorescence in situ hybridization, and single-gene assays can characterize specific and limited numbers of molecular alterations, NGS is unique in its ability to evaluate hundreds of genetic alterations in parallel.After starting ibrutinib, the patient achieved a complete resolution of lymphadenopathy within 2 months and normalization of white blood cell count within 6 months, a response pattern to ibrutinib known as partial response with lymphocytosis. He continues to receive therapy.Next-generation sequencing is a recently developed, cost-efficient, and rapid way to obtain information on a large panel of genes of interest in various malignancies.Although multiple Clinical Laboratory Improvement Amendments–certified NGS platforms are now available, no guidelines currently incorporate NGS into routine clinical management of CLL or other cancers.Many alterations discovered through NGS analysis will be of uncertain clinical significance. In this setting, treatment recommendations should be interpreted with caution.

Diagnostic

A 64-year-old man was diagnosed with chronic lymphocytic leukemia (CLL). He presented with progressive inguinal lymphadenopathy and a leukocytosis of 144 000/µL with 97% lymphocytes (intermediate modified Rai stage). Bone marrow cytogenetics and fluorescence in situ hybridization demonstrated 11q and 13q deletions. He received fludarabine, cyclophosphamide, and rituximab, achieving a complete remission. Six months later, he experienced disease recurrence. He received bendamustine plus rituximab, with resolution of lymphadenopathy and lymphocytosis. Prolonged cytopenias precluded continuation of therapy, and lymphadenopathy and lymphocytosis again recurred. A next-generation sequencing (NGS) panel was ordered on peripheral blood to evaluate for potentially targetable genomic alterations (Table).CARD11 mutation is associated with ibrutinib resistance, therefore ibrutinib should not be used.CARD11 mutation is found only in a subclonal population and thus ibrutinib should be avoided.The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib may be considered.The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib should not be considered.

how do you interpret these test results?

How do you interpret these results?

The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib should not be considered.

CARD11 mutation is found only in a subclonal population and thus ibrutinib should be avoided.

The significance of the amino acid exchange in CARD11 is a variant of unknown significance, so treatment with ibrutinib may be considered.

CARD11 mutation is associated with ibrutinib resistance, therefore ibrutinib should not be used.

c

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2475441

A 50-year-old man was evaluated for a 5-month history of blurry vision. He had been diagnosed with the metabolic syndrome many years previously but has not seen his physician in years. He reported no current use of medications. On examination, he had a body mass index of 30.6 and a blood pressure of 160/102 mm Hg. A dilated examination of the retina is shown in the Figure.Order magnetic resonance imaging (MRI) of the brain What Would You Do Next?

Measure hemoglobin A1c level

Evaluate for hypercoagulable disorders

Order carotid ultrasound

Order magnetic resonance imaging (MRI) of the brain

Diabetic retinopathy (DR)

D

Order magnetic resonance imaging (MRI) of the brain

The retinal examination shows DR, and a diagnosis of diabetes should be made by hemoglobin A1c or fasting plasma glucose level or by oral glucose tolerance test. Tight glucose control, blood pressure lowering, and cholesterol lowering will help prevent worsening of the retinopathy. Ophthalmic management is also indicated.The key to correct diagnosis is recognizing microaneurysms, intraretinal hemorrhages, and cotton-wool spots as signs of nonproliferative diabetic retinopathy (NPDR) and the arteriolar narrowing suggesting long-standing hypertension. Hypercoagulable disorders may cause retinal vein occlusion, but ophthalmoscopy would show dilated, tortuous veins and intraretinal hemorrhages in the distribution of the affected vein(s). Carotid ultrasound and echocardiogram can identify an embolic source for an occluded retinal arterial branch, appearing as diffuse retinal whitening in the distribution of a branch occlusion or acutely as a “cherry red spot” in the region of the central retinal artery with later pallor of the optic nerve. If there is papilledema, brain MRI may be necessary to look for a mass lesion (optic disc with indistinct borders and elevation).The prevalence of DR in US patients with diabetes is 28.5% for all DR and 4.4% for vision-threatening DR,1 with 12 000-24 000 new cases of vision loss annually for patients aged 20 to 74 years.2In DR, vessel damage alters the integrity of the blood-retina barrier such that fluid and lipids leak out of the retina, causing diabetic macular edema (DME). NPDR is characterized by microaneurysms and intraretinal hemorrhages. More advanced changes include hard exudates (lipid deposits), cotton-wool spots (infarcts of nerve-fiber layer), venous dilation and beading, and intraretinal microvascular abnormalities (proliferation of new vessels). With advancing degrees of DR, blood vessels are blocked, and the damaged retina sends out signals that cause neovascularization (new blood vessel formation on the surface of the retina), resulting in proliferative DR.3,4 Vision loss can result from DME, macular ischemia, or sequelae of proliferative DR including vitreous hemorrhage and tractional retinal detachment (contraction of fibrovascular components of proliferative DR that causes retina elevation).3The insidious nature of type 2 diabetes often delays diagnosis, and microvascular complications including DR may exist when diabetes is diagnosed. The prevalence of DR at diagnosis (10%-37%) highlights the importance of prompt dilated fundus eye examination.5DR pathophysiology includes oxidative stress, advanced glycation end product formation, protein kinase C activation, vascular endothelial growth factor (VEGF) signaling, inflammation, and renin-angiotensin system activation.4 Medications targeting these factors, notably anti-VEGF agents and intraocular glucocorticoids, are used to manage DR.3Treating hyperglycemia, hypertension, and dyslipidemia reduces the DR incidence and progression.6,7 A comprehensive, multifactorial approach to control blood glucose, blood pressure, and cholesterol8 is recommended to reduce DR and other diabetes complications.The Diabetic Retinopathy Study showed that panretinal laser photocoagulation (PRP) improves outcomes in high-risk proliferative DR.6 PRP induces thermal burns in the peripheral retina, thereby removing diseased or ischemic retina, down-regulating VEGF, decreasing the oxygen requirement for the eye, and allowing oxygen to be directed to the more visually critical macula. The Early Treatment Diabetic Retinopathy Study showed the efficacy of focal laser coagulation for clinically significant macular edema.6 Focal laser seals visible leaking microaneurysms and treats areas of visible thickening and ischemia, stimulating the retinal pigment epithelial cells to remove fluid from the retina. Intravitreal injections of anti-VEGF agents that decrease vascular permeability reduce DME, improve vision, and are first-line management.9 The effects of anti-VEGF on proliferative DR are a viable alternative to panretinal photocoagulation.10 Ophthalmic treatment for DR depends on severity and response to therapy. Surgery is generally reserved for vitreous hemorrhage that does not clear and tractional retinal detachment.This patient’s retina examination revealed NPDR with DME as well as hypertensive changes. His vision was 20/25 in the right eye and 20/40 in the left. Optical coherence tomography showed intraretinal fluid in both eyes and subretinal fluid in the left. He had elevated levels of fasting plasma glucose (112 mg/dL [6.22 mmol/L] and hemoglobin A1c (6.9%). He received an intraocular injection of anti-VEGF in his left eye; his right eye is receiving close follow-up. Healthy lifestyle changes, weight loss, and metformin treatment were initiated as well as losartan for control of blood pressure.

General

A 50-year-old man was evaluated for a 5-month history of blurry vision. He had been diagnosed with the metabolic syndrome many years previously but has not seen his physician in years. He reported no current use of medications. On examination, he had a body mass index of 30.6 and a blood pressure of 160/102 mm Hg. A dilated examination of the retina is shown in the Figure.Order magnetic resonance imaging (MRI) of the brain

what would you do next?

What would you do next?

Order carotid ultrasound

Measure hemoglobin A1c level

Evaluate for hypercoagulable disorders

Order magnetic resonance imaging (MRI) of the brain

d

male

41-50

original

https://jamanetwork.com/journals/jama/fullarticle/2475444

A 19-year-old woman presented to her primary care physician for evaluation of oligomenorrhea. She has had fewer than 6 menstrual cycles per year since menarche at 13 years of age. Her last menstrual cycle was 9 months ago, and at that time, she sought gynecologic evaluation. Her gynecologist considered the possibility of polycystic ovary syndrome (PCOS) and obtained laboratory measurements for thyrotropin, prolactin, follicle-stimulating hormone, and luteinizing hormone but questioned the diagnosis of PCOS because of a normal luteinizing hormone-to-follicle-stimulating hormone ratio (Table 1). The gynecologist referred the patient to an endocrinologist.The patient reported having oily skin, acne, and excessive facial hair growth since menarche. Her friends noted thinning of her hair. She had recently gained 20 lb (9 kg) and has had a difficult time losing weight despite increasing her physical activity.On examination, the patient’s body mass index was 28 (calculated as weight in kilograms divided by height in meters squared), and she had excessive coarse dark hair on the chin and abdomen (upper and lower; Ferriman-Gallwey score of 9) and acne on the face and back. Laboratory results from her gynecological visit were reviewed and additional tests were obtained.The elevated testosterone level is consistent with polycystic ovary syndrome (PCOS).The normal fasting glucose level excludes abnormal glucose tolerance.The normal leuteinizing hormone-to-follicle-stimulating hormone ratio excludes PCOS.The diagnosis of PCOS requires documentation of polycystic ovaries by ultrasonography. How Do You Interpret These Results?

The elevated testosterone level is consistent with polycystic ovary syndrome (PCOS).

The normal fasting glucose level excludes abnormal glucose tolerance.

The normal leuteinizing hormone-to-follicle-stimulating hormone ratio excludes PCOS.

The diagnosis of PCOS requires documentation of polycystic ovaries by ultrasonography.

A

The elevated testosterone level is consistent with polycystic ovary syndrome (PCOS).

There are significant adverse reproductive and metabolic consequences associated with PCOS, and it is the most common endocrinopathy among women of reproductive age, affecting up to 10% of this population.2,3 The diagnosis of PCOS is frequently overlooked or delayed by clinicians.4 There is no single laboratory test to diagnose PCOS.4 The diagnostic criteria for PCOS are listed in Table 2.4,6,7 In women presenting with hyperandrogenism and oligoanovulation, screening with androgen assays or ultrasound of the ovaries may not be necessary if related disorders are ruled out.4As many as 25% of women with PCOS do not exhibit clinical features of hyperandrogenism. In these women, an elevated total and/or free testosterone level may be essential for the diagnosis.4,8 Total testosterone is most accurately measured by mass spectroscopy following liquid or gas chromatography or by radioimmunoassay after extraction chromatography.1 Free testosterone is a better indicator of a hyperandrogenic state and is most accurately measured by calculations based on formulas such as those proposed by Vermeulen.1,4,8 Direct commercial assays for free testosterone are inaccurate and should be avoided.1 Assays for total and free testosterone are not standardized, and normal ranges can vary between laboratories.1 Hence, information on sensitivity and specificity of these assays is lacking. Medicare midpoint reimbursement for total testosterone is $47.60 and for free testosterone is $46.95.This patient has PCOS based on chronic oligomenorrhea combined with clinical and biochemical evidence of elevated androgen levels. Normal levels of thyrotropin, prolactin, and 17-hydroxyprogesterone exclude thyroid dysfunction, hyperprolactinema, and nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The presence of a normal luteinizing hormone level or lack of an elevated luteinizing hormone-to-follicle-stimulating hormone ratio does not exclude PCOS.3Women with PCOS are at increased risk of metabolic complications. Based on the Endocrine Society Clinical Practice Guideline, an oral glucose tolerance test (OGTT) is recommended to detect abnormal glucose tolerance in adolescent and adult women with PCOS because fasting glucose levels are often normal.8 Glucose levels after a 75 g-oral glucose challenge show that one-third of women have impaired glucose tolerance, and as many as 10% have levels diagnostic of diabetes.8,9 Testing for hemoglobin A1c may be considered if a patient is unable or unwilling to complete an OGTT.8 Expert opinion in clinical practice guidelines suggests that women with PCOS, especially those who are overweight or obese, should be screened with a fasting lipid profile.8 Because of an increased prevalence of obstructive sleep apnea, anxiety, and depression in PCOS, expert opinion in clinical practice guidelines recommends that women with PCOS should be screened for obstructive sleep apnea, anxiety, and depression.8The presence of a polycystic ovary on ultrasound is not required for diagnosing PCOS, and its presence alone does not establish the diagnosis.5 Up to 30% of women who are of reproductive age with normal endocrine function have PCO morphology.5 This is especially true during adolescence when PCO morphology may be evident in the normal stages of reproductive maturation.8 Thus, the use of PCO morphology as a diagnostic criterion for PCOS is not recommended, particularly in adolescents.8The patient was informed of her diagnosis and treatment options including lifestyle modification to achieve weight loss, hormonal contraceptives for menstrual irregularity and clinical features of hyperandrogenism, and metformin therapy in the case of abnormal glucose tolerance or inability to lose weight, although this last indication is controversial.8 An OGTT revealed normal glucose tolerance. She was started on an oral contraceptive, referred to a dietician, and was advised to initiate an exercise program. During the patient’s return appointment, she had lost 4 kg and noted improvement of hirsutism and acne. She was instructed to continue with lifestyle modification and will be closely followed up for metabolic disorders.Women with PCOS are at increased risk for reproductive and metabolic disorders.Diagnosis of PCOS can be made based on chronic anovulation (<9 menstrual cycles/y) and clinical hyperandrogenism (acne, hirsutism, and androgenic alopecia) after other relevant endocrinopathies are excluded.Assessment of biochemical hyperandrogenism may be necessary to establish the diagnosis, but these assays are not standardized and vary in accuracy.Women with PCOS are at increased risk for reproductive and metabolic disorders.Diagnosis of PCOS can be made based on chronic anovulation (<9 menstrual cycles/y) and clinical hyperandrogenism (acne, hirsutism, and androgenic alopecia) after other relevant endocrinopathies are excluded.Assessment of biochemical hyperandrogenism may be necessary to establish the diagnosis, but these assays are not standardized and vary in accuracy.

Diagnostic

A 19-year-old woman presented to her primary care physician for evaluation of oligomenorrhea. She has had fewer than 6 menstrual cycles per year since menarche at 13 years of age. Her last menstrual cycle was 9 months ago, and at that time, she sought gynecologic evaluation. Her gynecologist considered the possibility of polycystic ovary syndrome (PCOS) and obtained laboratory measurements for thyrotropin, prolactin, follicle-stimulating hormone, and luteinizing hormone but questioned the diagnosis of PCOS because of a normal luteinizing hormone-to-follicle-stimulating hormone ratio (Table 1). The gynecologist referred the patient to an endocrinologist.The patient reported having oily skin, acne, and excessive facial hair growth since menarche. Her friends noted thinning of her hair. She had recently gained 20 lb (9 kg) and has had a difficult time losing weight despite increasing her physical activity.On examination, the patient’s body mass index was 28 (calculated as weight in kilograms divided by height in meters squared), and she had excessive coarse dark hair on the chin and abdomen (upper and lower; Ferriman-Gallwey score of 9) and acne on the face and back. Laboratory results from her gynecological visit were reviewed and additional tests were obtained.The elevated testosterone level is consistent with polycystic ovary syndrome (PCOS).The normal fasting glucose level excludes abnormal glucose tolerance.The normal leuteinizing hormone-to-follicle-stimulating hormone ratio excludes PCOS.The diagnosis of PCOS requires documentation of polycystic ovaries by ultrasonography.

how do you interpret these results?

How do you interpret these results?

The normal fasting glucose level excludes abnormal glucose tolerance.

The diagnosis of PCOS requires documentation of polycystic ovaries by ultrasonography.

The normal leuteinizing hormone-to-follicle-stimulating hormone ratio excludes PCOS.

The elevated testosterone level is consistent with polycystic ovary syndrome (PCOS).

d

female

11-20

original

https://jamanetwork.com/journals/jama/fullarticle/2474407

A 64-year-old man with type 2 diabetes, hypertension, and chronic kidney disease (CKD) presented with new weakness. Six months ago he had a myocardial infarction complicated by heart failure with an ejection fraction of 35%. His medications were lisinopril, metoprolol succinate, insulin, and furosemide. One week ago, he was diagnosed with cellulitis of the right leg and prescribed a 7-day course of trimethoprim-sulfamethoxazole. Two days ago he noticed generalized weakness, which had worsened over the last 24 hours. Physical examination showed resolving cellulitis on the right leg. Other than symmetrical 3/5 strength in the upper and lower extremities, his neurologic examination results were normal. An electrocardiogram was unchanged from 2 months ago. Laboratory results are shown in the Table. How Do You Interpret These Results?

Drug-induced hyperkalemia

Excessive potassium intake

Pseudohyperkalemia

Transcellular potassium shift

A

Drug-induced hyperkalemia

Potassium is typically measured with an ion-selective electrode that converts the activity of dissolved potassium in solution into an electric potential measured by a voltmeter. The test is usually obtained as part of an electrolyte panel at a cost of approximately $6.47.1 Samples are collected in tubes containing a clot activator for serum or heparin for plasma measurement of potassium concentration. Serum potassium concentration is typically 0.1 to 0.4 mEq/L greater than plasma due to release of potassium by platelets during the clotting process. Factitious hyperkalemia (pseudohyperkalemia) can occur with thrombocytosis (>600 000/µL), white blood cell neoplasia (>200 000/µL), and mechanical factors to include prolonged application of a tourniquet and fist clenching during the phlebotomy procedure.2Hyperkalemia is defined as a serum potassium concentration that is greater than the normal range (3.5-5.0 mEq/L). Prevalence is low (2%-3%) in the general population but as high as 50% in patients with CKD.3 Hyperkalemia is associated with increased mortality in patients with normal kidney function and in patients with CKD.4 Complications include sudden death from cardiac arrhythmias, muscle weakness, and impaired renal acidification. Values greater than 6.0 mEq/L should be addressed immediately and in some cases, intravenous calcium chloride and insulin administered with glucose may be required. A potassium value of less than 6.0 mEq/L is also of concern when the rate of increase in the potassium level is rapid (<24 hours).In evaluating hyperkalemia, pseudohyperkalemia should first be excluded, particularly in patients without risk factors (Box). Excessive intake of potassium-rich foods is an infrequent cause of hyperkalemia but can worsen the severity of hyperkalemia when renal excretion is impaired. Hyperglycemia and insulin deficiency can cause hyperkalemia due to a shift of potassium from the intracellular to extracellular space.2 A normal-gap metabolic acidosis, but not high-anion gap metabolic acidosis, can also cause potassium shift.6 Rhabdomyolysis, tumor lysis, and hemolysis are other potential causes of significant hyperkalemia in the hospital setting.Chronic kidney disease: risk is inversely related to GFR and increases substantially below an estimated GFR of 30 mL/min/1.73 m2Inhibition of renin release from juxtaglomerular cells: β-blockers; calcineurin inhibitors: cyclosporine, tacrolimus; nonsteroidal anti-inflammatory drugsbInhibition of aldosterone release from the adrenal gland: heparin; ketoconazoleBlockade of epithelial sodium channel in renal collecting duct: amiloride; triamterene; trimethoprimPotassium supplements, salt substitutes, certain herbs, and potassium-enriched foods in setting of impaired renal excretion.a A spectrum of abnormalities in the renin-angiotensin-aldosterone system have been described in patients with diabetes mellitus to include hyporeninemic hypoaldosteronism and normal renin release, but a diminished capacity to release aldosterone. Hypoaldosteronism, combined with dysfunction of the collecting duct due to diabetic nephropathy and treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers make these patients at particularly high risk for hyperkalemia.a A spectrum of abnormalities in the renin-angiotensin-aldosterone system have been described in patients with diabetes mellitus to include hyporeninemic hypoaldosteronism and normal renin release, but a diminished capacity to release aldosterone. Hypoaldosteronism, combined with dysfunction of the collecting duct due to diabetic nephropathy and treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers make these patients at particularly high risk for hyperkalemia.bAspirin at low doses does not contribute to hyperkalemia because the inhibitory effect on renal prostaglandins is minimal.5bAspirin at low doses does not contribute to hyperkalemia because the inhibitory effect on renal prostaglandins is minimal.5Sustained hyperkalemia is generally due to decreased renal excretion, which can be caused by (1) a primary decrease in sodium delivery to the distal nephron (eg, in patients with decompensated congestive heart failure); (2) a primary decrease in mineralocortiocoid level or activity (eg, in diabetics with hyporeninemic hypoaldosteronism); or (3) dysfunction of the cortical collecting duct (the primary site of renal potassium secretion). These conditions can coexist. Drugs that interfere with the renin-angiotensin-aldosterone axis can also impair renal potassium excretion.7Hyperkalemia was the result of trimethoprim in the tubular lumen acting as a competitive inhibitor of the epithelial sodium channel. Sodium movement through this channel, located in the distal nephron and modulated by aldosterone, leads to a lumen-negative potential, creating a driving force for potassium secretion.6 Trimethoprim blocks this channel in a manner similar to the potassium-sparing diuretic amiloride, thereby decreasing the driving force and resulting in impaired potassium secretion.8 CKD in the setting of diabetes mellitus and ongoing treatment with medications that impair renal potassium excretion increased the patient’s risk for this complication. There was nothing in the clinical history to suggest a recent increase in potassium intake. Pseudohyperkalemia is unlikely given the presence of hyperkalemia risk factors and symptoms of weakness. Hyperglycemia was not sufficiently severe to cause a transcellular potassium shift. The metabolic acidosis is due to the inhibitory effect of hyperkalemia on ammonium availability, thereby limiting net acid excretion by the kidney.9 Generalized weakness due to hyperkalemia is the result of inactivation of sodium channels caused by depolarization of skeletal muscle cells leaving the cell refractory to further stimuli. The absence of changes on an electrocardiogram does not exclude urgent treatment of hyperkalemia because the electrocardiogram has poor sensitivity and specificity in predicting the actual potassium concentration.10In most instances, the clinical characteristics, basic laboratory data (white blood cell count, platelet count, basic metabolic profile), and assessment of the patient’s risk for hyperkalemia are sufficient to determine if there is a renal potassium excretion disturbance.In addition to replacing trimethoprim-sulfamethoxazole with clindamycin and not administering lisinopril for 48 hours, the patient was treated with 50 mL of 50% dextrose and 10 U of regular insulin. The weakness resolved promptly, and 4 hours later the serum potassium level was 4.6 mEq/L and remained within the normal range thereafter. Preventing hyperkalemia requires recognizing patients at risk and selecting appropriate medication doses according to renal function.Patients with elevated potassium levels who have no risk factors for hyperkalemia and a normal electrocardiogram should undergo a repeat potassium level to exclude pseudohyperkalemia.Transcellular potassium movement can occur in hypertonic states, insulin deficiency, and hyperchloremic metabolic acidosis and account for transient increases in serum potassium.Increased dietary intake of potassium causes hyperkalemia only in the presence of impaired renal function.Sustained hyperkalemia is generally due to impaired renal potassium excretion due to 1 or more of the following: (1) severely limited distal sodium delivery; (2) decreased mineralocorticoid levels or activity; and (3) distal renal tubular defects.Sudden death from cardiac arrhythmias is the most dangerous consequence of hyperkalemia.

Diagnostic

A 64-year-old man with type 2 diabetes, hypertension, and chronic kidney disease (CKD) presented with new weakness. Six months ago he had a myocardial infarction complicated by heart failure with an ejection fraction of 35%. His medications were lisinopril, metoprolol succinate, insulin, and furosemide. One week ago, he was diagnosed with cellulitis of the right leg and prescribed a 7-day course of trimethoprim-sulfamethoxazole. Two days ago he noticed generalized weakness, which had worsened over the last 24 hours. Physical examination showed resolving cellulitis on the right leg. Other than symmetrical 3/5 strength in the upper and lower extremities, his neurologic examination results were normal. An electrocardiogram was unchanged from 2 months ago. Laboratory results are shown in the Table.

how do you interpret these results?

How do you interpret these results?

Transcellular potassium shift

Excessive potassium intake

Pseudohyperkalemia

Drug-induced hyperkalemia

d

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2431076

A woman in her 80s presented with a 1-week history of progressive, painful blisters and ulcers of the groin. This was associated with enlargement of the tongue over the past 3 months, leading to difficulty with mastication. She also reported numbness with no associated weakness of her distal lower limbs for 3 months. This restricted her mobility to the extent that she required diapers. However, she declined any further investigations for her peripheral neuropathy. She had IgG λ-type multiple myeloma complicated by anemia and lytic lesions in the calvarium, which was managed conservatively with transfusions. She was taking folic acid and intramuscular cyanocobalamin supplements owing to deficiencies attributed to a dietary cause. On examination, there were circinate purpuric patches with erosions on the natal cleft, buttocks, inguinal creases, and vulva (Figure, A). Hemorrhagic flaccid bullae were observed on the posterior perineum. This was accompanied by macroglossia, glossitis, and a hemorrhagic erosion on the hard palate (Figure, B). There were purpuric macules periorbitally and on the lips, inframammary folds, forearms, and thighs. Laboratory findings revealed a platelet count of 171 × 103/μL (reference range, 140-440 × 103/μL), prothrombin time of 11.7 seconds (reference range, 9.9-11.4 seconds), activated partial thromboplastin time of 36.0 seconds (reference range, 25.7- 32.9 seconds), and serum zinc levels of 34.4 μg/dL (reference range, 72.4-124.4 μg/dL). (To convert zinc to micromoles per liter, multiply by 0.153.) Results from initial punch biopsies from a purpuric macule on the right inframammary fold and a blister at the perineum were inconclusive. A repeated biopsy from a hemorrhagic blister at the left groin was performed (Figure, C and D).A, Purpura and erosions at the buttocks. B, Clinical findings of macroglossia and glossitis with purpura of the lips. C, Punch biopsy specimen of a flaccid bulla showing the floor of a subepidermal blister lined by fibrin and a chronic inflammatory infiltrate. D, Scattered short eosinophilic amorphous bands in the dermis. What Is Your Diagnosis?

Bullous pemphigoid

Bullous amyloidosis

Herpes simplex infection

Cutaneous candidiasis

B. Bullous amyloidosis

B

Bullous amyloidosis

A 6-mm punch biopsy specimen of a flaccid hemorrhagic bulla on the left thigh revealed the floor of a subepidermal blister, lined by fibrin and a chronic inflammatory infiltrate (Figure, C). The dermis and subcutis contained scattered short eosinophilic bands (Figure, D), which demonstrated apple-green birefringence on polarized light microscopy following Congo red staining. Results of a direct immunofluorescence test were negative. A swab from the base of a perineal ulcer was negative for herpes simplex virus polymerase chain reaction. The patient chose to be treated with supportive measures. Her perineal ulcers were treated with dressings and regular cleansing. Zinc supplementation of 50 mg daily was commenced with improvement in her pain and ulcers.Cutaneous involvement is present in 30% of primary systemic amyloidosis, usually in the form of periorbital waxy papules and intertriginous purpura.1 Other rare manifestations include alopecia, sclerodermoid changes, verrucous lesions, and onychodystrophy.2,3 Bullous amyloidosis is also an unusual manifestation. Clues to the diagnosis include the presence of hemorrhagic bullae in an intertriginous distribution, occurring on a background of skin fragility and macroglossia. Because our patient wore diapers, the perineal region would have been prone to trauma, resulting in perineal blistering and ulceration as the main presenting feature.Differential diagnosis include blistering disorders at areas of friction, such as bullous pemphigoid, porphyria cutanea tarda, and epidermolysis bullosa acquisita, which can be excluded by histological and direct immunofluorescence studies. Genital herpes and zinc deficiency are also considered differential diagnoses.Systemic involvement, such as infiltration of the heart, kidneys, and nervous system, has been found in 74% of patients with bullous amyloidosis, but with no association of preferential organ involvement.2Histopathologically, bullous amyloidosis is characterized by deposition of fibrillar proteins that show apple-green birefringence on Congo red staining with polarized microscopy. The level of split is subepidermal or intradermal, and the infiltrate is pauci-inflammatory.4 The diagnosis of bullous amyloidosis is challenging because small amounts of amyloid may not be detectable on conventional amyloid stains, which was the case in the first biopsy for our patient. Optimal thickness of tissue sections measuring 6 to 8 µm is preferred because thinner sections can lead to false-negative findings.2,4 If results from initial investigations are negative for bullous amyloidosis but clinical suspicion remains high, a repeated skin biopsy for histologic examination or for more sensitive studies, such as electron microscopy, should be considered.5Capillary fragility owing to amyloid deposition in the vascular walls,6 splitting of amyloid deposits in the dermis following trauma, and disruption of the dermoepidermal junction either due to amyloid deposition or following transepidermal elimination of dermal amyloid deposits are all possible mechanisms of blistering in amyloidosis.7Treatment of bullous amyloidosis is often unsatisfactory, but oral corticosteroids, alkylating agents, and proteasome inhibitors have been used with varying success.6 The prognosis for the patient described herein is poor given her presentation of systemic AL amyloidosis on a background of multiple myeloma, with a median survival of 1 to 2 years from diagnosis.8This case serves as a reminder that unusual cutaneous phenomenon, such as perineal blisters, can be an important diagnostic sign for primary systemic amyloidosis, and a high index of suspicion should be maintained.

Dermatology

A woman in her 80s presented with a 1-week history of progressive, painful blisters and ulcers of the groin. This was associated with enlargement of the tongue over the past 3 months, leading to difficulty with mastication. She also reported numbness with no associated weakness of her distal lower limbs for 3 months. This restricted her mobility to the extent that she required diapers. However, she declined any further investigations for her peripheral neuropathy. She had IgG λ-type multiple myeloma complicated by anemia and lytic lesions in the calvarium, which was managed conservatively with transfusions. She was taking folic acid and intramuscular cyanocobalamin supplements owing to deficiencies attributed to a dietary cause. On examination, there were circinate purpuric patches with erosions on the natal cleft, buttocks, inguinal creases, and vulva (Figure, A). Hemorrhagic flaccid bullae were observed on the posterior perineum. This was accompanied by macroglossia, glossitis, and a hemorrhagic erosion on the hard palate (Figure, B). There were purpuric macules periorbitally and on the lips, inframammary folds, forearms, and thighs. Laboratory findings revealed a platelet count of 171 × 103/μL (reference range, 140-440 × 103/μL), prothrombin time of 11.7 seconds (reference range, 9.9-11.4 seconds), activated partial thromboplastin time of 36.0 seconds (reference range, 25.7- 32.9 seconds), and serum zinc levels of 34.4 μg/dL (reference range, 72.4-124.4 μg/dL). (To convert zinc to micromoles per liter, multiply by 0.153.) Results from initial punch biopsies from a purpuric macule on the right inframammary fold and a blister at the perineum were inconclusive. A repeated biopsy from a hemorrhagic blister at the left groin was performed (Figure, C and D).A, Purpura and erosions at the buttocks. B, Clinical findings of macroglossia and glossitis with purpura of the lips. C, Punch biopsy specimen of a flaccid bulla showing the floor of a subepidermal blister lined by fibrin and a chronic inflammatory infiltrate. D, Scattered short eosinophilic amorphous bands in the dermis.

what is your diagnosis?

What is your diagnosis?

Herpes simplex infection

Cutaneous candidiasis

Bullous amyloidosis

Bullous pemphigoid

c

female

81-90

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2436030

A man in his early 40s with a medical history significant for verruca vulgaris, dyshidrotic eczema, and human immunodeficiency virus (HIV) diagnosed 1 year prior to presentation reported a chief complaint of dry, swollen lips. The patient reported a 1-month history of “puffy and bumpy” lips. He also described his lower lip as sometimes becoming “dry and scaly” during this time but denied any bleeding from the area. On physical examination, there were several erythematous papules at the vermillion border of the lower lip within a background of edema (Figure, A and B). In addition, the patient had slight fissuring of the tongue, but the remainder of the oral mucosa was normal and intact. Findings of a complete review of systems were unremarkable, other than occasional headaches. The patient denied fevers, night sweats, abdominal pain, neurologic symptoms, chest pain, cough, and shortness of breath. He disclosed full compliance with his HIV highly active antiretroviral therapy (HAART), which included ritonavir, darunavir, etravirine, and raltegravir. He also reported taking sumatriptan as needed for headaches. Numerous laboratory tests were performed, including a complete blood cell count, complete metabolic panel, CD4 count, HIV viral load, and assays for C-reactive protein, erythrocyte sedimentation rate, angiotensin-converting enzyme, and rapid plasma reagin; all results were normal except for a slightly elevated angiotensin converting enzyme level (84 µg/L; normal, 9-67 µg/L). His CD4 count was within normal limits (520 cells/µL) and HIV viral load was undetectable. A biopsy was performed on the right lower lip (Figure, C and D).Clinical images (A and B) show persistent, nontender swelling of the lips in a patient with human immunodeficiency virus, showing erythematous papules at the vermillion border and edema of the lower lip. C and D, Histologic images of a biopsy specimen from a papule on the lower lip show, at low magnification (C), a nodular, nonnecrotizing granulomatous dermatitis and, at higher magnification (D), the presence of epithelioid histiocytes with admixed lymphocytes. What Is Your Diagnosis?

Oral sarcoidosis

Postherpetic granulomatous reaction

Granulomatous cheilitis

Crohn disease

C. Granulomatous cheilitis

C

Granulomatous cheilitis

The biopsy specimen showed nodular, nonnecrotizing granulomatous dermatitis most consistent with granulomatous cheilitis (Figure, C). Higher-power magnification (Figure, D) demonstrated the presence of epithelioid histiocytes with admixed lymphocytes. The lack of well-formed granulomas disfavors the diagnosis of cutaneous sarcoid. In addition, thorough examination of the patient’s skin and eyes revealed no other findings consistent with sarcoidosis, and a recent chest radiograph showed nothing remarkable. The patient was treated with topical corticosteroid cream, but returned to clinic 3 months later with minimal improvement in his symptoms. Other treatment options, including intralesional corticosteroids, tetracyclines, and hydroxychloroquine, were discussed with him at that time.Granulomatous cheilitis is characterized as a nontender chronic swelling of the lips.1 Also known as Miescher cheilitis, it is considered a manifestation of orofacial granulomatosis, a clinical term used to describe orofacial swelling caused by noninfectious, nonnecrotizing granulomatous disorders of the lips and face in the absence of systemic disease. It is a rare disorder that primarily affects young adults but can occur at any age and has no predisposition to race, sex, or age. Many factors have been speculated to contribute in the disease process, including genetic susceptibility, atopy, and infections.2 There have also been previous reports of patients with HIV undergoing HAART therapy who have subsequently developed granulomatous cheilitis.3,4 However, as with most cases of granulomatous cheilitis, the relationship has not been proven to be causal, and the disease is often characterized as idiopathic with no clear etiology.Patients will usually be asymptomatic early in the disease process, typically complaining only of intermittent swelling of the lips. The swelling can be isolated to the upper or lower lip but can also affect both lips simultaneously. In most cases, granulomatous cheilitis is an isolated finding; however, it is not uncommon to see fissuring of the tongue. Also, though exceedingly rare, it has been reported to be associated with facial nerve palsy, otherwise known as Melkersson-Rosenthal syndrome.5 As the disease progresses, the frequency and duration of attacks increase until the symptoms become persistent.6 This can result in functional impairment and severe cosmetic disfigurement, both of which can significantly reduce a person’s quality of life.Lip biopsy is often necessary for the diagnosis and can assist in ruling out other diseases with similar oral involvement, such as angioedema, oral sarcoidosis, Crohn disease, or infections. Typically, histologic analysis will show scattered, small noncaseating granulomas containing epithelioid histiocytes. However, it must be noted that granulomatous inflammation is not always present, especially early in the disease process, and histologic analysis might show only edema and perivascular infiltration of lymphocytes and plasma cells. Therefore, the diagnosis of granulomatous cheilitis is frequently one of exclusion.As reviewed by Banks et al,7 treatment of granulomatous cheilitis has proven to be a very difficult task and highly unpredictable. Depending on the patient, response to treatment is highly variable, and complete remission is uncommon. Multiple therapies, used alone or in combination, have been reported to show some efficacy in individual patients. Some of these include topical, intralesional, and systemic corticosteroids, antibiotics, and immunomodulators. Patients with severe and refractory cases that fail to respond to conservative medical management may benefit from surgical excision of excess tissue.8

Dermatology

A man in his early 40s with a medical history significant for verruca vulgaris, dyshidrotic eczema, and human immunodeficiency virus (HIV) diagnosed 1 year prior to presentation reported a chief complaint of dry, swollen lips. The patient reported a 1-month history of “puffy and bumpy” lips. He also described his lower lip as sometimes becoming “dry and scaly” during this time but denied any bleeding from the area. On physical examination, there were several erythematous papules at the vermillion border of the lower lip within a background of edema (Figure, A and B). In addition, the patient had slight fissuring of the tongue, but the remainder of the oral mucosa was normal and intact. Findings of a complete review of systems were unremarkable, other than occasional headaches. The patient denied fevers, night sweats, abdominal pain, neurologic symptoms, chest pain, cough, and shortness of breath. He disclosed full compliance with his HIV highly active antiretroviral therapy (HAART), which included ritonavir, darunavir, etravirine, and raltegravir. He also reported taking sumatriptan as needed for headaches. Numerous laboratory tests were performed, including a complete blood cell count, complete metabolic panel, CD4 count, HIV viral load, and assays for C-reactive protein, erythrocyte sedimentation rate, angiotensin-converting enzyme, and rapid plasma reagin; all results were normal except for a slightly elevated angiotensin converting enzyme level (84 µg/L; normal, 9-67 µg/L). His CD4 count was within normal limits (520 cells/µL) and HIV viral load was undetectable. A biopsy was performed on the right lower lip (Figure, C and D).Clinical images (A and B) show persistent, nontender swelling of the lips in a patient with human immunodeficiency virus, showing erythematous papules at the vermillion border and edema of the lower lip. C and D, Histologic images of a biopsy specimen from a papule on the lower lip show, at low magnification (C), a nodular, nonnecrotizing granulomatous dermatitis and, at higher magnification (D), the presence of epithelioid histiocytes with admixed lymphocytes.

what is your diagnosis?

What is your diagnosis?

Postherpetic granulomatous reaction

Oral sarcoidosis

Granulomatous cheilitis

Crohn disease

c

male

41-50

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2458752

A 41-year-old woman presented with a rapidly growing, painful nodule on her upper cutaneous lip (Figure, A) as well as several smaller papules on her face and neck, all of which had developed within the preceding 6 months. She was otherwise asymptomatic.A, Centrally depressed, firm, pink 1.1-cm nodule on the upper cutaneous lip and skin-colored papule on the left medial cheek (above marker dots). B, Cup-shaped tumor demonstrated keratinocyte atypia with a central core of keratinaceous debris. C, Sebaceous tumor with a modestly increased ratio of basaloid cells to sebocytes.The patient’s medical history included diabetes mellitus type 2, hypercholesterolemia, hypertension, and depression. Review of her family medical history revealed that her paternal grandfather died from melanoma and that her father died from colon cancer. She stated that most of the men in her family had died from some form of cancer by the fourth decade of life.On physical examination, a tender, centrally depressed, firm, pink 1.1-cm nodule was present on her upper cutaneous lip (Figure, A). Three other skin-colored to pink papules were present on her face and neck. Shave biopsies of all 4 skin lesions were performed (Figure, B and C). What Is Your Diagnosis?

Cowden syndrome

Muir-Torre syndrome

Birt-Hogg-Dube syndrome

Basal cell nevus syndrome

B. Muir-Torre syndrome

B

Muir-Torre syndrome

Histopathologic examination of the upper cutaneous lip lesion demonstrated a cup-shaped tumor with keratinocyte atypia and a central core of keratinaceous debris, consistent with a squamous cell carcinoma, keratoacanthoma type. Microscopic examination of the lesion on the left medial cheek showed a sebaceous tumor with a modestly increased ratio of basaloid cells to sebocytes, consistent with a sebaceous adenoma. The 2 other biopsies performed revealed another squamous cell carcinoma and a second sebaceous adenoma. Immunohistochemical staining of the sebaceous adenoma and keratoacanthoma demonstrated absence of PMS2 and decrease of MLH1 protein expression. Owing to these findings, the patient was referred to the genetics department.Genetic testing revealed a heterozygous deleterious mutation in MLH1 resulting in the loss of 1 functional copy of MLH1. The BROCA panel findings were negative for 51 other gene loci mutations, including PMS2, MSH2, and MSH6.The patient’s squamous cell carcinomas were treated with Mohs surgery. Cancer screening including colonoscopy, mammography, and transvaginal ultrasonography were performed, and findings were negative for cancer. The patient underwent a prophylactic hysterosalpingo-oophorectomy per her geneticist’s recommendations.Muir-Torre syndrome (MTS) is a rare, autosomal dominant genodermatosis characterized by the presence of at least 1 sebaceous neoplasm, excluding sebaceous hyperplasia, or 2 or more keratoacanthomas in combination with at least 1 visceral malignant neoplasm. Muir-Torre syndrome is a phenotypic subtype of hereditary nonpolyposis colorectal cancer syndrome (HNCCS), or Lynch syndrome. Internal cancers associated with MTS include colonic, genitourinary, breast, endometrial, biliary, and pancreatic, with colon cancer being the most common.1-3Cutaneous manifestations of MTS precede the diagnosis of visceral cancer in 22% to 60% of cases.1 Sebaceous adenoma is the most commonly associated cutaneous neoplasm, occurring in nearly 70% of patients with MTS; therefore, the presence of 2 or more sebaceous adenomas should alert the clinician to the possibility of MTS. Sebaceous epithelioma and sebaceous carcinoma are present in roughly 30% of cases, and keratoacanthomas occur in approximately 20% of cases. At least 4 DNA mismatch repair (MMR) genes have been implicated in the pathogenesis of MTS, including MSH2, MSH6, MLH1, and PMS2. Despite most HNCCS cases having germline mutations of MLH1, germline mutations in patients with MTS are most commonly of MSH2. Loss of MMR genes has been shown to cause microsatellite instability, giving way to an increased risk of cancer formation.4-6The Mayo Muir-Torre syndrome risk score algorithm7 can be used to help identify patients who are at high risk for MTS and should be referred for genetic testing. It includes 4 variables: (1) age at sebaceous neoplasm diagnosis (younger than 60 years is a positive finding); (2) total number of sebaceous neoplasms (2 or more is a positive findings); (3) personal history of any Lynch-related cancer; and (4) family history of any Lynch-related cancer.4 Having 2 or more sebaceous neoplasms alone, or any 2 positive findings in the 4 criteria of the Mayo algorithm, is highly suggestive of MTS.Owing to their significantly increased lifetime risk of visceral cancer, patients with MTS require early and frequent cancer screening. Annual hemoccult testing and annual to biannual colonoscopy starting at age 25 years is recommended. Since most colon cancer develops at or proximal to the splenic flexure in patients with MTS, complete colonoscopy rather than sigmoidoscopy alone is required.1 Yearly transvaginal ultrasonography is recommended to screen for gynecologic cancer.8,9 Yearly urinalysis beginning between age 25 to 35 years may be considered.Cowden syndrome, basal cell nevus syndrome, and Birt-Hogg-Dubé syndrome are other autosomal dominant genodermatoses with increased cancer risk. Cowden syndrome results from PTEN gene mutations and is characterized by multiple mucocutaneous hamartomas and an increased risk for breast, thyroid, renal, endometrial, and colorectal cancers. Clinical manifestations of basal cell nevus syndrome, resulting from PTCH gene mutation, include multiple basal cell carcinomas, keratocystic odontogenic tumors of the jaw, palmar and plantar pits, congenital skeletal abnormalities, and less commonly, medulloblastomas. Finally, Birt-Hogg-Dubé syndrome, caused by folliculin gene mutation, is characterized by the presence of fibrofolliculomas, trichodiscomas, pulmonary cysts with spontaneous pneumothoraces, and renal tumors.10

Dermatology

A 41-year-old woman presented with a rapidly growing, painful nodule on her upper cutaneous lip (Figure, A) as well as several smaller papules on her face and neck, all of which had developed within the preceding 6 months. She was otherwise asymptomatic.A, Centrally depressed, firm, pink 1.1-cm nodule on the upper cutaneous lip and skin-colored papule on the left medial cheek (above marker dots). B, Cup-shaped tumor demonstrated keratinocyte atypia with a central core of keratinaceous debris. C, Sebaceous tumor with a modestly increased ratio of basaloid cells to sebocytes.The patient’s medical history included diabetes mellitus type 2, hypercholesterolemia, hypertension, and depression. Review of her family medical history revealed that her paternal grandfather died from melanoma and that her father died from colon cancer. She stated that most of the men in her family had died from some form of cancer by the fourth decade of life.On physical examination, a tender, centrally depressed, firm, pink 1.1-cm nodule was present on her upper cutaneous lip (Figure, A). Three other skin-colored to pink papules were present on her face and neck. Shave biopsies of all 4 skin lesions were performed (Figure, B and C).

what is your diagnosis?

What is your diagnosis?

Cowden syndrome

Basal cell nevus syndrome

Birt-Hogg-Dube syndrome

Muir-Torre syndrome

d

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2443247

A young man presented for a second opinion regarding acquired color blindness and visual loss. He was recently hospitalized for confusion, short-term memory loss, vomiting, and diarrhea. He also experienced hair loss (Figure 1), a facial rash, hoarseness, and painful peripheral neuropathy in his feet. His blood pressure on admission was 150/102 mm Hg, his pulse was 118 beats/min, and ophthalmic examination findings demonstrated decreased visual acuity and dyschromatopsia. He reported difficulty opening his eyelids during hospitalization but denied any history of diplopia. Results of a complete blood cell count, comprehensive metabolic panel, and erythrocyte sedimentation rate were within reference limits, and computed tomography of the head without contrast showed no abnormalities. A lumbar puncture showed normal opening pressure with a mildly elevated protein level in the cerebrospinal fluid.Alopecia was noted in our patient in addition to temporal thinning of the lateral half of the eyebrows.On our examination, best-corrected visual acuity was 20/70 OU. Extraocular motility was full in both eyes, and confrontational visual field test findings were full in all quadrants. The patient missed 4 color plates on Ishihara pseudoisochromatic testing. The slitlamp examination revealed an unremarkable anterior segment, and results of dilated ophthalmoscopy showed temporal optic nerve pallor in both eyes. The macula, vessels, and retinal periphery were unremarkable on examination. Automated perimetry showed bilateral central scotomas, and results of a multifocal electroretinogram were normal.Check vitamin B12 levels and ask about smoking history What Would You Do Next?

Test for mitochondrial optic neuropathies

Check blood and urine for heavy metals

Check vitamin B12 levels and ask about smoking history

Rule out an underlying neoplastic process

Thallium poisoning

B

Check blood and urine for heavy metals

Thallium, a heavy metal that does not occur freely in nature, was first discovered in 1861 by Crookes1 as a byproduct of sulfuric acid production. Thallium is used clinically in nontoxic doses for nuclear imaging, such as cardiac stress testing, and commercially in infrared optics, electronics, semiconductor materials, and imitation jewelry. Thallium was a common ingredient in rat poisons and insecticides but was banned for this use in the United States in 1972 owing to contamination of wildlife.2 Because it is colorless, odorless, and tasteless, thallium has a well-documented history of malicious use as a poison in popular culture3 and in the scientific literature.4,5The toxic effects of thallium result from its similarity to potassium in charge and ionic size. Thallium is readily absorbed through the skin and gastrointestinal tract and enters cells through the potassium uptake pathway. Thallium displaces potassium in a number of biological processes and inhibits a number of key enzymes, such as sodium-potassium adenosine triphosphatase. Thallium therefore interferes with cellular membrane integrity in the peripheral and central nervous systems4 and is associated with axonal degeneration.6The prognosis for thallium poisoning is guarded and depends on the amount of exposure, body weight, and time to onset of treatment. The lethal dose for humans is 15 to 20 mg/kg of body weight, and the reported mortality rate is 6% to 15%.6 Initial symptoms of thallium poisoning resemble gastroenteritis (nausea, vomiting, abdominal pain, and diarrhea) and appear within 8 to 12 hours of exposure. Neurologic symptoms follow a few days later with a painful ascending sensory neuropathy, one of the hallmarks of thallium poisoning, along with confusion, lethargy, tremor, and ataxia. Dermatologic symptoms include alopecia—another hallmark—occurring 1 to 2 weeks after exposure (Figure 1), acneiform eruptions, a papulomacular rash, and Mees lines (a characteristic white band in the nail bed) (Figure 2). Ophthalmologic findings of poisoning include hair loss of the lateral half of the eyebrows (Figure 1), ptosis, ophthalmoplegia, and keratitis. Toxic optic neuropathy with eventual optic atrophy frequently occurs, and patients often have decreased contrast sensitivity, central scotomas, and abnormal color vision (tritanomaly).5,6 To our knowledge, one case of central retinal depression on multifocal electroretinography has been reported.5 Treatment for thallium poisoning consists of supportive care and elimination of the heavy metal from the body through hemodialysis and oral administration of Prussian blue, which binds thallium ions in the gut and aids in thallium elimination through the stool.Characteristic Mees lines (horizontal white bands) are seen in the nail beds.During his initial hospitalization, the patient’s constellation of symptoms left his physicians puzzled regarding the cause. Results of testing for syphilis, tick-borne disease, and serum antinuclear antibodies were normal. Levels of thyrotropin, free thyroxine, free metanephrine, and normetanephrine were within normal limits. Magnetic resonance imaging of the abdomen failed to reveal a neuroendocrine tumor. A careful history with specific inquiry about possible exposure to heavy metals or toxic chemicals proved to be the key in arriving at a diagnosis. Through this history, we learned that the patient is a graduate student who works in a chemistry laboratory containing thallium. Although no other students or faculty were affected, and the thallium was sealed without evidence of tampering, occupational exposure was the likely culprit. Thallium is not included in standard urinalysis for heavy metals, which only tests for arsenic, mercury, and lead, and likely contributed to a delay in diagnosis. His blood thallium level was greater than 100 µg/L (reference limit, <5 µg/L), which decreased to 25 µg/L 1 week after starting oral Prussian blue therapy and undergoing 3 sessions of hemodialysis.

Ophthalmology

A young man presented for a second opinion regarding acquired color blindness and visual loss. He was recently hospitalized for confusion, short-term memory loss, vomiting, and diarrhea. He also experienced hair loss (Figure 1), a facial rash, hoarseness, and painful peripheral neuropathy in his feet. His blood pressure on admission was 150/102 mm Hg, his pulse was 118 beats/min, and ophthalmic examination findings demonstrated decreased visual acuity and dyschromatopsia. He reported difficulty opening his eyelids during hospitalization but denied any history of diplopia. Results of a complete blood cell count, comprehensive metabolic panel, and erythrocyte sedimentation rate were within reference limits, and computed tomography of the head without contrast showed no abnormalities. A lumbar puncture showed normal opening pressure with a mildly elevated protein level in the cerebrospinal fluid.Alopecia was noted in our patient in addition to temporal thinning of the lateral half of the eyebrows.On our examination, best-corrected visual acuity was 20/70 OU. Extraocular motility was full in both eyes, and confrontational visual field test findings were full in all quadrants. The patient missed 4 color plates on Ishihara pseudoisochromatic testing. The slitlamp examination revealed an unremarkable anterior segment, and results of dilated ophthalmoscopy showed temporal optic nerve pallor in both eyes. The macula, vessels, and retinal periphery were unremarkable on examination. Automated perimetry showed bilateral central scotomas, and results of a multifocal electroretinogram were normal.Check vitamin B12 levels and ask about smoking history

what would you do next?

What would you do next?

Check vitamin B12 levels and ask about smoking history

Test for mitochondrial optic neuropathies

Rule out an underlying neoplastic process

Check blood and urine for heavy metals

d

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2448576

A healthy white man in his late 70s was referred to the retina clinic for evaluation of nerve fiber layer infarcts (cotton-wool spots). He had been experiencing nonprogressive diminished vision in his left eye for 6 weeks. He denied any history of diabetes or past ocular problems and reported having mild hypertension for which he was taking lisinopril. Review of systems was positive for fatigue of his tongue while eating but he denied any jaw claudication, fevers, malaise, joint pain, or weight loss. His best-corrected visual acuity was 20/25 OD and 20/30 OS. Pupillary and anterior segment examination in both eyes were unremarkable with the exception of bilateral nuclear sclerotic cataracts. Dilated fundus examination of the right eye showed a nerve fiber layer infarct (NFLI) inferior to the optic nerve (Figure 1A). In the left eye, there were several scattered NFLIs in the peripapillary region (Figure 1B). Fluorescein angiography (FA) showed relatively normal flow without evidence of occlusion or vasculitis. An extensive inflammatory and infectious laboratory workup revealed a hemoglobin level of 12.6 g/dL and elevated erythrocyte sedimentation rate and C-reactive protein level of 54 mm/h and 6.16 mg/L, respectively (to convert hemoglobin to grams per liter, multiply by 10, and C-reactive protein to nanomoles per liter, multiply by 9.524). Antinuclear antibody testing was positive (1:80 with homogenous pattern). Further workup including human immunodeficiency virus testing was nonrevealing.Fundus photographs of the right and left eye demonstrating nerve fiber layer infarcts in the peripapillary region. Media clarity is affected by nuclear sclerotic cataracts in both eyes.Refer patient to primary care physician for management of his hypertension What Would You Do Next?

