Concordance Analysis of the 23-Gene Expression Signature (myPath Melanoma) With Fluorescence In Situ Hybridization Assay and Single Nucleotide Polymorphism Array in the Analysis of Challenging Melanocytic Lesions: Results From an Academic Medical Center.

BACKGROUND: Fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) arrays are well-established molecular tests for the analysis of challenging melanocytic lesions. A 23-gene expression signature (GES), marketed as myPath Melanoma, is a recently introduced molecular test that categorizes melanocytic lesions as "benign," "malignant," and "indeterminate." There are few studies on the concordance between FISH, SNP, and GES in the analysis of melanocytic lesions. METHODS: A single-institution retrospective analysis of 61 contiguous cases of challenging melanocytic lesions with molecular analysis by 2 or more techniques. The primary objective was to determine the intertest agreement, which was calculated as percent agreement. A secondary objective was to determine the combined-test performance, that is, the frequency of obtaining a successful test (a test with an abnormal or normal, benign or malignant result) when 2 or more molecular tests were performed. RESULTS: Of the 61 cases, 58 cases were submitted for analysis using the GES assay, 44 cases were submitted for FISH analysis, and 21 cases were submitted for SNP array analysis. Percent agreement between GES and FISH array was 50.9% (18/34), which improved to 69.7% (18/23) when indeterminate/equivocal results were excluded. Similarly, percent agreement between GES and SNP array was 57.1% (8/14); this improved to 77.8% (7/9) when indeterminate/equivocal results were excluded. In 44% of cases submitted for GES and FISH and in 39% of cases submitted for GES and SNP, one test was successful and the other was not. CONCLUSION: For challenging melanocytic lesions, the choice of a molecular test is consequential as the GES assay correlated with FISH and SNP arrays approximately only half of the time. This improved when cases with indeterminate/equivocal results were excluded from the calculations. The combined-test analysis supports the utility of conducting more than one molecular test, as this increased the odds of obtaining a successful test.

Kikuchi-Fujimoto disease preceded by lupus erythematosus panniculitis: do these findings together herald the onset of systemic lupus erythematosus?

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare disorder that must be distinguished from systemic lupus erythematosus (SLE). Although a minority of patients with KFD develop SLE, most patients have a self-limited disease. Importantly, KFD can have skin manifestations resembling cutaneous lupus. Therefore, the diagnosis of SLE should be predicated on a complete rheumatologic workup and not on the constellation of skin disease and lymphadenitis. Nonetheless, as our exceedingly rare case illustrates, patients who do not initially meet diagnostic criteria for SLE require dermatologic follow-up. We present a young adult woman who had a remote history of KFD and later presented with combined features of discoid lupus and lupus erythematosus panniculitis (LEP). On subsequent rheumatologic workup, she fulfilled criteria for SLE. We discuss the differential diagnosis of both KFD and LEP and emphasize how strong communication among dermatologists and other healthcare providers is essential in the management of patients with KFD.

A diagnostically-challenging case of melanoma ex blue nevus with comprehensive molecular analysis, including the 23-gene expression signature (myPath melanoma).

Melanoma ex blue nevus (MEBN) is a rare, aggressive, and potentially lethal neoplasm. Distinguishing MEBN from an atypical cellular blue nevus can be very challenging. We report a diagnostically difficult case of MEBN with lymph node metastases, in which single nucleotide polymorphism array and fluorescence in situ hybridization were used to arrive at the correct diagnosis. It was also analyzed by the recently-introduced proprietary 23-gene expression signature test. To the best of our knowledge, this is the second reported case of MEBN analyzed by the 23-gene expression signature, which provided a false-negative result. More studies are needed to assess the sensitivity and specificity of this test in various melanocytic proliferations.

Cutaneous manifestations of systemic viral diseases in neonates: an update.

PURPOSE OF REVIEW: Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate. RECENT FINDINGS: HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis. SUMMARY: Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.

Comparing Whole Slide Imaging and Light Microscopy to Identify Tumor in en face Frozen Sections.

OBJECTIVE: To assess accuracy of whole slide imaging (WSI) in the interpretation of permanent and frozen sections in surgical pathology and the identification of tumors in cutaneous en face frozen sections. METHODS: Twenty glass slides containing cutaneous en face frozen sections were selected from twenty cases of keratinocyte carcinomas treated with Mohs micrographic surgery. Ten slides contained tumor and ten did not. A blinded dermatologic surgeon used traditional light microscopy (LM) to assess physical slides for tumor presence and type, while noting the confidence (scale 1-10) and time (min) in making the determination. After a seven-day washout period, the surgeon repeated this process using WSI of the same slides, each de-identified and scanned at 20x using the Aperio AT2 (Leica Biosystems). RESULTS: Percent agreement between LM and WSI was 100%, with Cohen's kappa of 1.0. The average time taken to determine tumor presence was significantly greater using WSI than LM. Similarly, the surgeon was significantly more confident using LM than WSI. CONCLUSION: This proof-of-concept study suggests that diagnostic concordance is excellent between LM and WSI in the evaluation of Mohs frozen sections. However, WSI was cumbersome to use, not ergonomic, and required significantly more time.