Cappel, Mark A.

PURPOSEMore than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.PATIENTS AND METHODSGenes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables.RESULTSExpression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%).CONCLUSIONA combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

A female presented in the sixth decade of life with a history of undifferentiated small cell carcinoma of the right breast in clinical remission, status-post chemotherapy and resection 6 years previously, presented with a chronic anterior knee skin nodule that grew in size over the prior 5–6 weeks. She had no history of opportunistic infections or recent immunosuppression. As it grew, the nodule became tender to touch. Examination revealed a 4–6 mm superficial purple-red nodule. Also, a similar lesion was present on the dorsum of her left foot for the past year, which also recently grew and became tender. The patient did report frequently kneeling on soil when gardening in Florida. She reported no other symptoms. Due to a concern for cutaneous metastasis of the patient’s previously diagnosed small cell carcinoma of the breast, the anterior knee lesion was biopsied. Histology revealed histocyte-rich inflammation with foci of acute inflammation as well as pigmented fungal forms. Subsequent fungal culture of excised tissue grew Cladophialophora bantiana, identified by ribosomal gene DNA sequencing.

AbstractBackgroundAngioimmunoblastic T‐cell lymphoma (AITL) is a systemic peripheral T‐cell lymphoma with a follicular helper T‐cell (TFH) immunophenotype that frequently involves the skin. However, the histopathology of cutaneous involvement by AITL has not been fully established.MethodsWe reviewed the clinicopathological features of 19 patients seen at our institution with AITL involving the skin. Pan‐T‐cell and TFH marker expression was evaluated by immunohistochemistry. Epstein‐Barr virus (EBV) was detected using in situ hybridization (ISH) for Epstein‐Barr virus‐encoded small RNA (EBER). T‐cell receptor (TCR) gene rearrangement was evaluated by PCR.ResultsAITL affected both trunk and extremities in 15/19 cases (79%). Perivascular infiltration by small and/or medium‐sized lymphocytes was seen in 18/19 (95%). Granulomatous inflammation was identified in 4/19 (21%). Aberrant loss of CD2, CD5, or CD7 was identified in 1/18 (6%), 2/18 (11%), or 7/19 (37%) cases, respectively. Seventeen of eighteen evaluable cases (95%) expressed 2 to 3 TFH markers: PD‐1 in 19/19 (100%), BCL6 in 94% (17/18), and CD10 in 37% (7/19). EBV‐positive cells were detected in 3/18 (17%) with varying density. Clonal TCR gene rearrangement was identified in 9/11 (82%).ConclusionsCutaneous involvement by AITL shows relatively non‐specific histopathological features. However, an immunohistochemical panel including TFH markers and EBER ISH is useful in differential diagnosis.

AbstractPemphigus herpetiformis (PH), a rare type of pemphigus, is characterized by immunologic findings consistent with pemphigus but with a unique clinical and pathologic presentation. PH was first described as resembling dermatitis herpetiformis clinically, but because of its variable presentation, it can also resemble linear immunoglobulin A bullous dermatosis and bullous pemphigoid. We reviewed reported cases to analyze the most frequent clinical, pathologic, and immunologic characteristics and to propose corresponding diagnostic criteria. Through a comprehensive review of Medline and PubMed databases, 96 publications and 158 cases were identified. After reviewing the reported characteristics of PH, we suggest the following diagnostic criteria: Clinical: 1) pruritic herpetiform intact blisters with/without erosions; and/or 2) pruritic annular or urticarial erythematous plaques with/without erosions; Pathologic: 1) intraepidermal eosinophils or neutrophils, or both; and/or 2) intraepidermal split with/without acantholysis; Immunologic: 1) direct immunofluorescence showing immunoglobulin G with/without C3 intercellular deposits; and/or 2) indirect immunofluorescence showing immunoglobulin G to epithelial cell surface; and/or 3) detection of serum autoantibodies against desmogleins (1,3) or desmocollins (1,2,3), or both. Diagnosis requires one clinical, one pathologic, and one immunologic feature. We also report three new cases diagnosed at our institution to demonstrate the applicability of the suggested criteria.

BACKGROUND Extramammary Paget's disease (EMPD) is a rare intraepithelial malignancy with high recurrence rates following standard surgical treatments, ranging from 22% to 60% in large retrospective reviews. OBJECTIVE To evaluate the local recurrence rate of Mohs micrographic surgery (MMS) supplemented with intraoperative immunohistochemistry for cytokeratin-7 (MMS + CK-7) for primary and recurrent EMPD. MATERIALS AND METHODS Retrospective, multi-center, cross-sectional study of patients treated using MMS + CK-7. Demographic, clinicopathologic, treatment, and follow-up data were obtained by chart review. RESULTS The observed local recurrence rate for MMS + CK-7 is 3.3% (2/61 tumors) with a mean follow-up of 43.5 months (1–120 months). Local recurrence occurred in 2.3% (1/43) of primary tumors and 5.6% (1/18) of recurrent tumors. Kaplan–Meier 5-year tumor-free rates are 94.6% overall, 97.1% for primary tumors, and 80.0% for recurrent tumors. The Kaplan–Meier 5-year tumor-free rates for all EMPD tumors treated with MMS + CK-7 versus a historical cohort of MMS alone are 94.6% versus 72.0% (p = .012). CONCLUSION MMS + CK-7 is an effective treatment for EMPD, demonstrating improved outcomes compared with historical controls.