Proceed with temporal artery biopsy

Refer patient to primary care physician for management of his hypertension

Refer for rheumatologic workup

Observe and reevaluate in 2 months

Giant cell arteritis

A

Proceed with temporal artery biopsy

Given the examination findings and elevated inflammatory markers, the patient underwent a temporal artery biopsy (TAB), which was positive for giant cell arteritis (GCA). The patient started receiving 60 mg of oral prednisone. Nerve fiber layer infarcts can be seen in a wide variety of ocular and systemic conditions. These include ischemia (diabetes, hypertension, and retinal vein occlusion), neoplasia (leukemia and lymphoma), infections (human immunodeficiency virus), immunologic diseases (systemic lupus erythematosus), medications (interferon), and radiation, among others. In this patient, there were no other retinal findings characteristic of chronic hypertension. Moreover, he did not fulfill any criteria for the diagnosis of systemic lupus erythematosus. Although most patients with GCA have markedly elevated inflammatory markers, the elevated erythrocyte sedimentation rate and C-reactive protein values in this patient were suggestive of GCA in the appropriate clinical setting, and the TAB confirmed the diagnosis.Prompt recognition of GCA and initiation of systemic steroids, even before performing TAB, are imperative to prevent irreversible vision loss. The diagnostic yield of TAB is highest within 2 weeks of initiating corticosteroid therapy; however, the rate of biopsy positivity is still very good within 4 weeks of therapy.1 It is estimated that as many as 40% of GCA presentations are atypical, and nearly 21% of patients with GCA who have visual symptoms do not have other manifestations.2-4 Nerve fiber layer infarcts can be an early manifestation of GCA, and their presence raises the suspicion for this condition when associated with characteristic symptoms, elevated inflammatory markers, or findings on FA indicating retinal or choroidal nonperfusion.5,6 In this case, a thorough review of systems was positive only for a complaint of tongue fatigue while eating, and the FA was unremarkable.In summary, this case demonstrates that NFLIs can be an early manifestation of GCA, even before the development of severe vision loss. Their presence should alert the clinician to consider performing a thorough review of systems and obtain laboratory tests as deemed indicated. Their presence in this patient led to the early diagnosis of this visually threatening systemic condition.The patient had subjective improvement of his visual symptoms and resolution of the NFLIs on follow-up examination at 1 month after his initial presentation (Figure 2).Fundus photograph of the left eye showing near complete resolution 1 month after the initiation of systemic steroids.

Ophthalmology

A healthy white man in his late 70s was referred to the retina clinic for evaluation of nerve fiber layer infarcts (cotton-wool spots). He had been experiencing nonprogressive diminished vision in his left eye for 6 weeks. He denied any history of diabetes or past ocular problems and reported having mild hypertension for which he was taking lisinopril. Review of systems was positive for fatigue of his tongue while eating but he denied any jaw claudication, fevers, malaise, joint pain, or weight loss. His best-corrected visual acuity was 20/25 OD and 20/30 OS. Pupillary and anterior segment examination in both eyes were unremarkable with the exception of bilateral nuclear sclerotic cataracts. Dilated fundus examination of the right eye showed a nerve fiber layer infarct (NFLI) inferior to the optic nerve (Figure 1A). In the left eye, there were several scattered NFLIs in the peripapillary region (Figure 1B). Fluorescein angiography (FA) showed relatively normal flow without evidence of occlusion or vasculitis. An extensive inflammatory and infectious laboratory workup revealed a hemoglobin level of 12.6 g/dL and elevated erythrocyte sedimentation rate and C-reactive protein level of 54 mm/h and 6.16 mg/L, respectively (to convert hemoglobin to grams per liter, multiply by 10, and C-reactive protein to nanomoles per liter, multiply by 9.524). Antinuclear antibody testing was positive (1:80 with homogenous pattern). Further workup including human immunodeficiency virus testing was nonrevealing.Fundus photographs of the right and left eye demonstrating nerve fiber layer infarcts in the peripapillary region. Media clarity is affected by nuclear sclerotic cataracts in both eyes.Refer patient to primary care physician for management of his hypertension

what would you do next?

What would you do next?

Refer patient to primary care physician for management of his hypertension

Observe and reevaluate in 2 months

Proceed with temporal artery biopsy

Refer for rheumatologic workup

c

male

71-80

White

original

https://jamanetwork.com/journals/jama/fullarticle/2473467

A 64-year-old African American woman presented to the emergency department for evaluation of bleeding mouth sores, tender crusted plaques on her scalp, and blisters on her skin. Three weeks previously, she noticed painful erosions throughout her mouth. A week later, painful blisters appeared on her upper extremities, trunk, and thighs. She also reported 2 pruritic and painful lesions on her scalp that had appeared 6 months prior, shortly after a chemical hair treatment. She had a history of alcohol, tobacco, cocaine, and marijuana use but denied current illicit drug use. She had not taken any medications prior to the appearance of the lesions. The patient reported a 2.25-kg weight loss, subjective fevers, and chills but no urinary symptoms.On admission, the patient was tachycardic (113/min), but she was afebrile and other vital signs were normal. Physical examination revealed crusted plaques on her scalp bilaterally (Figure). Erosive stomatitis involving the lower lip, buccal mucosa, hard palate, soft palate, and tongue was noted (Figure). Multiple well-circumscribed, round-to-oval bullae, erosions, and hyperpigmented patches were noted on her upper extremities, trunk, and thighs (Figure). Laboratory evaluation revealed a serum creatinine level of 7.1 mg/dL (627.6 μmol/L), up from a baseline (10 days prior) level of 0.9 mg/dL (79.6 μmol/L). Urinalysis revealed a specific gravity of 1.015 and was positive for hyaline casts and protein but negative for white blood cells, red blood cells, and bacteria. A complete blood cell count was unremarkable. Results of human immunodeficiency virus screen and urine drug screen were normal.Left, Crusted plaques on scalp of patient. Center, Erosive stomatitis of the lower lip, buccal mucosa, hard palate, soft palate, and tongue. Right, Bullae and erosions on the upper back. What Would You Do Next?

Treat with oral acyclovir

Perform renal biopsy

Treat with oral corticosteroids

Perform skin biopsy for immunofluorescence

Pemphigus vulgaris

D

Perform skin biopsy for immunofluorescence

The key clinical feature is the presence of cutaneous bullae and erosions with oral involvement. Although this patient’s physical examination was classic for pemphigus vulgaris, her case was complicated by acute renal failure. Differential diagnosis for the eruption includes bullous lupus, the pemphigoid group of disorders, evolving Stevens-Johnson syndrome (SJS), and widespread herpes simplex virus (HSV) infection complicated by erythema multiforme major. Unlike pemphigus vulgaris, bullous lupus and the pemphigoid group of disorders present with tense bullae that are less likely to rupture, and oral involvement is less frequent. Although SJS and HSV usually involve the oral mucosa, SJS presents with coalescing bullae causing widespread desquamation of the skin, and HSV presents as grouped vesicles rather than individual bullae.The next best step is to confirm a diagnosis of pemphigus vulgaris by direct or indirect immunofluorescence or by enzyme-linked immunosorbent assay (ELISA) for circulating autoantibodies to desmoglein (Dsg) 1 or 3. Empirical therapy with acyclovir or corticosteroids should not be initiated before definitive diagnosis. Renal biopsy is an invasive procedure and is not the most appropriate next step prior to assessment of fluid status.Pemphigus vulgaris is a rare and potentially fatal autoimmune disease causing blisters to the oral mucosa and skin.1-4 The incidence is 1 to 5 per million per year.1-3 If left untreated, the mortality rate is 75%.1-3,5 The disease usually presents between 40 and 60 years of age and is most commonly diagnosed in persons of Mediterranean and Jewish descent.3,5Pemphigus is caused by IgG autoantibodies directed against Dsg 1, Dsg 3, or both on the surface of keratinocytes, which causes the cells to separate from one another, resulting in blisters.3 In pemphigus vulgaris, antibodies are primarily directed at the cell adhesion molecule Dsg 3, which is predominantly present in the suprabasal layer of the epidermis and in the oral mucosal epithelium.3,6 Anti–Dsg 3 antibodies are found in the mucosal-dominant type of pemphigus vulgaris, whereas both anti–Dsg 3 and anti–Dsg 1 are found in the mucocutaneous type.3Pemphigus vulgaris presents with flaccid bullae on the skin that rupture, leaving behind erosions.1,3,5,7 The oral mucosa is the most common site of presentation.3-5,7 Diagnosis is based on clinical features, suprabasal acantholysis on histology, and at least 1 positive immunochemical test result (direct immunofluorescence, indirect immunofluorescence, or ELISA).3,5,7High-potency systemic corticosteroids (1.0 mg/kg per day) are the mainstay of treatment.1-5,8 However, long-term use of high-potency systemic corticosteroids is associated with severe complications, including osteoporosis and susceptibility to infections.2,3 An alternative treatment regimen is a lower dose of systemic corticosteroids used with adjuvant immunosuppressive therapy with azathioprine or mycophenolate mofetil.1-5,8 Recently, rituximab has been shown to be an effective alternative to high-potency systemic corticosteroids for patients with refractory pemphigus vulgaris or contraindications to systemic steroids.8,9A shave biopsy from a back lesion showed suprabasal acantholysis and bulla. Direct immunofluorescence testing of punch biopsies from the edges of lesions on the back and scalp showed intercellular deposition of IgG and C3 in the lower epidermis. Indirect immunofluorescence on monkey esophagus substrate revealed serum cell surface IgG antibodies. Testing with ELISA revealed elevated anti–Dsg 1 and anti–Dsg 3 antibodies (132 U and 187 U, respectively). Therapy was initiated with an oral anesthetic rinse, oral prednisone (60 mg daily), and topical corticosteroids. With intravenous fluid administration, the patient’s creatinine level corrected to 0.7 mg/dL (61.9 μmol/L), suggesting acute renal failure most likely attributable to decreased oral intake secondary to pain. The patient was discharged with follow-up in dermatology clinic to initiate azathioprine as an outpatient.

General

A 64-year-old African American woman presented to the emergency department for evaluation of bleeding mouth sores, tender crusted plaques on her scalp, and blisters on her skin. Three weeks previously, she noticed painful erosions throughout her mouth. A week later, painful blisters appeared on her upper extremities, trunk, and thighs. She also reported 2 pruritic and painful lesions on her scalp that had appeared 6 months prior, shortly after a chemical hair treatment. She had a history of alcohol, tobacco, cocaine, and marijuana use but denied current illicit drug use. She had not taken any medications prior to the appearance of the lesions. The patient reported a 2.25-kg weight loss, subjective fevers, and chills but no urinary symptoms.On admission, the patient was tachycardic (113/min), but she was afebrile and other vital signs were normal. Physical examination revealed crusted plaques on her scalp bilaterally (Figure). Erosive stomatitis involving the lower lip, buccal mucosa, hard palate, soft palate, and tongue was noted (Figure). Multiple well-circumscribed, round-to-oval bullae, erosions, and hyperpigmented patches were noted on her upper extremities, trunk, and thighs (Figure). Laboratory evaluation revealed a serum creatinine level of 7.1 mg/dL (627.6 μmol/L), up from a baseline (10 days prior) level of 0.9 mg/dL (79.6 μmol/L). Urinalysis revealed a specific gravity of 1.015 and was positive for hyaline casts and protein but negative for white blood cells, red blood cells, and bacteria. A complete blood cell count was unremarkable. Results of human immunodeficiency virus screen and urine drug screen were normal.Left, Crusted plaques on scalp of patient. Center, Erosive stomatitis of the lower lip, buccal mucosa, hard palate, soft palate, and tongue. Right, Bullae and erosions on the upper back.

what would you do next?

What would you do next?

Perform renal biopsy

Treat with oral acyclovir

Treat with oral corticosteroids

Perform skin biopsy for immunofluorescence

d

female

61-70

African American

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2474666

A male neonate was born at 25 weeks’ gestation by cesarean delivery because of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in his primigravid mother, who also had systemic lupus erythematosus managed with hydroxychloroquine, aspirin, and prednisone during pregnancy. The patient’s premature birth was complicated by acute respiratory distress that necessitated intubation and necrotizing enterocolitis that required parenteral nutrition. At birth, the patient was found to be mildly anemic (hemoglobin level, 11.0 g/dL [to convert to grams per liter, multiply by 10]) and thrombocytopenic (platelet count, 120 × 103/µL [to convert to 109/L, multiply by 1]) with concomitant intraventricular hemorrhage. Although afebrile, he was treated empirically for sepsis with vancomycin hydrochloride and cefepime hydrochloride. A cerebrospinal fluid culture result was positive for Staphylococcus epidermidis, but the results of additional blood cultures were negative for organisms. On day 8 after birth, a 0.5-cm, circular, crusted papule with a surrounding rim of erythema on the left hip was noted (Figure, A). A punch biopsy of the lesion was performed (Figure, B and C).A, Crusted circular papule with a surrounding rim of erythema and induration on the left hip. B, Biopsy specimen revealing epidermal necrosis with fungal elements within the superficial dermis (hematoxylin-eosin, original magnification ×20). C, Biopsy specimen highlighting branching and septate hyphae within the superficial dermis (specimen was stained with Gomori methenamine silver, original magnification ×40). What Is Your Diagnosis?

Pressure ulcer

Cutaneous fungal infection

Neonatal lupus erythematosus

Ecthyma gangrenosum

B. Cutaneous fungal infection

B

Cutaneous fungal infection

Histopathologic examination of the biopsy specimen revealed a necrotic ulcer with branching, septate hyphae within the superficial dermis without angioinvasion. Chest radiography, abdominal ultrasonography, and funduscopic examination revealed no evidence of disseminated fungal infection, and fungal blood culture results were negative for organisms. A tissue culture yielded Aspergillus fumigatus, confirming the diagnosis of primary cutaneous aspergillosis. Given the patient’s extreme prematurity and numerous comorbidities, surgical debridement was not attempted. The patient was successfully treated with intravenous liposomal amphotericin B alone for 21 days and eventually discharged home.Aspergillus (Aspergillus flavus and Aspergillus fumigatus being the most common human pathogens) is a ubiquitous environmental fungus that produces conidia in soil and vegetation. These fungal elements exhibit airborne dissemination and can contaminate ventilation systems. In fact, aspergillosis outbreaks have been reported in connection with construction near hospitals.1 Infection can occur from primary inoculation of the skin by contaminated objects, such as implanted foreign bodies, surgical instruments, or intravenous catheters, which usually produce a single lesion or a cluster of lesions. Multiple dispersed cutaneous lesions alternatively would suggest dissemination from a bloodstream infection, most often from a pulmonary source related to spore inhalation.2Cutaneous aspergillosis is most frequently diagnosed in immunocompromised individuals in the context of transplantation, human immunodeficiency virus infection, iatrogenic immunosuppression, or, as in this case, extreme prematurity. The incidence of aspergillosis has alarmingly increased at least 3-fold in the last 10 years, which is likely related to improved survival of immunocompromised patients, namely, premature neonates and those with hematologic malignant neoplasms.3 A review4 of 26 deep cutaneous fungal infections in a pediatric population revealed that Aspergillus was the most commonly isolated species in 44% of cases, followed by Candida in 33%. Specific risk factors in these cases included broad-spectrum antibiotic use (90% of cases) and neutropenia (50% of cases). Compromised skin barrier is another critical risk factor that allows entry and spread of Aspergillus within subepidermal tissues. Prior reports5-7 have accordingly linked cutaneous aspergillosis to traumatic insults, including thermal burns, lacerations, and even adhesive tape. In our case, there was no known history of trauma, but the patient was exposed to broad-spectrum antibiotics given the concern for sepsis and prednisone due to maternal lupus. Although antibiotics are thought to destroy protective flora to permit fungal growth, systemic corticosteroids impart a dual risk owing to impaired skin integrity in addition to immunosuppression.Early recognition of neonatal cutaneous fungal infections is critical to successful treatment because lethal dissemination can occur from a skin inoculation site. Cutaneous aspergillosis, like other deep fungal infections of the skin, often begins as a nonspecific erythematous papule or nodule. However, as fungi proliferate, lesions can develop a central pustule (from neutrophilic infiltration), ulceration or crusting (from epidermal necrosis), or purpura (from vascular compromise).8 These signs should prompt urgent dermatologic consultation because diagnosis of cutaneous aspergillosis is most effectively established by skin biopsy, which allows histopathologic examination and tissue culture to permit speciation and antifungal susceptibility testing.The recognized first-line treatment of aspergillosis in neonates is intravenous amphotericin B, but voriconazole has been used successfully in select instances. Isolated lesions of primary cutaneous aspergillosis are often treated with surgical resection to reduce the risk of dissemination from skin via vascular invasion; however, nonsurgical cure has been reported with amphotericin B alone9 or with voriconazole and micafungin after initial amphotericin B treatment.10 In our case, liposomal amphotericin B alone was used for 21 days, and the lesion resolved without recurrence or evidence of dissemination. Surgical debridement was deferred because of the patient’s extreme prematurity and numerous comorbidities, which made him a very high-risk surgical candidate.

Pediatrics

A male neonate was born at 25 weeks’ gestation by cesarean delivery because of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in his primigravid mother, who also had systemic lupus erythematosus managed with hydroxychloroquine, aspirin, and prednisone during pregnancy. The patient’s premature birth was complicated by acute respiratory distress that necessitated intubation and necrotizing enterocolitis that required parenteral nutrition. At birth, the patient was found to be mildly anemic (hemoglobin level, 11.0 g/dL [to convert to grams per liter, multiply by 10]) and thrombocytopenic (platelet count, 120 × 103/µL [to convert to 109/L, multiply by 1]) with concomitant intraventricular hemorrhage. Although afebrile, he was treated empirically for sepsis with vancomycin hydrochloride and cefepime hydrochloride. A cerebrospinal fluid culture result was positive for Staphylococcus epidermidis, but the results of additional blood cultures were negative for organisms. On day 8 after birth, a 0.5-cm, circular, crusted papule with a surrounding rim of erythema on the left hip was noted (Figure, A). A punch biopsy of the lesion was performed (Figure, B and C).A, Crusted circular papule with a surrounding rim of erythema and induration on the left hip. B, Biopsy specimen revealing epidermal necrosis with fungal elements within the superficial dermis (hematoxylin-eosin, original magnification ×20). C, Biopsy specimen highlighting branching and septate hyphae within the superficial dermis (specimen was stained with Gomori methenamine silver, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Cutaneous fungal infection

Neonatal lupus erythematosus

Ecthyma gangrenosum

Pressure ulcer

a

male

21-30

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2427487

A Hispanic man in his 20s with no known medical history presented with worsening abdominal pain over 5 days, persistent pruritus, and scleral icterus. The patient noted swelling on the right side of the neck and a 5-kg weight loss over the past 2 months. He reported a history of moderate alcohol consumption, drinking 1 beer per day during the week and approximately 5 to 8 beers over the weekend, but denied any use of nutritional supplements or illicit drugs. There was no recent travel outside the state. Human immunodeficiency virus test results on admission were negative. Physical examination revealed scleral icterus, jaundice, and a fixed right supraclavicular lymph node conglomerate measuring 6 × 3 cm. There was no cervical, left supraclavicular, axillary, or inguinal lymphadenopathy. Computed tomography of the neck, chest, abdomen, and pelvis demonstrated a large right supraclavicular lymph node, extensive mediastinal lymphadenopathy, a large extracardiac mass abutting the left atrium, hepatomegaly, and multiple splenic lesions. Laboratory evaluation demonstrated a total serum bilirubin level of 10.5 mg/dL with a direct component of 8.4 mg/dL (to convert to micromoles per liter, multiply by 17.104). Renal function was normal. Mild leukopenia and slight thrombocytopenia in the absence of associated anemia was noted on initial complete blood cell count. A liver biopsy was performed, with results shown in Figure 1.Hepatic biopsy at time of presentation shows a portal tract containing both hepatic artery and hepatic vein branches (hematoxylin-eosin, original magnification ×40).Vanishing bile duct syndrome associated with Hodgkin lymphoma What Is Your Diagnosis?

Acute hepatitis associated with Epstein-Barr virus infection

Vanishing bile duct syndrome associated with Hodgkin lymphoma

Sarcoidosis

Metastatic cholangiocarcinoma secondary to primary sclerosing cholangitis

B. Vanishing bile duct syndrome associated with Hodgkin lymphoma

B

Vanishing bile duct syndrome associated with Hodgkin lymphoma

A right cervical lymph node core biopsy was CD15+, CD20−, CD30+, consistent with classic Hodgkin lymphoma. Liver biopsy revealed absent bile ducts with associated hepatocellular and canalicular cholestasis. There was no inflammation, lymphomatous infiltration, or necrosis present. Staining for CK7 showed a decreased number of small bile ducts (Figure 2). A diagnosis of vanishing bile duct syndrome (VBDS) secondary to stage IV Hodgkin lymphoma was made.CK7 Immunostaining highlighting bile duct damage and reduction in number of surrounding bile ducts (original magnification ×40).Hepatic involvement in Hodgkin lymphoma is common and more frequent in advanced disease.1 Etiologies of cholestasis in these patients include direct intrahepatic parenchymal involvement, extrahepatic biliary obstruction secondary to lymphadenopathy, drug toxicity, and underlying liver disease. Paraneoplastic manifestations of Hodgkin lymphoma include idiopathic cholestasis and VBDS. Ductopenia, defined as loss of interlobular bile ducts in more than 50% of portal tracts within a histologic specimen, helps distinguish between these 2 entities. An ideal biopsy sample is 3 cm long with at least 11 portal tracts (>20 is optimal).2 Immunostaining for biliary elements may improve diagnostic yield. Direct hepatic involvement from lymphoma is absent in most specimens.Vanishing bile duct syndrome was first described in 3 patients with Hodgkin lymphoma presenting with severe intrahepatic cholestasis. Liver biopsy demonstrated absent bile ducts and a characteristic “burned out appearance” of the portal tracts.3 The cause of VBDS is unclear, but biliary duct damage due to cytokine release from lymphoma cells seems likely.4 No specific biliary epithelial-associated autoantibody has been found in Hodgkin-associated VBDS.5 Our patient’s disease was positive for Epstein-Barr virus, but this has no known association with VBDS.Historically considered a poor prognostic factor, VBDS was associated with a 1-year overall survival of 43% in a series of 37 affected patients.6 Hepatic damage appeared reversible. Improved outcomes in VBDS correlate with more efficacious lymphoma therapies. Hepatic impairment at time of diagnosis often limits use of optimal cytotoxic therapy. Subtotal lymphoid irradiation (STLI) for patients with early-stage nonbulky Hodgkin lymphoma has failure-free survival rates of 81% to 93%, compared with 94% to 96% with chemotherapy alone.7 For patients with VBDS and early-stage disease, definitive therapy with STLI is a reasonable treatment option. Patients with advanced disease can receive high-dose steroids and ursodiol to facilitate administration of dose-reduced chemotherapy.8 Development of antibody-drug conjugates with improved hepatic tolerance such as brentuximab vedotin offers new options for patients with Hodgkin lymphoma–associated VBDS.Our patient initially received corticosteroids, with minimal improvement in his cholestasis. Given his advanced disease, young age, and excellent performance status, a trial of dose-reduced brentuximab vedotin (1.2 mg/kg) was administered. After 3 cycles of dose-reduced brentuximab, repeat imaging showed partial response. Cholestasis improved but the patient’s intractable pruritus persisted. He started biliary apheresis with resolution of symptoms after 15 sessions.9 He had a complete response after 6 cycles of doxorubicin, bleomycin sulfate, vinblastine sulfate, and dacarbazine and has returned to work with no sequelae of treatment 1 year after diagnosis. To our knowledge, this is the first report of a patient receiving up-front brentuximab to achieve temporary control of VBDS prior to definitive treatment with conventional chemotherapy.

Oncology

A Hispanic man in his 20s with no known medical history presented with worsening abdominal pain over 5 days, persistent pruritus, and scleral icterus. The patient noted swelling on the right side of the neck and a 5-kg weight loss over the past 2 months. He reported a history of moderate alcohol consumption, drinking 1 beer per day during the week and approximately 5 to 8 beers over the weekend, but denied any use of nutritional supplements or illicit drugs. There was no recent travel outside the state. Human immunodeficiency virus test results on admission were negative. Physical examination revealed scleral icterus, jaundice, and a fixed right supraclavicular lymph node conglomerate measuring 6 × 3 cm. There was no cervical, left supraclavicular, axillary, or inguinal lymphadenopathy. Computed tomography of the neck, chest, abdomen, and pelvis demonstrated a large right supraclavicular lymph node, extensive mediastinal lymphadenopathy, a large extracardiac mass abutting the left atrium, hepatomegaly, and multiple splenic lesions. Laboratory evaluation demonstrated a total serum bilirubin level of 10.5 mg/dL with a direct component of 8.4 mg/dL (to convert to micromoles per liter, multiply by 17.104). Renal function was normal. Mild leukopenia and slight thrombocytopenia in the absence of associated anemia was noted on initial complete blood cell count. A liver biopsy was performed, with results shown in Figure 1.Hepatic biopsy at time of presentation shows a portal tract containing both hepatic artery and hepatic vein branches (hematoxylin-eosin, original magnification ×40).Vanishing bile duct syndrome associated with Hodgkin lymphoma

what is your diagnosis?

What is your diagnosis?

Metastatic cholangiocarcinoma secondary to primary sclerosing cholangitis

Acute hepatitis associated with Epstein-Barr virus infection

Sarcoidosis

Vanishing bile duct syndrome associated with Hodgkin lymphoma

d

male

21-30

Hispanic

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2456109

A woman in her 70s was referred to our tertiary care center for an asymptomatic mass of the gastric fundus. Her medical history was significant for chronic gastritis, which was being treated with esomeprazole 20 mg; a laparoscopic cholecystectomy 18 years prior; and excision of a 26-mm Merkel cell carcinoma of the left knee with negative results of the sentinel lymph node biopsy (stage II) 19 months prior. Results of the patient’s follow-up examinations were negative until a high-resolution computed tomographic scan showed a 45 × 40-mm intraluminal protruding mass with slightly enlarged lymph nodes along the lesser curvature of the gastric fundus (Figure, A). Results of fluorine 18–labeled fluorodeoxyglucose and gallium citrate Ga 68–labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (DOTATOC) positron emission tomography confirmed the presence of a metabolically active mass in the gastric fundus (maximum standardized uptake value, 6) with intense 68Ga–DOTATOC uptake (maximum standardized uptake value, 24) as well as mild 68Ga–DOTATOC uptake in 2 lymph nodes of the lesser curvature.A, Multislice computed tomographic scan showing the 45 × 40-mm mass in the gastric fundus. B, Endoscopic image showing the endophytic lesion in the posterior wall of the gastric fundus at the esophagogastric junction.Preoperative workup was completed via esophagogastroduodenoscopy, which showed the presence of the polypoid lesion in the posterior wall of the gastric fundus at the level of the esophagogastric junction (Figure, B). Multiple biopsies were performed at the time of the endoscopy. What Is Your Diagnosis?

Gastrointestinal stromal tumor

Type III neuroendocrine tumor of the stomach

Gastric metastasis of Merkel cell carcinoma

Gastric adenocarcinoma

C. Gastric metastasis of Merkel cell carcinoma

C

Gastric metastasis of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an uncommon and highly malignant cutaneous tumor of neuroendocrine origin. Exposure to UV radiation and immunosuppression are major predisposing factors to MCC. Merkel cell polyomavirus also has been implicated in the pathogenesis of MCC.1Merkel cell carcinoma has aggressive biological behavior characterized by rapid growth, early distant metastasis, and poor prognosis. The most common metastatic sites include the skin, lymph nodes, liver, lungs, and central nervous system.2 Recurrence is common, with 90% of relapses occurring within 2 years.3 Both locoregional and distant relapses are frequent, with some unusual recurrence sites occasionally reported. The prognosis of metastatic MCC is generally poor, with an estimated median survival time of 9 months.4 Gastric metastases from MCC are extremely uncommon, with fewer than 10 cases reported in the English-language literature.5-7In previously reported cases of MCC, severe gastrointestinal bleeding was the main symptom. Various treatment approaches have been reported, with the option of surgical resection limited to selected cases. However, in most patients who underwent surgical resection, the results were poor. Surgery, when performed, was characterized by major resections performed in an open procedure.5,6 In the present case, in consideration of the patient’s age as well as the location and the biological features of the tumor, laparoscopic intragastric surgery was attempted as previously described for gastrointestinal stromal tumors or submucosal tumors of the stomach.8Laparoscopic intragastric surgery represents a minimally invasive technique for the treatment of gastric endophytic lesions of the posterior wall and/or at the gastroesophageal junction. Initially described by Ohashi in 1995 to resect early gastric cancers that could not be treated by endoscopic mucosal resection,9 laparoscopic intragastric surgery has evolved with respect to both technological advances and tactical innovations. The adoption of cuffed ports for the insufflation of the stomach allows the creation of a working space and the use of laparoscopic instruments to perform a multiport laparoscopic resection.In our patient, multiport placement allowed the 2 main phases of surgery to be performed while minimizing invasiveness: (1) laparoscopic exploration and resection with negative results of intraoperative histopathologic analysis of the suspicious lymph nodes of the lesser curvature, and (2) laparoscopic intragastric full-thickness resection of the gastric metastasis by the use of an endoscopic stapling device with specimen extraction through the mouth with the use of an endobag (Video).The patient’s postoperative course was uneventful and, owing to the minimization of surgical stress and the adoption of an enhanced recovery program, it was characterized by early resumption of gut and physical functions with discharge on postoperative day 5. The diagnosis of gastric metastasis of MCC was confirmed on histopathologic examination. The resection margins of the 4-cm MCC were free of tumor and the absence of nodal involvement was confirmed. No adjuvant treatment was offered and, 12 months after surgery, the patient is alive and disease free.

Surgery

A woman in her 70s was referred to our tertiary care center for an asymptomatic mass of the gastric fundus. Her medical history was significant for chronic gastritis, which was being treated with esomeprazole 20 mg; a laparoscopic cholecystectomy 18 years prior; and excision of a 26-mm Merkel cell carcinoma of the left knee with negative results of the sentinel lymph node biopsy (stage II) 19 months prior. Results of the patient’s follow-up examinations were negative until a high-resolution computed tomographic scan showed a 45 × 40-mm intraluminal protruding mass with slightly enlarged lymph nodes along the lesser curvature of the gastric fundus (Figure, A). Results of fluorine 18–labeled fluorodeoxyglucose and gallium citrate Ga 68–labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-D-Phe1-Try3-octreotide (DOTATOC) positron emission tomography confirmed the presence of a metabolically active mass in the gastric fundus (maximum standardized uptake value, 6) with intense 68Ga–DOTATOC uptake (maximum standardized uptake value, 24) as well as mild 68Ga–DOTATOC uptake in 2 lymph nodes of the lesser curvature.A, Multislice computed tomographic scan showing the 45 × 40-mm mass in the gastric fundus. B, Endoscopic image showing the endophytic lesion in the posterior wall of the gastric fundus at the esophagogastric junction.Preoperative workup was completed via esophagogastroduodenoscopy, which showed the presence of the polypoid lesion in the posterior wall of the gastric fundus at the level of the esophagogastric junction (Figure, B). Multiple biopsies were performed at the time of the endoscopy.

what is your diagnosis?

What is your diagnosis?

Gastrointestinal stromal tumor

Gastric adenocarcinoma

Gastric metastasis of Merkel cell carcinoma

Type III neuroendocrine tumor of the stomach

c

female

71-80

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2466598

We present the case of a 40-year-old man who was admitted to our hospital with acute abdominal pain on the right flank. A similar episode had occurred 1 month before admission that improved spontaneously.A physical examination did not reveal any clinical abnormities, but the patient reported dysuria and abnormally frequent urination. A computed tomographic scan of the abdomen revealed nephrolithiasis with a 4-mm kidney stone on the right side and a slightly congested right kidney. During computed tomography, we incidentally found a 10 × 10 × 8-cm mass in the tail of the pancreas (Figure 1), as well as thrombosis of the splenic vein. His medical history was uneventful, and there was no weight loss. However, the patient’s father had died of a pancreatic carcinoma the previous year at the age of 65 years. The patient’s laboratory values, including cancer antigen 19-9 and carcinoembryonic antigen levels, were normal.Computed tomographic (CT) scans of the abdomen reveal the mass in the pancreas (arrowheads). What Is Your Diagnosis?

Cystadenoma

Cystadenocarcinoma

Hydatid cyst of the pancreas

Main duct intraductal papillary mucinous neoplasia

C. Hydatid cyst of the pancreas

C

Hydatid cyst of the pancreas

Computed tomographic findings suggested either a macrocystic cystadenoma or a solid papillary pancreatic tumor. The cystic lobulated appearance, along with some calcification, was reminiscent of a hydatid cyst. We therefore performed serological tests, which were positive for antibodies of Echinococcus granulosus (enzyme-linked immunosorbent assay: 2.30 optical density; normal value, <0.50 optical density) (indirect hemagglutination: 1024 titer; normal value, <128 titer) and negative for antibodies of Echinococcus multilocularis.Three weeks prior to surgery, albendazole therapy was initiated and pneumococcal, meningococcal, and influenza vaccinations were performed. A pancreatectomy and splenectomy were performed, as well as an en bloc resection of the cyst (Figure 2) without perforation. The postoperative period was uneventful, and the patient was discharged from the hospital in good condition. Hydatid disease is still a frequent helminthic infection in endemic areas such as the Mediterranean region, the Middle East, South America, North and East Africa, and Australia.Echinococcal disease (ie, hydatid disease), the most common type of echinococcosis, is caused by larval forms (hydatid cysts) of tapeworms of the genus Echinococcus. The tapeworm’s primary host is the canine small intestine. The intermediate hosts, who become infected by contact with the infected dog’s feces, are sheep and cattle.1 Humans may be infected by contact with host animals or by eating raw meat or intestines. The larva enters the portal vein and is carried to the liver, lungs, and other organs.1More than 90% of all hydatid cysts initially develop in the liver and lungs.2 Primary hydatid cysts in the pancreas are very rare, and less than 1% of all cysts develop in the pancreas.3-5 Fifty-seven percent of hydatid cysts develop in the head, 24% in the corpus, and 19% in the tail of the pancreas.6 Other organs such as the kidneys, spleen, brain, heart, bones, breast, and ovaries may also be affected.The symptoms of hydatid disease depend on size and location of the cyst and result from pressure on adjacent structures.1 Some authors reported cases of acute pancreatitis due to mechanical compression of the pancreatic duct by hydatid cysts.1,2,6,7 To avoid spontaneous rupture of the cysts, surgical removal is recommended as the treatment of choice.7During the past decade, several surgical procedures that depended on the location of the cyst (including pancreatectomy with and without splenectomy, cyst fenestration, and cystectomy) have been reported.2 It is necessary to avoid rupture of the cyst, and a complete evacuation of the cyst should be performed.7 Hydatidosis must be considered as a differential diagnosis for patients with cystic lesions of the pancreas,8 especially in endemic areas or if the patient was originally from an endemic area.

Surgery

We present the case of a 40-year-old man who was admitted to our hospital with acute abdominal pain on the right flank. A similar episode had occurred 1 month before admission that improved spontaneously.A physical examination did not reveal any clinical abnormities, but the patient reported dysuria and abnormally frequent urination. A computed tomographic scan of the abdomen revealed nephrolithiasis with a 4-mm kidney stone on the right side and a slightly congested right kidney. During computed tomography, we incidentally found a 10 × 10 × 8-cm mass in the tail of the pancreas (Figure 1), as well as thrombosis of the splenic vein. His medical history was uneventful, and there was no weight loss. However, the patient’s father had died of a pancreatic carcinoma the previous year at the age of 65 years. The patient’s laboratory values, including cancer antigen 19-9 and carcinoembryonic antigen levels, were normal.Computed tomographic (CT) scans of the abdomen reveal the mass in the pancreas (arrowheads).

what is your diagnosis?

What is your diagnosis?

Main duct intraductal papillary mucinous neoplasia

Cystadenoma

Hydatid cyst of the pancreas

Cystadenocarcinoma

c

male

31-40

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2434740

A woman in her 50s presented for evaluation of intermittent epigastric pain, palpitations, and hot flashes for 2 months. The patient had a history of an ovarian cyst treated conservatively, and cosmetic breast augmentation. She had a 10 pack-year smoking history and denied alcohol or illicit drug use. Examination revealed distant heart sounds but otherwise had unremarkable results. An echocardiogram demonstrated a mass in the left ventricular myocardium. Cardiac magnetic resonance imaging was obtained to further assess the mass lesion. This revealed multiple intramyocardial masses involving the left ventricle, the largest of which measured 2.7 × 2.2 cm; aortopulmonary window lymphadenopathy; and moderate pericardial effusion (Figure). Computed tomographic imaging of the chest, abdomen, and pelvis with contrast failed to reveal discrete masses or lymphadenopathy elsewhere. A transcutaneous biopsy of the left ventricular mass was nondiagnostic. What Is Your Diagnosis?

Lymphoma

Melanoma

Rhabdomyoma

Metastatic carcinoma

D. Metastatic carcinoma

D

Metastatic carcinoma

Repeated biopsy via thoracotomy revealed small blue cells with necrosis; a ribbon-like, nested, and vaguely rosetted invasive growth pattern; high mitotic activity; and a Ki-67 index of 52%. Immunohistochemical stains were positive for cytokeratin, CD56, and synaptophysin. The window lymph node was involved with metastatic disease. This was consistent with a high-grade metastatic neuroendocrine carcinoma. Somatostatin receptor scintigraphy and [18F]fluorodeoxyglucose positron-emission tomography showed increased radiotracer uptake in the myocardial masses but failed to localize the primary tumor. Serum biomarker test results for chromogranin A, pancreastatin, 5-HIAA, and neurokinin A were within normal limits. A 92-gene cancer classification assay on the biopsied specimen confirmed the diagnosis and localized the primary to the pancreas with 90% probability.Cardiac magnetic resonance imaging is the preferred imaging modality for the evaluation of incidental cardiac masses seen on echocardiogram because it can determine the extent of the tumor involvement and cellular characteristics, as well as any associated complications. Cardiac tumors are generally divided into primary (benign in 75% of cases) and include rhabdomyomas; and secondary from metastatic disease (100-1000–fold more common), which should be considered first.1 In absolute numbers, carcinoma of the lung and breast account for most cardiac metastases, but the highest percentages of cardiac involvement occur with melanoma, leukemia, and lymphoma.2In examining the possibilities of multiple intramyocardial masses, rhabdomyomas are more common in children and tend to regress with age. Melanoma deposits usually invade all chambers of the myocardium and are hyperintense on T1-weighted images due to the melanin component. Lymphoma invasion of the heart is grossly discernible, unlike leukemia, and can involve epicardium, myocardium, or endocardium in a patient with lymphadenopathy elsewhere.1,2 Our patient did not have evidence of widespread disease, prompting use of the genomic profiling assay, which has been shown to correctly identify the site of origin in 95% of cases of neuroendocrine carcinoma of unknown primary.3Neuroendocrine tumors (NETs) encompass a heterogeneous group of tumors that arise from neuroendocrine tissue and exhibit varied clinical behavior. The incidence has been increasing, and the prevalence is even greater due to the indolent nature of the disease.4 Pancreatic NETs are foregut derivatives; they have an incidence of 1/100 000 per year and account for 1% to 2% of all pancreatic neoplasms. The majority of them are functional, but 15% can be nonfunctional and present late with symptoms of local mass effect or metastasis.4 The World Health Organization grades gastrointestinal and pancreatic NETs using the mitotic rate and Ki-67 index. A high-grade tumor is classified on the basis of a mitotic rate of greater than 20/10 per high-powered field or a Ki-67 index of greater than 20%,4 as seen in our patient.Surgery is the standard of treatment for resectable pancreatic NETs, but most patients present with advanced disease that is unresectable and warrants systemic therapy.5 Multiple agents have been used for low- to intermediate-grade tumors. Somatostatin analogs (ie, octreotide acetate and lanreotide acetate) are usually first line therapy, due to their safety profile and possible antiproliferative effects.5 Biologically targeted therapies include the vascular endothelial growth factor pathway inhibitor sunitinib malate, and the mammalian target of rapamycin (mTOR) inhibitor everolimus, both of which showed a significantly longer median progression-free survival compared with placebo (11.4 vs 5.5 months for sunitinib and 11.6 vs 4.6 months for everolimus).6,7 Temozolomide, an oral alkylating agent, has shown variable response rates when used in combination with other agents. The most promising combination is with capecitabine, in which 30 patients with advanced pancreatic NETs showed 70% response rate and a median progression-free survival of 18 months.8 Prospective studies are limited to phase 2 single-institution trials.5Platinum-based chemotherapy (ie, platinum and etoposide phosphate) is first-line therapy for high-grade tumors, but some evidence suggests poor response (15% vs 42%) in tumors with a moderately high proliferation rate (Ki-67 < 55%).9 Temozolomide-based therapy is now commonly used as a second-line therapy after disease progression during platinum-based therapy.9 Our patient elected not to undergo platinum-based therapy in favor of a less toxic approach. She was therefore treated with octreotide long-acting release at a dose of 30 mg monthly and temozolomide at a dose of 200 mg/m2 on days 10 to 14, together with capecitabine at a dose of 750 mg/m2 twice daily on days 1 to 14. She responded to treatment with minimal increase in cardiac tumor size for a follow-up period of 16 months, indicating less aggressive tumor characteristics.

Oncology

A woman in her 50s presented for evaluation of intermittent epigastric pain, palpitations, and hot flashes for 2 months. The patient had a history of an ovarian cyst treated conservatively, and cosmetic breast augmentation. She had a 10 pack-year smoking history and denied alcohol or illicit drug use. Examination revealed distant heart sounds but otherwise had unremarkable results. An echocardiogram demonstrated a mass in the left ventricular myocardium. Cardiac magnetic resonance imaging was obtained to further assess the mass lesion. This revealed multiple intramyocardial masses involving the left ventricle, the largest of which measured 2.7 × 2.2 cm; aortopulmonary window lymphadenopathy; and moderate pericardial effusion (Figure). Computed tomographic imaging of the chest, abdomen, and pelvis with contrast failed to reveal discrete masses or lymphadenopathy elsewhere. A transcutaneous biopsy of the left ventricular mass was nondiagnostic.

what is your diagnosis?

What is your diagnosis?

Melanoma

Lymphoma

Rhabdomyoma

Metastatic carcinoma

d

female

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2471553

A 55-year-old woman diagnosed with invasive ductal carcinoma of the left breast (T3N1M0, stage IIIA) in December 2012 was treated with neoadjuvant chemotherapy comprising docetaxel (75 mg/m2) and trastuzumab (8 mg/kg initially, then 6 mg/kg every 3 weeks), followed by 3 courses of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2), prior to modified radical mastectomy of the left breast. In September 2013, she began receiving trastuzumab treatment and received adjuvant radiotherapy (5000 Gy in 25 fractions) 1 month later. In June 2014, she developed a generalized nonpruritic, nontender rash, without fevers or other constitutional symptoms. Physical examination showed multiple red-brown plaques and papules of various sizes on the chest, abdomen, back, and limbs (Figure 1). Laboratory evaluation revealed pancytopenia (white blood cells, 1460/μL; hemoglobin, 8.3 g/dL; and platelets, 99 000/μL [leukocyte differential: 0% blasts, 0% promyeloctes, 0% myelocytes, 0% metamyelocytes, 0% banded neutrophils, 30.1% segmented neutrophils, 4.1% eosinophils, 0.7% basophils, 0.7% monocytes, 64.4% lymphocytes]). A follow-up computed tomography scan of the chest and abdomen showed no evidence of local recurrence or distant metastasis.Generalized multiple red-brown plaques and papules of various sizes on patient’s torso.Perform a screening test for syphilis (rapid plasma reagin) What Would You Do Next?

Discontinue trastuzumab

Obtain a skin biopsy

Prescribe topical steroids

Perform a screening test for syphilis (rapid plasma reagin)

Therapy-related leukemia cutis.

B

Obtain a skin biopsy

A key to the diagnosis is the development of a generalized erythematous, infiltrative maculopapular eruption after cancer chemotherapy and radiotherapy. Histopathologic analysis showed diffuse infiltration of atypical cells with round nuclei, fine chromatin, small nucleoli, and eosinophilic cytoplasm. Immunohistochemical staining was positive for myeloperoxidase, focally positive for c-kit, and negative for CD3, CD20, cytokeratin AE1/AE3, and CD34 in the dermis and superficial subcutis, establishing the diagnosis of therapy-related leukemia cutis.Therapy-related leukemia—most commonly acute myeloid leukemia (TAML)—is a complication that develops several months to years or even decades after exposure to cytotoxic agents, radiotherapy, or both.1,2 TAML accounts for 10% to 20% of AML cases.1Several chemotherapeutic agents, including alkylating agents, topoisomerase inhibitors, and taxanes, are associated with the development of TAML and myelodysplastic syndromes (MDS).1 In a recent study by the National Surgical Adjuvant Breast and Bowel Project, 43 of 8563 patients with breast cancer (0.5%) developed AML/MDS after treatment with doxorubicin and cyclophosphamide.3 The risk of secondary leukemia is believed to be associated with the type of cytotoxic drugs used, the cumulative dose and intensity of chemotherapeutic agents, and cumulative-dose ionizing radiation.1,4 TAML is classified into 2 major types on the basis of the causative cytotoxic agents: alkylating agent– or radiation-related and topoisomerase II inhibitor–related. Different genetic pathways have been implicated in the pathogenesis of therapy-related leukemia. Alkylating agent– or radiation-related leukemia is often associated with deletions of monosomies of chromosomes 5 and 7 and has a relatively longer latency period (4-6 years) before development of leukemia. In contrast, leukemia caused by topoisomerase inhibitors is associated with MLL gene rearrangements and has a relatively shorter latency period (12-36 months).5Leukemia cutis is defined as infiltration of leukemic cells or their precursors into the epidermis, dermis, or subcutaneous tissue. The frequency of leukemia cutis differs widely by leukemia type. The highest incidence is seen in patients with acute monocytic leukemia and acute myelomonocytic leukemia (3% to 13% in separate case series).6 Lesions of leukemia cutis often manifest as single or multiple reddish to violaceous papules, plaques, and nodules, or as a generalized erythematous maculopapular eruption.1 The legs are most frequently involved, followed by the arms, back, chest, scalp, and face.1 The lesions are usually not painful, tender, or pruritic.1,7Several infectious and inflammatory or reactive processes in patients with cancer may simulate clinical features of leukemia cutis, including cutaneous metastases of primary malignancies, Sweet syndrome, drug eruptions, mycosis fungoides, secondary syphilis, and viral exanthema.1 Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is characterized by painful rash and fevers and is associated with cancer, infection, and drugs. Characteristic pathologic findings in Sweet syndrome differentiate it from leukemia cutis.8Leukemia cutis most commonly occurs concurrently with marrow-based disease, but it can also occur as isolated skin disease. In either case, systemic therapy is necessary, because isolated leukemia cutis often heralds the development of full-blown leukemia. Treatment regimens may differ based on disease subtype and treatment tolerability.1,9 Some patients may benefit from early evaluation for allogeneic bone marrow transplantation. The prognosis of leukemia cutis is poor, even for patients receiving aggressive treatment. Median survival for TAML is 6.9 months, shorter than for de novo AML,1 and 1 study showed that 88% of patients with leukemia cutis die within 1 year of diagnosis.10The patient was prescribed idarubicin and cytosine arabinoside. Bone marrow biopsy was not performed prior to initiation of chemotherapy. A bone marrow aspiration 1 month after chemotherapy showed hypocellularity without poorly differentiated blasts. A computed tomography scan of the chest and abdomen repeated 1 month after the skin biopsy was unremarkable. The patient died of sepsis and intracerebral hemorrhage 4 months later.

General

A 55-year-old woman diagnosed with invasive ductal carcinoma of the left breast (T3N1M0, stage IIIA) in December 2012 was treated with neoadjuvant chemotherapy comprising docetaxel (75 mg/m2) and trastuzumab (8 mg/kg initially, then 6 mg/kg every 3 weeks), followed by 3 courses of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2), prior to modified radical mastectomy of the left breast. In September 2013, she began receiving trastuzumab treatment and received adjuvant radiotherapy (5000 Gy in 25 fractions) 1 month later. In June 2014, she developed a generalized nonpruritic, nontender rash, without fevers or other constitutional symptoms. Physical examination showed multiple red-brown plaques and papules of various sizes on the chest, abdomen, back, and limbs (Figure 1). Laboratory evaluation revealed pancytopenia (white blood cells, 1460/μL; hemoglobin, 8.3 g/dL; and platelets, 99 000/μL [leukocyte differential: 0% blasts, 0% promyeloctes, 0% myelocytes, 0% metamyelocytes, 0% banded neutrophils, 30.1% segmented neutrophils, 4.1% eosinophils, 0.7% basophils, 0.7% monocytes, 64.4% lymphocytes]). A follow-up computed tomography scan of the chest and abdomen showed no evidence of local recurrence or distant metastasis.Generalized multiple red-brown plaques and papules of various sizes on patient’s torso.Perform a screening test for syphilis (rapid plasma reagin)

what would you do next?

What would you do next?

Discontinue trastuzumab

Perform a screening test for syphilis (rapid plasma reagin)

Prescribe topical steroids

Obtain a skin biopsy

d

female

51-60

White

original

https://jamanetwork.com/journals/jama/fullarticle/2470421

A 37-year-old woman who had had a tattoo placed on her left arm in a tattoo parlor 2 weeks previously presented with gradually worsening swelling and itching in the red ink area of the tattoo (Figure). Topical hydrocortisone cream (1%) applied for 1 week had provided no benefit. She had no fever or any other systemic symptoms. She was otherwise in excellent health, with no history of allergies, no recent travel, and no animal exposure or trauma to her arm.Swelling and keloid formation within red ink area of tattoo.On examination, the patient was afebrile and appeared healthy. Marked swelling and keloid formation within the red ink area of the tattoo were noted. There was no drainage, local warmth or tenderness, or pustule formation. Notably, there was no swelling or discoloration over the black ink area of the tattoo. Laboratory tests showed a white blood cell count of 10 000 cells/µL (60% neutrophils, 33% lymphocytes, and 6% eosinophils), normal hemoglobin level, and normal platelet count.Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary culturesReassure patient and follow up in 2 weeks What Would You Do Next?

Prescribe oral antibiotics

Prescribe higher-potency topical steroids

Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary cultures

Reassure patient and follow up in 2 weeks

Mycobacterium chelonae infection of the tattoo

C

Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary cultures

C. Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary culturesThe worsening of this lesion despite a trial of topical steroids suggests the possibility of an infectious process. The clinical appearance of the lesion does not provide a clear etiologic pathogen; therefore, a punch biopsy for histopathological examination and microbiological stains and cultures would be the most appropriate next step. Punch biopsy showed acid-fast bacilli on rhodamine-auramine staining, and acid-fast bacillary cultures grew M chelonae. Empirical antibacterial therapy would not be advisable in the absence of signs of cellulitis. Higher-strength topical steroids may be helpful if a diagnosis of cutaneous lupus or tattoo pigment allergic reaction is established after punch biopsy. It is not appropriate to simply monitor a symptomatic, worsening skin lesion within a new tattoo.The nontuberculous mycobacteria (NTM) are environmental opportunistic organisms that can produce clinical disease in any part of the body, including skin and soft tissue. These acid-fast bacilli are classified on the basis of their speed of growth on media as either rapidly growing mycobacteria or slowly growing mycobacteria. The overall incidence of cutaneous NTM infections is reported as between 0.9 and 1.7 per 100 000 person-years.1 Cutaneous infections have commonly been reported after traumatic injury or after cosmetic or surgical procedures.2 In the last decade, outbreaks associated with these organisms have been seen after cosmetic procedures in nail salons3 or tattoo parlors.4,5 These procedure-related outbreaks of cutaneous NTM infections were most often caused by rapidly growing mycobacteria including M chelonae, Mycobacterium abscessus, and Mycobacterium fortuitum.6M chelonae is a ubiquitous organism that can be found in municipal tap water, soil, and dust. It is commonly acquired from the environment by inoculation or inhalation. Among procedure-related outbreaks, mycobacterial infection is frequently associated with contaminated tap water, although contamination of tattoo ink or dyes used for skin marking may occur during the manufacturing process.5,7M chelonae infection of skin and soft tissue can present as subcutaneous abscesses, nodules, nonhealing wounds or skin ulcers, and folliculitis. Symptoms typically develop 2 to 3 weeks after infection has occurred. Although staphylococcal and streptococcal skin infections are much more common, clinicians should consider the rare possibility of infection with nontuberculous mycobacteria in patients with skin infections associated with tattoos. Cutaneous lesions often require punch biopsy and histopathological examination to rule out other infectious causes (eg, pseudomonas) or noninfectious causes (eg, sarcoid, cutaneous lupus, foreign-body granuloma, or tattoo ink allergic reaction). The gold standard for diagnosis of NTM infection is the identification of mycobacterium species in culture from a tissue biopsy.8A prolonged course of combination antibiotics (3-6 months) is usually necessary to eradicate NTM infections, even with early clearing of lesions. Given the indolent nature of these infections, careful observation is generally acceptable while awaiting biopsy and culture results for species identification and antibiotic susceptibilities. M chelonae is generally susceptible to clarithromycin, linezolid, rifampin, imipenem, tobramycin, amikacin, sulfonamides, and clofazamine.2 It is recommended to use combination antimicrobial therapy to minimize the risk of macrolide resistance.2 Abscess formation, nonhealing ulcerations, lesions with resistant organisms, or extensive disease are indications for surgical intervention. Clinical improvement in 95% of cases has been reported in an outbreak of M chelonae infection associated with tattoo ink.5To prevent procedure-related infections, use of sterile saline instead of tap water is recommended for dilution of tattoo ink. Confirmed NTM infections should be reported to the local health department.A punch biopsy showed extensive red tattoo pigment in superficial and mid dermis, along with heavy granulomatous inflammation. Aerobic and fungal cultures were negative; an acid-fast bacillary culture grew M chelonae susceptible to clarithromycin, doxycycline, amikacin, and linezolid but resistant to the fluoroquinolones. A combination of oral clarithromycin and doxycycline was given for about 4 months, and the patient’s symptoms gradually resolved.

General

A 37-year-old woman who had had a tattoo placed on her left arm in a tattoo parlor 2 weeks previously presented with gradually worsening swelling and itching in the red ink area of the tattoo (Figure). Topical hydrocortisone cream (1%) applied for 1 week had provided no benefit. She had no fever or any other systemic symptoms. She was otherwise in excellent health, with no history of allergies, no recent travel, and no animal exposure or trauma to her arm.Swelling and keloid formation within red ink area of tattoo.On examination, the patient was afebrile and appeared healthy. Marked swelling and keloid formation within the red ink area of the tattoo were noted. There was no drainage, local warmth or tenderness, or pustule formation. Notably, there was no swelling or discoloration over the black ink area of the tattoo. Laboratory tests showed a white blood cell count of 10 000 cells/µL (60% neutrophils, 33% lymphocytes, and 6% eosinophils), normal hemoglobin level, and normal platelet count.Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary culturesReassure patient and follow up in 2 weeks

what would you do next?

What would you do next?

Prescribe higher-potency topical steroids

Prescribe oral antibiotics

Perform a punch biopsy and send for bacterial, fungal, and acid-fast bacillary cultures

Reassure patient and follow up in 2 weeks

c

female

31-40

White

original

https://jamanetwork.com/journals/jama/fullarticle/2470424

A 59-year-old white man in good health, with no family history of prostate cancer, visited his primary care physician. His digital rectal examination (DRE) revealed an enlarged prostate without nodules. He previously made an informed decision to undergo prostate-specific antigen (PSA) screening for prostate cancer. His PSA history is displayed in the Table.The patient’s slow rise in prostate-specific antigen (PSA) level and enlarged prostate are consistent with benign prostatic hyperplasia, and his probability of prostate cancer is less than 10%.The patient’s rise in PSA level means his probability of prostate cancer is more than 50%.The patient’s probability of prostate cancer is approximately 6% for a high-grade cancer and 18% for a low-grade cancer.Variability in the patient’s PSA level makes it likely the tests were done in different laboratories. How Do You Interpret These Results?

The patient’s slow rise in prostate-specific antigen (PSA) level and enlarged prostate are consistent with benign prostatic hyperplasia, and his probability of prostate cancer is less than 10%.

The patient’s rise in PSA level means his probability of prostate cancer is more than 50%.

The patient’s probability of prostate cancer is approximately 6% for a high-grade cancer and 18% for a low-grade cancer.

Variability in the patient’s PSA level makes it likely the tests were done in different laboratories.

C

The patient’s probability of prostate cancer is approximately 6% for a high-grade cancer and 18% for a low-grade cancer.

The operating characteristics of the PSA test for prostate cancer screening depend on the definition of disease. The Prostate Cancer Prevention Trial (PCPT), a large study that obtained biopsies on men regardless of PSA level, provides the most relevant data. Twenty-two percent of PCPT participants had prostate cancer, and approximately one-quarter of these men had a Gleason score of at least 7.1 Men at average risk have an approximate 3% probability of dying of prostate cancer.2 At a PSA threshold greater than 4.0 ng/mL, PSA was 20.5% sensitive and 93.8% specific when any histologic prostate cancer was considered disease.1 However, cancers that are well-differentiated are indolent and generally do not need early detection. If only cancers with a Gleason score of at least 7 are considered disease, then sensitivity increases to 40.4%, and specificity would be 90.0%. The PCPT investigators have published a risk calculator that uses race/ethnicity, age, PSA level, family history, DRE result, and history of prostate biopsy to estimate the probability of high-grade (Gleason ≥7) and low-grade (Gleason <7) prostate cancer.3There is no absolute threshold for considering a biopsy based on a specific PSA level or the estimated risk of prostate cancer from the calculator. In the European Randomized Study of Prostate Cancer Screening, the trial that found a significant reduction in prostate cancer mortality with screening, a testing frequency of every 4 years and a biopsy threshold of at least 3.0 ng/mL was generally used.4 Modeling studies suggest that with biennial testing, a biopsy threshold of greater than 4.0 ng/mL is associated with a slightly higher probability of prostate cancer death than lower thresholds but with a reduced risk of false-positive results.5 Another reasonable approach is to use the estimated probabilities from the PCPT calculator in a shared decision-making process with men facing the biopsy decision.6 In the Prostate Cancer Intervention vs Observation Trial, a prespecified subgroup analysis suggested radical prostatectomy was associated with lower mortality among participants with a baseline PSA level of greater than 10 ng/mL when compared with men with lower PSA levels. This finding implies the PSA level at which prostate cancers (those needing and amenable to curative treatment) progress beyond curability may be higher than the commonly used threshold of greater than 4 ng/mL.7The perceived limited performance of total PSA has led to exploration of PSA derivatives such as PSA velocity (PSAV). However, analyses have not shown improvements in discrimination when PSAV is added to total PSA.8Although a PSA test only costs about $40, the real financial costs of screening are incurred with follow-up testing, including biopsies and subsequent treatments.9Clinical practice guidelines emphasize the importance of only performing PSA screening for men like this patient who have made an informed decision to proceed.2 His PSAV does not appreciably reduce his probability of prostate cancer estimated by the PCPT calculator.The percentage of PSA circulating free is sometimes used to estimate the likelihood of prostate cancer for men with mildly elevated PSA levels. However, finding reassuring levels of free PSA (>25%) is unusual.2 New prostate cancer biomarkers are emerging but have not yet been shown to be associated with lower prostate cancer mortality.The patient elected to closely monitor his PSA level. Thus, he avoided undergoing a biopsy and its complications2 and the possibility of being diagnosed with an inconsequential prostate cancer. Strategies to avoid overtreatment of prostate cancers include forms of observation such as active surveillance with close monitoring for evidence of cancer progression.2 However, the majority of US men with low-risk prostate cancers have been treated aggressively, although data from some practices indicate an increased use of active surveillance after 2010.10 It is possible this patient harbors a high-risk prostate cancer, and that it could progress beyond curability before a diagnosis is made. It is necessary to periodically recalculate cancer risk through use of the risk calculator and rediscussion of the new results.There is no one “right” prostate-specific antigen (PSA) threshold to trigger a biopsy.An online risk calculator can be used to estimate the probability of high- and low-grade prostate cancer depending on patient characteristics including PSA levels.3As with the decision to perform a PSA test initially, informed patients should participate in the biopsy decision.

Diagnostic

A 59-year-old white man in good health, with no family history of prostate cancer, visited his primary care physician. His digital rectal examination (DRE) revealed an enlarged prostate without nodules. He previously made an informed decision to undergo prostate-specific antigen (PSA) screening for prostate cancer. His PSA history is displayed in the Table.The patient’s slow rise in prostate-specific antigen (PSA) level and enlarged prostate are consistent with benign prostatic hyperplasia, and his probability of prostate cancer is less than 10%.The patient’s rise in PSA level means his probability of prostate cancer is more than 50%.The patient’s probability of prostate cancer is approximately 6% for a high-grade cancer and 18% for a low-grade cancer.Variability in the patient’s PSA level makes it likely the tests were done in different laboratories.

how do you interpret these results?

How do you interpret these results?

The patient’s probability of prostate cancer is approximately 6% for a high-grade cancer and 18% for a low-grade cancer.

Variability in the patient’s PSA level makes it likely the tests were done in different laboratories.

The patient’s rise in PSA level means his probability of prostate cancer is more than 50%.

The patient’s slow rise in prostate-specific antigen (PSA) level and enlarged prostate are consistent with benign prostatic hyperplasia, and his probability of prostate cancer is less than 10%.

a

male

51-60

White

original

https://jamanetwork.com/journals/jama/fullarticle/2468876

A 53-year-old man with chest pain was referred to undergo an exercise treadmill test (ETT). He reported substernal chest pain, lasting less than 5 minutes, which sometimes occurred if he ran more than 2 miles. He had no other symptoms.The patient's medical history included hypertension (controlled with lisinopril and hydrochlorothiazide), a low-density lipoprotein level of 155 mg/dL, and a high-density lipoprotein level of 44 mg/dL. He did not smoke or have family history of premature coronary artery disease (CAD). The patient’s physical examination results were unremarkable, blood pressure was 134/80 mm Hg, body mass index was 26 (calculated as weight in kilograms divided by height in meters squared), and resting electrocardiogram (ECG) results were normal.The patient had no chest pain during ETT. Results are reported in the Table.Further testing is unnecessary because the patient is asymptomatic and has high exercise capacity.Further testing is needed because of the ST depressions during recovery.Further testing is unnecessary because ST depressions are not significant unless 2 mm or greater.Further testing is needed because inferolateral ST depressions indicate obstructive coronary artery disease in the right coronary artery, the left circumflex artery, or both arteries. How Do You Interpret These Results?

Further testing is unnecessary because the patient is asymptomatic and has high exercise capacity.

Further testing is needed because of the ST depressions during recovery.

Further testing is unnecessary because ST depressions are not significant unless 2 mm or greater.

Further testing is needed because inferolateral ST depressions indicate obstructive coronary artery disease in the right coronary artery, the left circumflex artery, or both arteries.

B

Further testing is needed because of the ST depressions during recovery.

ETT is used to evaluate symptomatic patients with an intermediate pretest probability of CAD who can exercise and have normal resting ST segments.1,2 ETT with imaging is appropriate when pretest probability of CAD is high or baseline ST abnormalities are present (resting depression ≥1 mm; or left ventricular hypertrophy with repolarization abnormalities, preexcitation, or digoxin therapy).2 Pharmacologic stress testing or coronary computed tomography angiogram (CCTA) are often preferred with left bundle-branch block and ventricular pacing because both increase the likelihood of false-positive perfusion defects with exercise.1Sensitivity of ETT for obstructive CAD is approximately 68% in men and 61% in women, and specificity is approximately 77% in men and 70% in women.1,2 Although imaging tests have a higher diagnostic accuracy to detect obstructive CAD, a randomized trial in women comparing ETT vs ETT with myocardial perfusion imaging (MPI) showed no difference in 2-year cardiovascular events but a 48%-cost savings for ETT alone.3 Total Medicare reimbursement for ETT is $75 to $95 (http://www.cms.gov/apps/physician-fee-schedule).Estimated pretest probability is based on age, sex, anginal symptoms, and comorbidities.4 Multiple algorithms estimate pretest probability; most overestimate risk in contemporary cohorts.2,4,5 Definitions of intermediate risk range from a 10% to 90% probability to a 30% to 70% probability for obstructive disease. The pretest probability for this patient was intermediate to high given his atypical angina (inconsistently produced by exercise), age, and sex.Approximately 8% of patients experience ST-segment depressions only during recovery. These changes have a similar association with cardiovascular events as depressions that begin during exercise.6 Downsloping or horizontal ST depressions are considered significant when they last at least 1 minute.1 Adults with ST-segment depressions that resolve within 1 minute of recovery have a low prevalence of CAD on subsequent testing.7 In contrast, ST depressions that persist several minutes into recovery have high specificity. Leads V4 through V6 are the most accurate for identifying ischemia, but they do not correlate with the site of ischemia. Of all ETT parameters, exercise capacity has the greatest prognostic significance for survival, and it is interpreted based on age- and sex-based standards.8 Among men referred for stress testing, the relative risk of death was 4.5 (those who achieved <6 metabolic equivalents vs >13 metabolic equivalents).8 The Duke Treadmill Score predicts 4-year risk of death based on a weighted combination of exercise duration, ST depressions, and symptoms. Estimated annual mortality1 is less than 1% for individuals with scores greater than 5.Despite this patient’s excellent exercise capacity and absence of symptoms, his prolonged ST-segment depressions indicate an elevated cardiovascular risk. Further evaluation is needed.Selective use of additional testing after an abnormal or inconclusive ETT can clarify risk. Given the patient’s intermediate to high pretest probability, an initial workup with exercise stress echocardiography, exercise MPI, or CCTA would have been reasonable.5,9 Imaging and ETT results may be complementary, enhancing CAD diagnosis and prognosis estimates.10 Local expertise, patient age, body habitus, and comorbidities should be considered when selecting an imaging modality.9 Older patients with coronary calcification may undergo functional testing instead of CCTA because CCTA results are less accurate when coronary calcification levels are high. For patients who are obese, testing by MPI or CCTA may be preferable to echocardiogram because these tests generate higher-quality images.The patient was administered a regimen of aspirin and atorvastatin. A CCTA demonstrated 3-vessel obstructive CAD. A PET-MPI was obtained to determine the magnitude of ischemia and the role of revascularization. Testing identified severe ischemia in the distribution of the left anterior descending and circumflex arteries. The patient underwent a coronary angiogram and subsequent coronary artery bypass graft surgery. He tolerated the procedure well and has resumed exercising.Although routine acquisition of both CCTA and MPI is usually not required, the data from both examinations aided this patient’s decision between medical therapy and revascularization.Exercise treadmill testing (ETT) is useful for initial evaluation of intermediate-risk patients who can exercise and have normal baseline ST segments.Individuals who can perform activities of daily living without difficulty are reasonable candidates for ETT.Cardiovascular imaging improves accuracy for detecting obstructive CAD compared with ETT alone, but it can often be deferred for patients with a normal electrocardiogram (ECG) who can achieve an adequate workload.Exercise capacity measured by ETT has a stronger association with cardiovascular and total mortality than ST-segment depressions.Data from ETT and cardiovascular imaging provide complementary prognostic information.

Diagnostic

A 53-year-old man with chest pain was referred to undergo an exercise treadmill test (ETT). He reported substernal chest pain, lasting less than 5 minutes, which sometimes occurred if he ran more than 2 miles. He had no other symptoms.The patient's medical history included hypertension (controlled with lisinopril and hydrochlorothiazide), a low-density lipoprotein level of 155 mg/dL, and a high-density lipoprotein level of 44 mg/dL. He did not smoke or have family history of premature coronary artery disease (CAD). The patient’s physical examination results were unremarkable, blood pressure was 134/80 mm Hg, body mass index was 26 (calculated as weight in kilograms divided by height in meters squared), and resting electrocardiogram (ECG) results were normal.The patient had no chest pain during ETT. Results are reported in the Table.Further testing is unnecessary because the patient is asymptomatic and has high exercise capacity.Further testing is needed because of the ST depressions during recovery.Further testing is unnecessary because ST depressions are not significant unless 2 mm or greater.Further testing is needed because inferolateral ST depressions indicate obstructive coronary artery disease in the right coronary artery, the left circumflex artery, or both arteries.

how do you interpret these results?

How do you interpret these results?

Further testing is needed because of the ST depressions during recovery.

Further testing is unnecessary because ST depressions are not significant unless 2 mm or greater.

Further testing is unnecessary because the patient is asymptomatic and has high exercise capacity.

Further testing is needed because inferolateral ST depressions indicate obstructive coronary artery disease in the right coronary artery, the left circumflex artery, or both arteries.

a

male

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2429197

A woman in her 70s with a medical history that was significant for polycythemia vera and acute myelogenous leukemia was seen for evaluation of textural skin changes on her face that had been present for 2½ years. She denied having pruritus or pain, but her skin had a rough sandpapery sensation. She reported that the involvement extended to her neck, the upper part of her chest, and her bilateral forearms. She associated the onset of the textural changes with her diagnosis of polycythemia vera. She stated that it began before her diagnosis of acute myelogenous leukemia and the initiation of treatment with hydroxyurea 4 years later. She had previously received treatment with long courses of triamcinolone acetonide cream, 0.1%, bacitracin ointment, and a combination antibiotic ointment of neomycin sulfate, polymyxin B, and bacitracin, with no improvement of her skin’s condition. Her additional daily medication regimen included donepezil hydrochloride, melatonin, and aspirin, 81 mg.Findings from the patient’s physical examination revealed background erythema with numerous rough horny spicules at the follicular ostia on her face, ears, and neck; the upper part of her chest; and her bilateral forearms. Findings from the rest of her examination revealed a pigmented macule on her right cheek. Two punch biopsy specimens were obtained from her right cheek and right postauricular area and submitted for histopathologic examination (Figure).Histopathologic images (hematoxylin-eosin) of the punch biopsy specimen from the right side of the lateral neck. What Is The Diagnosis?

Trichodysplasia spinulosa–associated polyomavirus

Demodex folliculorum–associated spinulosus

Ulerythema ophryogenes

Hyperkeratotic spicules of multiple myeloma

B. Demodex folliculorum–associated spinulosus

B

Demodex folliculorum–associated spinulosus

Findings from histopathologic examination revealed numerous Demodex folliculorum mites in the follicular infundibula with associated hyperkeratosis, focal lichenoid lymphocytic infiltrates, and scattered Civatte bodies (Figure). The patient was prescribed permethrin cream, 5%, nightly for 7 days and then twice weekly thereafter. She reported improvement in her skin’s roughness but stopped using the cream because of a burning sensation of her skin that also correlated with an increase in her hydroxyurea dosage. Her treatment was then changed to ivermectin, 12 mg, 2 doses weekly, and her hydroxyurea dose was concurrently decreased with almost complete resolution of her clinical findings. She now takes ivermectin intermittently as needed for spinulosus recurrence (approximately once per month).Demodexfolliculorum is a saprophytic mite that lives in the hair follicle infundibulum and subsists on sebum and skin cells. Although this mite is commonly found in adults without associated cutaneous pathologic findings, they may be considered pathogenic in patients with skin eruptions when there is increased density of the mites to more than 5/cm2, they are present in the dermis, or there is a documented clinical response to Demodex folliculorum–directed therapies.1,2 Predisposing factors for increased Demodex mite density include increased age, diabetes mellitus, hemodialysis, and immunosuppression.3Demodex folliculorum–associatedspinulosus has a clinically different appearance from Demodexfolliculorum–associated rosacea; thus, the clinical differential diagnosis should include the digitate keratosis disorders, such as multiple myeloma–associated hyperkeratotic spicules, trichodysplasia spinulosa–associated polyomavirus, and follicular hyperkeratosis, as well as ulerythema ophyrogenes.4 Biopsies will aid in distinguishing between these entities. The results from biopsies of Demodex folliculorum–associated spinulosus specimens revealed numerous D folliculorum mites protruding from hair follicles with surrounding hyperkeratosis and a lymphocytic infiltrate, whereas the results from biopsies of specimens from patients with the other conditions listed here may show incidental Demodex mites in the infundibulum.There are 3 previous case reports5-7 of Demodex folliculorum–associated spinulosus in the setting of polycythemia vera that was treated with hydroxyurea. Two of the 3 patients did not improve until hydroxyurea treatment was discontinued, while the third patient’s condition improved with prescribed permethrin cream, 1%.5-7 The authors of each case report concluded that the immunosuppressed state led to the development of spinulosus due to the Demodex mites although the pathogenesis is still unclear.5 We present another case of Demodex folliculorum–associated spinulosus in an elderly immunocompromised woman who was receiving treatment with hydroxyurea. We believe that Demodex folliculorum–associated spinulosus is an important entity to consider when evaluating a patient with follicular prominence because it is easily diagnosed by biopsy and may be easily treatable.

Dermatology

A woman in her 70s with a medical history that was significant for polycythemia vera and acute myelogenous leukemia was seen for evaluation of textural skin changes on her face that had been present for 2½ years. She denied having pruritus or pain, but her skin had a rough sandpapery sensation. She reported that the involvement extended to her neck, the upper part of her chest, and her bilateral forearms. She associated the onset of the textural changes with her diagnosis of polycythemia vera. She stated that it began before her diagnosis of acute myelogenous leukemia and the initiation of treatment with hydroxyurea 4 years later. She had previously received treatment with long courses of triamcinolone acetonide cream, 0.1%, bacitracin ointment, and a combination antibiotic ointment of neomycin sulfate, polymyxin B, and bacitracin, with no improvement of her skin’s condition. Her additional daily medication regimen included donepezil hydrochloride, melatonin, and aspirin, 81 mg.Findings from the patient’s physical examination revealed background erythema with numerous rough horny spicules at the follicular ostia on her face, ears, and neck; the upper part of her chest; and her bilateral forearms. Findings from the rest of her examination revealed a pigmented macule on her right cheek. Two punch biopsy specimens were obtained from her right cheek and right postauricular area and submitted for histopathologic examination (Figure).Histopathologic images (hematoxylin-eosin) of the punch biopsy specimen from the right side of the lateral neck.

what is the diagnosis?

What is your diagnosis?

Ulerythema ophryogenes

Trichodysplasia spinulosa–associated polyomavirus

Hyperkeratotic spicules of multiple myeloma

Demodex folliculorum–associated spinulosus

d

female

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2429552

A 12-year-old boy presented for evaluation of a 3-month history of ulcerated lesions on the dorsal aspect of his feet since returning from Pakistan, where his family was living. The patient had no history of medical problems. He was born in Spain and had received his childhood immunizations. He remembered insect bites on his feet, but the lesions later became ulcerated and painful. The patient denied experiencing fever, arthralgia, or a sore throat.Findings from the physical examination revealed 6 painful ulcerated, exudative nodules with a grayish membrane over the ulcers on the dorsal aspect of his feet (Figure 1). No signs of lymphangitis or lymphadenopathy were detected. A 4-mm punch biopsy specimen from one lesion was obtained and stained with hematoxylin-eosin and Gram stain for histopathologic analysis. Another skin specimen was cultured for microbiologic analysis. Ulcerated and exudative nodules with grayish membrane on the dorsal aspect of the feet. What Is Your Diagnosis?

Cutaneous tuberculosis

Ecthyma gangrenosum

Leishmaniasis

Cutaneous diphtheria

D. Cutaneous diphtheria

D

Cutaneous diphtheria

The results of the laboratory analyses were normal, and the results of a Mantoux test were negative. Tissue culture on blood agar and Tinsdale agar medium produced a growth of colonies of gram-positive rods that were identified as Corynebacterium diphtheriae biotype mitis. Elek test results were positive for a toxigenic strain of C diphtheriae. Streptococcus pyogenes was also isolated from the tissue culture. Results of a swab cultured from the patient’s oropharingeal mucosa were negative for C diphtheriae, as were results of the other 4 swabs obtained from his family and cultured.Diphtheria is an acute bacterial illness caused by toxigenic strains of C diphtheriae, Corynebacterium ulcerans, and Corynebacterium pseudotuberculosis.1 Since the introduction of immunization against diphtheria in the 1940s, its incidence in industrialized countries has declined,2 but it is still endemic in developing countries, such as Pakistan, Brazil, and in Eastern European countries.1 In Spain, diphtheria has been considered eradicated since 1987 when the last 2 cases were reported.3Cutaneous diphtheria is defined as an inflammatory lesion that rapidly evolves to a chronic nonhealing ulcer in which toxigenic or nontoxigenic strains of Corynebacterium are isolated.4 These ulcers are frequently coinfected with pathogens such as Staphylococcus aureus and S pyogenes.4,5 Diagnosis is performed by culture plates from swabs of the infection site (Figure 2A).5 Tissue biopsy is not essential for diagnosis, and it has not been previously described in the literature (Figure 2B). Many patients remember insect bites or previous injuries to the same site. Cutaneous diphtheria can be an important source for the dissemination of the infection in populations with low vaccination rates and can cause respiratory tract and cutaneous infections in individuals who have contact with the patient. It may also lead to pharyngeal involvement by a process of autoinfection. Systemic toxic manifestations are possible when patients are unvaccinated, although the slow release of toxin from the ulcer may allow time for a protective immune response to develop.2,5 Penicillin or erythromycin are considered first-line treatments. It is important to provide antibiotic prophylaxis to individuals who have close contact with the patient. Both patients and those in close contact with them should receive a full primary course of immunization or a booster dose to prevent spread of the disease.4,6A, Tinsdale agar medium demonstrates the ability of Corynebacterium diphtheriae to produce black (or brown) colonies surrounded by a dark brown halo within the medium. B, Ulcer biopsy specimen showing an epidermis with acanthosis and overlying parakeratosis and a dense lymphoplasmacytic infiltrate in the dermis (hematoxylin-eosin, original magnification x40). With confirmation of the diagnosis of cutaneous diphtheria, our patient was treated with a combination of oral amoxicillin and clavulanic acid, 20 mg/kg/d, for 14 days and received a new booster vaccination for tetanus and diphtheria although he had completed the national childhood vaccination program. The ulcers healed, with residual hyperpigmentation and minimal scarring.This case highlights the importance of considering cutaneous diphtheria in travelers who present with chronic cutaneous ulcers on return from countries in which the disease is endemic. Prompt diagnosis allows early and appropriate treatment and may help to prevent further outbreaks of this illness.

Dermatology

A 12-year-old boy presented for evaluation of a 3-month history of ulcerated lesions on the dorsal aspect of his feet since returning from Pakistan, where his family was living. The patient had no history of medical problems. He was born in Spain and had received his childhood immunizations. He remembered insect bites on his feet, but the lesions later became ulcerated and painful. The patient denied experiencing fever, arthralgia, or a sore throat.Findings from the physical examination revealed 6 painful ulcerated, exudative nodules with a grayish membrane over the ulcers on the dorsal aspect of his feet (Figure 1). No signs of lymphangitis or lymphadenopathy were detected. A 4-mm punch biopsy specimen from one lesion was obtained and stained with hematoxylin-eosin and Gram stain for histopathologic analysis. Another skin specimen was cultured for microbiologic analysis. Ulcerated and exudative nodules with grayish membrane on the dorsal aspect of the feet.

what is your diagnosis?

What is your diagnosis?

Cutaneous diphtheria

Ecthyma gangrenosum

Cutaneous tuberculosis

Leishmaniasis

a

male

11-20

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2440975

A 6-month-old daughter of nonconsanguineous parents was seen with multiple polycyclic dark to less dark brown, partly livid shimmering macules, which covered large areas of the back, neck, buttocks, and lower extremities (Figure, A). According to her mother, new lesions had appeared during the past weeks on the shoulders. Physical examination revealed coarse facial features, hepatomegaly (7 cm below the costal arch), distinctive lumbar kyphosis, and muscular hypotonia compared with her twin brother. Dermoscopy showed faint clouds of nonhomogeneously distributed light brown pigment.A, Polycyclic, brown, partly livid shimmering macules covered large areas of the back, neck, buttocks, and lower extremities. B, Fusiform and dendritic cells were found scattered in the dermis (hematoxylin-eosin, original magnification ×100). C, Immunohistological staining of the same specimen (original magnification ×200). S-100 protein positivity identified these cells as melanocytes. D, A triangle-shaped first lumbar vertebral body is shown. What Is Your Diagnosis?

Child abuse

Morquio syndrome

GM1 gangliosidosis

Hurler-Scheie syndrome

C. GM1 gangliosidosis

C

GM1 gangliosidosis

Histopathological examination of a skin biopsy specimen revealed a slightly hyperpigmented epidermis with a moderate increase in melanocytes on S-100 protein and Melan-A staining. In the dermis, multiple S-100 protein–positive fusiform and dendritic cells were found (Figure, B and C), which were also positive on Fontana-Masson staining. Therefore, the histopathological pattern was consistent with a mongolian spot (nevus fuscoceruleus).However, the kyphosis, coarse facial features, muscular hypotonia, and hepatomegaly were consistent with a lysosomal storage disease. Further investigations revealed a cardiomyopathy (left ventricular hypertrophy and mitral insufficiency), as well as ultrasonographic abnormalities in the brain (voluminous hyperechoic basal ganglia). Fundoscopic examination demonstrated a cherry-red spot on the retina. Spot urine analysis was negative for glycosaminoglycans. A chest radiograph showed paddle-shaped ribs, as well as a triangle-shaped body of the first lumbar vertebra (Figure, D), favoring the diagnosis of a lysosomal storage disease.β-Galactosidase activity in peripheral blood leukocytes was also significantly reduced, which is indicative of type I (infantile) GM1 gangliosidosis. Subsequent genetic analysis identified a homozygous mutation in exon 2 of the GLB1 gene (c.176G>A p.R59H) (OMIM 611458), confirming the diagnosis. The OMIM accession number of the phenotype (type I GM1 gangliosidosis) is 230500.Nevi fuscocerulei are benign melanocytic congenital birthmarks with a diameter of 3 to 10 cm. They localize in the lumbosacral region, usually resolve during childhood, and predominate in Asian (ie, mongolian spots), American Indian, and African populations.Widespread mongolian spots can be indicative of inborn errors of metabolism, in particular lysosomal storage diseases. Most frequently, these errors include GM1 gangliosidosis (15 cases reported)1-8 and Hurler-Scheie syndrome, followed by Niemann-Pick disease, Hunter syndrome, and α-mannosidosis.9GM1 gangliosidosis is an autosomal recessive disease. More than 165 mutations in the GLB1 gene (3p22.3), encoding β-galactosidase, have been described. The missense mutation p.R59H (c.176G>A) is the most common mutation found in European patients with GM1 gangliosidosis.10 Enzyme deficiency results in toxic accumulation of GM1 gangliosides in many tissues. In the most severe form (type I), symptoms become apparent by age 6 months. Patients develop hepatosplenomegaly, skeletal abnormalities, intellectual disability, loss of vision, distinctive facial features, and gingival hypertrophy. They die within the first 2 to 3 years of life. In type II (onset, 1½ to 5 years), there is delayed motor and cognitive development. Life expectancy is shortened.In the adult form (onset, 3-30 years), patients develop dystonia and vertebral abnormalities. Life expectancy correlates with the level of β-galactosidase activity.GM1, one of the major gangliosides, is known to increase nerve growth factor (NGF) activity, mediated by the tropomyosin-related kinase (Trk) receptor. In melanocytes, NGF-activated Trk receptor promotes proliferation and is speculated to inhibit transdermal migration. Therefore, mongolian spots in GM1 gangliosidosis are thought to be caused by arrested transdermal migration of melanocytes from the neural crest into the epidermis, leading to their entrapment and proliferation in the dermis.5,6,8,9Multiple and extensive nevi fuscocerulei merit special attention. In some lysosomal storage diseases (eg, Hurler-Scheie syndrome and Hunter syndrome), early diagnosis allows treatment with recombinant enzyme therapy or stem cell transplantation. In untreatable conditions such as the case reported herein, early diagnosis is important for genetic counseling of at-risk families.

Dermatology

A 6-month-old daughter of nonconsanguineous parents was seen with multiple polycyclic dark to less dark brown, partly livid shimmering macules, which covered large areas of the back, neck, buttocks, and lower extremities (Figure, A). According to her mother, new lesions had appeared during the past weeks on the shoulders. Physical examination revealed coarse facial features, hepatomegaly (7 cm below the costal arch), distinctive lumbar kyphosis, and muscular hypotonia compared with her twin brother. Dermoscopy showed faint clouds of nonhomogeneously distributed light brown pigment.A, Polycyclic, brown, partly livid shimmering macules covered large areas of the back, neck, buttocks, and lower extremities. B, Fusiform and dendritic cells were found scattered in the dermis (hematoxylin-eosin, original magnification ×100). C, Immunohistological staining of the same specimen (original magnification ×200). S-100 protein positivity identified these cells as melanocytes. D, A triangle-shaped first lumbar vertebral body is shown.

what is your diagnosis?

What is your diagnosis?

GM1 gangliosidosis

Hurler-Scheie syndrome

Morquio syndrome

Child abuse

a

female

0-10

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2442468

A woman in her 50s was seen by her physician with a 1-month history of gait unsteadiness and imbalance and was suspected to have neuropathy, but she then went to the emergency department reporting 2 successive transient episodes, each lasting less than 1 hour, of acute dizziness, disorientation, gait dysfunction, and confusion. Urinalysis revealed a urinary tract infection, but computed tomography (CT) of the head showed extensive mass lesions with bilateral edema. Magnetic resonance imaging (MRI) of the brain delineated expansile mass lesions of the splenium of the corpus callosum, with T2–fluid-attenuated inversion recovery hyperintensity in the bilateral parietal lobes, left thalamus, and midbrain (Figure, A); administration of contrast revealed multiple ring-enhancing lesions (Figure, B). The woman’s medical history was significant for type 2 diabetes mellitus (DM), hypertension, recurrent urinary tract infections, onychomycosis, end-stage renal failure, and a history of living, unrelated donor renal transplant 12 years earlier, kidney transplant rejection, and prior episodes of syncope. Medications included tacrolimus, mycophenolate mofetil hydrochloride, prednisone (1 mg/d), losartan potassium, and insulin. Family history was notable for her father having died of lung cancer and her mother had heart disease and DM. Social history did not reveal any unusual exposures. Physical examination results showed a transplant surgical scar and onychomycosis. Neurologic findings revealed reasonably preserved mental status, with bedside examination revealing normal attention, language, and orientation but mild memory deficits for short-term recall (2 of 3 words recalled at a 5-minute delay) and long-term fund of knowledge. Cranial nerve, motor, sensory, and reflex examination results were significant only for gait ataxia, with an inability to perform tandem gait. Blood test results were consistent with DM. Findings from cerebrospinal fluid (CSF) examination included a white blood cell count of 9/µL, with differential examination showing 84% lymphocytes, 13% monocytes, and 3% neutrophils; red blood cell count of 1080/µL; protein level, 180 mg/dL; and glucose level, 87 mg/dL. Flow cytometry revealed B and T lymphocytes but no monoclonal populations of cells. Polymerase chain reaction amplification tests on CSF revealed no evidence of cytomegalovirus or herpes simplex virus 1 or 2 genetic material. Serum and CSF serologic test results were negative for antibodies to toxoplasma; testing using polymerase chain reaction on blood for Epstein-Barr virus (EBV) revealed minimal (very low positive) viral DNA at 52 IU/mL. A CT scan of the chest, abdomen, and pelvis showed a small, subpleural nodule; fatty liver; diverticulosis; failed native kidneys; and normal transplanted kidney. Whole-body positron emission tomography revealed hypermetabolic regions in the brain. Dexamethasone sodium phosphate and levetiracetam were administered. The patient underwent a diagnostic procedure.Brain magnetic resonance imaging showing unsuspected mass lesions. A, A T2 fluid-attenuated inversion recovery (FLAIR) sequence illustrating prominent T2 hyperintensity in the right more than the left parietal white matter suggestive of edema, an expansive mass lesion on the right more than the left splenium of the corpus callosum, and an infiltrative mass lesion in the left thalamus extending into the mesencephalon. B, A T1 sequence after administration of gadolinium contrast agent. Ring-enhancing regions are visible in the right parietal lobe and splenium of the corpus callosum, and a more solidly enhancing lesion is seen in the left thalamus as well as some apparent leptomeningeal enhancement. What Is Your Diagnosis?

Central nervous system toxoplasmosis

Metastatic carcinoma

Central nervous system lymphoma

Posttransplant lymphoproliferative disorder

D. Posttransplant lymphoproliferative disorder

D

Posttransplant lymphoproliferative disorder

The presence of subacute gait disorder, initially without other symptoms, in a patient who had received a renal transplant prompted the diagnosis of peripheral neuropathy, presumably due to DM and posttransplant medications.1 However, there were no significant sensory findings on examination, episodic transient central nervous system dysfunction occurred, and brain imaging showed highly abnormal findings, clearly indicating a multifocal cerebral process despite her otherwise reasonably intact neurologic status. The imaging results, as well as her medication regimen–associated immunocompromised state, suggested the possibility of either neoplastic or infectious processes.1-5 Glioblastoma may occur at a higher incidence in patients who undergo renal transplant,1 and metastatic carcinoma is also within the differential diagnosis (especially since there was a lung nodule), but CSF pleocytosis would be atypical for either of these neoplastic processes. Infection, particularly toxoplasmosis, is a serious concern in any patient who is receiving immunosuppressive therapy, but the negative antibody titers in both serum and CSF made this less likely. The main diagnostic considerations in this patient were central nervous system lymphoma vs posttransplant lymphoproliferative disorder (PTLD).2-5 The prominently multifocal nature of the process argues slightly more for PTLD, as does the presence of detectable EBV viral copies in the blood, but the main reason to suspect PTLD is that it would be the more common disorder in this setting of subacute brain lesions with mass effect, pleocytosis, an elevated CSF protein level, and demonstrable EBV blood viral load in a patient approximately 10 years after renal transplant who was receiving immunosuppressive medications. The diagnostic procedure was stereotactic biopsy of the right parietal lobe lesion, and examination by the pathology laboratory confirmed a dense lymphoplasmacytic cell infiltrate with perivascular prominence. The small, atypical-appearing lymphocyte population was positive for CD19 and CD20, confirming B-cell lineage, and in situ hybridization was positive for EBV, confirming a diagnosis of EBV-associated PTLD in the brain. Posttransplant lymphoproliferative disorder occurs in approximately 2% of renal transplant recipients over 10 years, but it may occur in as many as 10% of heart, lung, or pancreas transplant recipients.3 Posttransplant lymphoproliferative disorder develops on a spectrum from polyclonal B-cell hyperplasia to monoclonal tumors, such as classic lymphoma.3-5 Apparently EBV, which infects most individuals early in life, reactivates in the immunosuppressed host causing B-cell proliferative expansion. Treatment of PTLD requires a delicate balance between decreased immunosuppression that might improve PTLD but compromise the transplant and adequate immunosuppression to preserve the transplant. In this patient, monthly cycles of methotrexate sodium and rituximab were added with significant improvement over 3 months.

Neurology

A woman in her 50s was seen by her physician with a 1-month history of gait unsteadiness and imbalance and was suspected to have neuropathy, but she then went to the emergency department reporting 2 successive transient episodes, each lasting less than 1 hour, of acute dizziness, disorientation, gait dysfunction, and confusion. Urinalysis revealed a urinary tract infection, but computed tomography (CT) of the head showed extensive mass lesions with bilateral edema. Magnetic resonance imaging (MRI) of the brain delineated expansile mass lesions of the splenium of the corpus callosum, with T2–fluid-attenuated inversion recovery hyperintensity in the bilateral parietal lobes, left thalamus, and midbrain (Figure, A); administration of contrast revealed multiple ring-enhancing lesions (Figure, B). The woman’s medical history was significant for type 2 diabetes mellitus (DM), hypertension, recurrent urinary tract infections, onychomycosis, end-stage renal failure, and a history of living, unrelated donor renal transplant 12 years earlier, kidney transplant rejection, and prior episodes of syncope. Medications included tacrolimus, mycophenolate mofetil hydrochloride, prednisone (1 mg/d), losartan potassium, and insulin. Family history was notable for her father having died of lung cancer and her mother had heart disease and DM. Social history did not reveal any unusual exposures. Physical examination results showed a transplant surgical scar and onychomycosis. Neurologic findings revealed reasonably preserved mental status, with bedside examination revealing normal attention, language, and orientation but mild memory deficits for short-term recall (2 of 3 words recalled at a 5-minute delay) and long-term fund of knowledge. Cranial nerve, motor, sensory, and reflex examination results were significant only for gait ataxia, with an inability to perform tandem gait. Blood test results were consistent with DM. Findings from cerebrospinal fluid (CSF) examination included a white blood cell count of 9/µL, with differential examination showing 84% lymphocytes, 13% monocytes, and 3% neutrophils; red blood cell count of 1080/µL; protein level, 180 mg/dL; and glucose level, 87 mg/dL. Flow cytometry revealed B and T lymphocytes but no monoclonal populations of cells. Polymerase chain reaction amplification tests on CSF revealed no evidence of cytomegalovirus or herpes simplex virus 1 or 2 genetic material. Serum and CSF serologic test results were negative for antibodies to toxoplasma; testing using polymerase chain reaction on blood for Epstein-Barr virus (EBV) revealed minimal (very low positive) viral DNA at 52 IU/mL. A CT scan of the chest, abdomen, and pelvis showed a small, subpleural nodule; fatty liver; diverticulosis; failed native kidneys; and normal transplanted kidney. Whole-body positron emission tomography revealed hypermetabolic regions in the brain. Dexamethasone sodium phosphate and levetiracetam were administered. The patient underwent a diagnostic procedure.Brain magnetic resonance imaging showing unsuspected mass lesions. A, A T2 fluid-attenuated inversion recovery (FLAIR) sequence illustrating prominent T2 hyperintensity in the right more than the left parietal white matter suggestive of edema, an expansive mass lesion on the right more than the left splenium of the corpus callosum, and an infiltrative mass lesion in the left thalamus extending into the mesencephalon. B, A T1 sequence after administration of gadolinium contrast agent. Ring-enhancing regions are visible in the right parietal lobe and splenium of the corpus callosum, and a more solidly enhancing lesion is seen in the left thalamus as well as some apparent leptomeningeal enhancement.

what is your diagnosis?

What is your diagnosis?

Metastatic carcinoma

Posttransplant lymphoproliferative disorder

Central nervous system lymphoma

Central nervous system toxoplasmosis

b

female

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2430466

A 7-month-old boy was referred for monocular nystagmus and failure to thrive. He was born at full term weighing 3.63 kg after a normal pregnancy, labor, and delivery. He grew appropriately until 3 months of age, after which his weight dropped from the 50th percentile to the fifth percentile in 2 months despite maintenance of a fairly adequate caloric intake. The patient had multiple episodes of emesis. Results of his gastrointestinal evaluation were normal. At 6 months of age, he developed a constant rapid nystagmus of the right eye.On presentation, he was a happy, engaged, alert child with an emaciated appearance (Figure, A). His head was of normal size, although it appeared large relative to his small body size. During the examination, the patient was socially interactive and visually attentive. He had normal, optokinetic responses and brisk pupillary responses with no relative afferent pupillary defect. He had a rapid pendular horizontal nystagmus, with no associated strabismus, head nodding, or torticollis (Video). The patient looked readily toward objects held in the peripheral visual field of either eye. The retinal examination showed normal-sized optic discs without swelling or pallor. The patient had no history or findings suggestive of neurofibromatosis type 1.A, On presentation, the patient appeared emaciated but alert. B, T1 fluid-attenuated inversion recovery sagittal magnetic resonance (MR) image showing large globular suprasellar mass enveloping the optic chiasm (arrows).Perform magnetic resonance imaging of the brain and spine What Would You Do Next?

Perform electrooculography

Perform visual evoked potential test

Perform magnetic resonance imaging of the brain and spine

Perform blood culture

Russell diencephalic syndrome of infancy

C

Perform magnetic resonance imaging of the brain and spine

Magnetic resonance imaging of the brain showed a homogeneous enhancing mass within the suprasellar region measuring approximately 2.8 × 3.2 × 5.4 cm, suggestive of chiasmatic glioma (Figure, B), and a small nodular lesion in the medulla. There was no associated hydrocephalus. Magnetic resonance imaging of the spine showed a homogeneously enhancing 4-mm nodule along the thecal sac. Multifocal cauda equina nerve root tiny nodularities, possibly leptomeningeal enhancement, were noted. Results of genetic testing for NF1 were negative.The differential diagnosis of acquired monocular nystagmus in infancy includes spasmus nutans, chiasmal or hypothalamic glioma, and congenital unilateral visual loss.1 Spasmus nutans is a benign clinical entity characterized by the triad of nystagmus, head nodding, and an abnormal head position. The nystagmus is characteristically asymmetrical and may be monocular. The association of chiasmal glioma with spasmus nutans is usually signaled by 1 or more of the following clinical findings: a relative afferent pupillary defect, optic atrophy or disc swelling, large head size, café au lait spots, and coexistent neurologic dysfunction or emaciation.2 Our patient had monocular nystagmus with no other features of spasmus nutans. His body habitus provided the critical clue to the diagnosis of Russell diencephalic syndrome of infancy, which was confirmed by the results of MR imaging.In 1951, Russell3 first described the clinical entity of diencephalic syndrome as consisting of profound emaciation in infancy with an absence of subcutaneous adipose tissue despite a normal or only slightly diminished caloric intake. Affected children have a paradoxically alert appearance with motor overactivity, euphoria, and normal or accelerated linear growth.3,4 Resting energy expenditure studies can demonstrate a hypermetabolic state.4 Drop et al5 hypothesized that a lipolytic peptide, B-lipotropin, which is produced in excess by a tumor, could explain the decrease in subcutaneous tissue and release of excess human growth hormone. Possible roles of the hormones leptin and ghrelin have also been suggested.6Diencephalic syndrome has since been described almost exclusively in young children with space-occupying lesions of the hypothalamic-optic chiasm region.7 These tumors are larger, occur at a younger age (usually <12 months), and behave more aggressively than similarly located tumors without diencephalic syndrome.4,6 One study found an association between diencephalic syndrome and early dissemination of gliomas.8 In another study, all tumors associated with diencephalic syndrome had either a BRAF fusion mutation or NF1 mutations, both of which are associated with a more favorable survival in low-grade gliomas.4 Since our patient did not have any biopsy or resection, the BRAF status of his tumor is unknown.Treatment options for Russell diencephalic syndrome are limited by tumor involvement of the optic chiasm and adjacent anterior visual pathways, which precludes surgical resection. Adjuvant radiotherapy has been shown to be beneficial; however, radiotherapy in young children carries significant long-term morbidity.9 Recent studies have demonstrated the efficacy of chemotherapy supplemented with nutritional support as the first line of treatment, with favorable overall survival and metabolic outcomes.4 Long-term sequelae of Russell diencephalic syndrome include visual and pituitary dysfunction, learning difficulties, and paradoxical inappropriate weight gain.Tumors associated with diencephalic syndrome often have a poor response to treatment, requiring multiple courses of therapy over time. Given the rarity of diencephalic syndrome, studies with a large number of patients and long-term follow-up are limited. One study reported a 5-year progression-free survival of 22%, with all children remaining alive at a median follow-up of 5.3 years.4The patient was treated with a chemotherapeutic regimen consisting of carboplatin and vincristine.9 Following 10 weeks of induction chemotherapy, successive MR imaging showed progression of the suprasellar mass with mild interval progression of the leptomeningeal disease. He was then treated with vinblastine monotherapy. At the last follow-up after 5 months of vinblastine monotherapy, the patient continues to do well clinically with weight gain and good vision, although MR imaging showed mild enlargement of the suprasellar mass with stable leptomeningeal disease.

Ophthalmology

A 7-month-old boy was referred for monocular nystagmus and failure to thrive. He was born at full term weighing 3.63 kg after a normal pregnancy, labor, and delivery. He grew appropriately until 3 months of age, after which his weight dropped from the 50th percentile to the fifth percentile in 2 months despite maintenance of a fairly adequate caloric intake. The patient had multiple episodes of emesis. Results of his gastrointestinal evaluation were normal. At 6 months of age, he developed a constant rapid nystagmus of the right eye.On presentation, he was a happy, engaged, alert child with an emaciated appearance (Figure, A). His head was of normal size, although it appeared large relative to his small body size. During the examination, the patient was socially interactive and visually attentive. He had normal, optokinetic responses and brisk pupillary responses with no relative afferent pupillary defect. He had a rapid pendular horizontal nystagmus, with no associated strabismus, head nodding, or torticollis (Video). The patient looked readily toward objects held in the peripheral visual field of either eye. The retinal examination showed normal-sized optic discs without swelling or pallor. The patient had no history or findings suggestive of neurofibromatosis type 1.A, On presentation, the patient appeared emaciated but alert. B, T1 fluid-attenuated inversion recovery sagittal magnetic resonance (MR) image showing large globular suprasellar mass enveloping the optic chiasm (arrows).Perform magnetic resonance imaging of the brain and spine

what would you do next?

What would you do next?

Perform blood culture

Perform electrooculography

Perform magnetic resonance imaging of the brain and spine

Perform visual evoked potential test

c

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2436652

A man in his 40s with a history of chronic blurry vision in both eyes (worse in the right eye) had latent extrapulmonary tuberculosis that had been treated with antitubercular therapy 1 year earlier. Oral prednisone provided visual improvement. However, the therapy was complicated by avascular hip necrosis that required total hip arthroplasty, and his visual symptoms recurred with corticosteroid tapering.At presentation, his visual acuity was 20/150 OD and 20/15 OS. The anterior segment was normal in both eyes. Dilated ophthalmoscopic examination of the right eye revealed a diffuse subretinal yellow mass and an exudative retinal detachment temporal to the fovea (Figure 1). Ophthalmoscopic examination of the left eye was normal. B-scan of the right eye showed a dome-shaped choroidal lesion with an apical height of 3.4 mm and medium to high internal reflectivity. Fluorescein angiography demonstrated heterogeneous leakage, and optical coherence tomography of the macula showed subretinal fluid with irregular retinal and choroidal thickening. Results from extensive workup for infectious and autoimmune etiologies (including serum angiotensin-converting enzyme, lysozyme, lumbar puncture, magnetic resonance imaging of the brain and orbits, and computed tomography of the chest) were negative, except for positive purified protein derivative skin testing and positive interferon-γ release assay (QuantiFERON-TB Gold; Cellestis, Inc).Large choroidal tuberculoma at presentation. In a fundus view of the right eye, a moderate amount of subretinal fluid is seen adjacent to the lesion, involving the fovea center. B-scan (not shown) measured an apical height of 3.4 mm. What Would You Do Next?

Consult infectious diseases for alternative antitubercular therapy

Initiate corticosteroid-sparing immunosuppressive therapy

Inject intravitreous triamcinolone acetonide

Perform pars plana vitrectomy with intravitreous methotrexate

Choroidal granuloma secondary to tuberculosis (tuberculoma)

D

Perform pars plana vitrectomy with intravitreous methotrexate

Choroidal granulomas secondary to tuberculosis (tuberculomas) typically respond well to antitubercular therapy and systemic corticosteroids,1 but inflammatory damage to the macula can limit visual outcomes. We demonstrated rapid regression of a tuberculoma with pars plana vitrectomy and intravitreous methotrexate administration, followed by placement of a dexamethasone intravitreous implant (OZURDEX; Allergan, Inc), in a patient who developed intolerance to and was unable to continue a regimen of systemic corticosteroids. Vitrectomy is an accompaniment to pharmacotherapy for ocular inflammatory disease.2 While methotrexate is widely used for primary intraocular lymphoma,3 it is a folate antagonist that can affect infectious uveitis.4 Rapid regression of lymphoma with ocular involvement using methotrexate and vitrectomy may relate to the effects on inflammation and the microorganism itself.2,4Choroidal infiltration is the most common ocular tuberculosis manifestation of blood dissemination and is frequently unilateral, with solitary or multiple amelanotic lesions of the posterior pole.5 Extrapulmonary tuberculosis affecting the eye mimics ocular inflammatory disease,6 and most patients with intraocular tuberculosis have no history of pulmonary or systemic tuberculosis.5 Ocular tuberculosis requires systemic antitubercular therapy, and treatment is similar to that of pulmonary tuberculosis. Therapy should be directed against the infection and the inflammatory reaction. For that reason, placement of a sustained-release dexamethasone intravitreous implant may have off-label use in infectious posterior uveitis.5The patient underwent diagnostic pars plana vitrectomy with intravitreous methotrexate administration (400 µg/0.1 mL). Visual acuity improved to 20/50 OD on postoperative day 1, with resolution of subfoveal fluid. At 1 week after surgery, a dexamethasone intravitreous implant was placed, and the choroidal lesion continued to rapidly regress, with a marked reduction in subretinal fluid (Figure 2A). Visual acuity at 1 month was 20/30. There was definitive resolution of the yellow subretinal choroidal infiltration (Figure 2B), and no subretinal fluid remained. At 2 months after surgery, resolution was sustained, with only pigmentary abnormalities in the temporal macula. Findings from vitreous biopsy and cultures, including polymerase chain reaction and acid-fast smear, were negative. The patient continues treatment with systemic antitubercular therapy for presumed multidrug-resistant extrapulmonary tuberculosis.Choroidal tuberculoma at follow-up. A, One week after vitrectomy at the time of dexamethasone intravitreous implant placement. B-scan (not shown) measured an apical height of 3.1 mm. B, One month after surgery there was complete resolution of subretinal fluid, and B-scan measured an apical height of 1.6 mm.

Ophthalmology

A man in his 40s with a history of chronic blurry vision in both eyes (worse in the right eye) had latent extrapulmonary tuberculosis that had been treated with antitubercular therapy 1 year earlier. Oral prednisone provided visual improvement. However, the therapy was complicated by avascular hip necrosis that required total hip arthroplasty, and his visual symptoms recurred with corticosteroid tapering.At presentation, his visual acuity was 20/150 OD and 20/15 OS. The anterior segment was normal in both eyes. Dilated ophthalmoscopic examination of the right eye revealed a diffuse subretinal yellow mass and an exudative retinal detachment temporal to the fovea (Figure 1). Ophthalmoscopic examination of the left eye was normal. B-scan of the right eye showed a dome-shaped choroidal lesion with an apical height of 3.4 mm and medium to high internal reflectivity. Fluorescein angiography demonstrated heterogeneous leakage, and optical coherence tomography of the macula showed subretinal fluid with irregular retinal and choroidal thickening. Results from extensive workup for infectious and autoimmune etiologies (including serum angiotensin-converting enzyme, lysozyme, lumbar puncture, magnetic resonance imaging of the brain and orbits, and computed tomography of the chest) were negative, except for positive purified protein derivative skin testing and positive interferon-γ release assay (QuantiFERON-TB Gold; Cellestis, Inc).Large choroidal tuberculoma at presentation. In a fundus view of the right eye, a moderate amount of subretinal fluid is seen adjacent to the lesion, involving the fovea center. B-scan (not shown) measured an apical height of 3.4 mm.

what would you do next?

What would you do next?

Initiate corticosteroid-sparing immunosuppressive therapy

Inject intravitreous triamcinolone acetonide

Consult infectious diseases for alternative antitubercular therapy

Perform pars plana vitrectomy with intravitreous methotrexate

d

male

41-50

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2467314

A healthy young girl presented in June 2014 with a 4-week history of a painless, enlarging lesion on her right thumb that started as a small erythematous blister. She reported recently injuring her hand on a metal fence at home and biting her nails frequently. She lives on a farm in Ohio and has extensive direct contact with sheep and cows; family pets include a cat, a dog, and a hamster. There was no known recent travel or contact with anyone with a similar lesion. She reported mild tender lymphadenopathy of the right axilla but denied fever.Examination revealed an erythematous, 1 × 1.5-cm, well-defined eroded pustule with central crusting and an erythematous border (Figure). There were several slightly enlarged, mildly tender lymph nodes noted in the right axilla.Eroded and crusted pustule with surrounding inflammation on the thumb.Complete blood cell count, erythrocyte sedimentation rate, and basic metabolic panel results were unremarkable. Findings on radiography revealed focal soft-tissue swelling with no evidence of foreign body, subcutaneous gas, or osseous involvement. What Is Your Diagnosis?

Herpetic whitlow

Cutaneous anthrax

Orf

Sporotrichosis

C. Orf

C

Orf

The results of polymerase chain reaction for herpes simplex virus types 1 and 2 performed on the lesion were negative. The results of bacterial and fungal cultures were also negative. The clinical presentation along with the history of exposure to sheep were most suggestive of orf. Permission for a skin biopsy for histologic evaluation was declined by the patient and caregiver. A diagnosis of orf was confirmed by polymerase chain reaction analysis of a swab specimen of the lesional contents; testing was performed by the Centers for Disease Control and Prevention.Orf, also known as contagious echthyma and contagious pustular dermatitis, is a zoonotic infection that principally infects sheep and goats and is caused by a double-stranded DNA virus that belongs to the Parapoxvirus genus.1 It is transmitted through direct or indirect contact with infected animals, in particular through contact with saliva.2 Therefore, orf infection typically involves the hands and is most frequently seen in professionally exposed persons, such as butchers, sheep shearers, and veterinary surgeons. Exposure may also occur through contact with infected animals in petting zoos, livestock fairs, and holiday manger scenes.2,3 Nontraditional means by which orf has been transmitted to humans include household meat processing, animal slaughter, and contact with infected fomites.3 The manner in which children may interact with infected animals can lead to the presence of lesions on atypical sites, such as facial lesions.3 Human transmission of orf does not occur.Infected animals typically manifest sore mouth, which is characterized by painful oral blisters and crusts that interfere with eating. There are 2 commercially available veterinary vaccines, but some sheep farm operators produce their own vaccine from the scabs of previously infected animals. Vaccines are fully virulent and infectious to humans who have contact with the vaccine itself or with vaccinated animals. Immunity conferred by vaccines or natural infection is not complete or lifelong, and vaccine failures have been reported.1,3The incubation period varies from 4 days to 2 weeks, and skin lesions generally appear on the fingers, hands, or forearms after a 3- to 7-day incubation period. Clinical presentation is that of a lesion that progresses through the following 6 stages in 4 to 8 weeks: (1) in the maculopapular stage, an erythematous, often tender macule or papule is noted at the exposure site; (2) in the target stage, the lesion acquires an erythematous center, which may be composed of a shallow ulcer with an outer white halo and peripheral erythema; (3) in the acute stage, a weeping nodule is noted; (4) in the regenerative phase, the exudate begins to dry (5); in the papillomatous stage, a papilloma-like lesion with a dry crust forms; and (6) in the last stage, the lesion resolves with minimal scarring.2 Significant lymphadenopathy is uncommon in orf infection. Associated signs and symptoms in immunocompetent hosts are rare but include fever, malaise, lymphadenitis, lymphangitis, and secondary bacterial infection.2Orf is mainly a clinical diagnosis supported by a history of contact with infected animals. Diagnostic assays are available to facilitate the differentiation of orf virus infection from other parapoxvirus infections, such as pseudocowpox, because the clinical presentation is indistinguishable. The differential diagnosis also includes atypical mycobacterial infection, tularemia, cutaneous anthrax, herpetic whitlow, and ecthyma. Standard and real-time polymerase chain reaction assays can confirm the diagnosis. Testing is available at the Poxvirus Laboratory of the Centers for Disease Control and Prevention.4Treatment generally consists of local wound care because spontaneous resolution is the rule in immunocompetent persons, although secondary bacterial infection may occur. Several case reports and a case series suggest that use of topical imiquimod may facilitate healing, in particular in immunocompromised persons.5 Misdiagnosis may result in inappropriate therapeutic interventions. When presented with a patient with an isolated pustular lesion on the hand, physicians should consider a diagnosis of orf and elicit an appropriate history.

Pediatrics

A healthy young girl presented in June 2014 with a 4-week history of a painless, enlarging lesion on her right thumb that started as a small erythematous blister. She reported recently injuring her hand on a metal fence at home and biting her nails frequently. She lives on a farm in Ohio and has extensive direct contact with sheep and cows; family pets include a cat, a dog, and a hamster. There was no known recent travel or contact with anyone with a similar lesion. She reported mild tender lymphadenopathy of the right axilla but denied fever.Examination revealed an erythematous, 1 × 1.5-cm, well-defined eroded pustule with central crusting and an erythematous border (Figure). There were several slightly enlarged, mildly tender lymph nodes noted in the right axilla.Eroded and crusted pustule with surrounding inflammation on the thumb.Complete blood cell count, erythrocyte sedimentation rate, and basic metabolic panel results were unremarkable. Findings on radiography revealed focal soft-tissue swelling with no evidence of foreign body, subcutaneous gas, or osseous involvement.

what is your diagnosis?

What is your diagnosis?

Herpetic whitlow

Sporotrichosis

Orf

Cutaneous anthrax

c

female

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2448769

A man in his 60s presented to the clinic with a 5-month history of sudden-onset, progressively worsening dysphonia, dry cough, and the sensation of a lump in his throat. He described a progressively worsening voice with use to the point where he was nearly aphonic by the end of his workday. He denied any heartburn, hemoptysis, pain, neck masses, or smoking history. Prior treatment with 2 rounds of oral antibiotics and 1 round of oral steroids from his primary care physician did not improve his symptoms. Objectively, the patient’s voice was rough, diplophonic, and very strained. Videostroboscopic examination in the clinic revealed a broad-based submucosal mass in the anterior two-thirds of the right true vocal fold (Figure, A) that disrupted vibration of both vocal folds owing to its size and anterior location (Figure, B and Video). Findings from the remainder of his head and neck examination were unremarkable. The patient was taken to the operating room for microdirect laryngoscopy under general anesthesia (Figure, C). A microflap incision along the lateral aspect of the right true vocal fold mass was performed, and a firm, submucosal, tan-colored, seemingly encapsulated, multilobulated mass was removed en bloc with narrow margins and sent for permanent section analysis (Figure, D). The mass was deep to the epithelium of the true vocal fold and superficial to the vocal ligament.A and B, Clinical views of endoscopic appearance of the anterior right true vocal fold mass. A, View showing vocal folds abducted. B, View showing vocal folds adducted. C and D, Intraoperative endoscopic views. C, Submucosal mass. D, A microflap incision was performed along the lateral aspect of the lesion and a multilobulated, firm submucosal mass deep to the epithelium but superficial to the vocal ligament was resected. What Is Your Diagnosis?

True vocal fold polyp

Vocal fold squamous cell carcinoma

True vocal fold myxoma

Thyroarytenoid muscle rhabdomyoma

C. True vocal fold myxoma

C

True vocal fold myxoma

Myxomas are nonmetastatic tumors of mesenchymal origin that most commonly develop in cardiac muscle and skeletal muscle of the extremities. Myxomas in the head and neck region are uncommon and most frequently develop in the perioral soft tissue surrounding the mandible or the mandible itself.1 Extragnathic myxomas are very rare. When they occur, laryngeal myxomas can develop in any anatomic subsite of the larynx.2 Myxomas that develop on the true vocal fold tend to cause dysphonia and/or breathing disturbance more rapidly than myxomas that develop at other subsites, leading to early patient presentation and diagnosis.3,4 In this patient, the mass and stiffness of the diseased right vocal fold along with the mass crossing the midline and physically lateralizing the anterior left vocal fold led to disruption of the mucosal wave bilaterally.While myxoma should be included in the differential of any submucosal lesion, operative exploration is required to fully characterize the disease and obtain tissue for pathologic analysis. Intraoperatively, a multinodular, rubbery to firm, gray-white lesion is encountered. While a myxoma can arise from any mesenchymal tissue, true vocal fold myxomas are often found in the superficial lamina propria and can be clearly separated from the overlying epithelium and underlying vocal ligament.1,4 The diagnosis is confirmed by histologic examination with identification of stellate cells and an irregular matrix of reticular fibers and extracellular matrix. Cellular atypia, mitotic figures, vascularity and cellular necrosis are usually absent but can be found in nearly granulation tissue if the myxoma has elicited an inflammatory response.4Of the possible answers in this quiz, the anatomic description should allow elimination of squamous cell carcinoma, which would arise from the overlying vocal fold epithelium, and thyroarytenoid muscle rhabdomyoma, which would arise from the muscle deep to the vocal ligament. While an organized vocal fold polyp in this location would be atypical, ultimately pathologic analysis would be required to differentiate this disorder from a mesenchymal tumor, such as a myxoma.Treatment of laryngeal myxoma includes extirpation of the disease. Given that recurrence rates of head and neck myxomas can be as high as 28%, others have advocated for en bloc, wide excision of these tumors to reduce the risk of recurrence.1,5 Yet preservation of as much epithelium, superficial lamina propria and vocal ligament as possible in the true vocal fold is critical to maximize postoperative voice. Because direct visualization with video laryngoscopy allows effective surveillance, microlaryngeal excision with limited margins should be the treatment of choice for true vocal fold myxomas. Long-term surveillance is needed because laryngeal myxomas can recur several years after initial resection.2

General

A man in his 60s presented to the clinic with a 5-month history of sudden-onset, progressively worsening dysphonia, dry cough, and the sensation of a lump in his throat. He described a progressively worsening voice with use to the point where he was nearly aphonic by the end of his workday. He denied any heartburn, hemoptysis, pain, neck masses, or smoking history. Prior treatment with 2 rounds of oral antibiotics and 1 round of oral steroids from his primary care physician did not improve his symptoms. Objectively, the patient’s voice was rough, diplophonic, and very strained. Videostroboscopic examination in the clinic revealed a broad-based submucosal mass in the anterior two-thirds of the right true vocal fold (Figure, A) that disrupted vibration of both vocal folds owing to its size and anterior location (Figure, B and Video). Findings from the remainder of his head and neck examination were unremarkable. The patient was taken to the operating room for microdirect laryngoscopy under general anesthesia (Figure, C). A microflap incision along the lateral aspect of the right true vocal fold mass was performed, and a firm, submucosal, tan-colored, seemingly encapsulated, multilobulated mass was removed en bloc with narrow margins and sent for permanent section analysis (Figure, D). The mass was deep to the epithelium of the true vocal fold and superficial to the vocal ligament.A and B, Clinical views of endoscopic appearance of the anterior right true vocal fold mass. A, View showing vocal folds abducted. B, View showing vocal folds adducted. C and D, Intraoperative endoscopic views. C, Submucosal mass. D, A microflap incision was performed along the lateral aspect of the lesion and a multilobulated, firm submucosal mass deep to the epithelium but superficial to the vocal ligament was resected.

what is your diagnosis?

What is your diagnosis?

Vocal fold squamous cell carcinoma

Thyroarytenoid muscle rhabdomyoma

True vocal fold myxoma

True vocal fold polyp

c

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2456056

A woman in her 70s presented with a 4-day history of new-onset, left-sided acute epistaxis described as episodes of bright red bleeding and clotting from the left anterior nare, occurring multiple times per day, lasting minutes each time, and stopped with pressure. She denied other sinonasal symptoms, history of epistaxis, nasal trauma, or surgery. Clinical evaluation revealed a soft-tissue mass filling the left nasal cavity and based on the mucosal surface of the anterolateral nasal vestibule. Noncontrast paranasal sinus computed tomography showed a 1.2 × 0.8-cm ovoid soft-tissue mass opacifying the posterior aspect of the left nasal vestibule (Figure, A, arrowhead). Endoscopic excision under local anesthesia was performed to remove a broad-based soft-tissue mass from the left nasal vestibule mucosa with a cuff of grossly healthy submucosa. A tissue specimen was biopsied (Figure, B-D). The patient had an uneventful postoperative course, and her epistaxis symptoms were resolved at the 5-month follow-up.A, Noncontrast paranasal sinus computed tomographic image. B-D, Histopathologic images from the nasal cavity mass, original magnifications ×100. What Is Your Diagnosis?

Angiomyolipoma

Angiofibroma

Nasal angioleiomyoma

Hemangioma

C. Nasal angioleiomyoma

C

Nasal angioleiomyoma

Microscopically, nasal angioleiomyoma presents as a well demarcated polypoid mass, lined by nasal mucosa with prominent, increased, interweaving submucosal vascular channels, perivascular spindle cells, and mature adipose tissue (Figure, B). Some areas are rich in back-to-back vascular vessels with interlacing spindle cells, and some areas have less vessels and predominately adipose tissue. The vessels have prominent, thick walls without elastic lamina, with slitlike to angulated lumen lined by flat endothelium. The surrounding bland spindle cells are mature, smooth muscle cells arranged in a fascicular pattern that are blended with the outer wall of the vessels. These findings are consistent with nasal angioleiomyoma, venous subtype.The clinical presentation of acute epistaxis without trauma resolved after endoscopic excision, and the microscopic finding of thick-walled vascular vessels with interlacing spindle cells favor a diagnosis of nasal angioleiomyoma, venous subtype. The diagnosis is confirmed by positive immunostains of CD31 and smooth-muscle actin (Figure, C and D). Because of the abundant mature adipose cells present in the specimen together with the thick-walled vessels and the smooth muscle cells, angiomyolipoma is also a diagnostic consideration. However, it is ruled out based on the absence of HMB-45 stain. Leiomyoma is another consideration but is excluded histologically because of the prominent vascularity.Leiomyomas and angioleiomyomas are extremely uncommon in the head and neck area, comprising less than 1% of all cases, and among these, only 3% occurred in the nasal cavity.1-3 Nasal angioleiomyoma is also known as vascular leiomyoma, or angiomyoma. It was first described by Maesaka and Nakahashi4 in 1966. The etiology is unclear; Wenig5 hypothesized that they might originate from the smooth muscle of the nasal vascular wall. The rare occurrence might be partially explained by the lack of smooth muscle in the nasal cavity. The presenting symptoms are nonspecific and related to the mass effect and vascularity of the lesion: nasal obstruction, discharge, epistaxis, pain and headache.6 The World Health Organization Classification of Tumours of Soft Tissue and Bone adopted the subtyping of angioleiomyoma by Morimoto7 into 3 types: solid, cavernous, and venous. Usually a lesion only has one type of tumor. All 3 types have well-differentiated mature smooth muscle cells without, or very rarely with, mitosis. The solid type has smooth muscle bundles around slit like vascular channels. In this type, the vessels are great in number but small in size. The venous type has vascular channels with thick, muscular walls; the outer layer of the muscular walls blends with smooth muscle bundles. The cavernous type has dilated vascular channels and lesser amounts of smooth muscle. The muscular vessel wall is difficult to distinguish from the smooth muscle bundles. Angioleiomyomas in the head and neck area are often venous type, as is our case. Angioleiomyomas occur in a female to male ratio of 2:1.8 Based on this observation and the presence of increased pain during menstrual cycles and pregnancy, Marioni et al9 surmised that the tumor might be hormone dependent. However, there is not enough evidence to support this theory.10Angioleiomyoma is benign, and the prognosis is excellent. It is considered cured by surgical resection. Most of the cases are limited to the nasal cavity; therefore, an endoscopic excision is the preferred surgical method of removal. Local recurrence is very rare, and to our knowledge, no malignant transformation has been reported.

General

A woman in her 70s presented with a 4-day history of new-onset, left-sided acute epistaxis described as episodes of bright red bleeding and clotting from the left anterior nare, occurring multiple times per day, lasting minutes each time, and stopped with pressure. She denied other sinonasal symptoms, history of epistaxis, nasal trauma, or surgery. Clinical evaluation revealed a soft-tissue mass filling the left nasal cavity and based on the mucosal surface of the anterolateral nasal vestibule. Noncontrast paranasal sinus computed tomography showed a 1.2 × 0.8-cm ovoid soft-tissue mass opacifying the posterior aspect of the left nasal vestibule (Figure, A, arrowhead). Endoscopic excision under local anesthesia was performed to remove a broad-based soft-tissue mass from the left nasal vestibule mucosa with a cuff of grossly healthy submucosa. A tissue specimen was biopsied (Figure, B-D). The patient had an uneventful postoperative course, and her epistaxis symptoms were resolved at the 5-month follow-up.A, Noncontrast paranasal sinus computed tomographic image. B-D, Histopathologic images from the nasal cavity mass, original magnifications ×100.

what is your diagnosis?

What is your diagnosis?

Angiomyolipoma

Hemangioma

Angiofibroma

Nasal angioleiomyoma

d

female

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2463110

A teen-aged boy with a recent history of resolved streptococcal pharyngitis presented with dizziness, vomiting, unstable gait, and headaches of 2 weeks’ duration. Laboratory evaluation revealed a sodium level of 109 mEq/L. Rapid correction to 136 mEq/L occurred, resulting in lethargy, aphasia, and ataxia. He was diagnosed as having idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH). Magnetic resonance imaging (MRI) demonstrated an abnormal signal within the basal ganglia and insular cortex. A 2.5 × 1.5 × 1.8-cm mass was found in the superior right maxillary sinus with extension into the infundibulum (Figure, A). Computed tomographic (CT) scans of the sinuses without intravenous contrast demonstrated that the mass had calcifications. Owing to persistent hyponatremia (sodium level, 125-130 mEq/L) and an identifiable lesion, the patient was taken to the operating room for biopsy. He underwent a maxillary antrostomy with near-complete removal of the mass. Over the subsequent 2 weeks, the hyponatremia resolved and the patient was left with slight dysarthria and difficulties with fine-motor movements. The submucosa contained a small, round, blue-cell tumor growing in circumscribed lobules and nests separated by vascularized fibrous stroma. The neoplastic cells had uniform, small, round nuclei with scant cytoplasm. Cells were arranged in a pseudorosette pattern (Figure, B). The nuclei demonstrated dispersed, salt and pepper nuclear chromatin and inconspicuous nucleoli. The cells were surrounded by a neurofibrillary matrix. There were prominent microcalcifications. No mitotic figures were seen. The tumor cells were diffusely positive for immunohistochemical marker synaptophysin (Figure, C). Results from cytokeratin staining were negative (Figure, D).A, T1-weighted postgadolinium magnetic resonance image, coronal view. B-D, Histopathological images. B, Hematoxylin-eosin, original magnification ×100. C, Tissue positivity for synaptophysin, original magnification ×200. D, Tissue negativity for cytokeratin, original magnification ×200. What Is Your Diagnosis?

Inverted papilloma

Fungal ball

Esthesioneuroblastoma

Sinonasal undifferentiated carcinoma

C. Esthesioneuroblastoma

C

Esthesioneuroblastoma

Esthesioneuroblastoma (ENB), or olfactory neuroblastoma, is a rare malignant neoplasm believed to arise from the olfactory epithelium that lines the superior nasal vault. Esthesioneuroblastoma has a bimodal age distribution, with most patients in the sixth and seventh decade. Although ENBs are atypical, there have been few reports of ectopic ENBs, including isolated maxillary sinus lesions.1The original staging system was proposed by Kadish et al.2 Our patient would be classified as having a Kadish stage B tumor (disease confined to the nasal cavity and paranasal sinuses) vs a stage A tumor (disease limited to nasal fossa) and stage C (extension beyond the paranasal sinuses). More recently, a TNM staging has been proposed.3Patients with ENB most commonly present with unilateral nasal obstruction (70%) followed by epistaxis (41%), which are fairly nonspecific.2 Cross-sectional imaging is required for tumor staging, and MRI is obtained in cases in which there is concern about intraorbital or intracranial extension. Although paraneoplastic syndromes are rare in ENB, antidiuretic and, less commonly, adrenocorticotropic hormones (ACTH) are the most common causes.1,4,5 It has been estimated that of the 1300 reported cases of ENB in the literature, only 26 (2%) are associated with SIADH. In roughly half of these cases, SIADH presents before the diagnosis of ENB is known, similar to the patient described herein. In rare cases, SIADH can proceed the primary diagnosis by more than a decade.5 Ectopic ACTH production due to ENB can lead to Cushing syndrome. Removal of the tumor usually results in reversal of the paraneoplastic syndrome.The differential diagnosis of a maxillary sinus lesion includes nasal polyposis, inverted papilloma, and mycetoma (the latter 2 especially, given the areas of calcifications). Indeed, clinical suspicion for ENB or any malignant process was extremely low given the patient’s age, lack of bony destruction, and enhancement in the nasal vault. Yet up to 20% of all ENBs are diagnosed before the age of 20 years.6 Finally, an isolated maxillary sinus lesion is an atypical presentation for ENB.5Once we determined that the lesion was of neuroendocrine differentiation, other sinonasal tumors had to be eliminated. Sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), and small-cell carcinoma have overlapping histologic features. Esthesioneuroblastoma is characterized by staining positive for synaptophysins and chromogranin and staining weakly for epithelial markers, such as cytokeratin. Meanwhile SNUC stains strongly for cytokeratin and weakly for chromogranin. SNEC can stain positive for both. It is important to differentiate ENB from SNEC/SNUC because the latter 2 disease processes have poor locoregional and distant control, thus requiring postoperative chemotherapy in the treatment plan.7The case was further complicated by the rapid correction of the hyponatremia, which caused central pontine myelinolysis. Patients may develop catatonia, mutism, parkinsonism, and dystonia.8 Furthermore, a recent streptococcus infection with neurologic changes can be a feature of pediatric autoimmune neuropsychiatric disorders. Typical manifestations include tics, obsessive compulsive, dystonia, and choreic movements, none of which were present in our patient.9The uncertain neurologic prognosis of this patient resulted in a delay in his surgical diagnosis, but he did regain most of his neurologic function after the initial surgery. He subsequently underwent a wide endoscopic resection of the residual tumor bed, including a medial maxillectomy (combined endoscopic and sublabial approach) and inferior turbinate resection. The margins were clear of disease. Postoperative radiation therapy (RT) was recommended based on studies showing the benefits of postoperative RT in disease-specific survival.6 However, this remains controversial because other studies, including a meta-analysis,10 have shown no significant difference in survival. To date, the patient is free from recurrent disease.

General

A teen-aged boy with a recent history of resolved streptococcal pharyngitis presented with dizziness, vomiting, unstable gait, and headaches of 2 weeks’ duration. Laboratory evaluation revealed a sodium level of 109 mEq/L. Rapid correction to 136 mEq/L occurred, resulting in lethargy, aphasia, and ataxia. He was diagnosed as having idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH). Magnetic resonance imaging (MRI) demonstrated an abnormal signal within the basal ganglia and insular cortex. A 2.5 × 1.5 × 1.8-cm mass was found in the superior right maxillary sinus with extension into the infundibulum (Figure, A). Computed tomographic (CT) scans of the sinuses without intravenous contrast demonstrated that the mass had calcifications. Owing to persistent hyponatremia (sodium level, 125-130 mEq/L) and an identifiable lesion, the patient was taken to the operating room for biopsy. He underwent a maxillary antrostomy with near-complete removal of the mass. Over the subsequent 2 weeks, the hyponatremia resolved and the patient was left with slight dysarthria and difficulties with fine-motor movements. The submucosa contained a small, round, blue-cell tumor growing in circumscribed lobules and nests separated by vascularized fibrous stroma. The neoplastic cells had uniform, small, round nuclei with scant cytoplasm. Cells were arranged in a pseudorosette pattern (Figure, B). The nuclei demonstrated dispersed, salt and pepper nuclear chromatin and inconspicuous nucleoli. The cells were surrounded by a neurofibrillary matrix. There were prominent microcalcifications. No mitotic figures were seen. The tumor cells were diffusely positive for immunohistochemical marker synaptophysin (Figure, C). Results from cytokeratin staining were negative (Figure, D).A, T1-weighted postgadolinium magnetic resonance image, coronal view. B-D, Histopathological images. B, Hematoxylin-eosin, original magnification ×100. C, Tissue positivity for synaptophysin, original magnification ×200. D, Tissue negativity for cytokeratin, original magnification ×200.

what is your diagnosis?

What is your diagnosis?

Inverted papilloma

Sinonasal undifferentiated carcinoma

Esthesioneuroblastoma

Fungal ball

c

male

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2463449

A woman in her 60s presented to the emergency department with a 3-week history of enlarging and painful cervical masses. She reported a distant history of breast cancer and a recent history of an oral cavity lesion, which was not biopsied or followed up. She did not have any known tuberculosis exposure, recent foreign travel, exposure to unpasteurized food, history of immunodeficiency, or alcohol or tobacco use. She did not have fever, chills, cough, dysphagia, or odynophagia. Physical examination revealed a healthy-appearing woman with normal vital signs. She was found to have bilateral cervical lymphadenopathy, which included fixed and bulky nodes in level IB and IIA and nontender level IV and V nodes. An oral cavity examination revealed no evidence of masses or lesions, floor of mouth and base of tongue were soft, and the palatine tonsils had no lesions or ulcers. Flexible laryngoscopy revealed no evidence of pharyngeal or laryngeal lesions. Contrast-enhanced computed tomographic (CT) scans of the neck (Figure) revealed bilateral lymphadenopathy with central necrosis.Computed tomographic scan with contrast. A, At the level of mandible. B, At the level of thyroid cartilage. C, Through the sphenoid. D, Through the temporomandibular joint. What Is Your Diagnosis?

Squamous cell carcinoma

Lymphoma

Tuberculous lymphadenitis

Papillary thyroid carcinoma

C. Tuberculous lymphadenitis

C

Tuberculous lymphadenitis

In the United States, the incidence of extrapulmonary tuberculosis (TB), without concurrent pulmonary disease, is 5.4%, with 30% to 50% of cases involving TB lymphadenitis.1 Isolated peripheral TB lymphadenitis represents approximately 13% to 30% of reported cases.2 Cervical TB lymphadenitis, also known as scrofula or “King’s evil” because it was believed to be cured by the touch of royalty, is the most common site of TB lymphadenitis.2 Over two-thirds of cases of TB lymphadenitis present with predominantly cervical involvement.1The diagnosis of scrofula, though, may be challenging. Lack of systemic symptoms in immunocompetent patients and characteristics that mimic other, more common, diseases are among the reasons. Only one-third of patients have a history of TB.2 The differential diagnosis for cervical lymphadenopathy includes malignant diseases, like lymphoma, or cystic-appearing metastasis, such as papillary thyroid carcinoma or squamous cell carcinoma. It also includes atypical mycobacterial infections, sarcoidosis, reactive lymphadenopathy, and other infections, such as cat scratch disease.Inconsistent clinical features increase the diagnostic dilemma, but classic descriptions are of painless, enlarging, unilateral lymphadenopathy.2,3 Lymph nodes tend to be firm and discrete early in the course of disease and become increasingly fluctuant and matted.1 Upper deep cervical, submandibular, and posterior triangle lymph nodes have been most frequently implicated, and usually only a single level of lymph nodes is involved.2,4 Typical systemic symptoms, including fever, weight loss, and night sweats, are present in a small percentage of patients.2,3Three stages of disease may be evident on CT or magnetic resonance imaging. Stage 1 is characterized by homogeneous attenuation of involved nodes with homogeneous contrast enhancement that corresponds to granuloma formation without necrosis. In stage 2 the involved nodes display central necrosis. Stage 3, typically seen in patients undergoing treatment, shows lymphadenopathy with focal calcifications.5 Sonographic features of scrofula include predominantly hypoechoic nodes with heterogenous echo pattern and intranodal necrosis; indistinct nodal pattern, nodal matting, or nodal clumping; poorly defined anechoic areas in the perinodal soft tissue with or without sinus or abscess formation; or vascular distribution with apparently avascular areas and displaced vascularity on Doppler ultrasonography . When lymph nodes display 2 or more features on ultrasonography, the specificity and sensitivity for diagnosis are 95% and 80%, respectively.6Sensitivity and specificity of fine-needle aspiration (FNA) are 46% to 77% and 93% to 100%, respectively.1,7 Excisional biopsy, though, remains the gold standard for diagnosis.8 Histopathologic features include epithelioid cell granulomas and central caseous necrosis with multinucleated giant cells.6 Finding mycobacterium on acid-fast bacilli (AFB) smear, histopathologic examination, or positive mycobacterial cultures establish the diagnosis.3 A positive AFB smear from FNA is present in 10% to 75% of cases; the degree of central necrosis of the node is directly correlated with yield on AFB.2 Although culture is the only way to definitively establish the diagnosis, it is now accepted that suggestive histopathologic findings on FNA, along with an appropriate clinical history and positive results on a purified protein derivative test, is enough to begin anti-TB treatment.2 Further distinguishing this entity from atypical mycobacterial infections is performed using interferon-γ release assays, particularly QuantiFERON-TB Gold In-Tube assay (QFT; Cellestis/Qiagen).9 If diagnosis cannot be established by these methods, a trial of anti-TB treatment can be initiated to evaluate for a clinical response and/or excisional biopsy is performed.Current treatment includes a 6-month course of multidrug anti-TB chemotherapy consisting of isoniazid, rifampin, and ethambutol with pyrazinamide for the first 2 months.3 While some authors have found an acceptable medical cure rate, others advocate surgical excision in some cases. Surgery is typically reserved for patients with persistent cervical lymphadenopathy despite medical management, those with a single level of disease, or those with overlying skin changes suggestive of atypical non-TB mycobacterial infections.10 If performed, surgical excision still requires anti-TB chemotherapy.In the case described herein, the patient underwent anti-TB chemotherapy treatment with a good clinical response at the initial follow-up.

General

A woman in her 60s presented to the emergency department with a 3-week history of enlarging and painful cervical masses. She reported a distant history of breast cancer and a recent history of an oral cavity lesion, which was not biopsied or followed up. She did not have any known tuberculosis exposure, recent foreign travel, exposure to unpasteurized food, history of immunodeficiency, or alcohol or tobacco use. She did not have fever, chills, cough, dysphagia, or odynophagia. Physical examination revealed a healthy-appearing woman with normal vital signs. She was found to have bilateral cervical lymphadenopathy, which included fixed and bulky nodes in level IB and IIA and nontender level IV and V nodes. An oral cavity examination revealed no evidence of masses or lesions, floor of mouth and base of tongue were soft, and the palatine tonsils had no lesions or ulcers. Flexible laryngoscopy revealed no evidence of pharyngeal or laryngeal lesions. Contrast-enhanced computed tomographic (CT) scans of the neck (Figure) revealed bilateral lymphadenopathy with central necrosis.Computed tomographic scan with contrast. A, At the level of mandible. B, At the level of thyroid cartilage. C, Through the sphenoid. D, Through the temporomandibular joint.

what is your diagnosis?

What is your diagnosis?

Papillary thyroid carcinoma

Tuberculous lymphadenitis

Squamous cell carcinoma

Lymphoma

b

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2468490

A woman in her 70s was referred to our hospital for evaluation of a dry cough, foreign body sensation in the throat, and mild dysphagia of 2 months’ duration. She had no dyspnea or hoarseness. Her medical history included hypertension, diabetes mellitus, and right-sided chronic otitis media of 4 years’ duration successfully treated surgically 1 year earlier (tympanoplasty type 1). On oral endoscopic examination, mild bilateral hyperemia of the tonsillar area and posterior pharyngeal wall were noted. A submucosal pulsatile mass was clearly visible in the right retropharyngeal area (Figure, A and B; Video). The base of tongue was normal. No other clinically significant abnormalities were noted. Part of the clinical findings were suggestive of laryngopharyngeal reflux disease, and oral esomeprazole, 40 mg/d, was prescribed. Head and neck magnetic resonance angiography was recommended (Figure, C and D). She was reevaluated after 15 days.A and B, Endoscopic examination of the oropharynx revealing a submucosal pulsatile mass in the right retropharyngeal area. C, Three-dimensional reconstruction. Abnormal medial course of the right internal carotid artery (arrow). D, T1-weighted gradient echo. Aberrant internal carotid artery in the retropharyngeal space. What Is Your Diagnosis?

Arteriovenous malformation of the oropharynx

Aberrant internal carotid artery

Cavernous hemangioma of the oropharynx

Internal carotid artery pseudoaneurysm

B. Aberrant internal carotid artery

B

Aberrant internal carotid artery

At reevaluation, the patient reported a slight improvement of her symptoms. Hyperemia of the tonsillar area and posterior pharyngeal wall was reduced. For this reason, continuation of the oral esomeprazole, 40 mg/d, was recommended for 3 months. Magnetic resonance angiography revealed that the cervical segment of right internal carotid artery (ICA) had an abnormal medial course (Figure, C and D) in the retropharyngeal space. The minimal distance between the mucosal surface and the ICA wall was 1 mm. Aberrant retropharyngeal ICA was diagnosed.The normal course of the cervical segment of the ICA runs straight to the skull base without significant deviation. Variations in the course are kinking, coiling, and S- or C-shaped elongation with displacement.1,2 Aberrant course of the ICA is a relatively frequent congenital variant found in approximately 10% to 40% in the general population.3 High-grade aberrations can be found in 5% to 6% of the population, and very rarely the ICA may lie in the oropharynx just beneath the mucosa.Patients may experience symptoms such as dysphagia, change in voice, dry cough, or foreign body sensation. Symptoms most often arise in elderly people if an embryological malformation becomes more pronounced owing to acquired conditions, such as arteriosclerosis and hypertension.3 Rarely, the aberrant ICA causes narrowing of the pharyngeal lumen with obstructive sleep apnea.4 In about 80% of cases, aberrant ICA is asymptomatic and incidentally noted during routine imaging of head and neck.5,6The etiology of ICA anomalies remains controversial. Potential causative factors include embryological maldevelopment and age-related loss of elasticity in the vessel wall. Particularly high-grade aberrations have often been attributed to a congenital malformation.2,7,8Pfeiffer and Ridder3 proposed a classification system for aberrant ICAs in relation to the location and distance from the pharyngeal mucosa. Basing on these parameters they classified the potential risk for ICA injury as low, moderate, high, and very high.A diagnosis of aberrant submucosal ICA has a number of clinically relevant implications for the anesthesiologist as well as for the surgeon. Injuries of the ICA may result in a life-threatening hemorrhage during tonsillectomy, uvulopalatopharyngoplasty, or incision and drainage of a peritonsillar abscess.5 Aberrant retropharyngeal ICA could pose a considerable additional risk of arterial puncture and/or injection of local anesthetics when performing the transoral glossopharyngeal nerve block.5When an aberrant ICA manifests as a submucosal pulsating mass, differential diagnoses include all vascular lesions, such as arteriovenous malformations, cavernous hemangioma, and ICA pseudoaneurysm.9 We conclude that aberrant retropharyngeal ICA is a potentially dangerous variant that, when diagnosed, should be noted in the medical records of the patients to prevent fatal complications.

General

A woman in her 70s was referred to our hospital for evaluation of a dry cough, foreign body sensation in the throat, and mild dysphagia of 2 months’ duration. She had no dyspnea or hoarseness. Her medical history included hypertension, diabetes mellitus, and right-sided chronic otitis media of 4 years’ duration successfully treated surgically 1 year earlier (tympanoplasty type 1). On oral endoscopic examination, mild bilateral hyperemia of the tonsillar area and posterior pharyngeal wall were noted. A submucosal pulsatile mass was clearly visible in the right retropharyngeal area (Figure, A and B; Video). The base of tongue was normal. No other clinically significant abnormalities were noted. Part of the clinical findings were suggestive of laryngopharyngeal reflux disease, and oral esomeprazole, 40 mg/d, was prescribed. Head and neck magnetic resonance angiography was recommended (Figure, C and D). She was reevaluated after 15 days.A and B, Endoscopic examination of the oropharynx revealing a submucosal pulsatile mass in the right retropharyngeal area. C, Three-dimensional reconstruction. Abnormal medial course of the right internal carotid artery (arrow). D, T1-weighted gradient echo. Aberrant internal carotid artery in the retropharyngeal space.

what is your diagnosis?

What is your diagnosis?

Aberrant internal carotid artery

Arteriovenous malformation of the oropharynx

Cavernous hemangioma of the oropharynx

Internal carotid artery pseudoaneurysm

a

female

71-80

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2398983

A 60-year-old man with advanced melanoma presented with headaches and increasing fatigue during treatment with ipilimumab. Several months earlier, he presented to the emergency department with shortness of breath. Imaging revealed pulmonary emboli and incidental groin lymphadenopathy. Biopsy of a lymph node showed melanoma. He then underwent inguinal lymph node dissection and was found to have 9 lymph nodes involved with melanoma (stage IIIC melanoma).He was then treated with ipilimumab (3 mg/kg), a monoclonal antibody to cytotoxic T lymphocyte antigen-4 (CTLA-4), every 3 weeks, as part of an investigational adjuvant therapy clinical trial. When presenting for his fourth and final dose of ipilimumab, he reported central headaches, severe fatigue, poor appetite, intermittent nausea, and a mild rash. On examination, vital signs were within normal limits. Physical examination had largely unremarkable results except for a slightly red, raised rash over his chest and proximal extremities.Laboratory testing showed the following: thyrotropin, 0.02 mIU/L (reference range, 0.3-5.0 mIU/L), and free thyroxine, less than 0.25 ng/dL (reference range, 0.5-1.2 ng/dL; to convert to picomoles per liter, multiply by 12.871). Cosyntropin stimulation test showed a cortisol peak level of 0.9 µg/dL (reference range, >20 µg/dL; to convert to nanomoles per liter, multiply by 27.588). He had low corticotropin (<5 pg/mL; reference range, 7-51 pg/mL; to convert to picomoles per liter, multiply by 0.22) and testosterone levels (<0.1 ng/mL; reference range, 2-11 ng/mL; to convert to nanomoles per liter, multiply by 0.0347). Magnetic resonance imaging (MRI) of the brain is shown in the Figure.Magnetic resonance imaging of the brain with contrast. What Is Your Diagnosis?

Neurosarcoid

Melanoma metastasis

Hypophysitis

Pituitary macroadenoma

C. Hypophysitis

C

Hypophysitis

Brain MRI revealed an enlarged, heterogeneously enhancing pituitary gland (Figure, arrowhead), with a thickened infundibular stalk and normal optic chiasm. Based on these clinical, radiographic, and laboratory findings, the patient received a diagnosis of autoimmune ipilimumab-induced hypophysitis (IH).Ipilimumab unleashes antitumor T-cell responses by blocking the CTLA-4 inhibitory molecule. However, the resultant T-cell activation may trigger immune-related adverse events (IRAEs). These include colitis, dermatitis, hepatitis, neuropathies, or endocrinopathies, such as hypophysitis.1,2The incidence of IH in patients with metastatic melanoma was approximately 1.5% in a large phase 3 study evaluating ipilimumab 3 mg/kg.1 Potential risk factors include male sex3,4 and older age.3 Newer anti–programmed death-1 (anti–PD-1) immune therapies induce hypophysitis in less than 1%, but in roughly 10% of patients treated with combination ipilimumab–anti–PD-1.5The clinical presentation of IH may include symptoms of mass effect (headache), compression of the optic chiasm (visual field defects), and glucocorticoid deficiency (easy fatigability, weakness, anorexia).6 Symptoms of IH usually develop 6 to 12 weeks after initiation of ipilimumab therapy.6 A high index of clinical suspicion is needed to prompt laboratory evaluation and therapeutic intervention. This condition can be life threatening in patients with profound adrenal insufficiency.6,7Pituitary assessment through hormone measurements and MRI establish the diagnosis. Initial MRI findings often include diffuse pituitary enlargement and homogeneous or heterogeneous pituitary enhancement with or without suprasellar extension.8 However, an unremarkable MRI does not rule out IH and does not preclude laboratory evaluation.9 Patients should be routinely and carefully monitored for IRAEs during treatment and follow-up. This should include laboratory and clinical assessment for hypophysitis. At least thyrotropin should be evaluated at every treatment, with a low threshold to check cortisol levels. Particular vigilance should be maintained after the third treatment dose.Ipilimumab-induced hypophysitis predominantly involves the anterior pituitary, notably the thyroid, adrenocortical, and gonadal axes. Preclinical models have recently identified CTLA-4 expression in thyrotropin-secreting cells in the anterior pituitary.2 This study also suggested that ipilimumab binds these cells and triggers the complement cascade and immune activation. Posterior pituitary dysfunction (diabetes insipidus) rarely develops.7Treatment for IH involves hormone replacement and possibly high-dose corticosteroid therapy. Close follow-up is needed to assess for resolution of hormonal deficiencies. Thyroid and gonadal function often normalizes, but cortisol deficiency may persist for years, and requires prolonged low-dose corticosteroid replacement (hydrocortisone 20 mg every morning and 10 mg every evening, or prednisone 5 mg daily).9High-dose corticosteroids are a staple for clinically significant IRAEs. Their use in hypophysitis, however, is controversial. Compared with physiologic glucocorticoid replacement doses, high-dose steroids do not seem to improve clinical outcomes as measured by speed or frequency of resolution.4 Common high-dose steroid regimens, if used, include methylprednisolone or prednisone 1 to 2 mg/kg/d for 1 week, tapered over approximately 4 weeks.7 Recent studies have suggested that corticosteroids do not compromise the activity of ipilimumab.7 Interestingly, hypophysitis may predict improved survival following ipilimumab therapy. A small, 17-patient cohort with IH had an improved median survival compared with unselected patients (19.4 vs 8.8 months).3 In addition, patients may safely continue ipilimumab therapy following IH and may be considered for anti–PD-1 therapy if subsequent therapy is needed.This patient had classic clinical, radiographic, and laboratory findings. After diagnosis, he was treated with levothyroxine sodium, testosterone, and high-dose prednisone. His central hypogonadism and hypothyroidism eventually resolved, but he has required ongoing low-dose prednisone therapy (5 mg daily). Otherwise, his headaches, rash, and fatigue rapidly improved. Repeated imaging, 2 years later, demonstrated resolution of his pituitary inflammation.

Oncology

A 60-year-old man with advanced melanoma presented with headaches and increasing fatigue during treatment with ipilimumab. Several months earlier, he presented to the emergency department with shortness of breath. Imaging revealed pulmonary emboli and incidental groin lymphadenopathy. Biopsy of a lymph node showed melanoma. He then underwent inguinal lymph node dissection and was found to have 9 lymph nodes involved with melanoma (stage IIIC melanoma).He was then treated with ipilimumab (3 mg/kg), a monoclonal antibody to cytotoxic T lymphocyte antigen-4 (CTLA-4), every 3 weeks, as part of an investigational adjuvant therapy clinical trial. When presenting for his fourth and final dose of ipilimumab, he reported central headaches, severe fatigue, poor appetite, intermittent nausea, and a mild rash. On examination, vital signs were within normal limits. Physical examination had largely unremarkable results except for a slightly red, raised rash over his chest and proximal extremities.Laboratory testing showed the following: thyrotropin, 0.02 mIU/L (reference range, 0.3-5.0 mIU/L), and free thyroxine, less than 0.25 ng/dL (reference range, 0.5-1.2 ng/dL; to convert to picomoles per liter, multiply by 12.871). Cosyntropin stimulation test showed a cortisol peak level of 0.9 µg/dL (reference range, >20 µg/dL; to convert to nanomoles per liter, multiply by 27.588). He had low corticotropin (<5 pg/mL; reference range, 7-51 pg/mL; to convert to picomoles per liter, multiply by 0.22) and testosterone levels (<0.1 ng/mL; reference range, 2-11 ng/mL; to convert to nanomoles per liter, multiply by 0.0347). Magnetic resonance imaging (MRI) of the brain is shown in the Figure.Magnetic resonance imaging of the brain with contrast.

what is your diagnosis?

What is your diagnosis?

Hypophysitis

Pituitary macroadenoma

Neurosarcoid

Melanoma metastasis

a

male

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2432608

A 65-year-old man was admitted to our hospital with a painful anal mass and fecal incontinence. The anal lesion appeared 1 year earlier and grew slowly to the current size. The patient reported bleeding from the rectum after defecation and denied weight loss or fever. The patient noted no other symptoms.His medical history included atopic dermatitis and pulmonary tuberculosis. There was no family history of gastrointestinal pathology. He had not undergone any previous abdominal surgery, except inguinal hernia repair. He claimed to be a heavy smoker. No history of sexually transmitted diseases was found. Physical examination revealed a 12 × 10-cm hard mass on the left side of the anus (Figure 1A). It was ulcerated, covered by purulent exudate, and very painful. The scrotum was mildly tender to palpation. Digital rectal examination and rectoscopy were not performed because of the pain and fecal incontinence. The abdomen was soft and nontender. Routine blood, liver, and renal function test results were normal, as were results for carcinoembryonic antigen and cancer antigen 19-9. Chest radiography showed no abnormalities. Computed tomographic scan of the pelvis showed a hypodense 12 × 7 × 3-cm mass extending to the anus, anal canal, and lower perirectal space (Figure 1B). Abdominal computed tomography showed no pathology.Clinical photograph of the giant perianal mass in the left perianal region (A) and abdominal computed tomographic scan showing the mass in the anus (B). What Is Your Diagnosis?

Giant perianal abscess

Giant condyloma

Anal adenocarcinoma

Anal squamous cell carcinoma

C. Anal adenocarcinoma

C

Anal adenocarcinoma

Histopathological analysis revealed moderately differentiated adenocarcinoma (Figure 2). A few days later, clinical signs of intestinal obstruction appeared and abdominoperineal resection of the rectum was performed to remove the mass in toto. To improve survival, the patient received adjuvant chemoradiotherapy. Eighteen months after resection, there has been no recurrence of disease.Microscopic findings of the anal adenocarcinoma (hematoxylin-eosin, original magnification ×40).Carcinomas of the anal canal are rare malignant neoplasms composing approximately 1% to 2% of all gastrointestinal carcinomas. The most frequent tumor of the anal canal is squamous cell carcinoma. It accounts for 97% of cases. Other less common neoplasms such as basal cell carcinoma, adenocarcinoma, melanoma, and neuroendocrine tumors account for the remaining 3% of cases.1-3Carcinomas of the anal canal have nonspecific clinical presentation. They often mimic more common benign conditions like hemorrhoids, fissures, perianal abscess, anal fistula, or pilonidal sinus. Early differentiation of these benign conditions from cancer is crucial for favorable outcomes in many patients. In our case, the patient misunderstood the symptoms of cancer as signs of hemorrhoids and therefore delayed appropriate treatment. His reluctance to see a physician led to an increase in tumor size to dimensions that are rarely seen.Diagnostic criteria and the standard treatment for adenocarcinoma and other carcinomas of the anal canal have not been clearly defined, in part because of the rarity of these lesions. Accurate histological diagnosis is vital to determine treatment and surgical management as survival patterns can differ among anal neoplasms. While reports suggest that for patients with squamous cell carcinoma chemoradiation offers survival and recurrence rates equivalent to surgery, adenocarcinoma is managed primarily by surgery.4,5 Abdominoperineal resection in combination with neoadjuvant chemoradiation is recommended rather than local resection for T2 and higher grades of adenocarcinoma.6,7 Other rare tumors of the anal canal respond poorly to chemoradiation, and surgery is the mainstay of their treatment.8 Reported disease-free 5-year survival varies from 21% to 58% according to the type and differentiation of the tumor.9In conclusion, carcinoma of the anal canal is so unusual that few physicians will be exposed to these lesions during their practice. Because benign lesions are much more common, it is important not to misinterpret malignant lesions as benign. As in our case, it usually results in delayed diagnosis and treatment. Because delay is associated with higher mortality, it is necessary to make an early diagnosis using detailed examination and biopsy if a lesion is suspect.

Surgery

A 65-year-old man was admitted to our hospital with a painful anal mass and fecal incontinence. The anal lesion appeared 1 year earlier and grew slowly to the current size. The patient reported bleeding from the rectum after defecation and denied weight loss or fever. The patient noted no other symptoms.His medical history included atopic dermatitis and pulmonary tuberculosis. There was no family history of gastrointestinal pathology. He had not undergone any previous abdominal surgery, except inguinal hernia repair. He claimed to be a heavy smoker. No history of sexually transmitted diseases was found. Physical examination revealed a 12 × 10-cm hard mass on the left side of the anus (Figure 1A). It was ulcerated, covered by purulent exudate, and very painful. The scrotum was mildly tender to palpation. Digital rectal examination and rectoscopy were not performed because of the pain and fecal incontinence. The abdomen was soft and nontender. Routine blood, liver, and renal function test results were normal, as were results for carcinoembryonic antigen and cancer antigen 19-9. Chest radiography showed no abnormalities. Computed tomographic scan of the pelvis showed a hypodense 12 × 7 × 3-cm mass extending to the anus, anal canal, and lower perirectal space (Figure 1B). Abdominal computed tomography showed no pathology.Clinical photograph of the giant perianal mass in the left perianal region (A) and abdominal computed tomographic scan showing the mass in the anus (B).

what is your diagnosis?

What is your diagnosis?

Giant condyloma

Giant perianal abscess

Anal squamous cell carcinoma

Anal adenocarcinoma

d

male

61-70

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2442531

A woman in her 40s was referred to our service owing to unusual findings detected on routine abdominal ultrasonography ordered by her gynecologist. The ultrasonographic scan showed a hepatic mass in the right lobe composing approximately 50% of the liver parenchyma. The patient was asymptomatic, and there were no significant findings on abdominal physical examination— the liver was not palpable. Results of whole blood analyses, including α-fetoprotein, were within the reference ranges. She had not received any medication, including contraceptive pills or hormones, for more than 10 years.Nine years before this examination, the patient underwent elective splenectomy and hepatic biopsy at another institution. However, she did not know the reason for removal of the spleen, and results of the histopathologic examination were not available. She had undergone a cesarean section at age 25 years. The patient had no history of trauma or other previous medical events.An abdominal computed tomographic scan revealed a well-defined, solid, heterogeneous mass, completely intrahepatic, with no enhancement and no liquid component, causing slight displacement of the right hepatic vein (Figure 1).Cross-sectional computed tomographic image of the abdomen shows a large, intrahepatic, 20-cm solid mass. What Is Your Diagnosis?

Hepatocellular carcinoma

Fibrolamellar carcinoma

Hepatic metastasis

Gossypiboma

D. Gossypiboma

D

Gossypiboma

Gossypiboma (or textiloma) denotes a cotton foreign body that has accidentally been retained inside the patient during an operation and is surrounded by an intense inflammatory foreign body reaction.1 Previous studies2 estimated the incidence of gossypiboma as 1 in 1000 to 1 in 1500 abdominal procedures. However, since there are many unreported cases and some patients remain asymptomatic for several years,3 the actual incidence is difficult to determine.An increased risk of retained foreign bodies has been correlated with emergency operations, sudden changes in the type of procedure, and high body mass index.4 A previous review5 identified that most gossypibomas were found in the abdomen (56%), pelvis (18%), and thorax (11%).Computed tomography is the technique of choice for detecting gossypibomas. The typical findings include a hypodense, heterogeneous, whorl-like spongiform mass with an external high-density wall that is further highlighted on contrast-enhanced imaging. The mass interior may contain trapped gas bubbles, indicating visceral perforation or abscess, or calcification.6 During laparotomy in our patient, multiple perihepatic dense adhesions were found and a right hepatic lobectomy was performed. The opening of the surgical specimen confirmed the diagnosis (Figure 2). Surgical specimen. Note the margin with normal liver tissue surrounding the mass. The tape measure included is in centimeters.Although gossypibomas in the abdomen are more common than at other sites, liver involvement is unusual. In a review of the literature, we found only 2 reports of gossypibomas described as solid and completely intrahepatic masses that were misdiagnosed as common bile duct stones7 and cholangiocarcinoma.8Before surgery, the patient was asymptomatic, with normal serum α-fetoprotein and liver enzyme levels, and had no history of hepatitis or cirrhosis. A computed tomographic image showed a large, well-circumscribed mass, with no portal vein involvement, composing almost 50% of the liver parenchyma. Even though there was a lack of information before hospitalization and the clinical presentation was not entirely typical, the most likely diagnosis at the time was fibrolamellar carcinoma. To the best of our knowledge, this is the first report of an intrahepatic gossypiboma as a solid mass completely encompassed by hepatic parenchyma mimicking a fibrolamellar carcinoma.Gossypiboma should be considered in the differential diagnosis of abdominal masses in any patient who has undergone previous abdominal surgery.9 Prevention, careful exploration of the surgical site, meticulous count of surgical materials, and routine use of radiopaque impregnated materials remain the best and most cost-effective methods for avoidance of leaving foreign bodies inside patients.10

Surgery

A woman in her 40s was referred to our service owing to unusual findings detected on routine abdominal ultrasonography ordered by her gynecologist. The ultrasonographic scan showed a hepatic mass in the right lobe composing approximately 50% of the liver parenchyma. The patient was asymptomatic, and there were no significant findings on abdominal physical examination— the liver was not palpable. Results of whole blood analyses, including α-fetoprotein, were within the reference ranges. She had not received any medication, including contraceptive pills or hormones, for more than 10 years.Nine years before this examination, the patient underwent elective splenectomy and hepatic biopsy at another institution. However, she did not know the reason for removal of the spleen, and results of the histopathologic examination were not available. She had undergone a cesarean section at age 25 years. The patient had no history of trauma or other previous medical events.An abdominal computed tomographic scan revealed a well-defined, solid, heterogeneous mass, completely intrahepatic, with no enhancement and no liquid component, causing slight displacement of the right hepatic vein (Figure 1).Cross-sectional computed tomographic image of the abdomen shows a large, intrahepatic, 20-cm solid mass.

what is your diagnosis?

What is your diagnosis?

Gossypiboma

Fibrolamellar carcinoma

Hepatic metastasis

Hepatocellular carcinoma

a

female

41-50

original

https://jamanetwork.com/journals/jama/fullarticle/2466091

A 73-year-old African American woman presented with a widespread scaly pruritic rash lasting 2 months. Her medical history included hypertension, diabetes, pulmonary sarcoidosis, and acid reflux, for which she takes amlodipine, carvedilol, repaglinide, hydroxychloroquine, and pantoprazole. Her history also included chronic renal insufficiency and chronic hepatitis C, for which she takes no medications. She reported no fevers, new skin exposures, oral ulcers, arthritis, alopecia, or photosensitivity and no worsening pulmonary symptoms of cough or shortness of breath. The rash did not improve after 2 weeks of applying topical triamcinolone ointment (0.1%).Physical examination revealed annular coalescing scaly patches with erythematous borders on her forehead, neck, back, and upper and lower extremities (Figure, panels A and B). Laboratory workup revealed an antinuclear antibodies titer of 1:80 with a speckled pattern, elevated Sjögren syndrome–related antigen A (SS-A) level (>8 AI), and no elevation of Sjögren syndrome–related antigen B (SS-B), ribonucleoprotein, double-stranded DNA, Smith, or anti-histone antibodies. Complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein level were within normal limits. Creatinine level was elevated but stable at 1.8 mg/dL (159.1 μmol/L). Skin biopsy revealed an inflammatory pattern of vacuolar interface dermatitis (Figure, panel C).A, Widespread annular and polycyclic scaly patches on the trunk and extremities. B, Magnified view of scaly patches, showing erythematous borders. C, Skin biopsy revealing vacuolar interface changes accompanied by hyperkeratosis, necrotic keratinocytes, and a superficial perivascular lymphocytic infiltrate in the dermis (hematoxylin-eosin, original magnification ×200).Obtain a chest radiograph to evaluate progression of sarcoidosis What Would You Do Next?

Obtain a chest radiograph to evaluate progression of sarcoidosis

Discontinue pantoprazole

Start oral prednisone

Order testing for anti–Mi-2 and anti–Jo-1 antibodies

Pantoprazole-induced subacute cutaneous lupus erythematosus

B

Discontinue pantoprazole

The atypical presentation of an older patient with a new-onset widespread skin eruption supports a drug-induced etiology. Clinicopathologic correlation in this patient confirmed subacute lupus erythematosus (SCLE). Of her medications, amlodipine and pantoprazole are most commonly implicated in drug-induced SCLE. A trial discontinuation of pantoprazole is often safe and requires minimal monitoring.Although rare cases of scaly ichthyosiform and psoriasiform cutaneous expressions of sarcoidosis have been reported, an expression with annular scaly lesions simulating SCLE has not been described. The patient has no pulmonary signs or symptoms warranting imaging for progressive pulmonary sarcoidosis. Anti–Mi-2 and anti–Jo-1 antibodies would help investigate dermatomyositis but not SCLE. Prednisone may alleviate cutaneous symptoms and mask the disease, delaying definitive treatment of removing the offending agent.Cutaneous involvement occurs in up to 85% of all patients with lupus erythematosus (LE).1 Cutaneous lupus is classified into 3 specific subtypes, each with varying association with systemic lupus erythematosus (SLE): acute (ACLE), SCLE, and chronic cutaneous lupus erythematosus (CCLE), the most common of which is discoid LE.2 Dermatopathologists may not be able to reliably distinguish these subtypes, requiring clinicopathologic correlation to establish a specific diagnosis.Although the sites of distribution may vary, SCLE is characterized by annular patches, polycyclic scaly patches, or both, which are primarily photodistributed. The lesions are typically symmetric, nonscarring, and longer-lasting than those of the acute subtype.3 Idiopathic SCLE is most commonly reported in women with mean ages in the 40s.1,2 SCLE tends to have mild if any systemic involvement.4 Serologically, SCLE has a higher association with Ro/SSA-antibodies than SLE (70% vs 40%).3 Antinuclear, double-stranded DNA, and Smith antibodies are less frequently positive.Drug-induced SCLE comprises roughly 20% of newly diagnosed cases. More than 100 agents have been implicated.5,6 The rash occurs within several weeks after drug initiation. Drug-induced SCLE presents in older patients and is more generalized to include the lower legs, an area typically spared in idiopathic SCLE.7 The eruption usually resolves within a few weeks of drug discontinuation but may persist for several months.8Historically, the most common causes of drug-induced SCLE include antihypertensive agents (thiazide diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers), interferons, tumor necrosis factor α antagonists, and antifungal agents such as terbinafine and griseofulvin.3,5 Comprehensive tables have been published.5,9Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in the world.10 Recent attention has been given to the role of PPIs in drug-induced SCLE, but the association is underrecognized.5,9,10 The most commonly cited SCLE-inducing PPIs are lansoprazole, omeprazole, pantoprazole, and esomeprazole.8,10 Reflaring of SCLE despite switching to another PPI has been described.10 On detailed questioning, this patient reported experiencing a similar eruption years prior while taking omeprazole.The case highlights a common challenging scenario, that of identifying the causative agent of a drug-induced rash in a patient with polypharmacy. Proton pump inhibitors are unique in that a trial discontinuation of these medications may be relatively safe. Because PPIs are widely used, knowledge of the association between SCLE and PPIs provides an opportunity to prevent diagnostic delays and adverse outcomes in affected patients.Because amlodipine and pantoprazole are potential causative agents of drug-induced SCLE, both medications were discontinued. One month later, amlodipine was restarted without recurrence of the rash. Eight months of follow-up showed persistent clearance without additional topical or systemic therapy. At 5 months, levels of antinuclear antibodies and SS-A and SS-B antibodies were unchanged. The prolonged resolution of symptoms following PPI discontinuation reinforced the diagnosis of drug-induced SCLE, with a PPI being the most likely agent.

General

A 73-year-old African American woman presented with a widespread scaly pruritic rash lasting 2 months. Her medical history included hypertension, diabetes, pulmonary sarcoidosis, and acid reflux, for which she takes amlodipine, carvedilol, repaglinide, hydroxychloroquine, and pantoprazole. Her history also included chronic renal insufficiency and chronic hepatitis C, for which she takes no medications. She reported no fevers, new skin exposures, oral ulcers, arthritis, alopecia, or photosensitivity and no worsening pulmonary symptoms of cough or shortness of breath. The rash did not improve after 2 weeks of applying topical triamcinolone ointment (0.1%).Physical examination revealed annular coalescing scaly patches with erythematous borders on her forehead, neck, back, and upper and lower extremities (Figure, panels A and B). Laboratory workup revealed an antinuclear antibodies titer of 1:80 with a speckled pattern, elevated Sjögren syndrome–related antigen A (SS-A) level (>8 AI), and no elevation of Sjögren syndrome–related antigen B (SS-B), ribonucleoprotein, double-stranded DNA, Smith, or anti-histone antibodies. Complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein level were within normal limits. Creatinine level was elevated but stable at 1.8 mg/dL (159.1 μmol/L). Skin biopsy revealed an inflammatory pattern of vacuolar interface dermatitis (Figure, panel C).A, Widespread annular and polycyclic scaly patches on the trunk and extremities. B, Magnified view of scaly patches, showing erythematous borders. C, Skin biopsy revealing vacuolar interface changes accompanied by hyperkeratosis, necrotic keratinocytes, and a superficial perivascular lymphocytic infiltrate in the dermis (hematoxylin-eosin, original magnification ×200).Obtain a chest radiograph to evaluate progression of sarcoidosis

what would you do next?

What would you do next?

Obtain a chest radiograph to evaluate progression of sarcoidosis

Start oral prednisone

Order testing for anti–Mi-2 and anti–Jo-1 antibodies

Discontinue pantoprazole

d

female

71-80

African American

original

https://jamanetwork.com/journals/jama/fullarticle/2466095

A 47-year-old man presented with persistent fatigue, vision loss, and low libido over the previous 2 months. He reported no headache, erectile dysfunction, breast tenderness or mass, arthralgias, edema, or increase in glove, ring, or shoe size. He was taking sertraline for treatment of anxiety disorder, and had a 15-year-old son. His examination was significant for the presence of bitemporal visual field defects on confrontation testing. He had no acromegalic features, gynecomastia, galactorrhea, or abnormal virilization. Testicular size was 20 mL for each. Laboratory tests were performed (Table), which revealed low serum testosterone and thyrotropin and elevated serum prolactin levels. A neuro-ophthalmic examination revealed the presence of symmetric superior temporal visual field defects on perimetry. Magnetic resonance imaging (MRI) was obtained to examine his brain.The patient has hyperprolactinemia due to a nonfunctioning pituitary adenoma.The patient has hyperprolactinemia due to thyroid disease.The patient has hyperprolactinemia due to a prolactinoma. How Do You Interpret These Test Results?

The patient has hyperprolactinemia due to a nonfunctioning pituitary adenoma.

The patient has hyperprolactinemia due to thyroid disease.

The patient has sertraline-induced hyperprolactinemia.

The patient has hyperprolactinemia due to a prolactinoma.

A

The patient has hyperprolactinemia due to a nonfunctioning pituitary adenoma.

Prolactin is a single-chain polypeptide hormone secreted by specialized pituitary cells (lactotrophs). Although prolactin has a major biological role in promoting postpartum lactation in women, its physiological role in men remains unclear. The lifetime prevalence of hyperprolactinemia is 90 per 100 000 women and 20 per 100 000 men.1 Prolactin secretion is continuously inhibited by dopamine of hypothalamic origin, acting on pituitary lactotrophs.2 Hyperprolactinemia may occur as a result of excess prolactin secretion, which can be caused by interruption of dopamine action. There are physiological, pituitary, and systemic causes (Box).3,4 To test for hyperprolactinemia, serum specimens should be obtained in the fasting, nonstressed state (avoiding sampling immediately after exercise or in the setting of acute illness or injury). Documenting hyperprolactinemia in a single specimen is usually sufficient. The Medicare midpoint reimbursement is $35.47 for the prolactin assay.5 Because prolactin is secreted intermittently in small bursts, repeat sampling is advisable if the first result is borderline.4 Mild hyperprolactinemia is nonspecific; etiologies include primary hypothyroidism and medications.6-8 Prolactin levels exceeding 200 µg/mL (normal level in men, ≤15 ng/mL) usually indicate the presence of a prolactinoma or a growth hormone–cosecreting pituitary tumor in the absence of renal insufficiency. Prolactin levels exceeding 500 µg/mL are diagnostic of a prolactinoma.2,4 There is a good correlation between tumor size and the magnitude of prolactin elevation in patients with prolactinomas, but not in patients with clinically nonfunctioning pituitary adenomas in whom the prolactin elevation is due to stalk compression, which interrupts dopamine outflow from the hypothalamus to the pituitary.2,4Other sellar lesions interrupting dopamine inhibition (clinically nonfunctioning pituitary adenomas, craniopharyngiomas, hypophysitis, and others)Medications (phenothiazines, haloperidol, risperidone, tricyclic antidepressants, metoclopramide, opioids, verapamil, and others)Chest wall injury or lesion (eg, thoracic zoster)The constellation of symptoms suggestive of hypogonadism (fatigue, low libido) and mass effect (bitemporal vision loss) prompted a test to assess the patient’s serum prolactin level, which was elevated. A brain MRI revealed a solid sellar mass, 2.5 cm in greatest diameter, impinging on the optic chiasm. This patient likely had a clinically nonfunctioning pituitary adenoma, causing hyperprolactinemia as a result of interruption of hypothalamic dopamine pathways to the pituitary lactotrophs. His serum prolactin level was disproportionately low in relation to the size of the sellar mass, suggesting that diagnosis was unlikely to be a prolactinoma. Sertraline and other serotonin reuptake inhibitors are unlikely to cause hyperprolactinemia.2,4 Primary hypothyroidism, characterized by a high serum thyrotropin level, is associated with hyperprolactinemia.2,4 In this patient, low thyrotropin may indicate early thyrotroph dysfunction resulting from mass effect. Clinical evaluation (including absence of suggestive facial features or acral enlargement) and a normal insulinlike growth factor-I level exclude acromegaly.Dopamine agonist therapy can be used to treat both hyperprolactinemia not caused by a pituitary tumor and presumed prolactin-secreting adenomas.2,4 Cabergoline is generally preferred over bromocriptine because it is more effective and better tolerated.2,4,9,10 However, dopamine agonist therapy is not likely to be effective in decreasing the size of clinically nonfunctioning pituitary adenomas. The patient should be referred to an experienced pituitary neurosurgeon for transsphenoidal surgery. Decompression of the optic chiasm generally restores vision unless there has been optic nerve atrophy from prolonged compression.The patient underwent transsphenoidal pituitary resection of the pituitary tumor, and the pathological diagnosis was consistent with a clinically nonfunctioning pituitary adenoma. His peripheral vision returned to normal on follow-up perimetry, 4 weeks later. A follow-up pituitary MRI revealed no evidence of residual tumor. His symptoms resolved, and his serum prolactin, testosterone, and thyrotropin levels normalized at 6 weeks postoperatively.Hyperprolactinemia has diverse causes, which may include physiological, pituitary, and systemic etiologies.Careful clinical evaluation, focused laboratory testing, and in many cases, pituitary imaging are important for elucidating the underlying cause of hyperprolactinemia and guiding appropriate patient management.Mild hyperprolactinemia (<100 µg/L) can be caused by large sellar masses, including nonfunctioning pituitary adenomas, necessitating a thorough investigation for the underlying cause.

Diagnostic

A 47-year-old man presented with persistent fatigue, vision loss, and low libido over the previous 2 months. He reported no headache, erectile dysfunction, breast tenderness or mass, arthralgias, edema, or increase in glove, ring, or shoe size. He was taking sertraline for treatment of anxiety disorder, and had a 15-year-old son. His examination was significant for the presence of bitemporal visual field defects on confrontation testing. He had no acromegalic features, gynecomastia, galactorrhea, or abnormal virilization. Testicular size was 20 mL for each. Laboratory tests were performed (Table), which revealed low serum testosterone and thyrotropin and elevated serum prolactin levels. A neuro-ophthalmic examination revealed the presence of symmetric superior temporal visual field defects on perimetry. Magnetic resonance imaging (MRI) was obtained to examine his brain.The patient has hyperprolactinemia due to a nonfunctioning pituitary adenoma.The patient has hyperprolactinemia due to thyroid disease.The patient has hyperprolactinemia due to a prolactinoma.

how do you interpret these test results?

How do you interpret these results?

The patient has hyperprolactinemia due to a nonfunctioning pituitary adenoma.

The patient has sertraline-induced hyperprolactinemia.

The patient has hyperprolactinemia due to a prolactinoma.

The patient has hyperprolactinemia due to thyroid disease.

a

male

41-50

original

https://jamanetwork.com/journals/jama/fullarticle/2449159

An 80-year-old woman with a history of diabetes mellitus, hypertension, gastric ulcers, celiac artery occlusion, and transient ischemic attacks presented with a painful rash on her flank of 2 days’ duration. She denied any history of trauma and had not applied anything topically in this area of skin. She denied fevers, systemic symptoms, joint pain, and skin thickening. Her medications included metformin, lansoprazole, venlafaxine, diltiazem, atorvastatin, oxycodone/acetaminophen, ramopril, reglan, zolpidem, and clopidogrel. Physical examination revealed an 8-cm solitary, erythematous plaque with vesiculation and central erosion on the right lateral area of her abdomen (Figure, A). The remainder of the physical examination was unremarkable. A punch biopsy showed a vacuolar interface dermatitis pattern, but a definitive clinical diagnosis was not established. She was treated with clobetasol cream (0.05%), and the plaque resolved in 4 weeks with postinflammatory hypopigmentation.Ten months later, the patient developed a tender, pink, indurated 7-cm plaque with telangiectasias and central ulceration in the same location, with no other cutaneous findings (Figure, B). No precipitating factors could be identified. A punch biopsy showed minimal inflammation, atrophy and hyperkeratosis of the epidermis, and edema, sclerosis, and absence of hair follicles in the dermis (Figure, C).Order laboratory studies for antinuclear, anti-Scl-70, and anti-centromere antibodiesPerform patch testing for a possible contact allergenObtain skin swab for varicella zoster virus direct fluorescent antibody level What Would You Do Next?

Order laboratory studies for antinuclear, anti-Scl-70, and anti-centromere antibodies

Obtain a detailed procedural history

Perform patch testing for a possible contact allergen

Obtain skin swab for varicella zoster virus direct fluorescent antibody level

Acute and chronic fluoroscopy-induced radiation dermatitis (FIRD)

B

Obtain a detailed procedural history

The biopsy findings in this patient are typical of radiation dermatitis and prompted an inquiry about prior radiation exposure. Patients may deny previous radiation exposure (as in this case) because of lack of knowledge about radiation use in procedures such as fluoroscopy. Detailed questioning revealed fluoroscopic placement of a celiac artery stent 6 weeks before the appearance of the lesion.Key features in the diagnosis of FIRD include a solitary plaque in an area previously exposed to fluoroscopy combined with histopathologic features of radiation dermatitis. Skin biopsy provides confirmatory evidence in this clinical setting and helps exclude other diagnostic considerations. Morphea (localized scleroderma) can have overlapping features with chronic radiation dermatitis, but the clinical history and localized skin findings in FIRD help exclude a connective tissue disease without serologic testing (eg, antinuclear antibody, anti-Scl-70). A recurrent rash with a geometric shape should prompt consideration for allergic contact dermatitis. The sclerotic texture of this plaque and the biopsy findings exclude contact dermatitis. The geometric shape of the lesion makes zoster highly unlikely; for this reason, the varicella zoster virus direct fluorescent antibody would be low yield.FIRD is a frequently unrecognized subset of radiation dermatitis with a variable time course.1,2 Eliciting an accurate history of radiation exposure can be challenging, because many patients may not be cognizant of past radiation exposure during fluoroscopic procedures. Radiation skin doses in fluoroscopic procedures can range from less than 1 mGy/min to as high as several Gy per minute in angiography cases.3 Percutaneous coronary angiography or intervention is the most common cause of FIRD2 and was first described in this setting in 1996.4 Risk of developing FIRD correlates directly with length and complexity of the procedure, and efforts to shorten procedures and shield patients can reduce patients’ risk.5 Other fluoroscopic procedures that can result in radiation dermatitis include radiofrequency catheter ablation, interventional neuroradiology, renal angioplasty, transjugular intrahepatic portosystemic shunt, and cardiac pacemaker placement.6,7 Proper recognition of clinical symptoms and a thorough medical and procedural history are key for diagnosing FIRD.Classification of FIRD includes acute, subacute, and chronic presentations, but patients can present with chronic FIRD without an acute phase.2 Acute radiation dermatitis typically presents 7 to 14 days after radiation exposure, from skin doses in the range of 2 to 5 Gy.3,8 Symptoms include erythema, epilation, bullae, ulceration, and skin necrosis. The clinical differential diagnosis includes herpes zoster, immunobullous diseases, fixed drug eruption, cellulitis, and a reaction from an arthropod or spider bite. Topical corticosteroids and analgesics, as well as barrier ointments such as petroleum jelly, are the main treatments for acute radiation dermatitis.Onset of chronic FIRD ranges from months to years and is characterized by telangiectasia, pruritus, atrophy, sclerosis, dyspigmentation, and ulceration in some cases. Rarely, cutaneous malignancies can develop within the radiation field many years later. The minimum cumulative skin dose for chronic FIRD is 10 to 15 Gy.3,5 FIRD occurs most frequently at the right anterolateral area of the chest, mid back, right lateral area of the trunk below the axilla, and scapular or subscapular region.2,5 The rash often has an angular or geometric appearance, with patients reporting pain, pruritus, discoloration, or ulceration. Histopathologic analysis can help distinguish chronic FIRD from diseases with similar clinical features (eg, scleroderma, infiltrating tumors, and lichen sclerosis). Histopathological features of chronic FIRD include dermal sclerosis, atypical fibroblasts, telangiectasia, and absence of hair follicles.2,5 Treatment of chronic FIRD includes protection from sunlight or further radiation and emollients. For patients with pruritus, pain, or ulceration, potent topical steroids, analgesics, or anesthetics (eg, lidocaine) can be used, with excision, grafting, or both used in complicated refractory cases. Close follow-up after radiation exposure facilitates early diagnosis, prevents unnecessary treatments, and allows long-term surveillance for postradiation malignancies.1,3,6,7The patient was given a fentanyl patch for pain and referred to a surgeon to consider possible surgical treatment.

General

An 80-year-old woman with a history of diabetes mellitus, hypertension, gastric ulcers, celiac artery occlusion, and transient ischemic attacks presented with a painful rash on her flank of 2 days’ duration. She denied any history of trauma and had not applied anything topically in this area of skin. She denied fevers, systemic symptoms, joint pain, and skin thickening. Her medications included metformin, lansoprazole, venlafaxine, diltiazem, atorvastatin, oxycodone/acetaminophen, ramopril, reglan, zolpidem, and clopidogrel. Physical examination revealed an 8-cm solitary, erythematous plaque with vesiculation and central erosion on the right lateral area of her abdomen (Figure, A). The remainder of the physical examination was unremarkable. A punch biopsy showed a vacuolar interface dermatitis pattern, but a definitive clinical diagnosis was not established. She was treated with clobetasol cream (0.05%), and the plaque resolved in 4 weeks with postinflammatory hypopigmentation.Ten months later, the patient developed a tender, pink, indurated 7-cm plaque with telangiectasias and central ulceration in the same location, with no other cutaneous findings (Figure, B). No precipitating factors could be identified. A punch biopsy showed minimal inflammation, atrophy and hyperkeratosis of the epidermis, and edema, sclerosis, and absence of hair follicles in the dermis (Figure, C).Order laboratory studies for antinuclear, anti-Scl-70, and anti-centromere antibodiesPerform patch testing for a possible contact allergenObtain skin swab for varicella zoster virus direct fluorescent antibody level

what would you do next?

What would you do next?

Obtain skin swab for varicella zoster virus direct fluorescent antibody level

Obtain a detailed procedural history

Perform patch testing for a possible contact allergen

Order laboratory studies for antinuclear, anti-Scl-70, and anti-centromere antibodies

b

female

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2398664

A woman in her mid-70s with a history of type 2 diabetes mellitus, end-stage renal disease, and coronary artery disease was admitted to the hospital for fever, lethargy, and altered mental status. On day 7 of her hospital stay, she developed severe, unremitting left ankle pain with purpuric lesions on the skin. She had previously undergone coronary artery bypass grafting with simultaneous aortic valve replacement and ileal conduit urinary diversion as a result of to recurrent upper urinary tract infections. Laboratory findings were significant for neutrophil-predominant leukocytosis (leukocyte count, 19 400/μL [to convert to ×109/L, multiply by 0.001]).Physical examination revealed multiple stellate, purpuric plaques with central flaccid bullae on the medial and lateral aspects of the left ankle (Figure, A). The remainder of her skin examination findings were unremarkable. Punch biopsy specimens were obtained along the border of normal and lesional skin (Figure, B and C), and she underwent transesophageal echocardiography.A, Stellate purpura with overlying flaccid bulla on the medial aspect of the ankle. B, Partially necrotic epidermis with intraepidermal bulla formation with marked perivascular infiltrates in the deep dermis and subcutaneous tissue (hematoxylin-eosin, original magnification ×25). C, A small blood vessel occluded with fibrinoid material with a perivascular lymphoneutrophilic infiltrate (hematoxylin-eosin, original magnification ×400). What Is Your Diagnosis?

Calciphylaxis

Septic emboli

Vasculitis

Necrotizing fasciitis

B. Septic emboli

B

Septic emboli

Histopathologic examination of biopsy specimens revealed a partially necrotic epidermis with intraepidermal bulla formation (Figure, B). In the dermis and subcutaneous fat, several small and medium blood vessels were occluded with fibrinoid material with perivascular lymphoneutrophilic infiltrates (Figure, C) consistent with embolic phenomena.The patient underwent transesophageal echocardiography that revealed a thickened native mitral valve with a 2.2 × 2.7-cm vegetation with abscess formation and mobile elements extending into the left ventricle consistent with infective endocarditis. Blood culture results were positive for Morganella morganii, and she was treated with intravenous ceftriaxone. After acute mental status changes, magnetic resonance imaging of the brain revealed multiple acute embolic infarcts in the bilateral cerebral hemispheres and cerebellum, and the patient subsequently died.Infective endocarditis (IE) affects 3 to 9 per 100 000 people, with inpatient mortality rates reaching 22%.1,2 The highest rates occur in patients older than 65 years with prosthetic valves, diabetes mellitus, receiving hemodialysis, or a history of IE.1Staphylococcus aureus, Streptococcus species, and enterococci are implicated in more than 80% of cases because of their tendency to adhere to damaged heart valves.2Diagnosing IE can be challenging, requiring fulfillment of modified Duke criteria, which are a set of clinical and pathologic findings used to estimate the likelihood a patient has IE. Typical signs and symptoms in the criteria are fever, positive blood culture results, vegetations apparent on echocardiography, or embolic phenomena on the skin.3 In addition, IE can present atypically, with initial symptoms attributable to a complication such as meningitis, stroke, or vasculitis.4 In our patient’s case, the diagnosis was not established until after she developed cutaneous manifestations from metastatic embolization of infected fragments to distant sites.Complete skin examination is essential in evaluating IE because a cutaneous portal of entry is found in 1 of 5 cases and dermatologic lesions suggestive of septicemia can help physicians reach a clinical diagnosis.5 These lesions include Osler nodes, which are defined as purpuric painful nodules on the palms or soles; Janeway lesions, which are erythematous painless macules in a similar distribution; vascular purpura, which are often localized on the back or lower extremities; and conjunctival hemorrhages.5 In addition, IE can present with atypical skin lesions that alert physicians to an internal infection. As examples, Nayak et al6 reported a case of bacterial IE that presented as Sweet syndrome, whereas Granel et al7 described a patient hospitalized for extensive livedo reticularis who was found to have latent IE from Coxiella burnetti.A study by Servy et al5 examined the prevalence of dermatologic manifestations in a French population of patients with IE. They found that 11.9% had skin manifestations, classified as purpura (8%), Osler nodes (2.7%), Janeway lesions (1.6%), and conjunctival hemorrhage (0.6%). Compared with patients with IE without skin findings, those with skin changes had significantly higher rates of extracardiac complications, including cerebral emboli (33% vs 18%).5 Notably, purpura was associated with larger cardiac vegetations (18.1 vs 13.7 mm), bicuspid aortic valve with Osler nodes (23% vs 4%), and Janeway lesions with extracerebral emboli (75% vs 31.8%).5This case has several unique aspects. Our patient developed native mitral valve IE after a prosthetic aortic valve replacement, which is uncommon. Also, M morganii, a gram-negative rod of the Enterobacteriaceae family, is normally found in the gastrointestinal tract of humans and infrequently causes nosocomial urinary tract infections. Infective endocarditis caused by non-HACEK (Haemophilus species, Aggregatibacter species, Cardiobacteriumhominis, Eikenellacorrodens, and Kingella species) gram-negative bacilli is rare, and in a large multinational prospective cohort of 2761 patients with IE, only one patient had M morganii as the causative pathogen.8The case illustrates how a complete skin examination is critical for diagnostic and prognostic purposes in IE, a rare life-threatening infection that often presents with skin manifestations. Because embolic events are one of the most frequent and severe complications, occurring in 30% to 50% of patients, it is important to identify those at greatest risk for such events before they occur.2

Dermatology

A woman in her mid-70s with a history of type 2 diabetes mellitus, end-stage renal disease, and coronary artery disease was admitted to the hospital for fever, lethargy, and altered mental status. On day 7 of her hospital stay, she developed severe, unremitting left ankle pain with purpuric lesions on the skin. She had previously undergone coronary artery bypass grafting with simultaneous aortic valve replacement and ileal conduit urinary diversion as a result of to recurrent upper urinary tract infections. Laboratory findings were significant for neutrophil-predominant leukocytosis (leukocyte count, 19 400/μL [to convert to ×109/L, multiply by 0.001]).Physical examination revealed multiple stellate, purpuric plaques with central flaccid bullae on the medial and lateral aspects of the left ankle (Figure, A). The remainder of her skin examination findings were unremarkable. Punch biopsy specimens were obtained along the border of normal and lesional skin (Figure, B and C), and she underwent transesophageal echocardiography.A, Stellate purpura with overlying flaccid bulla on the medial aspect of the ankle. B, Partially necrotic epidermis with intraepidermal bulla formation with marked perivascular infiltrates in the deep dermis and subcutaneous tissue (hematoxylin-eosin, original magnification ×25). C, A small blood vessel occluded with fibrinoid material with a perivascular lymphoneutrophilic infiltrate (hematoxylin-eosin, original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Vasculitis

Necrotizing fasciitis

Septic emboli

Calciphylaxis

c

female

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2423208

A man in his 50s of Indian descent presented with a pruritic eruption on his scalp, arms, neck, and feet. The eruption began during the summer 3 months before presentation. His medical history was significant for type 2 diabetes mellitus and hypertension, which were managed with metformin, glimepiride, and atenolol.Physical examination revealed hyperpigmented annular plaques with violaceous borders on his scalp and the superior part of his forehead (Figure, A). There were violaceous papules on the dorsal aspect of the hands (Figure, B), extensor surface of the arms, and the nape of the neck.Physical examination findings. A, Hyperpigmented annular plaques with violaceous borders on the scalp. B, Violaceous papules on the dorsal aspect of the hands. C, Histopathologic analysis of violaceous eruption on the hand. Lymphocytic infiltrate at the dermoepidermal junction (hematoxylin-eosin, original magnification ×10).A punch biopsy specimen was obtained and sent for histopathologic evaluation (Figure, C). What Is Your Diagnosis?

Discoid lupus erythematosus

Erythema dyschromicum perstans

Lichen planus actinicus

Polymorphous light eruption

C. Lichen planus actinicus

C

Lichen planus actinicus

A skin biopsy specimen of the left hand revealed a hyperkeratotic acanthotic epidermis with a prominent granular cell layer. At the dermoepidermal junction, there was a lichenoid predominantly lymphocytic infiltrate with interface change. On the basis of the clinical distribution of the eruption and corresponding histopathologic findings, a diagnosis of lichen planus (LP) actinicus was made. The patient was instructed to wear sun block on sun-exposed areas of the body. He was also prescribed clobetasol propionate, 0.05%, ointment with improvement of pruritus and the appearance of LP actinicus.Lichen planus actinicus is a rare subtype of LP that is not commonly seen in the United States. Most reported cases have occurred in individuals with dark complexions of Middle Eastern and Indian descent living in subtropical regions.1,2 Other names commonly used for this condition include actinic LP, summertime actinic lichenoid eruption, LP atrophicus annularis, and LP subtropicalis. The incidence of LP is less than 1% of the total population, whereas LP actinicus has been estimated at 1 case per million inhabitants per year.3There are 4 morphologic variants: annular hyperpigmented, melasma-like, dyschromic, and classic lichenoid. The annular hyperpigmented type is the most common form of LP actinicus and usually presents on the dorsum of the fingers and hands. All forms of LP actinicus are exacerbated by sun exposure and most remit during the winter.4 Our patient presented with both the classic lichenoid and annular hyperpigmented types.Lichen planus actinicus differs from classic LP by presenting in areas of sun-exposed skin, with a predilection for the head, dorsum of the hands, and extensor surfaces of the upper extremities, whereas classic LP usually spares the head and more commonly affects the trunk and the flexural extremities.2 Lichen planus actinicus also exhibits seasonal onset in the spring and summer, whereas classic LP reveals no seasonal predilection. The Koebner response is not commonly found in LP actinicus.4 Treatment consists of strict sun protection in conjunction with potent topical corticosteroids. Acitretin and cyclosporine have been reported to be useful in severe and relapsing cases, respectively.5,6

Dermatology

A man in his 50s of Indian descent presented with a pruritic eruption on his scalp, arms, neck, and feet. The eruption began during the summer 3 months before presentation. His medical history was significant for type 2 diabetes mellitus and hypertension, which were managed with metformin, glimepiride, and atenolol.Physical examination revealed hyperpigmented annular plaques with violaceous borders on his scalp and the superior part of his forehead (Figure, A). There were violaceous papules on the dorsal aspect of the hands (Figure, B), extensor surface of the arms, and the nape of the neck.Physical examination findings. A, Hyperpigmented annular plaques with violaceous borders on the scalp. B, Violaceous papules on the dorsal aspect of the hands. C, Histopathologic analysis of violaceous eruption on the hand. Lymphocytic infiltrate at the dermoepidermal junction (hematoxylin-eosin, original magnification ×10).A punch biopsy specimen was obtained and sent for histopathologic evaluation (Figure, C).

what is your diagnosis?

What is your diagnosis?

Polymorphous light eruption

Discoid lupus erythematosus

Lichen planus actinicus

Erythema dyschromicum perstans

c

male

51-60

Indian

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2426394

A woman in her 40s with a medical history of pulmonary embolism and deep venous thrombosis presented with a 6-month history of pruritic, pink scaling plaques on her face and neck (Figure, A). The lesions subsequently involved her chest, abdomen, and back and flared with sun exposure. A diagnosis of lupus erythematosus (LE) was favored, but the lesions failed to improve on a regimen that included hydroxychloroquine sulfate, fluocinonide ointment, 0.05%, and tacrolimus ointment, 0.1%. Biopsy samples were obtained for histopathologic evaluation.A, This case shows well-demarcated plaques with an overlying scale crust occurring in a photodistributed pattern on the central face. B, Hematoxylin-eosin, original magnification ×4. C, Hematoxylin-eosin, original magnification ×10.Laboratory findings were significant for positive antinuclear antibody titers at 1:640, lymphopenia, and normocytic anemia. Test results were negative or within normal limits for levels of antiribonucleoprotein, antihistone, antiphospholipid, anti-Smith, anti-Ro/Sjögren syndrome antigen A, and anti-La/Sjögren syndrome antigen B antibodies, C3, C4, CH50, rapid plasma reagin, and creatinine; erythrocyte sedimentation rate; and a comprehensive metabolic profile. Urinalysis results were within normal limits. A biopsy specimen was obtained (Figure, B and C). What Is Your Diagnosis?

Pemphigus erythematosus

Lupus erythematosus

Eczematous dermatitis

Pemphigus foliaceus

A. Pemphigus erythematosus

A

Pemphigus erythematosus

The biopsy specimen demonstrated epidermal acanthosis, spongiosis, and acantholytic keratinocytes (Figure, B and C). Dense lymphoplasmacellular infiltrate was seen in the dermis, with scattered neutrophils and eosinophils (Figure, C). Foci of eosinophilic spongiosis were also noted in the epidermis (Figure, C). Direct immunofluorescence showed granular and linear deposition of IgG and C3 at the basement membrane zone and abundant intercellular deposition of IgG and C3 in the upper two-thirds of the epidermis.The diagnosis of pemphigus erythematosus (PE) was confirmed by the patient’s clinical and histopathologic findings. She started therapy consisting of prednisone, 60 mg once daily, and dapsone, 200 mg once daily, with near resolution of the lesions. The prednisone dosage was tapered, the disease remained well controlled, and the lymphopenia, anemia, and skin eruption resolved.Pemphigus erythematosus (Senear-Usher syndrome) was described in 1926 by Senear and Usher1 as an autoimmune blistering condition with overlapping features of pemphigus foliaceus and LE. The clinical presentation of PE includes flaccid bullae that scale and crust, leading to erythematous hyperkeratotic plaques. In rare cases, the lesions have a papulosquamous appearance. Pemphigus erythematosus involves photodistributed areas, such as the face, trunk, and scalp. Infrequently, PE may progress into a generalized form of pemphigus foliaceus or an exfoliative erythroderma. Facial lesions are typically in a malar distribution.2 Mucosal lesions are rare.Pemphigus erythematosus is most common in middle-aged patients, with a slight female predominance.2 The targeted antigen is desmoglein 1, a desmosomal cadherin protein. Some patients have HLA haplotype associations—A10, A26, and DRW6—suggesting a genetic predisposition. Aside from LE, PE has been associated with coexisting immunologic diseases, most notably myasthenia gravis and thymoma.2 Drug-induced forms have been reported with penicillamine, captopril, propranolol hydrochloride, and heroin.2 Considered an indolent disease, the clinical differential diagnosis for PE includes other types of pemphigus, LE, and psoriasis.Diagnosis of PE relies on correlation of histologic features on hematoxylin-eosin staining along with direct immunofluorescence identification of autoantibodies. A subcorneal blister is noted with acantholytic keratinocytes. Scale-crust formation is often present. Interface changes along the dermoepidermal junction may be seen. Direct immunofluorescence demonstrates IgG and C3 deposition intercellularly and along the basement membrane in continuous and granular patterns, similar to the “lupus band.”3,4 This mixed pattern may be seen in PE and paraneoplastic pemphigus.Abnormal laboratory findings may be noted in patients with PE. In particular, an antinuclear antibody is often present in low titers in 30% to 83% of patients.5 Lymphopenia, anemia, thrombocytopenia, proteinuria, an elevated erythrocyte sedimentation rate, and rheumatoid factor may be present.5 Although most patients do not meet the American College of Rheumatology criteria for systemic LE, it has been reported to develop in some patients.4,5Photoprotection is key to preventing progression of PE lesions. Compared with pemphigus vulgaris, PE tends to be more responsive to treatment. Oral corticosteroids or corticosteroids combined with immunosuppressive agents appear to be the most effective. Addition of dapsone often hastens resolution of lesions and allows for lower doses of systemic corticosteroids. Methotrexate sodium, cyclophosphamide, and azathioprine sodium may be efficacious; however, their toxicity may limit use. Topical corticosteroids may be helpful for localized disease. In refractory cases, rituximab may be a useful alternative. Serum autoantibodies, particularly with enzyme-linked immunosorbent assays, can be used to monitor disease activity and treatment response.

Dermatology

A woman in her 40s with a medical history of pulmonary embolism and deep venous thrombosis presented with a 6-month history of pruritic, pink scaling plaques on her face and neck (Figure, A). The lesions subsequently involved her chest, abdomen, and back and flared with sun exposure. A diagnosis of lupus erythematosus (LE) was favored, but the lesions failed to improve on a regimen that included hydroxychloroquine sulfate, fluocinonide ointment, 0.05%, and tacrolimus ointment, 0.1%. Biopsy samples were obtained for histopathologic evaluation.A, This case shows well-demarcated plaques with an overlying scale crust occurring in a photodistributed pattern on the central face. B, Hematoxylin-eosin, original magnification ×4. C, Hematoxylin-eosin, original magnification ×10.Laboratory findings were significant for positive antinuclear antibody titers at 1:640, lymphopenia, and normocytic anemia. Test results were negative or within normal limits for levels of antiribonucleoprotein, antihistone, antiphospholipid, anti-Smith, anti-Ro/Sjögren syndrome antigen A, and anti-La/Sjögren syndrome antigen B antibodies, C3, C4, CH50, rapid plasma reagin, and creatinine; erythrocyte sedimentation rate; and a comprehensive metabolic profile. Urinalysis results were within normal limits. A biopsy specimen was obtained (Figure, B and C).

what is your diagnosis?

What is your diagnosis?

Pemphigus foliaceus

Eczematous dermatitis

Pemphigus erythematosus

Lupus erythematosus

c

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2397958

A man in his 30s presented with a 5-day history of bilateral redness, blurred vision, and photophobia. The patient had received a diagnosis of human immunodeficiency virus (HIV) infection 4 months before, with a nadir in his CD4 count of 11/μL. He started highly active antiretroviral therapy, with improvement in his CD4 count to 101/μL most recently. During the past few months, he had reported increasing fatigue and intermittent fevers thought to be owing to immune reactivation syndrome. In addition to highly active antiretroviral therapy, he received combined sulfamethoxazole and trimethoprim and azithromycin prophylaxis. His visual acuity was 20/150 OD and 20/100 OS, and intraocular pressures were 6 and 10 mm Hg, respectively. On slitlamp examination, both eyes were injected with diffuse mutton-fat keratic precipitates and had more than 50 cells per 1×1-mm slitlamp high-power beam in the anterior chamber. Results of a dilated ophthalmoscopic examination revealed bilateral vitritis, hyperemic optic nerves, and extensive whitening likely involving all layers of the retina (Figure 1). He was hospitalized and started therapy consisting of intravenous (IV) acyclovir sodium, 10 mg/kg every 8 hours, and prednisone, 30 mg/d. Samples for a laboratory workup for infectious causes were obtained. After 48 hours of treatment, his condition did not improve.Marked vitritis, hyperemia of the optic nerve, and coalescent areas of retinal whitening involving the posterior pole are seen in the left eye. Visual acuity is 20/100. Check laboratory results and add IV penicillin G What Would You Do Next?

Continue the same treatment

Increase the dose of the corticosteroids

Check laboratory results and add IV penicillin G

Vitreous tap/biopsy

Syphilitic retinitis/panuveitis

C

Check laboratory results and add IV penicillin G

C. Check laboratory results and add IV penicillin GThis patient presented with acute panuveitis and retinitis in the setting of HIV infection. The diagnostic dilemma is whether the presentation represents acute retinal necrosis secondary to a virus in the Herpesviridae family (herpes simplex virus, cytomegalovirus, or varicella-zoster virus) or is secondary to other infectious agents, including syphilis and toxoplasmosis. Results of a rapid plasma reagin test were positive at 1:128, and fluorescent treponemal antibody test results were also positive. Lumbar puncture results were unrevealing. The patient was diagnosed as having syphilitic retinitis/panuveitis. Therapy consisting of IV penicillin G potassium, 4 million U every 4 hours, was started, and administration of oral prednisone and topical corticosteroid drops continued. The patient was treated with IV penicillin G for 14 days in all, and visual acuity after 1 month returned to 20/20 OU with complete resolution of the retinal findings (Figure 2).The areas of retinitis resolved, and the eye is quiet. Retinal pigment epithelial changes in the periphery are seen. Visual acuity is 20/20. The worldwide incidence of syphilis has increased markedly in the last decade, with reemergences described in the United States, United Kingdom, France, and Australia.1,2 This new epidemic has been most often seen in men with male sexual partners.3 Infection rate 5 to 7 times higher is seen in the HIV-seropositive population.4Long known as “the great imitator,”5 syphilis may present with a broad array of ophthalmic manifestations. Posterior segment manifestations may include vitritis, retinal vasculitis, chorioretinitis, and papillitis and and have been found to be common in patients with HIV, irrespective of CD4 count.6 In HIV-seronegative patients, the most common manifestation is anterior uveitis.7Syphilitic retinitis can present with large confluent areas of retinal whitening that may resemble acute retinal necrosis. In one study,6 35% of patients with HIV and syphilis coinfection presented with necrotizing retinitis; another 30% presented with posterior placoid chorioretinitis. In patients with posterior placoid chorioretinitis, lesions tend to have atrophic centers without fluid or associated hemorrhage. The type of retinitis seen in our patient and described more often in HIV-seropositive patients with syphilitic retinitis typically manifests as retinal whitening that may involve the periphery, midperiphery, and, at times, the posterior pole.Diagnosis of active syphilis requires treponemal and nontreponemal tests. Nontreponemal investigations include the VDRL and rapid plasma reagin tests, which are typically used for screening purposes and monitoring treatment response. The treponemal tests include fluorescent treponemal antibody absorption and microhemagglutination assay for Treponema pallidum and are more sensitive than nontreponemal tests. A lumbar puncture and cerebrospinal fluid examination is recommended for patients with ocular syphilis. Neurosyphilis is defined as a white blood cell count of more than 5/μL (to convert to ×109 per liter, multiply by 0.001) or positive VDRL test results in cerebrospinal fluid samples. Findings in neurosyphilis depend on the stage of disease and may include strokelike symptoms due to vasculitis, focal intracranial gummas, or general paresis and, in late neurosyphilis, tabes dorsalis. Treatment of ocular syphilis is the same as that for neurosyphilis: 3 to 4 million U of aqueous IV penicillin G potassium every 4 hours for 10 to 14 days.Syphilitic retinitis responds very quickly to IV penicillin. This quick response may aid the physician in the diagnosis of this entity because a similar speed of response is not seen with viral retinitis.8 The visual prognosis in syphilis is usually excellent with early recognition and treatment. The physician must maintain a high level of suspicion of syphilis, particularly in patients with HIV, because syphilis can manifest in a variety of way. Prompt recognition and treatment can lead to an excellent visual outcome.

Ophthalmology

A man in his 30s presented with a 5-day history of bilateral redness, blurred vision, and photophobia. The patient had received a diagnosis of human immunodeficiency virus (HIV) infection 4 months before, with a nadir in his CD4 count of 11/μL. He started highly active antiretroviral therapy, with improvement in his CD4 count to 101/μL most recently. During the past few months, he had reported increasing fatigue and intermittent fevers thought to be owing to immune reactivation syndrome. In addition to highly active antiretroviral therapy, he received combined sulfamethoxazole and trimethoprim and azithromycin prophylaxis. His visual acuity was 20/150 OD and 20/100 OS, and intraocular pressures were 6 and 10 mm Hg, respectively. On slitlamp examination, both eyes were injected with diffuse mutton-fat keratic precipitates and had more than 50 cells per 1×1-mm slitlamp high-power beam in the anterior chamber. Results of a dilated ophthalmoscopic examination revealed bilateral vitritis, hyperemic optic nerves, and extensive whitening likely involving all layers of the retina (Figure 1). He was hospitalized and started therapy consisting of intravenous (IV) acyclovir sodium, 10 mg/kg every 8 hours, and prednisone, 30 mg/d. Samples for a laboratory workup for infectious causes were obtained. After 48 hours of treatment, his condition did not improve.Marked vitritis, hyperemia of the optic nerve, and coalescent areas of retinal whitening involving the posterior pole are seen in the left eye. Visual acuity is 20/100. Check laboratory results and add IV penicillin G

what would you do next?

What would you do next?

Increase the dose of the corticosteroids

Vitreous tap/biopsy

Continue the same treatment

Check laboratory results and add IV penicillin G

d

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2425882

A young man presented to the emergency department with a 1-day history of vision loss in the left eye. He had experienced eye redness for 1 week, which resolved with use of artificial tears; a mild posterior headache; and paresthesias of the left thumb and index and middle fingers.His medical history was significant for epilepsy as a child, although he had been seizure free for more than 10 years without medication. He had no ocular history, was not taking any medications, and had no known drug allergies. He smoked 2 to 4 packs of cigarettes per day, consumed 1 to 3 alcoholic drinks per day, and denied illicit drug use. He denied recent travel, vaccinations, systemic illnesses, or influenza-like symptoms.His best-corrected visual acuity was 20/20 OD and 20/100 OS. Amsler grid testing revealed a central scotoma in the left eye. No afferent papillary defect was apparent. Intraocular pressures were 16 mm Hg OU. Results of the external and anterior segment examinations were unremarkable, and no vitreous inflammation was noted. Figure 1 shows findings of the posterior segment examination. Results of the neurologic examination revealed decreased sensation to light touch, vibration, and temperature in his left upper and lower extremities.A, Subretinal and retinal pigment epithelial lesions (arrowheads) are visible in the left eye. B, Late staining of the macular lesion. The arrowheads outline the border of the area that was hypofluorescent in the early frames (not shown). The right eye showed similar findings. What Would You Do Next?

Initiate high-dose corticosteroid therapy

Obtain magnetic resonance imaging of the brain

Perform a retinal biopsy

Obtain computed tomography of the chest

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with presumed associated cerebral vasculitis

B

Obtain magnetic resonance imaging of the brain

Classic clinical findings such as bilateral postequatorial creamy gray-yellow placoid lesions at the level of the retinal pigment epithelium demonstrating early blockage and late staining on fluorescein angiography in a young, otherwise healthy patient are often sufficient for establishing a diagnosis of APMPPE. Before considering therapy, however, pertinent associated signs and symptoms should be addressed. This patient described a headache that, in the setting of a prodromal viral illness, has been described with APMPPE and does not always warrant neuroimaging.1 However, the presence of peripheral sensory deficits should prompt urgent magnetic resonance imaging (MRI) with diffusion-weighted imaging and apparent diffusion coefficient sequences to evaluate for signs of cerebral vasculitis.The rare inflammatory eye disease APMPPE has been associated with multiple systemic conditions, including Wegener disease, systemic lupus erythematosus, and erythema nodosum, although causative relationships have not been established. Central nervous system involvement, ranging in severity from headaches to diffuse cerebral vasculitis, stroke, and death, has also been described, with at least 17 cases of APMPPE-related cerebral stroke reported.2Optimal therapeutic regimens for APMPPE have not been established because the disease is so rare; however, corticosteroids and immunomodulatory agents are used variably. Some authors3,4 have posited that isolated APMPPE in an otherwise healthy young adult follows a self-limited clinical course and carries an excellent visual prognosis without treatment. Others2,5,6 have reported substantial rates of persistent visual field defects, metamorphopsia, and incomplete visual recovery while remaining equivocal regarding the role of systemic therapy. Several1,7,8 agree that despite the paucity of high-quality clinical evidence, rapid initiation of therapy is justified in patients with central nervous system involvement and that long-term immunomodulatory therapy may be necessary.The MRI in our patient revealed multiple hyperintense foci on diffusion-weighted imaging sequences and corresponding hypointensities on apparent diffusion coefficient sequences, consistent with acute stroke (Figure 2). Results of the cerebrospinal fluid sample analysis were normal. Results of the laboratory workup for tuberculosis, sarcoidosis, and syphilis were negative. The patient received a 3-day course of intravenous methylprednisolone sodium succinate (Solu-Medrol); soon after therapy was transitioned to oral prednisone, he developed new symptoms and was found to have new cerebral infarcts. Oral cyclophosphamide was added, and he continued this regimen for 7 months before the prednisone dose was tapered gradually. Five months after treatment initiation, the patient’s visual acuity was 20/20 OD and 20/25 OS, with no recurrence of the disease.Representative section of magnetic resonance imaging, which demonstrated foci of marked hyperintensity on diffusion-weighted imaging sequences and corresponding hypointensity on apparent diffusion coefficient sequences (inset), consistent with acute stroke.Most patients with APMPPE can expect an excellent overall prognosis. However, physicians of patients who demonstrate any neurologic signs or symptoms should consider prompt neuroimaging because delayed treatment of APMPPE-associated cerebral vasculitis can result in substantial morbidity or death.

Ophthalmology

A young man presented to the emergency department with a 1-day history of vision loss in the left eye. He had experienced eye redness for 1 week, which resolved with use of artificial tears; a mild posterior headache; and paresthesias of the left thumb and index and middle fingers.His medical history was significant for epilepsy as a child, although he had been seizure free for more than 10 years without medication. He had no ocular history, was not taking any medications, and had no known drug allergies. He smoked 2 to 4 packs of cigarettes per day, consumed 1 to 3 alcoholic drinks per day, and denied illicit drug use. He denied recent travel, vaccinations, systemic illnesses, or influenza-like symptoms.His best-corrected visual acuity was 20/20 OD and 20/100 OS. Amsler grid testing revealed a central scotoma in the left eye. No afferent papillary defect was apparent. Intraocular pressures were 16 mm Hg OU. Results of the external and anterior segment examinations were unremarkable, and no vitreous inflammation was noted. Figure 1 shows findings of the posterior segment examination. Results of the neurologic examination revealed decreased sensation to light touch, vibration, and temperature in his left upper and lower extremities.A, Subretinal and retinal pigment epithelial lesions (arrowheads) are visible in the left eye. B, Late staining of the macular lesion. The arrowheads outline the border of the area that was hypofluorescent in the early frames (not shown). The right eye showed similar findings.

what would you do next?

What would you do next?

Perform a retinal biopsy

Initiate high-dose corticosteroid therapy

Obtain magnetic resonance imaging of the brain

Obtain computed tomography of the chest

c

male

11-20

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2442838

A previously healthy 6-year-old boy presented with 6 days of fever (maximum temperature of 40°C), intermittent nonbilious emesis, and 4 days of crampy, diffuse abdominal pain. Physical examination findings were significant for ill appearance, bilateral nonexudative conjunctivitis, shotty bilateral anterior cervical lymphadenopathy, diffuse abdominal tenderness (greatest in the right upper quadrant), and associated rebound and guarding. There was also a blanching, erythematous, macular rash on his cheeks (Figure, A) and an intermittent, erythematous, reticular rash on his chest, abdomen, arms, and legs (Figure, B) that spared his palms and soles and flared with fever. The remainder of his examination findings were unremarkable. Laboratory studies were significant for an elevated aspartate transaminase level of 264 U/L (reference range, 12-47 U/L; to convert to microkatals per liter, multiply by 0.0167) and an alanine transaminase level of 251 U/L (reference range, 17-63 U/L; to convert to microkatals per liter, multiply by 0.0167). A complete blood cell count revealed leukopenia with a white blood cell count of 28 300/µL (to convert to ×109/L, multiply by 0.001) (neutrophils, 64%; lymphocytes, 18%; monocytes, 4%; eosinophils, 2%; basophils, 1%; and bands, 11%), a low-normal hemoglobin level of 11.4 g/dL (to convert to grams per liter, multiply by 10), and thrombocytopenia with a platelet count of 610 × 103/µL (to convert to ×109/L, multiply by 1). Computed tomography of the abdomen revealed a dilated appendix (7 mm) with mucosal hyperemia and an internal appendicolith; acute appendicitis could not be excluded radiographically, so the patient was admitted for further workup because of a concern for acute abdomen. The patient lives in the southeastern United States and had no reported history of unusual exposures or insect or tick bites.A, A blanching, erythematous, macular rash present on the patient’s cheeks. B, An example of an intermittent, erythematous, reticular rash present on the patient’s left arm. What Is Your Diagnosis?

Adenovirus

Ehrlichiosis

Epstein-Barr virus

Parvovirus B19

B. Ehrlichiosis

B

Ehrlichiosis

Additional laboratory results were as follows: erythrocyte sedimentation rate, 16 mm/h; C-reactive protein, 1.0 mg/dL (to convert to nanomoles per liter, multiply by 9.524); and rapid streptococcus, monospot test, and respiratory viral polymerase chain reaction panel (adenovirus, human metapneumovirus, parainfluenza), all negative. Serum Epstein-Barr virus and parvovirus B19 study results were also negative. Further history revealed that the family lived in a wooded area and had a dog with a history of ticks. Rickettsial studies, including Ehrlichia serologic tests, were performed, and the patient was prescribed doxycycline for suspected human monocytic ehrlichiosis (HME). Within 24 hours of doxycycline administration, there was a marked improvement in his clinical condition, and he was discharged home to complete a 7-day course of doxycycline. The IgM and IgG antibody titers for Ehrlichia chaffeensis were later found to be elevated at 1:160 and 1:1024, respectively (reference range, <1:20 for IgM and <1:64 for IgG), which was a greater than 4-fold increase in antibody titers, thus confirming the diagnosis of HME. Follow-up convalescent titers (24 days after discharge) revealed that the IgM antibody titer to E chaffeensis was less than 1:20 and the IgG titer was still 1:1024. His transaminase levels had normalized at 27 U/L of aspartate transaminase and 12 U/L of alanine transaminase. He had no other clinically apparent sequelae from the illness.Human monocytic ehrlichiosis refers to illness caused by one of the various tick-borne rickettsial proteobacteria of the Ehrlichia species (most commonly E chaffeensis or Ehrlichia ewingii).1 However, HME is now classified as a separate entity from human granulocytic anaplasmosis, previously known as human granulocytic ehrlichiosis, caused by Anaplasma phagocytophilum, although the 2 may have similar clinical presentations.1 Human monocytic ehrlichiosis is most common in the southeastern and southcentral United States because this is where the vector Amblyomma americanum (lone star tick) resides.2 In addition, HME is more commonly reported in the summer months and in males (60%).3Clinical signs and symptoms of HME generally present 1 to 2 weeks after initial exposure, and the disease can be fatal (1%-3% case fatality rate) if not recognized and treated promptly.1 The most common presentations include fever (50%-95%), rash (60%), and various systemic symptoms (20%-50%), such as headaches, chills, nausea, emesis, diarrhea, myalgias, malaise, or altered mental status.1,4 The most common laboratory findings are elevated transaminase levels (>80%), leukopenia (60%-70%), and hyponatremia (up to 70%).1,4 Although up to 50% of ehrlichiosis cases may present with gastrointestinal symptoms, it is exceedingly rare to present with an acute abdomen. Only 3 other cases of patients presenting with an acute abdomen could be found in the literature: 1 pediatric case with human granulocytic anaplasmosis and 2 adult cases (1 HME and 1 human granulocytic anaplasmosis case).5-7 Diagnosis of HME is made based on serologic testing; however, if there is clinical suspicion of HME, treatment should not be delayed while awaiting laboratory confirmation.3 Doxycycline is the first-line treatment for HME in both children and adults and is more likely to be effective if started immediately.3The differential diagnosis is broad for a child presenting with fever, emesis, rash, and abdominal pain. Adenovirus, parvovirus B19, and Epstein-Barr virus were considered and can present similarly to HME but were ruled out based on history, physical examination, and laboratory testing. Human monocytic ehrlichiosis can be difficult to diagnose due to its nonspecific initial symptoms, and patients may not report a history of a tick bite or exposure, but it should always be considered in the differential diagnosis for patients presenting with any combination of an acute abdomen, prolonged fever, nausea, emesis, conjunctivitis, and rash, accompanied by characteristic laboratory findings, such as pancytopenia, hyponatremia, or transaminitis, in the appropriate epidemiologic setting.

Pediatrics

A previously healthy 6-year-old boy presented with 6 days of fever (maximum temperature of 40°C), intermittent nonbilious emesis, and 4 days of crampy, diffuse abdominal pain. Physical examination findings were significant for ill appearance, bilateral nonexudative conjunctivitis, shotty bilateral anterior cervical lymphadenopathy, diffuse abdominal tenderness (greatest in the right upper quadrant), and associated rebound and guarding. There was also a blanching, erythematous, macular rash on his cheeks (Figure, A) and an intermittent, erythematous, reticular rash on his chest, abdomen, arms, and legs (Figure, B) that spared his palms and soles and flared with fever. The remainder of his examination findings were unremarkable. Laboratory studies were significant for an elevated aspartate transaminase level of 264 U/L (reference range, 12-47 U/L; to convert to microkatals per liter, multiply by 0.0167) and an alanine transaminase level of 251 U/L (reference range, 17-63 U/L; to convert to microkatals per liter, multiply by 0.0167). A complete blood cell count revealed leukopenia with a white blood cell count of 28 300/µL (to convert to ×109/L, multiply by 0.001) (neutrophils, 64%; lymphocytes, 18%; monocytes, 4%; eosinophils, 2%; basophils, 1%; and bands, 11%), a low-normal hemoglobin level of 11.4 g/dL (to convert to grams per liter, multiply by 10), and thrombocytopenia with a platelet count of 610 × 103/µL (to convert to ×109/L, multiply by 1). Computed tomography of the abdomen revealed a dilated appendix (7 mm) with mucosal hyperemia and an internal appendicolith; acute appendicitis could not be excluded radiographically, so the patient was admitted for further workup because of a concern for acute abdomen. The patient lives in the southeastern United States and had no reported history of unusual exposures or insect or tick bites.A, A blanching, erythematous, macular rash present on the patient’s cheeks. B, An example of an intermittent, erythematous, reticular rash present on the patient’s left arm.

what is your diagnosis?

What is your diagnosis?

Ehrlichiosis

Parvovirus B19

Epstein-Barr virus

Adenovirus

a

male

0-10

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2432649

A woman in her 60s was referred for a large, left-sided, progressively enlarging mandibular mass, present for approximately 7 months. She had no pain or neurosensory disturbances related to the lesion; however, she did have difficulty tolerating a regular diet owing to the bulk of the mass. She had no significant medical history, had quit smoking cigarettes 4 year prior to presentation, but had a 20 pack-year smoking history. Findings from the physical examination were notable for a 4.9-cm exophytic, nodular, slightly mobile mass of the left lower posterior alveolar ridge, involving the buccal and lingual gingiva. Teeth 20 to 24 were mobile. She had no cervical lymphadenopathy. Previous biopsy demonstrated squamous mucosa with ulceration and chronic inflammation. Contrasted computed tomography revealed an exophytic complex mass with areas of calcification and ossification inferiorly and a necrotic, cystic irregularly enhancing portion superiorly (Figure, A-C). An additional biopsy was performed (Figure, D). The mass was excised, and teeth 20 to 26 were removed. The alveolar ridge was recontoured, and the incision was closed primarily.A-C, Computed tomographic (CT) scans. A, Bone window, coronal view. B, Bone window, sagittal view. C, Soft-tissue window. D, Histopathologic image of biopsy specimen. What Is Your Diagnosis?

Parosteal osteosarcoma

Peripheral ossifying fibroma

Periosteal osteosarcoma

Sarcomatoid carcinoma

B. Peripheral ossifying fibroma

B

Peripheral ossifying fibroma

Peripheral ossifying fibroma (POF) accounts for less than 2% of oral cavity pathologic abnormalities.1 A benign, oral cavity lesion occurring predominantly in females, POF characteristically presents in the second decade of life. A POF can be sessile or pedunculated, is well-demarcated, and is mucosal colored. Thought to arise from the periodontal ligament in gingival tissue, a POF typically involves the soft tissue over the alveolar process of the anterior maxilla.2 It is a reactive lesion, related to inflammatory hyperplasia from gingival irritation, a foreign body, or dental appliances.Most POFs measure less than 2 cm3,4; large POFs are rare, with fewer than 15 reported.5 Little cross-sectional imaging information exists on POFs. Given the unusually large size and radiographic features of this lesion at presentation, a true neoplastic process was initially considered. The preoperative differential diagnosis, after POF, included parosteal osteosarcoma, periosteal osteosarcoma, peripheral odontogenic tumors, and sarcomatoid carcinoma. Parosteal osteosarcoma, the most common surface osteosarcoma, is low-grade and arises from periosseous tissue in major tubular bones (the femur, humerus, and tibia). Periosteal osteosarcoma arises from the inner germative layer of the periosteum, commonly in long bones, and radiographically has a “sunburst” pattern. Peripheral odontogenic tumors are true neoplasms of ectomesenchyme origin and may contain odontogenic epithelium and/or dysplastic dentin. Sarcomatoid carcinoma can make heterologous elements such as bone, and, owing to calcification on radiography, this entity remained on the differential diagnosis.On excision, the histologic differential diagnosis included ectopic meningioma owing to vaguely psammomatoid calcifications; however, a negative result on epithelial membrane antigen stain excluded this diagnosis. Bland morphologic characteristics and negative results from immunostains MDM2 and CDK4 excluded forms of low-grade osteosarcoma.Histologically, POF is demarcated yet unencapsulated and contains submucosal proliferation of bland, oval fibroblastic cells associated with formation of mineralized matrix, consisting of islands of woven bone cementum–like particles (Figure, D). Although a benign process, POF exhibits an expansile growth pattern, often resulting in disruption of surrounding structures, such as teeth and, as in this patient, maxillary cortical erosion. Radiographically, this POF is a well-defined, extraosseous, circumscribed mass that exhibits stippled mineralized matrix production inferiorly and soft-tissue density and ulceration superiorly (Figure, A-C). Treatment is complete surgical excision. Recurrence rates range from 7% to 16%, which may be due to incomplete excision and failure to address the causative irritant.6Large clinical variants of typically small lesions can be a clinical and radiographic conundrum. In this woman with a smoking history, a malignant process remained high on the differential diagnosis. However, pathologic correlation at the time of surgery allowed for appropriate treatment of this benign lesion.

General

A woman in her 60s was referred for a large, left-sided, progressively enlarging mandibular mass, present for approximately 7 months. She had no pain or neurosensory disturbances related to the lesion; however, she did have difficulty tolerating a regular diet owing to the bulk of the mass. She had no significant medical history, had quit smoking cigarettes 4 year prior to presentation, but had a 20 pack-year smoking history. Findings from the physical examination were notable for a 4.9-cm exophytic, nodular, slightly mobile mass of the left lower posterior alveolar ridge, involving the buccal and lingual gingiva. Teeth 20 to 24 were mobile. She had no cervical lymphadenopathy. Previous biopsy demonstrated squamous mucosa with ulceration and chronic inflammation. Contrasted computed tomography revealed an exophytic complex mass with areas of calcification and ossification inferiorly and a necrotic, cystic irregularly enhancing portion superiorly (Figure, A-C). An additional biopsy was performed (Figure, D). The mass was excised, and teeth 20 to 26 were removed. The alveolar ridge was recontoured, and the incision was closed primarily.A-C, Computed tomographic (CT) scans. A, Bone window, coronal view. B, Bone window, sagittal view. C, Soft-tissue window. D, Histopathologic image of biopsy specimen.

what is your diagnosis?

What is your diagnosis?

Parosteal osteosarcoma

Peripheral ossifying fibroma

Periosteal osteosarcoma

Sarcomatoid carcinoma

b

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2436623

A woman in her 40s with no significant medical history presented with a 4-year history of intermittent left-sided throat pain, which eventually progressed to left ear pain approximately 1 year prior to her presentation. She had not experienced any dysphagia, dysphonia, dyspnea, fevers, or weight loss. She had no significant use of tobacco or alcohol in the past. Findings from an otoscopic examination was unremarkable. Nasopharyngoscopy was performed and failed to reveal any masses, ulcerations, or mucosal lesions. A magnetic resonance image (MRI) revealed an enhancing 1 × 6-mm lesion in the left side of the posterolateral tongue base (Figure, A). A biopsy of the mass revealed an intermediate-grade infiltrating neoplasm forming solid sheets and glandular structures (Figure, B). The tumor cells stained positive for CK7 and p63, and negative for CK20, p16, and S-100 by immunohistochemical analysis. Stain for mucicarmine was positive in glandular areas (Figure, C). After establishing the diagnosis, the patient was taken to the operating room for a left base of tongue resection via suprahyoid approach along with a left-sided neck dissection of levels I to IV. The tumor was removed with negative margins, and no positive cervical lymph nodes were found on final pathologic analysis.A, Magnetic resonance (MRI) image of a lesion in the left side of the posterolateral tongue base. B and C, Histopathologic images. B, Intermediate-grade infiltrating neoplasm forming solid sheets and glandular structures. Hematoxylin-eosin, original magnification ×20. C, Mucicarmine stain in the glandular area, original magnification ×40. What Is Your Diagnosis?

Squamous cell carcinoma

Mucoepidermoid carcinoma

Acinic cell carcinoma

Adenoid cystic carcinoma

B. Mucoepidermoid carcinoma

B

Mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor arising in the salivary glands, and while it most commonly occurs in the parotid gland, it may arise in other major or rarely minor salivary glands.1 Overall, tumors of the minor salivary glands are more commonly malignant, with reports of up to 80% rates of malignant disease.1 The differential diagnosis of malignant minor salivary gland tumors should include MEC, polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma, acinic cell carcinoma, adenocarcinoma NOS, carcinoma ex pleomorphic adenoma, clear cell carcinoma, basal cell adenocarcinoma, and myoepithelial carcinoma.2 In addition, variants of squamous cell carcinoma should be excluded prior to diagnosing a salivary gland malignant neoplasm. Originally considered to be a high-grade MEC, adenosquamous carcinoma is a high-grade carcinoma of the mucosal tract with both glandular and squamous malignant differentiation that may closely resemble high-grade MECs.3 The tumor in our case lacked squamous dysplasia and was intermediate-grade, which excluded adenosquamous carcinoma. Interestingly, the location of salivary gland tumors on the tongue may be predictive of malignant disease.4 In one study,4 85% of malignant tumors involved the base of the tongue compared with 80% of benign tumors that were located on the middle and anterior portions of the tongue.Although rare, various case reports of MEC occurring in the tongue base have been described and often include a variety of presentations.5-7 An MEC occurring in this location often creates vague, nonspecific, and diverse symptoms in patients, such as dysphagia caused by MEC arising in a background of sialadenoma papilliferum,5 macroscopically mimicking ectopic thyroid to produce hemoptysis and sialorrhea,6 and heavy intraoral bleeding.7Histological evaluation with hematoxylin-eosin staining remains the gold standard for diagnosis.8 Microscopically, MEC originates from ductal cells and is composed of mucinous, epidermoid, and intermediate-type cells.7 Low-grade tumors are denoted by a high proportion of mucinous cells within cystic structures, whereas solid sheets of epidermoid cells compose high-grade tumors that may resemble squamous cell carcinoma.7 Intermediate-grade tumors have a mixture of both epidermoid and mucinous components.7 Although nonspecific, immunohistochemical analysis can assist in diagnosis.8 Salivary gland tumors show CK7+/CK20- expression, which aids in differentiating them from squamous cell carcinomas, although it does not differentiate between salivary gland tumors or between benign and malignant tumors.9 In addition, MECs have a recurrent cytogenic abnormality, MAML2 translocation, which can be detected via fluorescence in situ hybridization, and these are typically S-100 negative, reflecting the absence of myoepithelial differentiation and p63+, both of which help narrow down the differential among salivary gland tumors.8 p16 is a tumor suppressor protein that serves as an excellent surrogate marker of human papillomavirus (HPV), an important etiologic agent in some head and neck cancers.3The optimal imaging modality to evaluate tongue masses is MRI, which delineates soft-tissue involvement more precisely than computed tomography (CT), although obtaining a neck CT scan is recommended to evaluate for the presence of cervical lymph node metastases.10Surgical resection of malignant minor salivary gland tumors is commonly accepted as the primary treatment; however, base of tongue tumors are notoriously difficult to resect, with most patients requiring complex approaches via a transmandibular or suprahyoid approach.10 Despite these invasive interventions, patients can have positive surgical margins up to 46% of the time, which is probably due to a combination of a technically challenging resection, as well as the tendency for submucosal growth and perineural spread of these tumors.10 The management of a clinically negative neck remains controversial, and some advocate for elective neck dissection of levels I-III, especially in intermediate and high-grade tumors.10 Radiation therapy postoperatively is recommended for certain adverse prognostic factors, such as high-grade tumors, positive or close surgical margins, perineural invasion, or lymph node metastases.1,10 The prognosis is usually correlated with the histologic grade—a recent review10 found a 5-year regional recurrence-free survival of 100% for low-grade, 92% for intermediate-grade, and 57% for high-grade oropharyngeal MECs, of which most occurred in the base of tongue. They also found an overall 5-and 10-year survival rates of 78% and 68%, respectively.10 However, there may be potential problems with the reproducibility of histologic grading, which may affect its correlation with outcome.

General

A woman in her 40s with no significant medical history presented with a 4-year history of intermittent left-sided throat pain, which eventually progressed to left ear pain approximately 1 year prior to her presentation. She had not experienced any dysphagia, dysphonia, dyspnea, fevers, or weight loss. She had no significant use of tobacco or alcohol in the past. Findings from an otoscopic examination was unremarkable. Nasopharyngoscopy was performed and failed to reveal any masses, ulcerations, or mucosal lesions. A magnetic resonance image (MRI) revealed an enhancing 1 × 6-mm lesion in the left side of the posterolateral tongue base (Figure, A). A biopsy of the mass revealed an intermediate-grade infiltrating neoplasm forming solid sheets and glandular structures (Figure, B). The tumor cells stained positive for CK7 and p63, and negative for CK20, p16, and S-100 by immunohistochemical analysis. Stain for mucicarmine was positive in glandular areas (Figure, C). After establishing the diagnosis, the patient was taken to the operating room for a left base of tongue resection via suprahyoid approach along with a left-sided neck dissection of levels I to IV. The tumor was removed with negative margins, and no positive cervical lymph nodes were found on final pathologic analysis.A, Magnetic resonance (MRI) image of a lesion in the left side of the posterolateral tongue base. B and C, Histopathologic images. B, Intermediate-grade infiltrating neoplasm forming solid sheets and glandular structures. Hematoxylin-eosin, original magnification ×20. C, Mucicarmine stain in the glandular area, original magnification ×40.

what is your diagnosis?

What is your diagnosis?

Acinic cell carcinoma

Mucoepidermoid carcinoma

Squamous cell carcinoma

Adenoid cystic carcinoma

b

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2442630

A woman in her 70s with a 7-year history of essential thrombocythemia was diagnosed as having acute myelogenous leukemia 4 days prior to hospital admission for induction chemotherapy. She was febrile at admission and treated empirically with antifungal, antibiotic, and antiviral medications in the setting of cultures that were negative for organisms. The initial chemotherapy regimen failed, requiring a more aggressive regimen, which left her pancytopenic. During the course of the second chemotherapy treatment, she developed left-sided mandibular pain. A computed tomographic scan revealed cellulitic changes along the buccal cortex of the mandible and a small 2 × 12-mm abscess formation. At initial evaluation by the otolaryngology service on hospital day 32, she had decreased sensation at the left mandibular branch of the trigeminal nerve and ecchymoses along the mandibular buccal-gingival borders bilaterally with induration of the left floor of mouth and buccal mucosa (Figure, A). She continued to receive broad spectrum antimicrobial and antifungal coverage. By hospital day 38, the patient had developed evidence of ischemia and necrosis along the gingival and lingual aspects of the left mandibular alveolar ridge, extending past midline to involve mucosa on the right side. Magnetic resonance imaging revealed a 7 × 10 × 35-mm abscess involving both gingival and lingual aspects of the left anterior mandible (arrowheads) (Figure, B). Biopsy specimens of the right mandibular gingiva are shown in the Figure, C and D.A, Patient photograph. B, Magnetic resonance image of abscess. C and D, Histopathologic images from biopsy specimens. C, Original magnification ×250. D, Original magnification ×500. What Is Your Diagnosis?

Viral infection

Malignant neoplasm

Pemphigus vulgaris

Invasive necrotizing fungal gingivitis

D. Invasive necrotizing fungal gingivitis

D

Invasive necrotizing fungal gingivitis

The fungal spores that typically reside in the aerodigestive tract of the head and neck can become virulent and cause clinically significant disease, particularly in patients with severe or prolonged neutropenia. Fungal infections commonly result in rhinosinusitis or pulmonary disease in the immunocompromised patient.1 Local infections of the paranasal sinuses may extend to the palate and oral cavity, but isolated cases of invasive necrotizing fungal gingivitis (INFG) are exceedingly rare. To date, there are only 27 reported cases of INFG, all of which are within the oral and maxillofacial surgery and dental literature.1-8Invasive necrotizing fungal gingivitis is a rare clinical diagnosis that typically presents in patients newly diagnosed as having acute leukemia who are undergoing chemotherapeutic treatment.6 Prior to instituting any prophylactic measures, one Japanese institution estimated the rate of invasive gingival aspergillosis to be as high as 7.8% of those hospitalized for leukemia.5 When left untreated in a pancytopenic patient, INFG progresses rapidly without regard for anatomic boundaries and is almost uniformly fatal, especially in the case of invasive aspergillosis. Early diagnosis and prompt initiation of treatment, however, has been shown to drastically improve survival.1Early signs and symptoms of INFG include fever, gingival pain, facial swelling, grayish discoloration of the gingiva, and even frank ulceration or gingival necrosis.7 Granulomatous disease, neoplasms, and bacterial and viral infections should be considered when evaluating an immunocompromised patient presenting as described.6 Definitive diagnosis of INFG is confirmed with histologic review of biopsied tissue as well as pertinent culture results.1 When biopsying oral mucosa, one will encounter potentially 3 general types of mucosa: lining, masticatory, or special. This patient’s lesion involved the gingival mucosa, a type of masticatory mucosa, which covers both the medial and lateral surfaces of the alveolus.Histologic evaluation via hematoxylin-eosin and Gomori methenamine silver stains is required to make the diagnosis of any invasive fungal infection. Historically, confident differentiation between the 2 most common fungal organisms, Aspergillus and Mucorales, has been difficult and requires clear evidence of characteristic fungal hyphae branching patterns which may not always be present or conclusive.7Aspergillus species typically display septate hyphae with acute branching angles (approximately 45°), whereas Mucorales characteristically displays broad, aseptate hyphae (4-20 µm) with more obtuse branching patterns. Both Aspergillus and Mucorales have a predilection for vascular erosion, leading to thrombosis and resultant tissue necrosis of the surrounding area. Figure C demonstrates fungal hyphae (asterisks) seen in relief as clear holes and tubes outlined by the surrounding eosin-stained tissue and invading the walls of a muscular artery (yellow bars) leading to thrombosis (arrowheads); Figure D shows broad aseptate hyphae with obtuse branching, characteristic of mucormycosis. Although definitive tissue cultures were unable to be obtained in this patient, the pathologic finding seen in the Figure, C and D, make Mucorales the most likely causative agent in this patient.Owing to the rapidity at which INFG can progress, prompt initiation of aggressive treatment is essential for improving survival outcomes.7 Wide surgical excision and debridement are crucial for obtaining a therapeutic advantage, although the poor hematologic status of patients with INGF often complicates early surgical intervention.7,9 Concurrent administration of amphotericin B is also crucial in managing INFG.1,9 In cases of invasive aspergillosis, other triazole antifungal agents, such as voriconazole and itraconazole, have also shown efficacy.1 In addition to surgical and antifungal therapies, recovery of the patient’s innate immune system, potentially with the use of recombinant granulocyte colony-stimulating factor, also plays a vital role in enabling the patient to overcome an invasive fungal infection.10In conclusion, we report the case of a neutropenic patient with INFG secondary to Mucorales. The hastening of this patient’s death from INFG, on hospital day 40, underscores the importance of early clinical suspicion, detection, and treatment in all neutropenic patients, especially those undergoing treatment for acute leukemia.

General

A woman in her 70s with a 7-year history of essential thrombocythemia was diagnosed as having acute myelogenous leukemia 4 days prior to hospital admission for induction chemotherapy. She was febrile at admission and treated empirically with antifungal, antibiotic, and antiviral medications in the setting of cultures that were negative for organisms. The initial chemotherapy regimen failed, requiring a more aggressive regimen, which left her pancytopenic. During the course of the second chemotherapy treatment, she developed left-sided mandibular pain. A computed tomographic scan revealed cellulitic changes along the buccal cortex of the mandible and a small 2 × 12-mm abscess formation. At initial evaluation by the otolaryngology service on hospital day 32, she had decreased sensation at the left mandibular branch of the trigeminal nerve and ecchymoses along the mandibular buccal-gingival borders bilaterally with induration of the left floor of mouth and buccal mucosa (Figure, A). She continued to receive broad spectrum antimicrobial and antifungal coverage. By hospital day 38, the patient had developed evidence of ischemia and necrosis along the gingival and lingual aspects of the left mandibular alveolar ridge, extending past midline to involve mucosa on the right side. Magnetic resonance imaging revealed a 7 × 10 × 35-mm abscess involving both gingival and lingual aspects of the left anterior mandible (arrowheads) (Figure, B). Biopsy specimens of the right mandibular gingiva are shown in the Figure, C and D.A, Patient photograph. B, Magnetic resonance image of abscess. C and D, Histopathologic images from biopsy specimens. C, Original magnification ×250. D, Original magnification ×500.

what is your diagnosis?

What is your diagnosis?

Invasive necrotizing fungal gingivitis

Viral infection

Pemphigus vulgaris

Malignant neoplasm

a

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2443351

A man in his 20s presented with a painless, gradually increasing swelling in the right side of the neck of 6 years’ duration. There was no history of dysphagia, hoarseness of voice, dyspnea, or constitutional symptoms, such as fever, weight loss, or night sweats. Clinical examination revealed a 7 × 6-cm, well-defined, firm, nontender swelling extending from the angle of the mandible to the clavicle. Oropharyngeal examination revealed a mucosal bulge on the lateral pharyngeal wall with normal overlying mucosa. A computed tomographic (CT) scan of the neck was performed, which revealed a solid 7 × 8 × 10-cm right carotid space mass, with a few cystic areas and coarse specks of calcification within (Figure, A, yellow arrowhead). It showed heterogeneous postcontrast enhancement, predominantly around the calcific foci. It extended from the C2 to D1 vertebral level and displaced the right common carotid artery and internal jugular vein anterolaterally (Figure, A, red arrowhead). Fat planes around the mass were well maintained (Figure, B, arrowheads), and there was no bone destruction. No cervical lymphadenopathy was noted. A biopsy was performed from the mass (Figure, C and D).A, Axial postcontrast computed tomographic (CT) image of the neck. B, Coronal postcontrast CT image of the neck. C and D, Histopathologic images. C, Hematoxylin-eosin, original magnification ×200. D, Hematoxylin-eosin, original magnification ×400. What Is Your Diagnosis?

Extraskeletal chondrosarcoma

Malignant fibrous histiocytoma

Ancient schwannoma

Synovial sarcoma

C. Ancient schwannoma

C

Ancient schwannoma

Histopathologic findings revealed a spindle cell tumor arranged in Antoni A (densely cellular areas) and Antoni B areas (less cellular and myxoid matrix), with hyalinized and staghorn-type dilated blood vessels and Verocay bodies (Figure, C, arrowhead). The spindle cells focally showed nuclear enlargement and hyperchromasia, suggesting degenerative atypia (Figure, D, arrowheads). Chunky calcification was noted. Diagnosis of an ancient schwannoma (AS) was made. Intraoperatively, a tumor was seen arising from the right vagus nerve.Ancient schwannomas were first described in 1951 by Ackerman and Taylor1 as a long-standing schwannoma, which histologically shows hyalinized matrix, hypercellular areas, nuclear pleomorphism, and hyperchromatism. However, nuclear atypia is considered purely a degenerative change, which reflects the long-standing nature of the lesion, hence the term ancient schwannoma. Apart from the nuclear changes, other degenerative changes found in AS are predominance of Antoni type B cells with loss of alternate Antoni A and Antoni B areas, perivascular sclerosis, xanthomatous changes, calcification, hemorrhage, and hemosiderin-laden macrophages, and cystic changes.2-4Isobe et al5 described the radiological features of 24 cases of AS. These include well-circumscribed tumors that appear hypodense or isodense to muscle on CT and show multiple cystic areas and calcification within. Postcontrast enhancement is noted in the capsule and in the areas surrounding degeneration. On MRI, the Antoni B areas, which are the predominant components of AS, appear T1-hypointense and T2-hyperintense. Ancient schwannomas show strong postcontrast enhancement, which is characteristic of both Antoni A and Antoni B areas.Accurate radiological diagnosis is important because pathologically this tumor can be erroneously diagnosed as malignant. Ancient schwannomas may be radiologically misinterpreted as a soft-tissue, sarcoma-like extraskeletal chondrosarcoma; malignant fibrous histiocytoma; synovial sarcoma; or liposarcoma. Extraskeletal chondrosarcomas are commonly of myxoid or mesenchymal variety. On CT, both show chondroid matrix mineralization. The myxoid variant shows low attenuation on CT, appears T2-hyperintense, with mild peripheral to septal postcontrast enhancement. The mesenchymal variant appears isodense to muscle on CT and intermediate signal intensity on T2-weighted MRI. They show heterogeneous postcontrast enhancement.6 Malignant fibrous histiocytoma presents as well-defined lobulated lesion, exhibiting central areas of myxomatous tissue, calcification, necrosis, hemorrhage, bone destruction, and nodal metastases. On MRI, it is T1-hypointense or isointense, T2- hyperintense, and shows enhancement of the solid peripheral components.7 Synovial sarcoma usually presents as a well-defined lesion with dystrophic calcifications, necrosis, or hemorrhage within and nodal metastases. Bone involvement may manifest as erosions or marrow involvement.8 The imaging appearance of liposarcoma depends on the tumor grade and fat content, fat content being less in higher-grade tumors. Calcification is also reported in liposarcomas.9Our patient had a lesion in the carotid space, which is a rare site for soft-tissue sarcomas. Well-defined noninfiltrative margins despite the large size, long-standing history, lack of bone erosion, or nodal metastases pointed to a benign etiology. The common differentials of a benign neoplasm in carotid space are schwannomas, neurofibromas, and paragangliomas. Neurofibromas present as well defined homogenous low-density lesions showing no or minimal postcontrast enhancement. Calcification and cystic areas are rare. Paragangliomas are well defined, homogenous (when small) or heterogeneous (when large) lesions showing early marked contrast enhancement with rapid wash out. On T1-weighted MRI, they show classic “salt and pepper” appearance.Thus, our approach in this case was to initially identify this lesion as a benign entity and then differentiate it from other benign lesions in the carotid space.

General

A man in his 20s presented with a painless, gradually increasing swelling in the right side of the neck of 6 years’ duration. There was no history of dysphagia, hoarseness of voice, dyspnea, or constitutional symptoms, such as fever, weight loss, or night sweats. Clinical examination revealed a 7 × 6-cm, well-defined, firm, nontender swelling extending from the angle of the mandible to the clavicle. Oropharyngeal examination revealed a mucosal bulge on the lateral pharyngeal wall with normal overlying mucosa. A computed tomographic (CT) scan of the neck was performed, which revealed a solid 7 × 8 × 10-cm right carotid space mass, with a few cystic areas and coarse specks of calcification within (Figure, A, yellow arrowhead). It showed heterogeneous postcontrast enhancement, predominantly around the calcific foci. It extended from the C2 to D1 vertebral level and displaced the right common carotid artery and internal jugular vein anterolaterally (Figure, A, red arrowhead). Fat planes around the mass were well maintained (Figure, B, arrowheads), and there was no bone destruction. No cervical lymphadenopathy was noted. A biopsy was performed from the mass (Figure, C and D).A, Axial postcontrast computed tomographic (CT) image of the neck. B, Coronal postcontrast CT image of the neck. C and D, Histopathologic images. C, Hematoxylin-eosin, original magnification ×200. D, Hematoxylin-eosin, original magnification ×400.

what is your diagnosis?

What is your diagnosis?

Malignant fibrous histiocytoma

Synovial sarcoma

Ancient schwannoma

Extraskeletal chondrosarcoma

c

male

21-30

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2396581

A man in his 70s presented with blurred vision in his left eye. The patient had a history of myelodysplastic syndrome (refractory anemia with excess blasts–2), prostate cancer treated with prostatectomy and radiation therapy 5 years prior, and colonic adenocarcinoma treated with right hemicolectomy 6 years prior. Four months before presentation, his myelodysplastic syndrome transformed into acute myeloid leukemia (AML). He was randomized to experimental drug CPX-351 for induction, but treatment was discontinued as a result of renal failure. However, remission was successfully induced with mitoxantrone hydrochloride and etoposide therapy, as confirmed by bone marrow biopsy, and he was prescribed continuing melphalan therapy on an outpatient basis.Three days prior to presentation, the patient on awakening noticed an acute onset of blurred vision in his left eye without any pain, photophobia, diplopia, vision loss, or floaters. He had no history of ocular surgery or trauma. Visual acuity was 20/20 in the right eye and 20/30 in the left. External examination had unremarkable results. Pupillary and motility assessments had normal results. Intraocular pressure was elevated bilaterally, measuring 29 mm Hg in the right eye and 41 mm Hg in the left.Slitlamp examination of the right eye revealed a 0.5-mm hypopyon with small hemorrhages on the iris surface (Figure 1A). In the left eye, examination demonstrated a 1.5-mm hypopyon mixed with hemorrhage, 1+ cells in the anterior chamber, and small hemorrhages on the iris surface (Figure 1B). Bilaterally, gonioscopy revealed open angles with few hemorrhages in the angle but no neovascularization. Dilated fundoscopic examination had unremarkable results bilaterally, with no retinal hemorrhages or optic disc swelling.Color slitlamp photographs illustrating bilateral hypopyon (black arrowheads) with iris surface hemorrhages (white arrowheads). A, Right eye with 0.5-mm hypopyon with small hemorrhages on the iris surface and presumed infiltration. B, Left eye with 1.5-mm hypopyon mixed with hemorrhage and small iris surface hemorrhages and presumed infiltration. What Is Your Diagnosis?

Endogenous endophthalmitis

HLA-B27 uveitis

Herpes simplex uveitis

Leukemia relapse

D. Leukemia relapse

D

Leukemia relapse

Anterior chamber paracentesis was performed in the left eye, with cytologic analysis revealing myeloblasts in the aqueous humor, indicating a pseudohypopyon in the setting of AML relapse (Figure 2). Peripheral blood smear also demonstrated blast cells.Cytological evaluation of anterior chamber aqueous humor aspirate demonstrating myeloblasts (white arrowheads) (Wright stain, original magnification ×500).Pseudohypopyon is the accumulation of malignant cells in the anterior chamber, which differs from hypopyon, the infiltration of leukocytes due to infection or inflammation. Hypopyon is often seen in endogenous endophthalmitis, an intraocular infection seeded from blood-borne infections, and immunocompromised patients are especially susceptible.1Candida is the most common pathogen.2 Systemic evaluation is warranted, including blood, urine, and vitreous and aqueous humor cultures.1 HLA-B27 uveitis is a major cause of acute anterior uveitis, which can include the development of a unilateral or bilateral hypopyon.1 HLA-B27 is a class I major histocompatibility complex molecule associated with inflammatory rheumatic and gastrointestinal disorders. A carefully elicited history can identify associated systemic diseases, and tests for HLA-B27 can help diagnose HLA-B27 uveitis. Herpes simplex virus is widespread and can be found in almost all cadavers of persons 60 years or older at death.3 Although ocular involvement is a well-known complication of herpes simplex virus infection, hypopyon is rare.1,3Pseudohypopyon can present in a variety of leukemias, although the highest incidence (up to 18%) is associated with acute lymphoblastic leukemia.1 In a 1989 prospective 2-year study of ocular findings of 53 patients undergoing AML treatment, none developed pseudohypopyon,4 illustrating the rarity of this presentation at that time. Since then, there have been multiple cases documenting the pseudohypopyon in AML.5-7 Increased reports of pseudohypopyon in AML should prompt evolving clinical approaches.This unusual manifestation of AML relapse portends a grave prognosis. Among 15 patients, 13 died within months after presentation of the pseudohypopyon.5-7 At time of presentation, all 15 had already developed diffuse systemic disease, but not all involved the central nervous system. In our patient, no evidence of leukemia was detected by brain magnetic resonance imaging and he declined a lumbar puncture. Evaluation of cases with diffuse disease accompanying pseudohypopyon revealed that 9 of 14 patients received a diagnosis of either M4 or M5 AML.6 In the 1 case of long-term survival after presentation of the pseudohypopyon, the patient showed no other evidence of extramedullary leukemic infiltration outside the eye.5 This uncommonly successful outcome impresses the importance of prompt identification of AML relapse. The immune-privileged microenvironment, coupled with low penetration of chemotherapeutics, may allow the anterior chamber to shelter malignant seeds, leaving it susceptible to relapse.8 Thus, noninvasive eye examinations can be leveraged to monitor for signs of relapse.Treatment is varied but can include systemic chemotherapy and localized radiotherapy.9 Our patient opted to discontinue treatment and entered hospice care.In summary, for patients with a history of AML presenting with ocular and visual changes, a high index of suspicion must be maintained for relapse of leukemia. A dilated examination combined with slit lamp examination serves as a noninvasive approach to look for signs of ocular involvement such as pseudohypopyon, leukemic retinopathy, or optic nerve infiltrates. Anterior chamber paracentesis can confirm a suspected pseudohypopyon. Oncology and ophthalmology teams should collaborate to promptly assess for evidence of systemic relapse and initiate treatment.

Oncology

A man in his 70s presented with blurred vision in his left eye. The patient had a history of myelodysplastic syndrome (refractory anemia with excess blasts–2), prostate cancer treated with prostatectomy and radiation therapy 5 years prior, and colonic adenocarcinoma treated with right hemicolectomy 6 years prior. Four months before presentation, his myelodysplastic syndrome transformed into acute myeloid leukemia (AML). He was randomized to experimental drug CPX-351 for induction, but treatment was discontinued as a result of renal failure. However, remission was successfully induced with mitoxantrone hydrochloride and etoposide therapy, as confirmed by bone marrow biopsy, and he was prescribed continuing melphalan therapy on an outpatient basis.Three days prior to presentation, the patient on awakening noticed an acute onset of blurred vision in his left eye without any pain, photophobia, diplopia, vision loss, or floaters. He had no history of ocular surgery or trauma. Visual acuity was 20/20 in the right eye and 20/30 in the left. External examination had unremarkable results. Pupillary and motility assessments had normal results. Intraocular pressure was elevated bilaterally, measuring 29 mm Hg in the right eye and 41 mm Hg in the left.Slitlamp examination of the right eye revealed a 0.5-mm hypopyon with small hemorrhages on the iris surface (Figure 1A). In the left eye, examination demonstrated a 1.5-mm hypopyon mixed with hemorrhage, 1+ cells in the anterior chamber, and small hemorrhages on the iris surface (Figure 1B). Bilaterally, gonioscopy revealed open angles with few hemorrhages in the angle but no neovascularization. Dilated fundoscopic examination had unremarkable results bilaterally, with no retinal hemorrhages or optic disc swelling.Color slitlamp photographs illustrating bilateral hypopyon (black arrowheads) with iris surface hemorrhages (white arrowheads). A, Right eye with 0.5-mm hypopyon with small hemorrhages on the iris surface and presumed infiltration. B, Left eye with 1.5-mm hypopyon mixed with hemorrhage and small iris surface hemorrhages and presumed infiltration.

what is your diagnosis?

What is your diagnosis?

Leukemia relapse

Herpes simplex uveitis

HLA-B27 uveitis

Endogenous endophthalmitis

a

male

71-80

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2422333

A 57-year-old woman with a medical history of recurrent biliary colic was admitted with symptoms consistent with mild gallstone pancreatitis. Routine laboratory test results showed total bilirubin of 4.74 mg/dL (to convert to millimoles per liter, multiply by 17.104) and amylase of 1.041 U/L (to convert to microkatals per liter, multiply by 0.0167). An abdominal ultrasonography scan demonstrated gallstones and a mildly dilated common bile duct (CBD). Magnetic resonance imaging of the abdomen confirmed these results and revealed cholelithiasis. The patient consequently underwent urgent laparoscopic cholecystectomy with intraoperative cholangiography (Figure, A). Intraoperative cholangiography revealed an unusual anatomical variant and subsequent transcystic choledochoscopy was performed, which demonstrated a double lumen at the distal CBD (Figure, B). Multiple gallstones were found within a dilated region of cystic duct. What Is Your Diagnosis?

Choledochoduodenal fistula

Biloma

Gallbladder duplication with double cystic duct

Choledochal cyst and long common biliopancreatic channel

D. Choledochal cyst and long common biliopancreatic channel

D

Choledochal cyst and long common biliopancreatic channel

Choledochal cysts are rare and most commonly associated with a congenital abnormality of the pancreatobiliary junction (Figure, B). As a result, inverted flow of pancreatic secretions causes chronic inflammation of the biliary tract.1-3 Less frequently, similar cystic dilatations derive from embryonic proliferation of the biliary ductal cells or CBD obstruction.1,4 Choledochal cysts typically present in children with nonspecific symptoms including nausea, vomiting, and fever. The classic triad of right upper quadrant mass, pain, and jaundice are not always present.1 In the most severe cases, spontaneous perforation and peritonitis have been described.5 In adulthood, presentation can be incidental or more typically, as in this case, produces symptoms consistent with choledocholithiasis or acute pancreatitis. Rarely, choledochal cysts may present with cholangiocarcinoma secondary to longstanding pancreatic fluid reflux that results in chronic inflammation, ulceration, dysplasia, and subsequent malignant transformation.2,6,7 Therefore, early treatment of cystic dilation of the biliary tree is essential to avoid cholangitis, pancreatitis, and malignancy.Choledochal cysts have been classified by Todani et al3: type I involves extrahepatic biliary tree dilatation, which may be either Ia (cystic), Ib (focal), or Ic (fusiform). Type II cysts are also extrahepatic and characterized by saccular dilatation. Type III involves dilatation of the bile duct within the duodenum and type IV exhibits dilatation of both the intrahepatic and extrahepatic biliary tree. The presence of intrahepatic cysts is classified as type V. Type VI cysts were later classified by Serena Serradel et al8 describing only cystic duct dilatation but with a long biliopancreratic channel, as observed in our case.Surgical resection of the cyst and affected extrahepatic biliary tract, along with concomitant hepaticoenterostomy, is widely accepted in children owing to the high risk for extrahepatic bile duct cancer; however, this is debated in adults.8-10 In this case, the presence of pancreaticobiliary maljunction without biliary dilatation was thought to confer a low risk for cholangiocarcinoma but increase the risk for gallbladder carcinoma.2 In this case, the cyst was isolated to the cystic duct. As such, laparoscopic cholecystectomy and resection of the dilated cystic duct were performed as close as possible to the CBD (to prevent the high risk for malignancy) with reconstruction over a T-tube. Endoscopic sphincterotomy was also performed to improve common-channel biliary drainage. Histopathology findings revealed chronic cholecystitis, with no dysplasia or malignancy. Consequently, no further surgical resection was necessary and the patient remained well at follow-up.

Surgery

A 57-year-old woman with a medical history of recurrent biliary colic was admitted with symptoms consistent with mild gallstone pancreatitis. Routine laboratory test results showed total bilirubin of 4.74 mg/dL (to convert to millimoles per liter, multiply by 17.104) and amylase of 1.041 U/L (to convert to microkatals per liter, multiply by 0.0167). An abdominal ultrasonography scan demonstrated gallstones and a mildly dilated common bile duct (CBD). Magnetic resonance imaging of the abdomen confirmed these results and revealed cholelithiasis. The patient consequently underwent urgent laparoscopic cholecystectomy with intraoperative cholangiography (Figure, A). Intraoperative cholangiography revealed an unusual anatomical variant and subsequent transcystic choledochoscopy was performed, which demonstrated a double lumen at the distal CBD (Figure, B). Multiple gallstones were found within a dilated region of cystic duct.

what is your diagnosis?

What is your diagnosis?

Gallbladder duplication with double cystic duct

Biloma

Choledochal cyst and long common biliopancreatic channel

Choledochoduodenal fistula

c

female

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2426406

An elderly man presented to the emergency department with a 1-month history of new-onset, persistent lower abdominal and flank pain. The pain was sharp and constant with intermittent radiation to the back and associated anorexia with a 10-kg weight loss. He did not report any previous abdominal surgery. The patient stated that he had not had any procedures with intravascular instrumentation in the past year, dental cleanings, intravenous drug use, cutaneous abscesses, or recent trauma. Physical examination revealed he was afebrile and in normal sinus rhythm; there was minimal epigastric abdominal tenderness without signs of peritonitis and no palpable masses. Femoral pulses were palpable and symmetric. Laboratory examination revealed mild anemia (hematocrit, 35% [to convert to a proportion of 1.0, multiply by 0.01]), no leukocytosis, and an elevated erythrocyte sedimentation rate (71 mm/h). Blood and urine cultures were negative for organisms. A computed tomographic (CT) angiogram showed asymmetric attenuation surrounding the infrarenal aorta (Figure 1). On comparison, a CT scan that was performed 6 months before presentation had identified no aneurysmal disease.Computed tomographic scan with arterial phase intravenous contrast with asymmetric attenuation surrounding the infrarenal aorta. What Is Your Diagnosis?

Mycotic aneurysm

Inflammatory abdominal aortic aneurysm

Pseudoaneurysm

Infrarenal aortitis due to diverticulitis

B. Inflammatory abdominal aortic aneurysm

B

Inflammatory abdominal aortic aneurysm

The patient had chronic abdominal pain, weight loss, and an elevated erythrocyte sedimentation rate with abdominal aortic aneurysm (AAA) noted on imaging, which is suggestive of inflammatory AAA (IAAA).1 The CT scan showed a 3.8-cm infrarenal aortic aneurysm and periaortic hypoattenuation without contrast blush, emphysema, or fluid collection.The pathogenesis for IAAA remains elusive, with recent studies1,2 suggesting a mechanism similar to that of noninflammatory AAA. Although the diseases were once believed to have 2 different causes, more recent data suggest that degenerative (atherosclerotic) aneurysms have mild or moderate inflammatory infiltrate, whereas, IAAAs are an extreme presentation of such inflammation.1 The causal factor for this inflammation is yet to be discovered; however, tobacco smoking is strongly associated as a risk factor. The incidence is estimated to be 3% to 10% of all AAAs and located most commonly in the infrarenal portion of the aorta.2 Takayasu arteritis, giant cell arteritis, Behçet disease, and polyarteritis nodosa can also lead to aneurysm formation of inflammatory origin.The diagnosis of IAAA is most reliably ascertained with CT of the abdomen with contrast, which has a sensitivity estimated at 83%.3 Ultrasonography identifies aneurysmal disease and can be used to monitor changes in size, but it has a lower sensitivity than CT for detecting an inflammatory component. There is thickening of the adventitia seen in imaging as periaortic fibrosis and described as a “rind” around the aorta.4 The periaortic and retroperitoneal soft tissues may be enhanced with contrast and are void of air or fluid, unlike aneurysms of an infectious source that have an eccentric saccular appearance with mural air or perivascular fluid collection.5 Adjacent structures may be involved in the inflammatory process, which make open repair of these lesions challenging with higher complication and mortality rates than noninflammatory AAA repair. Infected aortic aneurysms, commonly known as mycotic aneurysms, are also a type of vasculitis, but these are associated with fever, leukocytosis, and blood cultures positive for organisms.Surgical repair is the treatment for IAAA. There is increased risk for reoperation secondary to pseudoaneurysm formation.6 With the introduction of endovascular repair options, the mortality incidence has decreased 3-fold compared with open repair. Reports7 show decreased morbidity (eg, injury to the duodenum or ureter) and regression or resolution of perianeurysmal fibrosis with endovascular aneurysm repair.Our patient received urgent treatment with endovascular aneurysm repair using a 28 × 90-mm aortic graft (AFX Endovascular Graft; Endologix) with 20 × 30-mm iliac limbs. A completion angiogram (Figure 2) showed adequate graft position with no aneurysm and no evidence of an endoleak. The patient had an uneventful postoperative course with resolution of the symptoms.Completion angiogram of deployed endograft in infrarenal aorta and excluded aneurysm.

Surgery

An elderly man presented to the emergency department with a 1-month history of new-onset, persistent lower abdominal and flank pain. The pain was sharp and constant with intermittent radiation to the back and associated anorexia with a 10-kg weight loss. He did not report any previous abdominal surgery. The patient stated that he had not had any procedures with intravascular instrumentation in the past year, dental cleanings, intravenous drug use, cutaneous abscesses, or recent trauma. Physical examination revealed he was afebrile and in normal sinus rhythm; there was minimal epigastric abdominal tenderness without signs of peritonitis and no palpable masses. Femoral pulses were palpable and symmetric. Laboratory examination revealed mild anemia (hematocrit, 35% [to convert to a proportion of 1.0, multiply by 0.01]), no leukocytosis, and an elevated erythrocyte sedimentation rate (71 mm/h). Blood and urine cultures were negative for organisms. A computed tomographic (CT) angiogram showed asymmetric attenuation surrounding the infrarenal aorta (Figure 1). On comparison, a CT scan that was performed 6 months before presentation had identified no aneurysmal disease.Computed tomographic scan with arterial phase intravenous contrast with asymmetric attenuation surrounding the infrarenal aorta.

what is your diagnosis?

What is your diagnosis?

Mycotic aneurysm

Infrarenal aortitis due to diverticulitis

Pseudoaneurysm

Inflammatory abdominal aortic aneurysm

d

male

71-80

original

https://jamanetwork.com/journals/jama/fullarticle/2441236

A woman in her 50s presented for evaluation of a growing, painful scar on the right side of her abdomen. She reported having a rectangular area of discolored skin for the past 10 years that developed as a result of a complication during an interventional radiology procedure for treatment of a splenic aneurysm. Two months prior to presentation this lesion became painful and enlarged, without improvement with triamcinolone cream or oral antibiotics. She also reported recent fevers, night sweats, nausea, and fatigue. She denied international travel, drug use, incarceration, and high-risk sexual behavior.The patient had a history of uterine cancer at age 25, for which she underwent hysterectomy and chemotherapy. She also had a history of breast cancer in her 40s, for which she underwent lumpectomy and tamoxifen therapy. She had undergone surgical excision of a gastric polyp in her early 50s. She had no history of radiation therapy.On physical examination she was well-appearing and afebrile, with normal vital signs. There was a 12 × 7–cm indurated pink and deep purple plaque on the right side of the abdomen, with 2 focal areas of ulceration (Figure). Extending outward from this plaque were finger-like projections of purple subcutaneous papules. Inferior to the plaque there was an approximately 3-cm, tender, orange-to-yellow patch. No lymphadenopathy or other skin lesions were noted.Obtain bacterial and mycobacterial cultures of ulcerated area and pursue treatment with a longer course of antibioticsObtain a computed tomography (CT) scan of the chest and abdomenCheck the patient’s human immunodeficiency virus (HIV) status What Would You Do Next?

Obtain bacterial and mycobacterial cultures of ulcerated area and pursue treatment with a longer course of antibiotics

Perform a skin biopsy for histopathologic examination

Obtain a computed tomography (CT) scan of the chest and abdomen

Check the patient’s human immunodeficiency virus (HIV) status

Cutaneous angiosarcoma

C

Obtain a computed tomography (CT) scan of the chest and abdomen

B. Perform a skin biopsy for histopathologic examinationThe key clinical feature is the patient’s report of a growing, painful skin lesion that has a bruise-like appearance at the periphery. A skin biopsy will reveal the correct diagnosis of cutaneous angiosarcoma. Culture of the lesion might grow colonizing bacteria but will not reach the correct diagnosis. CT scan of the chest and abdomen may be performed to evaluate for metastatic disease after diagnosis is confirmed by biopsy. HIV status should be checked in patients with Kaposi sarcoma, which may present similarly to cutaneous angiosarcoma.Angiosarcoma is an aggressive soft-tissue sarcoma that has a low incidence, accounting for approximately 1.6% of soft-tissue sarcomas in the United States.1 Angiosarcomas uniformly have a poor prognosis, with studies reporting 5-year survival of approximately 30% to 45%.1-3 Prognosis depends on the tumor site and patient age, with tumors of the head and neck having a lower survival compared with tumors of other sites.4Clinically, cutaneous angiosarcomas present as tender, violaceous-to-ecchymotic patches or plaques that grow rapidly. They typically develop in sites of prior radiation, sites of chronic lymphedema, or spontaneously on the head and neck of elderly individuals.1 Angiosarcomas range in size from less than 1 cm to more than 35 cm, with some studies reporting a worse prognosis for larger tumors.3,4 Postirradiation angiosarcoma tends to develop 5 to 10 years after radiation therapy but can also develop decades later.3,5 Stewart-Treves is a syndrome in which angiosarcoma develops within areas of chronic lymphedema.Skin biopsy is necessary to diagnose cutaneous angiosarcoma and reveals a blood vessel proliferation lined by atypical endothelial cells with prominent extravasation of erythrocytes.6 Angiosarcomas stain positively for endothelial markers including CD31, CD34, vascular endothelial growth factor, von Willebrand factor, and Ulex europaeus agglutinin 1.3,6 Immunohistochemical stains may be necessary to rule out other tumors.6 Differentiating angiosarcoma from Kaposi sarcoma can be challenging, but Kaposi sarcoma routinely stains positively for human herpesvirus 8, whereas angiosarcoma does not.3,6Angiosarcomas tend to metastasize hematogenously, most often to the lungs, but lymph node metastasis also occurs.3,7 The workup for metastatic disease includes CT scan of the chest and abdomen. The utility of sentinel lymph node biopsy for this tumor type is unknown.3First-line treatment for angiosarcoma is complete surgical excision. However, negative surgical margins are difficult to obtain, as tumors are often clinically ill-defined and can be large. Research exploring neoadjuvant and adjuvant radiation and chemotherapy is ongoing, but studies have mixed results and are limited by small sample sizes.3 Adjuvant radiation therapy is often recommended for non–radiation-induced angiosarcomas, with improved local disease control and overall survival.3Chemotherapy regimens typically include doxorubicin or paclitaxel. Paclitaxel has antiangiogenic properties and radiation-sensitizing effects.8 One study showed 5-year survival of 55.6% among patients who received chemotherapy with docetaxel or paclitaxel and radiation compared with 8.6% among patients who underwent standard treatment comprising surgical excision with adjuvant radiation therapy.9 The patients who received maintenance chemotherapy also had improved survival compared with those who did not. Targeted chemotherapies including sorafenib, a multikinase inhibitor, and bevacizumab, a monoclonal antibody to vascular endothelial growth factor A, are being evaluated.3,10 Despite recent advances, angiosarcoma remains an aggressive cancer with a poor prognosis.The patient was referred for chemotherapy, radiation therapy, and surgery. Workup for metastatic disease was negative. She received neoadjuvant paclitaxel and radiation prior to wide local excision with margins free of tumor. She is being monitored with routine CT scans every 2 to 3 months.

General

A woman in her 50s presented for evaluation of a growing, painful scar on the right side of her abdomen. She reported having a rectangular area of discolored skin for the past 10 years that developed as a result of a complication during an interventional radiology procedure for treatment of a splenic aneurysm. Two months prior to presentation this lesion became painful and enlarged, without improvement with triamcinolone cream or oral antibiotics. She also reported recent fevers, night sweats, nausea, and fatigue. She denied international travel, drug use, incarceration, and high-risk sexual behavior.The patient had a history of uterine cancer at age 25, for which she underwent hysterectomy and chemotherapy. She also had a history of breast cancer in her 40s, for which she underwent lumpectomy and tamoxifen therapy. She had undergone surgical excision of a gastric polyp in her early 50s. She had no history of radiation therapy.On physical examination she was well-appearing and afebrile, with normal vital signs. There was a 12 × 7–cm indurated pink and deep purple plaque on the right side of the abdomen, with 2 focal areas of ulceration (Figure). Extending outward from this plaque were finger-like projections of purple subcutaneous papules. Inferior to the plaque there was an approximately 3-cm, tender, orange-to-yellow patch. No lymphadenopathy or other skin lesions were noted.Obtain bacterial and mycobacterial cultures of ulcerated area and pursue treatment with a longer course of antibioticsObtain a computed tomography (CT) scan of the chest and abdomenCheck the patient’s human immunodeficiency virus (HIV) status

what would you do next?

What would you do next?

Check the patient’s human immunodeficiency virus (HIV) status

Obtain a computed tomography (CT) scan of the chest and abdomen

Perform a skin biopsy for histopathologic examination

Obtain bacterial and mycobacterial cultures of ulcerated area and pursue treatment with a longer course of antibiotics

b

female

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2441241

A 32-year-old woman presented with headaches of increasing severity that began approximately 3 years ago. The headaches were severe enough to interfere with daily activities, occurred several times weekly, and were associated with nausea, vomiting, photophobia, and sensitivity to noise. She had no focal neurological symptoms. Funduscopic and neurologic examination results were normal. A diagnosis of migraine headaches was made, but therapeutic trials with nonsteroidal anti-inflammatory drugs and sumatriptan were unsuccessful. Routine blood counts were normal except for a platelet count of 665 × 103/μL (Table).The elevated platelet count was most likely caused by a myeloproliferative disorderThe elevated platelet count most likely resulted from a transient and not reproducible findingThe elevated platelet count was most likely caused by stress of migraine attacksThe elevated platelet count was most likely caused by myelodysplastic syndrome How Do You Interpret These Test Results?

The elevated platelet count was most likely caused by a myeloproliferative disorder

The elevated platelet count most likely resulted from a transient and not reproducible finding

The elevated platelet count was most likely caused by stress of migraine attacks

The elevated platelet count was most likely caused by myelodysplastic syndrome

B

The elevated platelet count most likely resulted from a transient and not reproducible finding

Platelet counts are obtained using automated hematology analyzers as part of a complete blood cell count (CBC). Automated platelet counting is obtained using one of several methods: nonoptical electronic aperture impedance (the original Coulter principle) or, to better discriminate platelets from other similar-sized particles in whole blood, techniques that use optical light scatter, fluorescence, or flow cytometry.1 The Medicare cost of a CBC with platelet count is $56 (http://www.cms.gov/medicare-coverage-database/overview-and-quick-search.aspx). Time-consuming manual counting of platelets may be used as a reference method or to confirm abnormal platelet counts (especially thrombocytopenia) reported by automated instruments.There is substantial age-related variability in platelet counts. As compared with newborns, platelet counts are reduced by as much as 35% in older men and 25% in older women.2 Normal ranges for platelet counts are not currently reported by clinical laboratories to be different for older vs younger people. Thus, some elevated levels of platelets in older people may be age related and may not represent a pathologic disease state. In addition, platelet counts are highly heritable.3 Reference ranges for normal platelet counts vary even between the inhabitants of secluded communities (eg, several villages within a single area of Sardinia).4 Therefore, mildly elevated platelet counts may be due to older age or ethnicity.The patient’s platelet count of 665 000 is high enough to represent significant thrombocytosis, irrespective of the age, sex, and ethnicity differences in normal platelet counts. However, in a cohort of healthy individuals from the general population (≥5-y follow-up), fewer than 10% of those found to have thrombocytosis had confirmation of high platelet counts on CBC retesting 8 months later.5 However, in this patient, subsequent platelet counts confirmed thrombocytosis.The major causes of thrombocytosis can be divided into 2 groups: reactive (or secondary) thrombocytosis and clonal thrombocytosis. Reactive causes of thrombocytosis include transient processes such as acute blood loss, recovery (rebound) from thrombocytopenia, acute infection or inflammation, extreme physical exertion, or other stress. Sustained forms of reactive thrombocytosis include iron deficiency, hemolytic anemia, asplenia (eg, after splenectomy or autoinfarction of the spleen in sickle cell disease), cancer, chronic inflammatory or infectious diseases, and rare drug reactions.6 Reactive thrombocytosis is not harmful per se, even with extremely high platelet counts (eg, platelet counts can be >1 million in patients with active inflammatory bowel disease). However, the underlying etiology of thrombocytosis (eg, malignancy, chronic connective tissue disease, chronic infection) can be associated with increased risk of adverse outcomes. Recent evidence, however, suggests that very high platelet counts may contribute to cancer progression.7Among individuals with thrombocytosis, 80% to 90% are known to have reactive thrombocytosis.8Clonal thrombocytosis is the second most common category and is typically due to a chronic myeloproliferative neoplasm (MPN). The classical MPNs are related diseases of the bone marrow pluripotent hematopoietic stem cell, and include polycythemia vera, essential thrombocythemia, myelofibrosis, and chronic myelogenous leukemia. Although thrombocytosis is most prominent in essential thrombocythemia, the other MPNs are associated with varying degrees of thrombocytosis. Other bone marrow stem cell disorders, including some myelodysplastic syndromes, may be associated with thrombocytosis. These clonal disorders are associated with adverse events related to the thrombocytosis, including thrombotic, vascular, and bleeding complications and may therefore need to be controlled.When first evaluating a patient with thrombocytosis, the thrombocytosis should first be confirmed by repeating the platelet count assessment on a different day. Examining the peripheral blood smear is inexpensive and informative: the presence of giant platelets may be a clue to the presence of a bone marrow disorder such as an MPN. Once thrombocytosis has been confirmed, clinicians should investigate secondary causes of thrombocytosis. In some cases the underlying disorder is clear (eg, inflammatory bowel disease), but in other cases, the underlying disorder may be difficult to identify (eg, cancer, iron deficiency). The importance of identifying a cause for reactive thrombocytosis is that its early detection and prompt treatment may prove critical; the thrombocytosis is mainly just a marker for the underlying disorder in these patients and does not by itself require treatment.In this patient, repeat platelet counts remained elevated and no cause for a reactive thrombocytosis was identified. Establishing the diagnosis of a primary clonal thrombocytosis, such as one of the MPNs, consists of combining clinical findings (eg, abnormal blood counts, presence of splenomegaly, unusual thrombotic and vascular complications) and pathological findings on bone marrow aspirate and biopsy specimens. Specific somatic, typically not inheritable, mutations (determined in blood or bone marrow samples) are diagnostic markers for the MPNs. Such mutations affect only the hematopoietic stem cells and cause relatively autonomous proliferation of platelet and/or other blood cell precursors in the bone marrow. These include the janus kinase 2 (JAK2 V617F), MPL W515, JAK2 exon 12, and calreticulin (CALR) mutations.9 Chronic myelogenous leukemia, which occasionally presents with only thrombocytosis (without leukocytosis), is associated with the diagnostic BCR-ABL gene rearrangement mutation. Only about 10% to 15% of patients who meet current clinical diagnostic criteria for an MPN do not have one of these diagnostic mutations. In this case, the patient had a CALR mutation.Migraine headaches, among other cerebrovascular complications, have been linked to the MPNs, especially essential thrombocythemia.10 This patient was diagnosed as having essential thrombocythemia on the basis of the CALR mutation and characteristic bone marrow pathology. Hydroxyurea was initiated to reduce the platelet count. When her platelet count normalized within 2 weeks, the migraine headaches resolved.Slightly elevated platelet counts are often not reproducible on repeat testing.Normal reference ranges of platelet counts have a heritable determinant and may be slightly shifted up or down as a function of ethnicity, age, and sex.The most common cause of an elevated platelet count is a reactive thrombocytosis caused by a wide variety of acute and chronic underlying conditions.Clonal thrombocytosis is most commonly due to a myeloproliferative neoplasm and these forms of thrombocytosis can be complicated by serious thrombotic and bleeding events.Thrombocytosis caused by a myeloproliferative neoplasm is based on clinical and pathological findings; as many as 90% of such cases are associated with a diagnostic somatic mutation, most commonly the JAK2 V617F or CALR mutations.

Diagnostic

A 32-year-old woman presented with headaches of increasing severity that began approximately 3 years ago. The headaches were severe enough to interfere with daily activities, occurred several times weekly, and were associated with nausea, vomiting, photophobia, and sensitivity to noise. She had no focal neurological symptoms. Funduscopic and neurologic examination results were normal. A diagnosis of migraine headaches was made, but therapeutic trials with nonsteroidal anti-inflammatory drugs and sumatriptan were unsuccessful. Routine blood counts were normal except for a platelet count of 665 × 103/μL (Table).The elevated platelet count was most likely caused by a myeloproliferative disorderThe elevated platelet count most likely resulted from a transient and not reproducible findingThe elevated platelet count was most likely caused by stress of migraine attacksThe elevated platelet count was most likely caused by myelodysplastic syndrome

how do you interpret these test results?

How do you interpret these results?

The elevated platelet count was most likely caused by myelodysplastic syndrome

The elevated platelet count was most likely caused by stress of migraine attacks

The elevated platelet count most likely resulted from a transient and not reproducible finding

The elevated platelet count was most likely caused by a myeloproliferative disorder

c

female

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2293161

A man in his 20s was referred to our department because of the presence of a sticky material around the underarm hair for approximately 1 year. The patient explained that he usually plays soccer and sweats abundantly. He did not apply deodorant or any other products in the underarm, and he ensured proper hygiene of the area. The lesions did not produce itching. Physical examination revealed creamy yellow concretions along several hair shafts, in both armpits, with strong axillary odor (Figure, A). These concretions did not disappear when cleansed with alcohol. Hair samples of the affected areas were sent for microscopy examination (Figure, B-D) and microbiologic culture. Treatment with antiseptic soap and a miconazole nitrate cream was initiated. After 2 weeks of treatment, the lesions had resolved and the patient had normal axillary hairs. Confirmation of the suspected diagnosis was made with the results of complementary tests.A, Clinical photograph of axillary hairs shows creamy yellow concretions along several axillary hairs. B, Direct microscopic examination of the hair shaft (original magnification ×40). C, Periodic acid–Schiff stain (original magnification ×400). D, Grocott silver stain (original magnification ×400). What Is Your Diagnosis?

Artifactual peripilar hair casts

Trichomycosis axillaris

Pediculosis axillaris

White piedra

B. Trichomycosis axillaris

B

Trichomycosis axillaris

Direct microscopic examination showed a discontinuous coating of hair shafts by a thick layer of adherent bacterial structures (Figure, B). These microorganisms were oriented perpendicularly to the main axis of the hair, showing autofluorescence. The bacteria stained on periodic acid–Schiff (Figure, C), Gram, and Grocott silver stains (Figure, D). The bacterial structures can be seen going into the hair cortex. Examination with 20% hydrogen peroxide showed structures with mucinous appearance. Microbiology studies in agar blood culture identified abundant colonies of Corynebacterium spp. The results of microbiological tests confirmed the clinical diagnosis of trichomycosis axillaris.The patient came back after 2 weeks without relapse of the infectious process. He was informed of preventive measures to avoid recurrences and has been free of the condition for 6 months.Trichomycosis axillaris (TA) is a bacterial colonization of hairs commonly affecting the axillae, and sometimes the pubic area. It is characterized by the presence of concretions along the hair shafts, clinically observed as yellow, and rarely as red or black nodules.1,2 The pathogenic microorganism is a corynebacterium. In earlier reported cases of TA, Corynebacterium tenuis was identified as the pathogenic microorganism.1,3,4 In a recent publication by Bonifaz et al,5 the most common organism reported was Corynebacterium spp in 56 cases of TA, but different taxonomic species were identified. Kimura et al2 described a recent case caused by Corynebacterium propinquum.The diagnosis is clinical, by means of the identification of hair concretions. These concretions derive from bacterial colonization along the hair shaft containing dried apocrine sweat with a cementing substance generated by the bacteria.5 Microbiology laboratories can confirm the diagnosis by examination of hairs with hydrogen peroxide 20% solution and by growing Corynebacterium in agar blood culture. The bacteria show positive autofluorescence, as well as positivity for periodic acid–Schiff, Gram, and Grocott silver stains. In our case, remarkable invasion of the hair cortex by bacterial structures was observed, in contrast with the majority of reported cases, which describe involvement of hair shafts with keratin damage but respecting the hair cortex.6,7The treatment is based on shaving the hair in the axillary area and maintaining appropriate daily hygiene. In some cases, the use of topical antibiotics can be useful.5 Corynebacterium infections are related to excessive sweating; for this reason, roll-on deodorants containing an aluminum chloride solution (15%-20%) may be used for treatment and prevention.6,8Infection by a corynebacterium can produce 2 other different diseases, erythrasma and pitted keratolysis (PK). Erythrasma is a chronic infection of underarm or inguinal skin, presenting with brown symmetric patches. Pitted keratolysis is a condition confined to the plantar stratum corneum that confers a punctate appearance and a “rotten” odor.8Some patients with excessive sweating present the so-called corynebacterial triad, that is, the simultaneous presence of TA, erythrasma, and PK. Rho et al8 published a prospective study evaluating the prevalence of erythrasma and TA in Korean soldiers with PK during a period of 2 years. The most prevalent coexistence was with erythrasma, followed by simultaneous TA and PK; the coexistence of the 3 diseases was present in 13% of the patients.We have herein reported a case of TA confirmed by microbiological and microscopy findings, with atypical involvement of the hair cortex. The prevalence of this condition is likely underestimated because it may be chronic and/or asymptomatic and not come to medical attention. The name “trichomycosis” is misleading because this is not a fungal infection; this entity should thus be called trichobacteriosis.1,5

Dermatology

A man in his 20s was referred to our department because of the presence of a sticky material around the underarm hair for approximately 1 year. The patient explained that he usually plays soccer and sweats abundantly. He did not apply deodorant or any other products in the underarm, and he ensured proper hygiene of the area. The lesions did not produce itching. Physical examination revealed creamy yellow concretions along several hair shafts, in both armpits, with strong axillary odor (Figure, A). These concretions did not disappear when cleansed with alcohol. Hair samples of the affected areas were sent for microscopy examination (Figure, B-D) and microbiologic culture. Treatment with antiseptic soap and a miconazole nitrate cream was initiated. After 2 weeks of treatment, the lesions had resolved and the patient had normal axillary hairs. Confirmation of the suspected diagnosis was made with the results of complementary tests.A, Clinical photograph of axillary hairs shows creamy yellow concretions along several axillary hairs. B, Direct microscopic examination of the hair shaft (original magnification ×40). C, Periodic acid–Schiff stain (original magnification ×400). D, Grocott silver stain (original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Pediculosis axillaris

Trichomycosis axillaris

Artifactual peripilar hair casts

White piedra

b

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2301156

A healthy teenaged boy was seen with a papular eruption on the trunk and legs of 3 months’ duration. He had initially developed lesions on his legs, which then spread to his neck, chest, and buttocks. This eruption was asymptomatic, and the patient reported no history of vesiculation. His mother noted minimal evolution of the lesions, except for recent flattening of those on the legs. Physical examination showed numerous discrete (1 to 3 mm) smooth brown papules concentrated on the neck, chest, anterior and lateral thighs, and buttocks (Figure 1). Several lesions had a positive Darier sign (Figure 1A).A, Multiple small brown papules of the chest. Localized erythema developed around several lesions after firm stroking. B, Scattered small brown papules of the lateral thigh.There was no family history of similar lesions. A punch biopsy of a papule on the left thigh was performed, and the specimen was submitted for pathological review. What Is Your Diagnosis?

Eruptive vellus hair cysts

Urticaria pigmentosa

Eruptive syringoma

Lichen nitidus

C. Eruptive syringoma

C

Eruptive syringoma

Microscopic examination revealed multiple small cysts and ducts embedded in a fibrous stroma within the superficial dermis. These findings are shown in Figure 2.Biopsy specimen obtained from the thigh. Shown is a tumor in the superficial dermis composed of interconnecting eccrine strands and ducts dispersed in fibrous stroma. On high power (hematoxylin-eosin, original magnification ×200), the ducts appear to be lined by 2 layers of flattened cuboidal cells. There is a cuticle lining the lumina of a few of the ducts, one of which contains eosinophilic granular debris. Some of the ducts are associated with an epithelial strand, creating the tadpole shape characteristic of this lesion.Syringomas are benign neoplasms of intradermal eccrine ducts, which are most commonly seen in peripubertal girls and adult women.1,2 Four clinical variants exist,2 including localized, disseminated or eruptive, trisomy 21 associated,3 and familial forms. Syringomas have also been associated with Marfan syndrome and Ehlers-Danlos syndrome.1 Clinically, syringomas typically are seen as small skin-colored to slightly hyperpigmented asymptomatic papules on the face, particularly in the infraorbital region.1Generalized eruptive syringoma, a less common variant, is hypothesized to be secondary to inflammation, resulting in reactive gland proliferation.2,4 These lesions tend to appear in successive crops on anterior body surfaces, most often involving the neck, axillae, chest, abdomen, and genital region.2,5 The clinical presentation is often not diagnostic, and histopathological examination may be necessary for definitive diagnosis.2,5Rare clinical variants of eruptive syringomas include a milium-like syringoma6 and a form mimicking urticaria pigmentosa.7,8 In the milium-like variant, the milium structure has been shown to be of eccrine duct origin.6 Syringomas resembling urticaria pigmentosa have been found to contain increased numbers of mast cells.2,7,8Histologically, syringomas appear as well-circumscribed cystic lesions in the superficial dermis.2 Two flattened layers of epithelial cells, often with pink or pale cytoplasm,2 form nests and tubules2,5 surrounded by a dense and collagenous stroma.9 Cells comprising the tubules are generally of ductal differentiation and surround a central lumen of amorphous debris.5 The tubules often contain a comma-like tail,1 reminiscent of a tadpole.9 A histological variant known as clear cell syringoma is associated with diabetes mellitus and is identified by increased glycogen content of cells that make up the ductal epithelium.2,5Although spontaneous resolution of eruptive syringoma has been reported,1 treatment of this condition is often unsatisfactory.9,10 Therapeutic options include destructive methods such as dermabrasion, excision, laser resurfacing, cryotherapy, and electrosurgery.1,9 Topical and oral retinoids1 and topical atropine10 have also been tried, with varying degrees of success.2,9

Dermatology

A healthy teenaged boy was seen with a papular eruption on the trunk and legs of 3 months’ duration. He had initially developed lesions on his legs, which then spread to his neck, chest, and buttocks. This eruption was asymptomatic, and the patient reported no history of vesiculation. His mother noted minimal evolution of the lesions, except for recent flattening of those on the legs. Physical examination showed numerous discrete (1 to 3 mm) smooth brown papules concentrated on the neck, chest, anterior and lateral thighs, and buttocks (Figure 1). Several lesions had a positive Darier sign (Figure 1A).A, Multiple small brown papules of the chest. Localized erythema developed around several lesions after firm stroking. B, Scattered small brown papules of the lateral thigh.There was no family history of similar lesions. A punch biopsy of a papule on the left thigh was performed, and the specimen was submitted for pathological review.

what is your diagnosis?

What is your diagnosis?

Lichen nitidus

Eruptive vellus hair cysts

Eruptive syringoma

Urticaria pigmentosa

c

male

11-20

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2319714

A woman in her 50s presented with diffuse blue to slate-gray patches on her entire face immediately after administration of Q-switched Nd:YAG laser toning (Figure 1A). These pigmented lesions corresponded exactly to areas that had previously received laser treatment. Her history was remarkable for rheumatoid arthritis treated with oral gold salts 15 years ago, but the total dosage of gold salts could not be determined. Rechallenge with the original Q-switched Nd:YAG laser was administered on the right forearm, and a similar slate-gray macule developed immediately (Figure 1B). A skin biopsy specimen of the lesion on the right side of the woman’s face was obtained, and histopathologic evaluation was conducted.A, Diffuse blue to slate-gray patches developed on the face, corresponding exactly to areas that had previously received laser treatment. B, A rechallenge test administered on the right forearm with the original Q-switched Nd:YAG laser yielded a similar slate-gray macule (arrowhead). What Is Your Diagnosis?

Postinflammatory hyperpigmentation

Argyria

Chrysiasis

Tattoo pigmentation

C. Chrysiasis

C

Chrysiasis

The biopsy specimen demonstrated black particulate deposits in the reticular and papillary dermis predominantly in a superficial perivascular distribution (Figure 2). No inflammatory response was observed, and epidermal melanin pigmentation appeared normal.Histopathologic testing demonstrated black particulate deposits, predominantly in a superficial perivascular distribution (hematoxylin-eosin, original magnification ×400).Chrysiasis is a rare adverse effect among individuals who have received long-term gold salt therapy. Chrysiasis typically begins with mauve discoloration of the periorbital region, which deepens gradually into a blue to slate-gray color and extends to other sun-exposed areas.1 Laser-induced localized chrysiasis has also been reported2-4 to occur immediately after administration of Q-switched ruby laser, alexandrite laser, and Nd:YAG laser.Gold salts were used widely as a disease-modifying antirheumatic drug for treatment of rheumatoid arthritis in the 20th century, but the use declined with the approval of new drugs. The common cutaneous adverse effects of gold salt therapy include general pruritus, nonspecific maculopapular eruption, lichen planus–like dermatitis, pityriasis rosea–like dermatitis, and oral ulcers.5 Chrysiasis seems to be a rare cutaneous discoloration, mainly in sun-exposed areas, that may occur with cumulative gold salt doses as low as 1.05 g.1 In addition to skin, gold salt concentrates in the lens, cornea, and reticuloendothelial system.The pathomechanism of chrysiasis is not fully understood; however, the cumulative doses of gold salts and UV light have been suggested to play important roles. Trotter et al2 proposed that Q-switched laser can produce high peak power generated by a short pulse duration and development of an extremely high temperature that directly alters physiochemical properties in dermal gold deposits from crystalline to elemental gold, resembling colloid gold. The color of the colloid gold in solutions is blue-purple, which is similar to the pigmentation associated with chrysiasis. Yun et al3 observed that laser-induced chrysiasis in patients who receive therapy with gold salts is primarily an irradiance-dependent rather than a fluence-dependent phenomenon.The diagnosis of chrysiasis can be made primarily on clinical grounds in most cases in the setting of a history of gold salt use and characteristic facial lesions. In suspicious cases, we suggest that a rechallenge test with Q-switched laser may be considered in an unobvious site (as in Figure 1B) if a skin biopsy specimen cannot be obtained.The discoloration associated with chrysiasis can be disfiguring. Treatment remains limited but may be attempted with long-pulsed laser, 595-nm pulsed dye laser, or surgical excision if there are few lesions.3,4,6 Patients receiving gold salts should to be warned to avoid direct sunlight exposure to prevent progression of discoloration. We attempted treatments with pulsed dye laser and long-pulsed alexandrite laser, but the results were not satisfactory.It is important for clinicians to routinely screen patients for previous use of gold salt therapy before laser treatment, especially those who are older than 40 years with a history of rheumatic disease, to avoid this possibly irreversible adverse effect.

Dermatology

A woman in her 50s presented with diffuse blue to slate-gray patches on her entire face immediately after administration of Q-switched Nd:YAG laser toning (Figure 1A). These pigmented lesions corresponded exactly to areas that had previously received laser treatment. Her history was remarkable for rheumatoid arthritis treated with oral gold salts 15 years ago, but the total dosage of gold salts could not be determined. Rechallenge with the original Q-switched Nd:YAG laser was administered on the right forearm, and a similar slate-gray macule developed immediately (Figure 1B). A skin biopsy specimen of the lesion on the right side of the woman’s face was obtained, and histopathologic evaluation was conducted.A, Diffuse blue to slate-gray patches developed on the face, corresponding exactly to areas that had previously received laser treatment. B, A rechallenge test administered on the right forearm with the original Q-switched Nd:YAG laser yielded a similar slate-gray macule (arrowhead).

what is your diagnosis?

What is your diagnosis?

Argyria

Postinflammatory hyperpigmentation

Chrysiasis

Tattoo pigmentation

c

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2319719

A woman in her early 40s with a history of recurrent meningioma of the right sphenoid wing after tumor resections, followed by adjuvant radiation, presented with fluctuating vision in the right eye for several months. On examination, her best-corrected visual acuity was 20/20 OD and 20/20 OS. An external examination revealed ptosis of the right upper eyelid covering 40% of the surface of the eye. In each eye, the pupil, intraocular pressure, motility, and confrontational visual field were normal. An anterior segment examination revealed mild nuclear sclerotic cataracts in both eyes. A dilated fundus examination of the right eye was notable for revealing infarcts in several nerve fiber layers along the arcades and nasal to the optic disc and a few microaneurysms nasal to the optic disc. Fluorescein angiography of the right eye (Figure, A) revealed multiple areas of staining nasal to the nerve and inferotemporal to the nerve and to the areas of pinpoint leakage within the macula. No abnormalities were noted during the fundus examination of her left eye. She was observed and followed up every 4 months. One year later, the patient complained of a 1-month history of gradually worsening vision in the right eye. Her visual acuity was 20/400 OD and 20/20 OS. A fundus examination of the right eye revealed thickening in the macular region. Optical coherence tomography of the right eye (Figure, B) revealed a central macular thickness of 454 μm and the presence of subretinal fluid in the subfoveal region.A, Fluorescein angiography of the right eye illustrating areas of staining nasal to the nerve and inferotemporal to the nerve and to the areas of pinpoint leakage within the macula. B, Optical coherence tomography revealed a central macular thickness of 454 μm and the presence of subretinal fluid. What Would You Do Next?

A. Observation

B. Macular laser photocoagulation

C. Intravitreal anti–vascular endothelial growth factor therapy

D. Intravitreal corticosteroid therapy

Radiation retinopathy

C

C. Intravitreal anti–vascular endothelial growth factor therapy

Radiation retinopathy is a progressive, delayed-onset effect of exposure to radiation caused by damage to the retinal vasculature. Radiation retinopathy typically occurs when the total radiation dose exceeds 30 to 35 Gy and becomes apparent 12 to 24 months after receiving radiation.1 The management of radiation maculopathy is often challenging. Several forms of treatment for macular edema due to radiation retinopathy have been described, including focal laser photocoagulation, intravitreal anti–vascular endothelial growth factor therapy, intravitreal triamcinolone acetonide, and photodynamic therapy.A few forms of treatment for radiation retinopathy–related macular edema may be effective initially; however, their treatment effect is often not sustained. Kinyoun et al2 reported the results of macular photocoagulation for radiation maculopathy after external beam radiotherapy in 12 eyes of 8 patients. At a mean final follow-up of 39 months, 8 patients experienced improved Snellen acuity of at least 1 line (mean acuity of 20/100), although 4 eyes were treated more than once.2 Subsequently, Hykin et al3 performed a retrospective review comparing 19 patients with radiation-induced macular edema secondary to radioactive scleral plaque treated with macular photocoagulation with 23 similar patients followed by observation alone. The studies found that visual acuity improved by at least 1 Snellen line in 42% of patients treated with macular photocoagulation and in no observed patients initially at 6 months. However, no significant difference in visual acuity between the 2 groups was found after 2 years of follow-up.3 These studies2,3 demonstrate the limited visual benefit and the lack of durability of macular photocoagulation for the treatment of radiation retinopathy–related macular edema. The use of intravitreal triamcinolone has also been investigated. Shields et al4 reported in a prospective, nonrandomized, single-center case series of 31 patients with visually symptomatic radiation-induced maculopathy that after 1 intravitreal injection of 4.0 mg of triamcinolone, visual acuity was the same or improved in 91% of patients at 1 month. However, after 6 months, visual acuity worsened in 55% of patients, and this was related to either the reaccumulation of foveal edema or the development of retinal atrophy.4 Thus, the benefit of a single injection of intravitreal triamcinolone seemed to be short lived. Although multiple sequential injections of intravitreal triamcinolone might provide continued visual recovery, the adverse effects of glaucoma and cataract can be problematic.More recently, intravitreal bevacizumab has been investigated as a treatment option. Mason et al,5 in a retrospective case series, reported a decrease in mean foveal thickness in 10 patients treated with intravitreal bevacizumab and found an improvement in mean visual acuity from 20/100 to 20/86 at 6 weeks. Gupta and Muecke6 further illustrated the utility of intravitreal bevacizumab in improving vision in younger patients when an injection was given 1 week after the development of macular edema. Recently, Shah et al7 reported positive results in a retrospective nonrandomized comparative study of intravitreal bevacizumab injections at 4-month intervals after plaque radiotherapy for uveal melanomas in 292 patients. Patients in the bevacizumab-treated group had better visual acuity outcomes than did patients in the control group (15% of patients in the bevacizumab-treated group vs 28% of patients in the control group with best-corrected visual acuity worse than 5/200) and significantly reduced rates of macular edema detected on optical coherence tomographic images (25% of patients in the bevacizumab-treated group vs 40% of patients in the control group).7 Intravitreal bevacizumab may be useful in the treatment of radiation retinopathy–related macular edema.The patient had received a total of 54 Gy of external beam radiation, which put her at a moderately high risk of radiation retinopathy. The patient is relatively young and had macular edema for only a short duration of time on presentation. She was treated with 1 injection of intravitreal bevacizumab, which resulted in a reduction in central macular thickness from 454 to 222 μm and a resolution of subretinal fluid 1 month after injection with normalization of the foveal contour. She was subsequently followed up monthly, and her visual acuity improved from 20/400 to 20/70 at the 6-month follow-up.

Ophthalmology

A woman in her early 40s with a history of recurrent meningioma of the right sphenoid wing after tumor resections, followed by adjuvant radiation, presented with fluctuating vision in the right eye for several months. On examination, her best-corrected visual acuity was 20/20 OD and 20/20 OS. An external examination revealed ptosis of the right upper eyelid covering 40% of the surface of the eye. In each eye, the pupil, intraocular pressure, motility, and confrontational visual field were normal. An anterior segment examination revealed mild nuclear sclerotic cataracts in both eyes. A dilated fundus examination of the right eye was notable for revealing infarcts in several nerve fiber layers along the arcades and nasal to the optic disc and a few microaneurysms nasal to the optic disc. Fluorescein angiography of the right eye (Figure, A) revealed multiple areas of staining nasal to the nerve and inferotemporal to the nerve and to the areas of pinpoint leakage within the macula. No abnormalities were noted during the fundus examination of her left eye. She was observed and followed up every 4 months. One year later, the patient complained of a 1-month history of gradually worsening vision in the right eye. Her visual acuity was 20/400 OD and 20/20 OS. A fundus examination of the right eye revealed thickening in the macular region. Optical coherence tomography of the right eye (Figure, B) revealed a central macular thickness of 454 μm and the presence of subretinal fluid in the subfoveal region.A, Fluorescein angiography of the right eye illustrating areas of staining nasal to the nerve and inferotemporal to the nerve and to the areas of pinpoint leakage within the macula. B, Optical coherence tomography revealed a central macular thickness of 454 μm and the presence of subretinal fluid.

what would you do next?

What would you do next?

A. Observation

B. Macular laser photocoagulation

D. Intravitreal corticosteroid therapy

C. Intravitreal anti–vascular endothelial growth factor therapy

d

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2363071

A 10-year-old boy presented to a cornea subspecialty clinic with a 6-month history of intermittent redness, swelling, and itching of the right eye. He had seasonal allergies but was otherwise healthy. He had not been wearing his contact lenses since the episodes started. The patient’s symptoms persisted despite previous treatment regimens with topical corticosteroids for atopic conjunctivitis and topical antibiotics for staphylococcal blepharitis. Conjunctival cultures for bacteria or viruses (including adenovirus and herpes simplex virus) were negative.The patient’s visual acuity with eyeglasses was 20/20 OU. Findings from examination of the right eye were significant for lower eyelid follicles and mild conjunctival injection. A nontender preauricular lymph node was noted as well as a raised erythematous papule on the patient’s upper cheek (Figure 1A). Findings from examination of the skin revealed multiple raised papules on the right elbow and knee that were diagnosed as warts by the patient’s dermatologist (Figure 1B). These papules had been present for about 6 months and, despite the use of topical salicylic acid and cryotherapy, they continued to spread.External photograph of the patient's right eye at presentation. A, The photograph shows eyelid edema and erythema, conjunctival injection, and a raised inflamed papule on the upper cheek. B, Raised skin lesions on the patient’s elbow were visible at presentation.Continue giving the patient topical corticosteroids and/or cyclosporine What Would You Do Next?

Prescribe oral acyclovir

Continue giving the patient topical corticosteroids and/or cyclosporine

Prescribe oral cimetidine

Refer the patient to an allergist

Molluscum contagiosum

B

Continue giving the patient topical corticosteroids and/or cyclosporine

The key clinical feature in this case is the presence of multiple maculopapular skin lesions and chronic follicular conjunctivitis that did not respond to topical corticosteroid or antibiotic treatment. The combination of a cutaneous rash and conjunctivitis in children is most commonly due to allergic and/or atopic disease, herpes simplex virus infection, or molluscum contagiosum. The characteristics of the skin lesions can aid in the diagnosis. The patient’s signs and symptoms were limited to the right side (right eye, elbow, and knee), which is uncommon for atopic disease. Herpes simplex virus infection causes local characteristic periocular and perioral fluid-filled vesicles in clusters, with disseminated disease occurring only in severely immunocompromised individuals. Molluscum contagiosum skin lesions, on the other hand, are focal and umbilicated, as can be seen in our patient.Molluscum contagiosum is caused by a poxvirus that presents as focal dome-shaped skin papules, often with an umbilicated center. Lesions can be itchy and become intermittently inflamed. It is a common disease of childhood, often associated with atopy or immunodeficient states.1 It can involve any part of the body (except the palms and soles) because it is spread by direct skin-to-skin contact or autoinoculation after scratching a lesion. Each lesion contains live viruses in its central core. Thus, the disease is contagious until all lesions are gone, but autoinoculation can lead to the development of clusters of lesions.Diagnosis is clinical, especially in children, because excisional biopsy requires sedation. If a biopsy is performed, keratinocytes with cytoplasmic eosonophilic inclusion bodies (known as Henderson-Paterson bodies) are typically seen.2 Poxvirus particles can only be seen with electron microscopy.3 The only known host of molluscum contagiosum is humans. This fact limits our knowledge of the disease’s pathogenesis because the virus cannot be grown in cell culture or in an animal model of infection.Molluscum contagiosum is thought to be self-limited in immunocompetent children. Moreover, there is conflicting evidence of the efficacy of current therapeutic regimens, such as cryotherapy, curettage, oral cimetidine, topical cantharidin, podophyllotoxin, imiquimod, salicylic acid, or tretinoin.4 As such, the decision to treat molluscum contagiosum skin lesions is the result of a discussion with the patient’s parents or guardians as to the natural course of the disease and the potential adverse effects of each treatment option.Similarly, for unilateral chronic conjunctivitis due to molluscum contagiosum, no specific treatment recommendations exist other than removing any obvious molluscum eyelid lesions by excision or curettage. For cases in which no such lesions exist and the patient has been autoinoculating himself or herself by scratching skin lesions on other parts of the body, only supportive measures are traditionally used, such as topical corticosteroids and frequent lubrication. None of the destructive methods or topical agents listed above can be used safely in the periocular region. The typical chronicity of conjunctivitis and the persistent pruritus associated with molluscum contagiosum can lead to conjunctival scarring and ocular surface complications.Oral cimetidine is a histamine H2-receptor blocker with additional immunomodulatory properties that have been used with some success to treat molluscum contagiosum skin lesions that are refractory to topical therapies.5 Treatment efficacy of oral cimetidine correlates with the presence of atopic disease, with 75% of atopes responding to the treatment vs 14% of nonatopes.5Our patient was treated with oral cimetidine, 40 mg/kg/d, for 2 months. He experienced a single flare-up of his conjunctivitis during the first week of treatment and his eye has been uninflamed since then. The skin lesions on the patient’s elbow and knee also slowly resolved without using any other topical agents (Figure 2).Two months after treatment with oral cimetidine, the patient’s elbow lesions had almost resolved.

Ophthalmology

A 10-year-old boy presented to a cornea subspecialty clinic with a 6-month history of intermittent redness, swelling, and itching of the right eye. He had seasonal allergies but was otherwise healthy. He had not been wearing his contact lenses since the episodes started. The patient’s symptoms persisted despite previous treatment regimens with topical corticosteroids for atopic conjunctivitis and topical antibiotics for staphylococcal blepharitis. Conjunctival cultures for bacteria or viruses (including adenovirus and herpes simplex virus) were negative.The patient’s visual acuity with eyeglasses was 20/20 OU. Findings from examination of the right eye were significant for lower eyelid follicles and mild conjunctival injection. A nontender preauricular lymph node was noted as well as a raised erythematous papule on the patient’s upper cheek (Figure 1A). Findings from examination of the skin revealed multiple raised papules on the right elbow and knee that were diagnosed as warts by the patient’s dermatologist (Figure 1B). These papules had been present for about 6 months and, despite the use of topical salicylic acid and cryotherapy, they continued to spread.External photograph of the patient's right eye at presentation. A, The photograph shows eyelid edema and erythema, conjunctival injection, and a raised inflamed papule on the upper cheek. B, Raised skin lesions on the patient’s elbow were visible at presentation.Continue giving the patient topical corticosteroids and/or cyclosporine

what would you do next?

What would you do next?

Continue giving the patient topical corticosteroids and/or cyclosporine

Prescribe oral cimetidine

Prescribe oral acyclovir

Refer the patient to an allergist

a

male

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2432139

A 64-year-old man with coronary artery disease and an 80 pack-year smoking habit presented with 2 weeks of gait instability leading to frequent falls and 8 weeks of vertigo and double vision. He reported unintentional weight loss without fevers or decreased appetite. He denied any history of alcohol abuse. Medications included metoprolol and aspirin. On examination, he was alert and oriented and vital signs were normal; body mass index was 24. Neurologic examination revealed right eye heterotropia and nasal upshoot indicative of a fourth cranial nerve palsy (Figure 1A), left ptosis, flattening of the right nasolabial fold (Figure 1B), and bilateral restricted upgaze and ataxia (Video). Strength and reflexes were preserved. Results of a basic metabolic panel and complete blood cell count were normal. Screening for human immunodeficiency virus, Lyme disease, and drug use was negative. Contrast-enhanced magnetic resonance imaging (MRI) of the brain was unremarkable. Cerebrospinal fluid (CSF) sampling revealed elevated protein (75 mg/dL [reference range, 10-42]), lymphocyte predominant pleocytosis (21-66 cells/uL [reference range, 0-11]), and oligoclonal bands (OCBs). Pleural thickening was seen on routine chest radiography; chest computed tomography (CT) revealed mediastinal lymphadenopathy, subcentimeter pulmonary nodules, and calcified pleural plaques.A, Right fourth cranial nerve palsy. On adduction, the right eye turns upward. This finding (nasal upshoot) suggests the presence of a fourth nerve palsy. B, Mild left ptosis and flattening of the right nasolabial fold.Obtain a whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and paraneoplastic antibody evaluation What Would You Do Next?

Obtain evoked potentials

Obtain electromyography (EMG)

Check thiamine levels and start oral supplementation

Obtain a whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and paraneoplastic antibody evaluation

Anti-Ri antibody associated paraneoplastic neurologic disorder (PND)

D

Obtain a whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and paraneoplastic antibody evaluation

PND should be considered in any patient presenting with unexplained neurologic symptoms, particularly one whose age, smoking history, and imaging findings prompt concern for malignancy. Commercial laboratories routinely test for a limited set of antibodies associated with classic syndromes. A negative panel does not rule out PND, and clinical evaluation trumps antibody testing in treatment decisions. Early identification of underlying malignancy and timely initiation of tumor-directed and immunosuppressive therapies are imperative, as they may affect neurologic outcome.1An inflammatory CSF characterized by pleocytosis and elevated protein is typical of PND involving the central nervous system (CNS) but is not diagnostic.2 Classically associated with multiple sclerosis, OCBs may be found in any disorder that disrupts the blood-brain barrier. Evoked potentials can be useful in the diagnosis of subclinical multiple sclerosis but would not be helpful in this patient, whose clinical course and MRI findings are not consistent with this diagnosis.Symptoms of diplopia and ataxia should raise concern for Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome. Immunoglobulin G antibodies to GQ1b ganglioside are present in 85% of patients and can establish the diagnosis, but EMG helps differentiate MFS from mimics and is useful in antibody-negative patients.3 Areflexia—a classic feature of MFS—is absent in this patient, making option B incorrect.Patients with alcoholism or malnutrition are at risk of Wernicke encephalopathy, a complication of thiamine deficiency classically defined by a triad of gait ataxia, oculomotor dysfunction, and encephalopathy. A high index of suspicion could be warranted in this patient because few experience the complete triad, and failure to treat promptly can prove fatal.4 Thiamine is safe and effective, and intravenous administration should be initiated immediately on presentation. Oral administration would be insufficient.PNDs are a heterogenous group of immune-mediated syndromes associated with cancer. Although uncommon, their incidence (estimated at 1%) is greater than previously thought and likely to increase as means of detection improve along with patient survival. Although almost any malignancy can give rise to a PND, a disproportionate percentage (up to 5%) of patients with small cell lung cancer (SCLC) are affected.1PNDs result from an immune response against nervous system antigens ectopically expressed by tumor cells. The relative roles of B and T cells in pathogenesis is a subject of research, and many believe that antibodies to intracellular components may be a marker of disease rather than a direct cause.1,5Anti-Ri targets 2 neuron-specific RNA binding proteins. It was first identified in 1988 in a patient with breast cancer who presented with opsoclonus, myoclonus, and ataxia; initially, it was thought to be exclusively associated with this triad.6 Since then, research has revealed greater variability in presentation. A majority of patients do demonstrate ocular dysmotility and some degree of ataxia, but laryngospasm or jaw dystonia may occur in up to 25% of patients.7Patients with PND often present with early-stage or occult cancer, and FDG-PET/CT has been shown to increase the diagnostic yield for cancer among such patients, by as much as 18% according to one series.8 If negative, repeat screening every 6 months for at least 4 years is recommended.9Removal of the antigen source by treatment of an underlying malignancy is the mainstay of therapy, but prompt initiation of immunosuppression during symptom progression may be beneficial. Intravenous immunoglobulin is often used based on safety profile, particularly in patients who require surgery to establish a diagnosis. However, agents such as cyclophosphamide that affect T-cell response may be a better choice.10 Prognosis varies, but a majority of treated patients regain some neurologic function.7FDG-PET/CT revealed a hypermetabolic mediastinal lymph node, and biopsy provided the diagnosis of SCLC. Despite empirical treatment with intravenous immunoglobulin, the patient became wheelchair bound, but he stabilized with initiation of cisplatin and etoposide for SCLC. Eventually, he recovered the ability to ambulate short distances with a walker.

General

A 64-year-old man with coronary artery disease and an 80 pack-year smoking habit presented with 2 weeks of gait instability leading to frequent falls and 8 weeks of vertigo and double vision. He reported unintentional weight loss without fevers or decreased appetite. He denied any history of alcohol abuse. Medications included metoprolol and aspirin. On examination, he was alert and oriented and vital signs were normal; body mass index was 24. Neurologic examination revealed right eye heterotropia and nasal upshoot indicative of a fourth cranial nerve palsy (Figure 1A), left ptosis, flattening of the right nasolabial fold (Figure 1B), and bilateral restricted upgaze and ataxia (Video). Strength and reflexes were preserved. Results of a basic metabolic panel and complete blood cell count were normal. Screening for human immunodeficiency virus, Lyme disease, and drug use was negative. Contrast-enhanced magnetic resonance imaging (MRI) of the brain was unremarkable. Cerebrospinal fluid (CSF) sampling revealed elevated protein (75 mg/dL [reference range, 10-42]), lymphocyte predominant pleocytosis (21-66 cells/uL [reference range, 0-11]), and oligoclonal bands (OCBs). Pleural thickening was seen on routine chest radiography; chest computed tomography (CT) revealed mediastinal lymphadenopathy, subcentimeter pulmonary nodules, and calcified pleural plaques.A, Right fourth cranial nerve palsy. On adduction, the right eye turns upward. This finding (nasal upshoot) suggests the presence of a fourth nerve palsy. B, Mild left ptosis and flattening of the right nasolabial fold.Obtain a whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and paraneoplastic antibody evaluation

what would you do next?

What would you do next?

Obtain a whole-body fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan and paraneoplastic antibody evaluation

Check thiamine levels and start oral supplementation

Obtain electromyography (EMG)

Obtain evoked potentials

a

male

61-70

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2430939

A 7-week-old full-term girl was referred to our clinic for persistent and expanding diaper dermatitis present since 1 week of age. She was initially treated at an outside hospital with intravenous clindamycin hydrochloride for presumed perianal cellulitis and was discharged with a regimen of oral clindamycin hydrochloride. When the patient was aged 4 weeks, the lesion became ulcerated and she was admitted to our hospital. She was given intravenous antibiotics and mupirocin, 2%, ointment, triamcinolone, 0.1%, ointment, clotrimazole, 1%, cream, nystatin cream, and zinc oxide paste. Results of cultures for bacteria and herpes simplex virus were negative. The patient had no systemic symptoms and was discharged and scheduled for an outpatient dermatology appointment.Physical examination showed a well-nourished, well-developed infant whose gluteal region had well-demarcated ulcers with scalloped borders on either side of the midline, superior to the anal verge. There was no exudate or drainage. The base of the ulcers was covered with fibrinous material and the residue of topical medications. Bright red matted telangiectasias extended from the anus to the ulcers (Figure).Two well-demarcated ulcers covered with white fibrinous material. The ulcerations are superimposed on prominent red matted telangiectasias. What Is Your Diagnosis?

Acrodermatitis enteropathica

Ulcerated segmental infantile hemangioma

Candidal dermatitis

Jacquet erosive diaper dermatitis

B. Ulcerated segmental infantile hemangioma (IH)

B

Ulcerated segmental infantile hemangioma

Histopathologic examination showed a sharp demarcation of an ulcerated lesion with an increased number and diameter of dermal blood vessels. Results of staining of the endothelial cells of the vessels were diffusely and strongly positive for GLUT1.Ultrasonography of the spinal cord was performed given the concern for other congenital anomalies and demonstrated inferior displacement of the conus medullaris at L3-L4, suggesting a tethered spinal cord. Results of magnetic resonance imaging (MRI) of the spine, abdomen, and pelvis confirmed a tethered spinal cord, inserting into an intrathecal lipoma that extended from L4 to the inferior aspect of the thecal sac. Ultrasonography of the urinary system demonstrated no abnormalities. The patient was evaluated at a multidisciplinary vascular anomalies clinic and was given oral propranolol hydrochloride for the ulcerated IH.Segmental hemangiomas develop on specific anatomical boundaries and often have geographic, sharply defined borders. This appearance is in contrast with that of typical IHs, which usually arise from single macules that evolve into papules, nodules, or tumors.1 Segmental IHs of the lower extremity, lumbosacral area, or perineum are frequently associated with several internal anomalies, which were previously described as PELVIS (perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, skin tag) or SACRAL (spinal dysraphism; anogenital, cutaneous, renal, and urologic anomalies; associated with an angioma of lumbosacral localization) syndrome. Iacobas et al1 coined the acronym LUMBAR (lower-body infantile hemangioma and other skin defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies) to convey the currently known associated anomalies.One-third of all ulcerated hemangiomas are found in the perineum.2 Ulceration is more common in children with LUMBAR syndrome, found in 70% of reported cases. When present, ulceration occurs most commonly in the sacral region, followed by the lumbar and perineum or genital areas. Eighty-three percent of patients had evidence of myelopathy on MRI.1 The most frequently reported anomaly in LUMBAR syndrome is tethered spinal cord, seen in 75% of patients, including our patient.1Our patient’s lesion began as a large telangiectatic patch without the typical proliferative growth characteristic of IH; thus, it is better classified as IH with minimal or arrested growth (IH-MAG). In a retrospective case series by Suh and Frieden,3 the lower body was found to be the most common location for IH-MAG, occurring in 32 of 47 lesions (68%). Only 14 of these 47 lesions (30%) were in a segmental distribution. Infantile hemangioma with minimal or arrested growth was more frequent in girls and showed an increased association with extracutaneous anomalies.3 As in IH, results of staining of blood vessels in IH-MAG are positive for GLUT1, in contrast to vascular malformations, noninvoluting congenital hemangiomas, and rapidly involuting congenital hemangiomas.4The pathogenesis of LUMBAR syndrome is unknown. When a segmental hemangioma is located on the lower half of the body, a thorough physical examination of the abdomen, pelvis, and lower extremities is necessary. Iacobas et al1 recommend imaging of the spine, abdomen, and pelvis. While MRI is a more sensitive imaging modality to identify associated anomalies, ultrasonography is recommended in infants younger than 3 months to avoid risks associated with sedation. Ossification of the posterior spinal elements occurs at approximately 3 to 4 months of age, limiting use of ultrasonography beyond this age.5 The presence of high-risk features for spinal dysraphism, such as midline segmental hemangiomas, lipomas, and hypertrichosis, should prompt the physician to perform an MRI after 3 months of life even if the ultrasonogram showed no abnormalities.In addition, arterial anomalies may underlie a segmental IH of the lower limb or at sites distant from the primary segmental IH.1 There is limited use of MRI or magnetic resonance angiography in infants because of risks associated with anesthesia; therefore, arterial anomalies may be underreported in the literature. Segmental IH of the lower extremity should prompt physicians to screen for associated internal anomalies of LUMBAR syndrome.

Pediatrics

A 7-week-old full-term girl was referred to our clinic for persistent and expanding diaper dermatitis present since 1 week of age. She was initially treated at an outside hospital with intravenous clindamycin hydrochloride for presumed perianal cellulitis and was discharged with a regimen of oral clindamycin hydrochloride. When the patient was aged 4 weeks, the lesion became ulcerated and she was admitted to our hospital. She was given intravenous antibiotics and mupirocin, 2%, ointment, triamcinolone, 0.1%, ointment, clotrimazole, 1%, cream, nystatin cream, and zinc oxide paste. Results of cultures for bacteria and herpes simplex virus were negative. The patient had no systemic symptoms and was discharged and scheduled for an outpatient dermatology appointment.Physical examination showed a well-nourished, well-developed infant whose gluteal region had well-demarcated ulcers with scalloped borders on either side of the midline, superior to the anal verge. There was no exudate or drainage. The base of the ulcers was covered with fibrinous material and the residue of topical medications. Bright red matted telangiectasias extended from the anus to the ulcers (Figure).Two well-demarcated ulcers covered with white fibrinous material. The ulcerations are superimposed on prominent red matted telangiectasias.

what is your diagnosis?

What is your diagnosis?

Ulcerated segmental infantile hemangioma

Candidal dermatitis

Jacquet erosive diaper dermatitis

Acrodermatitis enteropathica

a

female

0-10

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2422190

A woman in her 60s presented to her primary care physician with a right-sided lower motor neuron facial nerve palsy. This resolved with oral steroids and antiviral drugs consistent with a presumed diagnosis of idiopathic facial nerve (Bell) palsy. Six months later the patient developed discomfort around her right ear, prompting a referral to the local otolaryngology service. Her medical history was significant for localized invasive ductal carcinoma of the right breast treated with wide local excision 13 years previously. At presentation she was considered disease-free. Findings from the clinical examination, including otoscopy, were unremarkable. A magnetic resonance imaging (MRI) scan revealed an 8-mm lesion within the right parotid gland with a spiculated border and ill-defined surrounding enhancement extending close to the stylomastoid foramen (Figure, A). This was of low T2 signal with no perineural spread evident. A fine-needle aspirate and core biopsy were obtained under ultrasonographic guidance. The cytologic findings showed loosely cohesive groups of atypical epithelial cells. Histologic examination of the core biopsy revealed an infiltrative lesion composed of cords and nests of medium-sized cells surrounded by a densely hyalinized stroma (Figure, B). The cells contained hyperchromatic vesicular nuclei with moderate amounts of eosinophilic cytoplasm (Figure, C). Immunohistochemical analysis showed the cells were diffusely positive for cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (Figure, D).A, Axial fast spoiled gradient echo gadolinium-enhanced magnetic resonance imaging (MRI) scan with fat suppression demonstrating lesion of the right parotid gland (arrowhead). B, Right parotid core biopsy specimen. C, Cells with hyperchromatic vesicular nuclei and moderate amounts of eosinophilic cytoplasm. D, Immunohistochemical (IHC) analysis for estrogen receptor. What Is Your Diagnosis?

Adenoid cystic carcinoma

Salivary duct carcinoma

Carcinoma ex pleomorphic adenoma

Metastatic breast carcinoma

D. Metastatic breast carcinoma

D

Metastatic breast carcinoma

The development of a parotid gland metastasis from a primary breast carcinoma is a rare event, with only 15 cases reported between 1982 and 2011.1 The 13-year interval between the diagnosis of breast cancer and the development of distant metastases is an unusual but recognized feature; indeed, distant metastases can occur up to several decades from the time of original diagnosis.2,3 It is hypothesized that such metastases may arise from tumor cells that exist for years to decades in a dormant state with subsequent reactivation of proliferation.4,5In the absence of corroborative clinical and radiological findings, the histological distinction between a primary and secondary salivary gland malignant neoplasm can be difficult, particularly on core biopsy specimens where the amount of tissue is usually scant. Among primary salivary gland tumors, salivary duct carcinoma in particular shares virtually identical histological features with ductal breast carcinoma, a fact that is unsurprising given that both carcinomas arise from exocrine organs that share similarities at the microscopic level.6 Immunohistochemical analysis can be helpful in cases where there is ambiguity on the basis of morphologic characteristics alone. While studies7,8 have found that some primary salivary gland malignant neoplasms can show patchy ER and PR expression, the presence of strong and diffuse positivity, as seen in this case, is more suggestive of metastatic breast carcinoma. Androgen receptor is relatively specific for salivary duct carcinoma and carcinoma ex-pleomorphic adenoma in the context of primary salivary gland neoplasms; however, it is also expressed in most ductal breast carcinomas and has a limited role in this case.9Ultimately, the question of whether the parotid lesion was a primary or secondary malignant neoplasm was resolved with the aid of a positron emission tomographic/computed tomographic scan. This demonstrated an fluorodeoxyglucose F 18-avid node in the superior mediastinum as well as fluorodeoxyglucose F 18–avid lesions affecting the spine, pelvis, and right fifth rib. The presence of multiple bony metastases in particular was felt to be more in keeping with the behavior of metastatic breast carcinoma than a salivary gland malignant neoplasm. Such metastases would also have precluded the option of radical curative surgery even if the parotid lesion was a primary malignant neoplasm.One apparently unique feature of this case was the presentation with a lower motor neuron facial nerve palsy in the absence of any palpable mass. This likely relates to the relatively deep location of the metastatic lesion adjacent to the facial nerve as it exits the skull base through the parotid gland at the stylomastoid foramen. All previously reported cases of facial nerve palsy secondary to breast cancer metastases in the parotid gland have occurred in association with a palpable swelling.1A further interesting aspect of this case relates to the complete resolution of the facial nerve palsy with steroid and antiviral treatment. While it is possible that the initial facial palsy was a completely coincidental Bell palsy, the chance of this condition occurring on the same side as a malignant parotid lesion and shortly before the development of local discomfort makes this possibility most unlikely. A more likely explanation for the resolution of the facial palsy is that the initial weakness may have been caused by local pressure on the facial nerve due to a small hemorrhage from the tumor or other cause of localized edema. Previously reported cases of facial nerve palsy secondary to breast cancer malignant neoplasms in the parotid gland have been persistent or progressive in nature.1Further management of this patient’s metastatic breast cancer was overseen by the breast oncology service, who initiated treatment with the aromatase inhibitor anastrozole. This resulted in a clinically significant reduction of all metastatic tumor burden on follow-up MRI scanning several months later.

General

A woman in her 60s presented to her primary care physician with a right-sided lower motor neuron facial nerve palsy. This resolved with oral steroids and antiviral drugs consistent with a presumed diagnosis of idiopathic facial nerve (Bell) palsy. Six months later the patient developed discomfort around her right ear, prompting a referral to the local otolaryngology service. Her medical history was significant for localized invasive ductal carcinoma of the right breast treated with wide local excision 13 years previously. At presentation she was considered disease-free. Findings from the clinical examination, including otoscopy, were unremarkable. A magnetic resonance imaging (MRI) scan revealed an 8-mm lesion within the right parotid gland with a spiculated border and ill-defined surrounding enhancement extending close to the stylomastoid foramen (Figure, A). This was of low T2 signal with no perineural spread evident. A fine-needle aspirate and core biopsy were obtained under ultrasonographic guidance. The cytologic findings showed loosely cohesive groups of atypical epithelial cells. Histologic examination of the core biopsy revealed an infiltrative lesion composed of cords and nests of medium-sized cells surrounded by a densely hyalinized stroma (Figure, B). The cells contained hyperchromatic vesicular nuclei with moderate amounts of eosinophilic cytoplasm (Figure, C). Immunohistochemical analysis showed the cells were diffusely positive for cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (Figure, D).A, Axial fast spoiled gradient echo gadolinium-enhanced magnetic resonance imaging (MRI) scan with fat suppression demonstrating lesion of the right parotid gland (arrowhead). B, Right parotid core biopsy specimen. C, Cells with hyperchromatic vesicular nuclei and moderate amounts of eosinophilic cytoplasm. D, Immunohistochemical (IHC) analysis for estrogen receptor.

what is your diagnosis?

What is your diagnosis?

Carcinoma ex pleomorphic adenoma

Adenoid cystic carcinoma

Salivary duct carcinoma

Metastatic breast carcinoma

d

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2426962

A male infant presented to the pediatric otolaryngology office for evaluation of a left postauricular mass. Initially the lesion appeared to be acutely inflamed with erythema, overlying crusting, and tenderness to palpation. The child was treated with a course of antibiotics. Four weeks after the initial evaluation, the acute inflammation had resolved, but the lesion had increased in size. The child was otherwise healthy, and the parents stated that he had no systemic symptoms such as fever or weight loss. On physical examination, a 1.5-cm superficial, ovoid firm lesion was noted in the left postauricular area (Figure, A). While the lesion was attached to the skin, it was mobile over the mastoid bone. There were no middle ear abnormalities on physical examination. Ultrasonography of the lesion revealed a nonvascular, well-circumscribed 1.7 × 1.4 × 0.6-cm lesion in the soft tissue posterior to the left ear. It demonstrated a heterogenous echotexture but was predominantly hypoechoic without internal vascularity or distinct calcifications. Excisional biopsy under general anesthesia was performed owing to rapid enlargement and unclear etiology of the lesion. The lesion had distinct borders and separated easily from the surrounding soft-tissue attachments. It was completely excised, including the overlying skin. Pathologic examination revealed a neoplasm extending from the reticular dermis into the subcutaneous adipose tissue (Figure, B). There were lobules of lipidized histiocytic cells with eosinophils in a background of collagen (Figure, C). The lesion stained negatively for S-100 and CD1a (Figure, D).A, Gross photograph of left postauricular mass. B-D, Histopathologic images (hematoxylin-eosin). B, High-powered (original magnification ×100) view depicting some pale areas representing lipidized cells. C, High-powered (original magnification ×400) view demonstrating pale, foamy cells (xanthoma cells). D, Neoplastic cells staining negatively for S100 (original magnification ×400). What Is Your Diagnosis?

Spitz nevus

Pyogenic granuloma

Juvenile xanthogranuloma

Dermatofibroma

C. Juvenile xanthogranuloma

C

Juvenile xanthogranuloma

Juvenile xanthogranulomas (JXGs) are rare, benign lesions that may present as cutaneous lesions of the head and neck. Juvenile xanthogranuloma is a non-Langerhans cell histiocytic disorder. These lesions typically manifest as nodules or papules in children. Juvenile xanthogranulomas are characterized by a slight male predominance.1,2 They may be present at birth or occur in infancy and typically resolve spontaneously without treatment. There is a predilection for the face and scalp, although they are known to affect the entire body, including visceral organs.1-3 The lesions may be solitary or multiple in nature.4 Ocular and testicular involvements are the most common noncutaneous locations; however, case reports have described visceral involvement in numerous sites, including the oral cavity, oropharynx, paranasal sinuses, temporal bone, and salivary glands.2 An association between multiple cutaneous lesions and visceral involvement has been proposed.4 In addition, patients with neurofibromatosis who develop JXGs are at greater risk of developing juvenile chronic myelomonocytic leukemia.5,6 Diagnosis can prove challenging because JXGs demonstrate variable presentation and histologic appearance. Diagnosis is typically based on medical history and findings from physical examination. Routine radiologic and laboratory studies are not warranted. Excisional biopsy may be necessary to confirm the diagnosis.Typical pathologic findings of JXG include a dense, dermal histiocytic infiltration with a variable representation of mononuclear, multinuclear, and spindle cells.1,3 The classic finding is the Touton giant cell, a cell characterized by a central ring of nuclei with peripheral eosinophilic or vacuolated cytoplasm. Touton giant cells are typically noted in a background of mononuclear cells.1 It has been proposed that early in the formation of JXG, the lesions are composed mainly of histiocytes, with rare eosinophils and Touton giant cells.4 As the lesion matures, it demonstrates classic Touton cells and vacuolated histiocytes.4 While Touton giant cells are considered the classic finding, they may be absent or sparse in presentation in these lesions and are not required for diagnosis. Immunohistochemical analysis demonstrates positive staining for vimentin, CD68, and factor XIIIa. Stains for CD1a are negative. Stains for S-100 are typically negative but can be weakly positive.1Spontaneous involution is common with cutaneous JXGs, with resolution typically noted from 6 months to 3 years following presentation.5 Extracutaneous lesions are more likely to persist and require intervention.2 Although JXGs are benign, they can cause structural and functional impairment depending on their location. In addition, JXG can occasionally be hemorrhagic. Excisional biopsy can serve to confirm diagnosis and improve function and aesthetics.2 Recurrence following excisional biopsy is rare, and the prognosis is excellent.4,5Juvenile xanthogranulomas may present a diagnostic challenge for otolaryngologists and should be included in the differential diagnosis in infants presenting with superficial, cutaneous lesions in the head and neck. Because most cases of JXG will spontaneously involute, observation should be considered. Excisional biopsy is warranted in patients with an unclear diagnosis or those with aesthetic and functional compromise related to the lesion.

General

A male infant presented to the pediatric otolaryngology office for evaluation of a left postauricular mass. Initially the lesion appeared to be acutely inflamed with erythema, overlying crusting, and tenderness to palpation. The child was treated with a course of antibiotics. Four weeks after the initial evaluation, the acute inflammation had resolved, but the lesion had increased in size. The child was otherwise healthy, and the parents stated that he had no systemic symptoms such as fever or weight loss. On physical examination, a 1.5-cm superficial, ovoid firm lesion was noted in the left postauricular area (Figure, A). While the lesion was attached to the skin, it was mobile over the mastoid bone. There were no middle ear abnormalities on physical examination. Ultrasonography of the lesion revealed a nonvascular, well-circumscribed 1.7 × 1.4 × 0.6-cm lesion in the soft tissue posterior to the left ear. It demonstrated a heterogenous echotexture but was predominantly hypoechoic without internal vascularity or distinct calcifications. Excisional biopsy under general anesthesia was performed owing to rapid enlargement and unclear etiology of the lesion. The lesion had distinct borders and separated easily from the surrounding soft-tissue attachments. It was completely excised, including the overlying skin. Pathologic examination revealed a neoplasm extending from the reticular dermis into the subcutaneous adipose tissue (Figure, B). There were lobules of lipidized histiocytic cells with eosinophils in a background of collagen (Figure, C). The lesion stained negatively for S-100 and CD1a (Figure, D).A, Gross photograph of left postauricular mass. B-D, Histopathologic images (hematoxylin-eosin). B, High-powered (original magnification ×100) view depicting some pale areas representing lipidized cells. C, High-powered (original magnification ×400) view demonstrating pale, foamy cells (xanthoma cells). D, Neoplastic cells staining negatively for S100 (original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Pyogenic granuloma

Spitz nevus

Dermatofibroma

Juvenile xanthogranuloma

d

male

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2426963

A man in his 60s presented to the oral and maxillofacial surgery department with a 7-month history of a painless progressive swelling of the anterior mandible. The patient was completely edentulous. He reported numbness of the lower lip and difficulty on swallowing. There was no remarkable weight loss. His medical history was significant for hypertension and coronary artery bypass surgery. On intraoral examination, the mass was hard in consistency with relatively normal overlying mucosa. Computed tomographic (CT) images with bone window showed a grossly expansile, multilocular, low-attenuation lesion of the anterior segment of the mandible (Figure, A and B). The images demonstrated severe erosion of the facial and lingual cortices with a remarkable scalloping pattern, and multiple wispy, ill-defined intralesional septa. Soft-tissue CT images indicated a cystic and solid nature of the mass (Figure, C and D). What Is Your Diagnosis?

Ameloblastoma

Central mucoepidermoid carcinoma

Ameloblastic carcinoma

Odontogenic myxoma

C. Ameloblastic carcinoma

C

Ameloblastic carcinoma

Ameloblastic carcinoma is an exceedingly rare malignant odontogenic tumor that may arise de novo or from a preexisting odontogenic lesion. As of 2014, a total number of 92 cases have been reported in literature.1 Ameloblastic carcinoma occurs in a wide range of age groups with a slight male predilection. It most commonly occurs in the ramus–third molar area of the mandible. Clinically, ameloblastic carcinoma usually causes painful expansion of the jaw.2A few cases of ameloblastic carcinoma have been reported to metastasize to regional lymph nodes, lung, liver, or bone marrow.3,4 However, it is believed that the pulmonary metastasis is due to aspiration from the oral lesion or possibly endotracheal intubation (which might release neoplastic cells into the lower airway) rather than a true lymphatic or hematogenous spread.4 Histologically, it shows features of ameloblastoma with cellular atypia. Because of the aggressive behavior and multilocular pattern of ameloblastic carcinomas, the differential diagnosis should include ameloblastoma, odontogenic myxoma, central mucoepidermoid tumor, and carcinoma originating in a dental cyst.5 In absence of metastasis, ameloblastic carcinoma may not be radiographically distinguishable from benign ameloblastoma. However, the finding of characteristic thin straight septa with less than expected bone expansion is very suggestive of odontogenic myxoma. The peripheral cortication of primary intraosseous mucoepidermoid carcinoma may be impressively thick, which belies its malignant nature. Because carcinoma could originate in the epithelial lining of an odontogenic cyst, the shape is often round or ovoid. However, as the malignant tissue progressively replaces cyst lining, the corticated hydraulic border becomes ill-defined. Nevertheless, the final diagnosis of ameloblastic carcinoma is often the result of histologic examination and/or the detection of metastatic lesions.The treatment of ameloblastic carcinoma includes en bloc resection along with radiotherapy as reported by many authors. Cases with nodal metastasis merit neck dissection with or without radiation therapy. However, radiotherapy and chemotherapy seem to have limited value in ameloblastic carcinoma.6 A survival rate of 5 years can be accepted as a standard in absence of local recurrence and metastasis.5

General

A man in his 60s presented to the oral and maxillofacial surgery department with a 7-month history of a painless progressive swelling of the anterior mandible. The patient was completely edentulous. He reported numbness of the lower lip and difficulty on swallowing. There was no remarkable weight loss. His medical history was significant for hypertension and coronary artery bypass surgery. On intraoral examination, the mass was hard in consistency with relatively normal overlying mucosa. Computed tomographic (CT) images with bone window showed a grossly expansile, multilocular, low-attenuation lesion of the anterior segment of the mandible (Figure, A and B). The images demonstrated severe erosion of the facial and lingual cortices with a remarkable scalloping pattern, and multiple wispy, ill-defined intralesional septa. Soft-tissue CT images indicated a cystic and solid nature of the mass (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Odontogenic myxoma

Central mucoepidermoid carcinoma

Ameloblastoma

Ameloblastic carcinoma

d

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2429577

A woman in her 60s presented with a history of persistent globus pharyngis spanning 2 decades. She stated that she had no other symptoms, and her family medical history was not remarkable. On examination, the rigid indirect laryngoscopy revealed yellowish floppy granular proliferation affecting the bilateral arytenoids and posterior aspects of the aryepiglottic folds, with symmetrical vocal cord motion (Figure, A). The main lesions were clearly demarcated from the surrounding normal mucosa. The patient then underwent microlaryngeal surgery with biopsy under general anesthesia. The nidus was fragile and bled copiously when traumatized. The specimens mounted on the hematoxylin-eosin slides showed eosinophilic amorphous material underlying the epithelium (Figure, B). Staining for thioflavin T revealed yellow-green fluorescence (Figure, C). The fibrillar component emitted a characteristic apple-green birefringence under polarized light after binding to Congo red dye. No clinical evidence of systemic involvement and/or plasma cell dyscrasia was found.A, Endoscopic examination demonstrated symmetric yellowish lesions affecting the arytenoids and posterior aspects of the aryepiglottic folds, with a patent airway and mobile vocal folds. B, Eosinophilic amorphous material underlying the epithelium (hematoxylin-eosin, original magnification ×200). C, Thioflavin T exhibited a typical yellow-green fluorescence after binding to amyloid fibrils (original magnification ×200). What Is Your Diagnosis?

Lipoma

Sarcoidosis

Localized laryngeal amyloidosis

Gouty tophi

C. Localized laryngeal amyloidosis

C

Localized laryngeal amyloidosis

The term amyloidosis describes a group of disorders encompassing extracellular aggregation of pathologic insoluble nonreactive fibrillar proteinaceous deposits in tissues, causing structural alteration and organ dysfunction.1-10 Prior to the establishment of the now-preferred nomenclature system for amyloid fibrils based on the circulating precursor protein,1-4,6,8 a classification based on differentiation between local and systemic distribution of amyloid was commonly applied.1-4,8 Occurrence of amyloidosis in the head and neck region is rare, with the larynx being the most frequently affected anatomic site.1-9Laryngeal amyloidosis (LA) accounts for around 1% of all laryngeal lesions, with higher predilection for the laryngeal ventricle.1,2,4 Laryngeal amyloidosis chiefly behaves as a harmless localized disease rather than as a part of systemic involvement.1-9 In most cases of LA, the amyloid fibrils are derived from immunoglobulin light chains, predominantly of the λ type.1-10 The pathogenesis for producing amyloid deposits is usually unknown, although the hypothesis of a localized plasma cell dyscrasia is currently accepted.3,4,6,7 Although several efforts have been made to identify the candidate causative factors for LA, evidence for such an association has not been observed.6,10 The usual clinical course is exclusively an insidious onset and indolent process with occasional multifocal occurrence and a preponderance for recurrence.1-8 Potential presenting manifestations vary depending on location and extent of associated amyloid deposits relative to influenced structures.1-9The macroscopic appearance of LA is diverse, ranging from inconspicuous hyalinization to diffuse to granular waxy swelling to obvious bosselated elevations visible during endoscopy.1-7,9 The gold standard for diagnosis demands a tissue biopsy demonstrating a largely acellular eosinophilic amorphous material on hematoxylin-eosin staining and characteristic changes with certain stains, such as Congo red staining, thioflavin fluorescent staining or methyl violet metachromatic staining. To exclude unusual systemic involvement, a thoroughly comprehensive assessment is warranted.1-6,9 Usually, the prognosis is excellent once the disease is confirmed to be localized in nature.1,3-5Treatment is mainly conservative, aimed at maintaining laryngeal function.1-10 For selected clinically relevant patients, staged endolaryngeal surgical reduction of amyloid lesions via either cold instrument stripping or microlaryngeal laser surgery remain the mainstay treatments and provide comparatively favorable results in terms of voice quality, functional preservation and disease control.1-8 Open-field procedures are recommended only when preservation of larynx function is infeasible or the patient’s condition is life-threatening.5-9 The concept of utilizing external beam radiation therapy (EBRT) in treating LA has been extrapolated from successful experiences with curing tracheobronchial amyloidosis and certain plasma cell disorders, with postulated mechanisms focusing on eliminating amyloidogenic plasma cells and modulating immune responses.9,10 The role of radiotherapy in treating laryngeal amyloidosis remained controversial. In 1967, E. P. Kitaevich, a Russian physician, introduced the first case who was effectively treated with irradiation. Celenk et al 9 and Truong et al10 advocated irradiation as part of the treatment program for laryngeal amyloidosis, especially for patients who had recurrent or residual disease after a surgical intervention.9,10 However, in light of the paucity of evidence of its efficacy, there is still no consensus on the use of EBRT as an alternative treatment option.9,10 For patients who have undergone treatment, long-term sustained regular follow-up is mandatory for early detection of recurrence, surveillance of potential systemic transformation, or, although less likely, detection of new stigma presenting in another organ.1-6,8,9In conclusion, we report the case of a patient with localized laryngeal amyloidosis presenting with a persistent globus sensation that was relieved after treatment with microlaryngeal laser surgery. This case illustrates the need for physicians to maintain awareness of this clinical entity and highlights the importance of endoscopic findings, especially for patients with ambiguous or inconsistent complaints. Because a limited number of cases have been reported, more treatment results are needed to establish a firm framework to guide physicians in selecting the best treatment option for patients with laryngeal amyloidosis.

General

A woman in her 60s presented with a history of persistent globus pharyngis spanning 2 decades. She stated that she had no other symptoms, and her family medical history was not remarkable. On examination, the rigid indirect laryngoscopy revealed yellowish floppy granular proliferation affecting the bilateral arytenoids and posterior aspects of the aryepiglottic folds, with symmetrical vocal cord motion (Figure, A). The main lesions were clearly demarcated from the surrounding normal mucosa. The patient then underwent microlaryngeal surgery with biopsy under general anesthesia. The nidus was fragile and bled copiously when traumatized. The specimens mounted on the hematoxylin-eosin slides showed eosinophilic amorphous material underlying the epithelium (Figure, B). Staining for thioflavin T revealed yellow-green fluorescence (Figure, C). The fibrillar component emitted a characteristic apple-green birefringence under polarized light after binding to Congo red dye. No clinical evidence of systemic involvement and/or plasma cell dyscrasia was found.A, Endoscopic examination demonstrated symmetric yellowish lesions affecting the arytenoids and posterior aspects of the aryepiglottic folds, with a patent airway and mobile vocal folds. B, Eosinophilic amorphous material underlying the epithelium (hematoxylin-eosin, original magnification ×200). C, Thioflavin T exhibited a typical yellow-green fluorescence after binding to amyloid fibrils (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Localized laryngeal amyloidosis

Sarcoidosis

Lipoma

Gouty tophi

a

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2430627

An adolescent female with a medical history significant for absent corpus callosum, polycystic ovarian syndrome, and papillary thyroid cancer status post–total thyroidectomy and I-131 ablation, presented with a 1-year history of submental swelling. She had no associated symptoms. On examination, she had a 6-cm nontender mass in the submentum. Her floor of mouth (FOM) was soft, and there was no cervical lymphadenopathy. Attempted open biopsy at the time of thyroidectomy revealed only adipose tissue. Ultrasonography (US) (Figure, A) revealed a well-circumscribed, avascular, homogeneous, isoechoic lesion, measuring 6.2 × 6.0 × 6.0 cm along the FOM and left submandibular regions. Magnetic resonance imaging (MRI) of the neck revealed the lesion within the FOM, above the mylohyoid muscle. The lesion involved the root of the tongue in the midline and extended to the left, causing significant thinning of the left mylohyoid muscle without extension through it. The lesion demonstrated a fluid signal with T2 hyperintensity (Figure B), T1 hypointensity (Figure, C), and peripheral rim enhancement. Mild restricted diffusion was also noted. The patient underwent transcervical excision of the mass (Figure, D). The mass was encapsulated and positioned above the mylohyoid muscle and extended into the FOM between bilateral genioglossus muscles. The mass was removed entirely via transcervical excision.A, Sagittal midline ultrasonography shows a floor of mouth lesion with uniform low-level echoes. B, Axial T2-weighted magnetic resonance image (MRI) revealing a hyperintense lesion involving the floor of mouth. C, Coronal postcontrast MRI revealing a T1 hypointense unilocular lesion involving the floor of the mouth and root of the tongue. D, Intraoperative photograph during mass excision. What Is Your Diagnosis?

Ranula

Lymphangioma

Dermoid cyst

Suprahyoid thyroglossal duct cyst

C. Dermoid cyst

C

Dermoid cyst

Dermoid cysts are relatively rare clinical entities in the head and neck. Histologically, dermoid cysts are lined by keratinizing squamous epithelium and contain elements of epidermal appendages such as hair follicles, sweat glands, and connective tissues.1 It is estimated that about 7% of dermoids occur in the head and neck, and approximately 1% to 2% are located in the FOM.2 The term dermoid cyst is often applied to epidermoid, dermoid, and teratoid cystic lesions. Both simple dermoids and epidermoids appear as well-demarcated cystic lesions. Dermoids contain dermal adnexal elements in addition to epithelial elements; they are cystic masses formed from epithelial rests and found along embryonic fusion lines.3 Dermoid cysts of the oral cavity (OC) tend to present in the midline anterior FOM during the second to third decade of life. They may be acquired or congenital.4 They tend to present as nontender masses that slowly progress in size. When located in the FOM with sufficient growth, they may be associated with respiratory or swallowing difficulties.5 These lesions are generally confined to the submental, submandibular, or sublingual space. Within the OC, they are most commonly reported in the sublingual location, followed by submental and submandibular regions. Sublingual dermoids are superior to the mylohyoid and may split the midline extrinsic tongue musculature, whereas submental dermoids lie between the mylohyoid and the platysma. Sublingual dermoids may elevate the tongue and appear similar to a ranula.4 These distinctions are important when considering clinical presentation and treatment: sublingual cysts tend to present as an FOM mass and are usually treated via intraoral approach, whereas submental and submandibular cysts tend to present as neck masses approached transcervically.6 The relationship of the lesion to the mylohyoid may be important for surgical planning. However, some authors7,8 have reported that while the mass’ relationship with the mylohyoid determines its space, it is the relationship with the geniohyoid that determines where the cyst presents clinically. In this patient, the cyst presented as a submental mass but was located primarily in the sublingual space.Computed tomography (CT), US, and MRI can be used for the diagnostic imaging of dermoid cysts. They tend to appear as cystic, well-demarcated masses with fatty and/or fluid contents; most have a definable wall without nodular soft tissue in or outside the wall.9 Dermoids are difficult to distinguish radiologically from epidermoid cysts, simple and plunging ranulas, abscesses, lymphangiomas, and suprahyoid thyroglossal duct cysts.9 Lymphangiomas appear as multiloculated cystic masses that involve multiple spaces, however they generally do not involve the sublingual space.9 Simple and plunging ranulas are low-signal masses with thin, nonenhancing walls that involve the sublingual space and, in the case of plunging ranulas, also involve the submandibular space.9 Dermoids and epidermoids are typically midline or paramidline in location in most cases. Simple dermoids generally cannot be differentiated from epidermoids. However, compound dermoids can be identified based on the presence of intralesional fat or calcification.On CT, both epidermoids and simple dermoids are unilocular, hypodense, well-circumscribed, and thin-walled lesions with peripheral enhancement. On US, cysts show mixed internal echoes from fat with echogenic foci and dense shadowing if calcifications are present.9 On MRI, dermoids are generally low signal intensity on T1 and high signal intensity on T2 with peripheral enhancement. The cysts may also show a fluid level on MRI.4Treatment of dermoid cysts is generally simple excision. Cysts above the mylohyoid muscle can usually be approached intraorally, allowing for preservation of the mylohyoid and an inconspicuous scar.10 Larger or submental masses generally require transcervical excision. Recurrence of these lesions is rare,5 but prevention of recurrence requires complete excision of the cyst.9

General

An adolescent female with a medical history significant for absent corpus callosum, polycystic ovarian syndrome, and papillary thyroid cancer status post–total thyroidectomy and I-131 ablation, presented with a 1-year history of submental swelling. She had no associated symptoms. On examination, she had a 6-cm nontender mass in the submentum. Her floor of mouth (FOM) was soft, and there was no cervical lymphadenopathy. Attempted open biopsy at the time of thyroidectomy revealed only adipose tissue. Ultrasonography (US) (Figure, A) revealed a well-circumscribed, avascular, homogeneous, isoechoic lesion, measuring 6.2 × 6.0 × 6.0 cm along the FOM and left submandibular regions. Magnetic resonance imaging (MRI) of the neck revealed the lesion within the FOM, above the mylohyoid muscle. The lesion involved the root of the tongue in the midline and extended to the left, causing significant thinning of the left mylohyoid muscle without extension through it. The lesion demonstrated a fluid signal with T2 hyperintensity (Figure B), T1 hypointensity (Figure, C), and peripheral rim enhancement. Mild restricted diffusion was also noted. The patient underwent transcervical excision of the mass (Figure, D). The mass was encapsulated and positioned above the mylohyoid muscle and extended into the FOM between bilateral genioglossus muscles. The mass was removed entirely via transcervical excision.A, Sagittal midline ultrasonography shows a floor of mouth lesion with uniform low-level echoes. B, Axial T2-weighted magnetic resonance image (MRI) revealing a hyperintense lesion involving the floor of mouth. C, Coronal postcontrast MRI revealing a T1 hypointense unilocular lesion involving the floor of the mouth and root of the tongue. D, Intraoperative photograph during mass excision.

what is your diagnosis?

What is your diagnosis?

Suprahyoid thyroglossal duct cyst

Dermoid cyst

Ranula

Lymphangioma

b

female

0-10

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2383138

A 50-year-old man with transformed marginal zone lymphoma presented with intensely painful lesions on his left foot for 2 days. He noted a childhood history of plantar warts and believed these lesions to be identical in appearance. He did not recall any injury or unusual exposure. He had received his third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) 2 weeks prior to presentation as well as an injection of granulocyte-colony stimulating factor. He was anticipating his fourth cycle of treatment the day of his presentation. He also complained of a pruritic rash on his left thigh that had started several days before the appearance of his plantar foot lesions. The patient was afebrile, and his vital signs were within normal limits. Physical examination revealed grouped, brown, flat-topped papules on his distal plantar left foot (Figure). It was exquisitely tender to palpation, and the patient was visibly uncomfortable when walking. He also demonstrated erythematous papules and plaques on his posterolateral thigh. A few areas had shallow erosions. Laboratory studies revealed pancytopenia, with a white blood cell count of 2800/μL, hemoglobin level of 11.6 g/dL, and a platelet count of 81 × 103/μL. His lactate dehydrogenase level was elevated at 914 U/L, and results of his comprehensive metabolic panel were unremarkable. (To convert white blood cell count to ×109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert lactate dehydrogenase to microkatals per liter, multiply by 0.0167.)Photographs of a patient with painful lesions on the foot. What Is Your Diagnosis?

Plantar warts

Shingles

Cutaneous lymphoma

Toxic erythema of chemotherapy

B. Shingles

B

Shingles

Direct fluorescence antigen testing and polymerase chain reaction (PCR) were performed on skin scrapings and confirmed the diagnosis of herpes zoster (shingles) in an unusual S2 dermatomal distribution. While the brown, flat-topped papules on the plantar aspect of the foot resemble warts, they lacked the characteristic dot-like structures and verrucous appearance. The patient’s scheduled chemotherapy for that day was cancelled, and he was started on valacyclovir, 1 g 3 times daily. Rapid clinical diagnosis is critical when patients are receiving chemotherapy, especially with cytopenia, to minimize the risk of disseminated infection. Chemotherapy was resumed 2 weeks later when he had recovered from the herpes zoster and all lesions had crusted over.A history of primary varicella zoster infection is nearly universal in adult populations of North America and results in the diffuse vesicular rash of varicella (chicken pox).1 Following primary infection, the varicella zoster virus (VZV) establishes latency within sensory dorsal root ganglia; reactivation manifests as herpes zoster and is typically heralded by a painful, unilateral vesicular eruption in a dermatomal distribution. According to Centers for Disease Control and Prevention estimates, 32% of Americans will experience herpes zoster during their lifetimes.2 The incidence of herpes zoster is higher in immunocompromised patients, particularly those with lymphoproliferative malignant neoplasms.3 In 13% to 50% of patients with lymphoma, herpes zoster may present with life-threatening, disseminated disease involving multiple, nonadjacent dermatomes as well as visceral sites.3 Disseminated disease is associated with a 6% to 17% mortality rate.4 In patients with cancer, an elevated risk of localized or disseminated VZV infection exists in patients specifically with Hodgkin disease, lymphoproliferative malignant lesions, lung cancer, and among those who received bone marrow transplantation.4The incidence of herpes zoster infection is significantly higher in patients with lymphoma compared with those with nonhematologic solid tumors, and risk factors include advanced stage and recent radiation therapy.5 A retrospective cohort study of adult patients with cancer noted the incidence of herpes zoster to be 31 per 1000 person-years for patients with hematologic malignant neoplasms and 12 per 1000 person-years in those with solid tumors. Patients with hematologic malignant neoplasms were twice as likely to develop herpes zoster as those with solid tumors and 5 times more likely than the general population.1Zostavax is a live, attenuated zoster vaccine, and administration may result in disseminated disease in the immunosuppressed. It is therefore contraindicated in patients with primary or acquired immunodeficiency states, including leukemia, lymphoma, or other malignant neoplasms affecting the bone marrow or lymphatic system.6 The Advisory Committee on Immunization Practices states that patients with leukemia in remission may receive the zoster vaccine as long as no chemotherapy or radiation was given in the past 3 months.6 Tseng et al7 suggested that the zoster vaccine affords effective protection when given to adults 60 years or older who subsequently were diagnosed as having cancer and had received chemotherapy.In summary, herpes zoster in the lumbar and sacral dermatomes can present with lesions in seemingly unrelated distribution (lateral thigh and plantar foot) and has multiple clinical presentations (wartlike and rashlike). Clinicians should maintain a high index of suspicion for herpes zoster in patients with cancer, especially those receiving chemotherapy. The quality of the pain out of proportion to the examination is often an indicator of herpes zoster infection. Treatment should be started empirically. Direct fluorescent antigen (DFA) testing on scrapings from active vesicular lesions is a rapid method for the detection of the virus and has a sensitivity and specificity of 88% and 94%, respectively. A VZV-specific PCR is often used in the instance where the results from DFA testing is negative but clinical suspicion for herpes zoster remains high. Sensitivity and specificity are both higher for PCR testing (97.6 and 100%, respectively).8

Oncology

A 50-year-old man with transformed marginal zone lymphoma presented with intensely painful lesions on his left foot for 2 days. He noted a childhood history of plantar warts and believed these lesions to be identical in appearance. He did not recall any injury or unusual exposure. He had received his third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) 2 weeks prior to presentation as well as an injection of granulocyte-colony stimulating factor. He was anticipating his fourth cycle of treatment the day of his presentation. He also complained of a pruritic rash on his left thigh that had started several days before the appearance of his plantar foot lesions. The patient was afebrile, and his vital signs were within normal limits. Physical examination revealed grouped, brown, flat-topped papules on his distal plantar left foot (Figure). It was exquisitely tender to palpation, and the patient was visibly uncomfortable when walking. He also demonstrated erythematous papules and plaques on his posterolateral thigh. A few areas had shallow erosions. Laboratory studies revealed pancytopenia, with a white blood cell count of 2800/μL, hemoglobin level of 11.6 g/dL, and a platelet count of 81 × 103/μL. His lactate dehydrogenase level was elevated at 914 U/L, and results of his comprehensive metabolic panel were unremarkable. (To convert white blood cell count to ×109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert lactate dehydrogenase to microkatals per liter, multiply by 0.0167.)Photographs of a patient with painful lesions on the foot.

what is your diagnosis?

What is your diagnosis?

Plantar warts

Cutaneous lymphoma

Shingles

Toxic erythema of chemotherapy

c

male

41-50

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2362334

A 52-year-old woman with a history of diabetes mellitus and cigarette smoking who had a prior laparoscopic cholecystectomy was referred to our institution for severe postprandial epigastric abdominal pain that had been ongoing for several months and unintentional weight loss. She had been prescribed total parenteral nutrition prior to referral. On presentation, her physical examination was remarkable for mild epigastric tenderness. The results of laboratory testing, including a complete blood cell count, chemistry values, liver function tests, and amylase and lipase levels, were unremarkable. Computed tomography demonstrated focal gastric thickening. Esophagogastroduodenoscopy with endoscopic ultrasonography was performed that confirmed a submucosal gastric mass (Figure, A). A fine-needle aspiration biopsy revealed benign and reactive glandular cells and debris. Magnetic resonance cholangiopancreatography demonstrated a 2.4-cm hypervascular and exophytic mass in the gastric antrum and locoregional lymphadenopathy (Figure, B).A, Endoscopic ultrasonography of the gastric antrum mass reveals an area of gastric thickening (arrowheads) corresponding to computed tomographic findings. During endoscopy, this area was visualized grossly as a bulge in the atrium along the incisura. A fine-needle aspiration biopsy was nondiagnostic, showing gastric antral-type mucosa without pathologic changes (inset). B, The coronal image in T2 phase reveals a 1.8 × 2.4 × 1.5-cm hypotense lesion (arrowhead) in the gastric antrum. The lesion was also enhanced on T1 arterial phase sequencing. What Is Your Diagnosis?

Gastrointestinal stromal tumor

Gastric cancer

Peptic ulcer disease

Ectopic pancreas

D. Ectopic pancreas

D

Ectopic pancreas

Pancreatic heterotopia, also referred to as an ectopic pancreas, is defined by the presence of aberrant pancreatic tissue that lacks anatomic connection with the body of the pancreas.1 Gastric ectopic pancreas is often asymptomatic and found incidentally during surgery or during an autopsy. Cadaveric studies have shown that gastric ectopic pancreas is present in 0.5% to 13.5% of the population.2,3 Other sites of an ectopic pancreas include the duodenum, small bowel, gallbladder, esophagus, mesentery, and mediastinum; location in the stomach accounts for 25% to 38% of all cases.4 A minority of patients with a gastric ectopic pancreas develop symptoms, which may include malignant degeneration, gastric outlet obstruction, early satiety, and chronic abdominal pain.The workup for gastric ectopic pancreas should include thorough history taking and physical examination, along with appropriate laboratory, imaging, and endoscopic studies. Computed tomography and magnetic resonance imaging studies usually reveal a nonspecific submucosal gastric mass or thickening; the differential diagnosis includes a gastrointestinal stromal tumor, leiomyoma, carcinoid, or carcinoma.5 Dynamic upper gastrointestinal contrast studies demonstrate a gastric luminal filling defect in 20% to 50% of patients.6,7 Endoscopy is a useful adjunct and provides better localization. Endoscopic ultrasonography with fine-needle aspiration may afford a tissue diagnosis. Histologically, gastric ectopic pancreas may be confined to the submucosa or involve the muscularis and serosal layers.8,9 Exocrine tissue is identified at the time of biopsy in approximately 50% of cases.5 Definitive diagnosis is sometimes elusive because overlying normal gastric mucosa can obscure lesions.Strong consideration should be given to surgical exploration in the case of suspected pancreatic heterotopia if symptomatic or to rule out malignancy when the diagnosis is uncertain. Localized excision is favored over a more extensive gastric resection when the diagnosis can be reasonably confirmed. Our patient underwent an open exploration and gastric wedge resection of the lesser curvature mass. A frozen section of the resected mass revealed ectopic pancreatic tissue. After an uneventful postoperative course, the patient’s abdominal pain completely resolved.

Surgery

A 52-year-old woman with a history of diabetes mellitus and cigarette smoking who had a prior laparoscopic cholecystectomy was referred to our institution for severe postprandial epigastric abdominal pain that had been ongoing for several months and unintentional weight loss. She had been prescribed total parenteral nutrition prior to referral. On presentation, her physical examination was remarkable for mild epigastric tenderness. The results of laboratory testing, including a complete blood cell count, chemistry values, liver function tests, and amylase and lipase levels, were unremarkable. Computed tomography demonstrated focal gastric thickening. Esophagogastroduodenoscopy with endoscopic ultrasonography was performed that confirmed a submucosal gastric mass (Figure, A). A fine-needle aspiration biopsy revealed benign and reactive glandular cells and debris. Magnetic resonance cholangiopancreatography demonstrated a 2.4-cm hypervascular and exophytic mass in the gastric antrum and locoregional lymphadenopathy (Figure, B).A, Endoscopic ultrasonography of the gastric antrum mass reveals an area of gastric thickening (arrowheads) corresponding to computed tomographic findings. During endoscopy, this area was visualized grossly as a bulge in the atrium along the incisura. A fine-needle aspiration biopsy was nondiagnostic, showing gastric antral-type mucosa without pathologic changes (inset). B, The coronal image in T2 phase reveals a 1.8 × 2.4 × 1.5-cm hypotense lesion (arrowhead) in the gastric antrum. The lesion was also enhanced on T1 arterial phase sequencing.

what is your diagnosis?

What is your diagnosis?

Gastric cancer

Ectopic pancreas

Gastrointestinal stromal tumor

Peptic ulcer disease

b

female

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2389259

A woman in her mid-50s presented to the clinic with a 6-month history of progressive swelling and pain on the right side of her neck. The patient described a history of sleep apnea, a remote transient ischemic attack with left-sided weakness, and a prior thyroidectomy. She had increasing fatigue during the last 6 months, as well as worsening anxiety. On physical examination, the neck was supple, with no palpable masses or lymphadenopathy, and had a well-healed transverse neck incision. Magnetic resonance imaging revealed a 1.1-cm, round, partially enhancing, cystic mass near the tail of the parotid gland that appeared hypointense on T2-weighted imaging (Figure 1). An enlarged and distended venous structure that measured up to 7 mm was also visualized in the area. Laboratory work revealed no abnormalities.Magnetic resonance images of the parotid gland. T1-weighted image (A) and T2-weighted image (B) revealing a round, partially enhancing, cystic mass near the tail of the parotid gland (white and red arrowheads). What Is Your Diagnosis?

Schwannoma

Pseudoaneurysm

Cavernous hemangioma

Paraganglioma

C. Cavernous hemangioma

C

Cavernous hemangioma

A right-sided neck exploration was performed. An enlarged and tortuous venous structure was excised from the right submandibular region. Cephalad to the parotid gland, a spherical, 1.5-cm mass with purple discoloration was identified. It was carefully dissected from the hypoglossal nerve, external carotid artery, and internal jugular vein. Gross examination revealed a cystic, clot-filled structure. An uncomplicated postoperative course followed, with complete resolution of symptoms. Pathologic examination revealed a dark-purple nodule, consistent with a cavernous hemangioma (Figure 2). The adjacent venous structure was described as a varicose vein. No findings were suggestive of a malignant tumor.Histopathologic image of the specimen. Dilated vessels lined by flattened endothelium are visualized (original magnification ×400).Cavernous hemangiomas are vascular malformations that represent the most common congenital lesion in humans and the most frequent benign tumor in children.1 They consist of a series of dilated, thin-walled capillaries with a single layer of endothelium and a thin adventitia.1 Hemangiomas may occur as a single mass or as part of a cluster of dilated vascular structures that have a mulberry appearance. Although hemangiomas are found throughout the body, the most common sites are the subcutaneous tissue, liver, and skeletal muscle. Approximately 65% are associated with structures of the head or neck, of which 86% are supratentorial and 24% infratentorial.1 Males and females are affected in equal parts. Hemangiomas may occur in a sporadic or familial fashion, related to mutations in CCM1, CCM2, and CCM3.2,3Despite being mostly asymptomatic, hemangiomas can be associated with a multitude of symptoms, ranging from headaches and seizures to severe focal neurologic deficits and hemorrhage.4On gross examination, cavernous hemangiomas appear as soft, purple, poorly defined, and discolored lesions that blanch on compression. Pathologic examination reveals thin-walled, dilated capillaries surrounded by a single layer of endothelium.1 Magnetic resonance imaging remains the diagnostic imaging of choice. Other imaging modalities, including radiography, computed tomography, and tagged red blood cell scans, are commonly used for additional characterization.1,5Treatment of cavernous hemangiomas is based on their location and symptoms and may include medical or surgical interventions. Asymptomatic lesions are observed and monitored with interval imaging studies. Sclerosing agents and corticosteroids have been used to shrink tumors and prevent scaring. Lesions that cause compressive symptoms, hemorrhage, seizures, or neurologic deficits require prompt intervention. Surgical planning must consider the risks and benefits of the procedure, especially for lesions deep in the central nervous system. Predictors of good surgical outcome included mesiotemporal location, small size, and absence of long and poorly controlled preoperative seizure history.6

Surgery

A woman in her mid-50s presented to the clinic with a 6-month history of progressive swelling and pain on the right side of her neck. The patient described a history of sleep apnea, a remote transient ischemic attack with left-sided weakness, and a prior thyroidectomy. She had increasing fatigue during the last 6 months, as well as worsening anxiety. On physical examination, the neck was supple, with no palpable masses or lymphadenopathy, and had a well-healed transverse neck incision. Magnetic resonance imaging revealed a 1.1-cm, round, partially enhancing, cystic mass near the tail of the parotid gland that appeared hypointense on T2-weighted imaging (Figure 1). An enlarged and distended venous structure that measured up to 7 mm was also visualized in the area. Laboratory work revealed no abnormalities.Magnetic resonance images of the parotid gland. T1-weighted image (A) and T2-weighted image (B) revealing a round, partially enhancing, cystic mass near the tail of the parotid gland (white and red arrowheads).

what is your diagnosis?

What is your diagnosis?

Cavernous hemangioma

Paraganglioma

Schwannoma

Pseudoaneurysm

a

female

51-60

White

original

https://jamanetwork.com/journals/jama/fullarticle/2429692

A 30-year-old woman presented to the rheumatology clinic after experiencing 2 months of fatigue and polyarthralgias of the wrists, hands, knees, and feet. She reported no joint swelling or morning stiffness. She previously saw her primary care physician who prescribed celecoxib (for joint pain) and ordered antinuclear antibody (ANA) testing, which was positive at a value of 1:80 (Table). She was then referred to the rheumatology clinic. The patient reported no history of fever, weight loss, photosensitivity, malar rashes, skin thickening, oral or nasal ulcers, weakness, Raynaud phenomenon, sicca symptoms, chest pain, shortness of breath, or abdominal pain. She was not taking any medications because 2 weeks after starting celecoxib, her joint pain resolved and she discontinued use without recurrence of pain. The patient had no family history of autoimmune diseases. On examination, her vital signs, including blood pressure, were normal; and results of skin, thyroid, musculoskeletal, mucus membranes, cardiovascular, pulmonary, and neurologic examinations were all normal. Additional test results, which were obtained after her rheumatology visit, are presented in the Table.The patient will develop SLE in the futureThe positive ANA test result is nonspecific and may be related to autoimmune thyroid disease How Do You Interpret These Test Results?

The patient has rheumatoid arthritis

The patient has systemic lupus erythematosus (SLE)

The patient will develop SLE in the future

The positive ANA test result is nonspecific and may be related to autoimmune thyroid disease

D

The positive ANA test result is nonspecific and may be related to autoimmune thyroid disease

ANAs result from dysregulation of the immune system, which leads to autoantibodies against a variety of cellular and nuclear antigens. The most common methods to test for ANA are indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). The IIF is the reference method because it has higher sensitivity than ELISA for patients with systemic lupus erythematosus.1 However, unlike ELISA, IIF is time intensive and requires technical expertise.1 The sensitivity of various ELISA platforms ranges from 69% to 97% with specificity between 81% and 97% for diagnosing SLE.2 ANA is frequently tested in patients with low pretest probability for SLE, resulting in a poor positive predictive value; 2.1% in one study from a tertiary referral center.3ANA is a nonspecific test and positive results can be seen in healthy individuals and in patients with autoimmune thyroid disease, idiopathic thrombocytopenic purpura, infections, and multiple sclerosis.4 ANA is present in as many as 45% of patients with autoimmune thyroid disease.5 The estimated prevalence of SLE in the United States is 0.24% (95% CI, 0.13%-0.35%)6 in people aged 17 years and older whereas the estimated prevalence of ANA in individuals 12 years and older is 13.8% (95% CI, 12.2%-15.5%).7 The approximate midpoint reimbursement by Medicare for ANA is $17.The patient is a young woman with an 8-week history of fatigue and polyarthralgias without swelling or morning stiffness. She had no other symptoms to suggest SLE or rheumatoid arthritis. Testing for ANA is most helpful in the evaluation of patients suspected of having SLE and may be helpful in the evaluation of patients suspected of having other rheumatologic diagnoses such as Sjögren syndrome, systemic sclerosis, juvenile idiopathic arthritis, inflammatory myositis, mixed connective tissue disease, drug-induced lupus, and autoimmune hepatitis.4 ANA is not helpful in the diagnosis of rheumatoid arthritis.4In this patient, an antithyroglobulin antibody level was checked because of symptoms of hypothyroidism and known association of positive ANA with autoimmune thyroid disease. The low titer ANA in this patient could be related to autoimmunity against the thyroid gland given her positive thyroglobulin antibody level. However, autoantibodies like ANA, anti-Ro (anti-SSA), anti-La (anti-SSB), anti–double-stranded DNA, and antiphospholipid antibodies may be present years prior to the onset of SLE.8 Patients with positive ANA levels should be counseled about warning signs and symptoms of connective tissue diseases. In cases of uncertainty, serial clinical evaluations may be helpful.Physicians are often faced with challenging clinical scenarios in which the diagnosis of a connective tissue disease is uncertain. In patients suspected of having SLE but not fulfilling ACR classification criteria, the presence of oral ulcers, renal disease (defined by as persistent proteinuria, cellular casts, or both), and anti–double-stranded DNA antibodies were predictors of evolution to definite SLE.9 Although not everyone with a positive ANA requires evaluation by a rheumatologist, in cases of uncertainty, it may be helpful to refer patients to a rheumatologist for evaluation. Testing all patients with a positive ANA for thyroid-specific antibodies is unnecessary and should be at the discretion of the evaluating physician.This patient was reassured that she does not have SLE. It is difficult to predict if she will develop SLE in the future. The signs and symptoms of both SLE and autoimmune thyroid disease were discussed because the presence of antithyroglobulin antibodies increases her future risk of thyroid dysfunction.10ANA is a highly sensitive test for SLE.Positive ANA results are nonspecific and can be found in healthy individuals (13.8% of the adult general population) and in those with other rheumatologic conditions and many nonrheumatologic conditions such as autoimmune thyroid disease.Testing for ANA in patients with low pretest probability for SLE may result in positive results of little clinical significance and cause undue anxiety in patients and their clinicians.

Diagnostic

A 30-year-old woman presented to the rheumatology clinic after experiencing 2 months of fatigue and polyarthralgias of the wrists, hands, knees, and feet. She reported no joint swelling or morning stiffness. She previously saw her primary care physician who prescribed celecoxib (for joint pain) and ordered antinuclear antibody (ANA) testing, which was positive at a value of 1:80 (Table). She was then referred to the rheumatology clinic. The patient reported no history of fever, weight loss, photosensitivity, malar rashes, skin thickening, oral or nasal ulcers, weakness, Raynaud phenomenon, sicca symptoms, chest pain, shortness of breath, or abdominal pain. She was not taking any medications because 2 weeks after starting celecoxib, her joint pain resolved and she discontinued use without recurrence of pain. The patient had no family history of autoimmune diseases. On examination, her vital signs, including blood pressure, were normal; and results of skin, thyroid, musculoskeletal, mucus membranes, cardiovascular, pulmonary, and neurologic examinations were all normal. Additional test results, which were obtained after her rheumatology visit, are presented in the Table.The patient will develop SLE in the futureThe positive ANA test result is nonspecific and may be related to autoimmune thyroid disease

how do you interpret these test results?

How do you interpret these results?

The patient has systemic lupus erythematosus (SLE)

The patient has rheumatoid arthritis

The patient will develop SLE in the future

The positive ANA test result is nonspecific and may be related to autoimmune thyroid disease

d

female

21-30

original

https://jamanetwork.com/journals/jama/fullarticle/2425720

A 67-year-old woman presented with fatigue for 4 weeks. She had a history of type 2 diabetes mellitus, hypertension, hyperlipidemia, and allergic rhinitis. Her medications included metformin, lisinopril, and verapamil. Her cardiac and pulmonary examinations were normal. She had no fever or lymphadenopathy. The spleen was palpable 5 cm below the left costal margin. Laboratory evaluation revealed a white blood cell (WBC) count of 91 ×103/μL, with 54% neutrophils, 1% blasts, 2% basophils, 8% metamyelocytes, 23% myelocytes, and 1% promyelocytes (increased immature granulocytes). Hemoglobin level was 11.7 g/dL and platelet count was 290 000 (Figure 1). What Would You Do Next?

Order a heterophile antibody test

Perform a bone marrow biopsy

Start cytarabine and daunorubicin chemotherapy

Order leukapheresis

Chronic myelogenous leukemia (CML)

B

Perform a bone marrow biopsy

The key to the diagnosis was the patient’s leukocytosis with a granulocytic predominance. These findings suggest either a leukemoid reaction due to an infection or a myeloid malignancy. The WBC count greater than 50 ×103/µL, splenomegaly, and lack of infectious symptoms make malignancy more likely. Specifically, infectious mononucleosis attributable to Epstein-Barr virus is unlikely without fever and lymphadenopathy, despite the presence of splenomegaly. The low percentage of blasts makes acute myeloid leukemia (AML) unlikely, and the lack of dysplastic cells reduces the likelihood of myelodysplastic syndrome. The high WBC count, increased granulocytes at different stages of maturation, absolute basophilia, and normocytic anemia support a diagnosis of CML.CML is a clonal myeloproliferative neoplasm arising from hematopoietic progenitor cells.1 A balanced reciprocal translocation of chromosomes 9 and 22, in which pieces of the chromosome are rearranged but no genetic material is gained or lost, results in formation of the Philadelphia (Ph) chromosome.1,2 This rearrangement leads to the BCR gene fusing with the ABL1 gene, creating an oncogene.2 This oncogene is translated into an oncoprotein with continuous tyrosine kinase activity that causes uncontrolled cell proliferation.2 The incidence of CML is 0.6 to 2.0 cases per 100 000, increases with age, and is higher in men.3 The advent of tyrosine kinase inhibitors (TKIs) led to prolonged survival, and annual all-cause mortality for patients with CML has decreased from a range of 10% to 25% in the first 10 years of treatment to 2%. In 2010, the prevalence of CML was 70 000 cases in the United States.4Approximately 30% to 50% of patients with CML are asymptomatic and are diagnosed based on an abnormal complete blood cell count during routine blood work.5 Symptoms of CML include fatigue due to anemia and early satiety and left upper quadrant discomfort due to splenomegaly.5 CML is a triphasic disease: the chronic phase is indolent with limited blasts; the accelerated phase demonstrates increasing WBC count, blasts, and splenomegaly; the blast phase resembles AML.1,5 CML is most often diagnosed during the chronic phase and is highly responsive to TKI therapy, but it will progress to the accelerated and blast phases in 3 to 5 years if untreated.1,5In addition to characteristic findings on the peripheral blood smear, CML is diagnosed by identification of the Ph chromosome on bone marrow cytogenetics and the BCR-ABL1 fusion gene by fluorescence in situ hybridization (FISH).6 Elevated BCR-ABL transcript levels measured by quantitative reverse transcriptase polymerase chain reaction (QPCR) also support the diagnosis.6CML was the first cancer for which a molecularly targeted therapy was developed. TKIs block the BCR-ABL oncoprotein, thus halting the constant signal for cell proliferation and survival, and are the primary therapy for chronic phase CML.6 Imatinib was the first TKI approved by the US Food and Drug Administration for CML (2001), followed by dasatinib and nilotinib.6The goal of TKI therapy is complete cytogenetic response (CCyR), defined as no cells with a Ph chromosome, by 12 months after initiation.6 Early CCyR is associated with better overall survival and decreased disease progression.7 Early major molecular response, defined as a 3-log reduction in BCR-ABL1 transcripts by QPCR from a standardized baseline, corresponding to 0.1% of initial transcripts present, is desirable, and the prognostic significance is under investigation.6,8,9 Patients who do not respond to TKIs or lose their response should be evaluated for BCR-ABL kinase mutations, such as T315I, that cause drug resistance.6 If a mutation is identified, patients may respond to a different TKI or alternative therapies, including stem cell transplantation.10A bone marrow biopsy showed hypercellular marrow, with increased granulocytes with a mild shift to immaturity. Cytogenetic analysis showed t(9;22) as the sole chromosome abnormality. FISH analysis revealed BCR-ABL1 fusion in 97% of analyzed cells, and BCR-ABL transcripts by QPCR in the peripheral blood were elevated by 122.68% above normal, confirming the CML diagnosis.One month after beginning therapy with dasatinib, the patient’s blood counts normalized and her splenomegaly resolved.

General

A 67-year-old woman presented with fatigue for 4 weeks. She had a history of type 2 diabetes mellitus, hypertension, hyperlipidemia, and allergic rhinitis. Her medications included metformin, lisinopril, and verapamil. Her cardiac and pulmonary examinations were normal. She had no fever or lymphadenopathy. The spleen was palpable 5 cm below the left costal margin. Laboratory evaluation revealed a white blood cell (WBC) count of 91 ×103/μL, with 54% neutrophils, 1% blasts, 2% basophils, 8% metamyelocytes, 23% myelocytes, and 1% promyelocytes (increased immature granulocytes). Hemoglobin level was 11.7 g/dL and platelet count was 290 000 (Figure 1).

what would you do next?

What would you do next?

Start cytarabine and daunorubicin chemotherapy

Order leukapheresis

Perform a bone marrow biopsy

Order a heterophile antibody test

c

female

61-70

White

original