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Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved., Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics., Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance., Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling., (Copyright © 2019 American Academy of Dermatology, Inc. All rights reserved.)

Background: Hidradenoma papilliferum (HP) is a benign tumor that primarily affects the anogenital area of adult women. Previously considered apocrine tumors, anogenital HP tumors are now interpreted as adenomas of mammary-like anogenital glands based on their histologic features., Objective: This clinical study was undertaken to determine whether vulvar HP is located on mammary-like anogenital gland sites and to describe its morphologic features., Methods: The clinical photographs of 52 histologically confirmed vulvar HP provided by 7 vulva specialists were analyzed., Results: In all, 90.4% of the HP were located on the interlabial sulcus, adjacent zone, or the perineum. These tumors were polymorphous in terms of number (1 or multiple), size (<1-4.5 cm), color (pink, red, blue), surface (ulcerated or not), and architecture (unilobular or multilobular)., Limitations: Eight histologic reports could not be reviewed by the authors but the contributors confirmed that the photographs sent were only those of histologically confirmed HPs., Conclusions: Vulvar HP is mainly located on mammary-like anogenital gland sites, thereby providing further evidence to their histogenesis. Although a nonulcerated or ulcerated tumor of the interlabial sulcus should evoke a HP diagnosis, the latter must be confirmed histologically., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied., Objective: We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family)., Methods: We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer., Results: The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families., Limitations: The study was not population based., Conclusions: This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Carney complex is an autosomal dominant endocrine disorder associated with skin involvement., Objective: To describe the dermatological signs of patients diagnosed with Carney complex (CNC) or primary pigmented adrenocortical nodular disease (PPNAD)., Methods: We conducted a prospective, single-center descriptive study of inpatients and outpatients at a university hospital endocrinology department. Sixteen patients from 14 families diagnosed with CNC or PPNAD were prospectively included in the study between September 2003 and March 2006. Data collected were age at enrollment; sex; Fitzpatrick skin phototype; the presence, location, and density of classic CNC skin lesions--lentigines, freckles, blue nevi, cutaneous myxoma--and other non-disease-specific skin lesions. Histopathologic analysis was carried out in cases in which the lesions were thought to be degenerative or to confirm the diagnosis. Patients were systematically assessed for endocrine and visceral involvement and genotyped for the PRKAR1A gene., Results: Twelve patients had lentiginosis (75%), 7 patients had blue nevi (43%), and 5 patients had cutaneous myxoma (31%). Patients could be classified into 3 groups based on skin signs: patients with no prominent skin lesions (n = 3), patients with skin lesions that could not be directly linked to CNC (n = 4), and patients with cutaneous lesions suggestive of CNC (n = 9). We found a correlation between dermatological and endocrine signs in 3 groups of patients: patients with few lesions, patients with an intermediate phenotype, and patients with both many endocrine signs and dermatological signs., Limitations: The classification proposed in our study should be validated on more patients., Conclusions: Skin manifestations are heterogeneous in patients with CNC, and skin phenotype seems to be correlated with endocrine phenotype.

Background: The coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy (BCM) is rare., Objective: Our aim was to assess the clinical and pathologic aspects of coexistent CTCL and BCM and to examine potential explanations for this association., Methods: We report six cases of concurrent CTCL and BCM in which B- and T-cell lineages were demonstrated by immunologic studies. The literature includes 13 additional cases. All 19 CTCL-BCM cases are reviewed., Results: CTCL either preceded or followed the BCM, which was a low-grade malignancy in most cases (16 of 19). Possible explanations for the association include a genetic predisposition, underlying viral infection, chemotherapy-induced carcinogenesis, stimulation of a B-cell clone by malignant helper T cells, and alterations in progenitor cells before determination of B- and T-cell lineage., Conclusion: An alteration in progenitor cells, with subsequent oncogenic activation of variable origin, might account for most cases of coexistent CTCL and BCM.

Background: Cutaneous changes associated with recombinant interleukin 2 (r IL-2) administration are frequent but have been rarely studied in a large series., Objective: We analyzed these clinical, microscopic, and immunologic changes., Methods: Patients with metastatic melanoma treated with r IL-2 were studied. The eruption was scored as mild or severe. Biopsy specimens were obtained for histopathology, ultrastructural analysis, and immunophenotyping. Chi-square and t tests were used for statistics., Results: Twenty-five patients were included. Eruptions were observed in 56 of 78 cycles (72%); 53 were mild with a burning pruriginous erythema, and 3 were severe with urticaria, necrotic lesions, and blisters. Regression was constant without sequelae. Pathologic changes were mild with a mononuclear cell infiltrate of activated helper T phenotype, expressing LFA-1. Keratinocytes and endothelial cells displayed intercellular adhesion molecule-1 and HLA-DR. Cells rarely expressed CD25., Conclusion: Administration of r IL-2 triggers non-treatment-limiting cutaneous inflammation.

The clinical and pathologic features of primary neuroendocrine carcinoma of the skin in 18 elderly patients are reported. The carcinomas arose in the dermis and subcutaneous tissues, particularly on the head and the upper extremities. One tumor occurred in an irradiated area. Using Gould's clinicopathologic classification, we have found four trabecular types, eleven intermediate cell types, and two small cell types. One tumor could not be classified. Other noteworthy pathologic features were association with invasive squamous cell carcinoma, lentiginous melanocytic hyperplasia, and presence of intratumoral melanocytes. Immunoreactivity for cytokeratins (56 kD), neurofilaments, neuron-specific enolase, and epithelial membrane antigen was observed. The paranuclear globular staining pattern of cytokeratins and neurofilaments was conspicuous. The ultrastructural features revealed paranuclear intermediate filament aggregates (fibrous bodies), neurosecretory granules, and cell junctions. In two metastatic tumors, high levels of catecholamines were found. The trabecular types were characterized by localized disease and a good prognosis. The patients with the small cell types died of distant metastases. Postoperative radiotherapy seemed to reduce the rate of local recurrences.

Choriocarcinoma is a malignant growth of trophoblastic cells characterized by the secretion of human chorionic gonadotropin. Primary choriocarcinoma arising in the placenta during a seemingly normal gestation is rare. Very few choriocarcinomas occurring simultaneously in mother and child have been reported so far. We describe an additional case of placental choriocarcinoma metastasizing to the newborn and showing many different cutaneous tumors. The primary tumor was found in the placenta. In the newborn, diagnosis was performed by skin biopsy only a few days after birth (by optic and electron microscopy). Immunohistochemical localization of human chorionic gonadotropin was performed by the immunoperoxidase technic with the use of monoclonal antibodies. This report describes an additional case and summarizes previously reported cases of placental choriocarcinoma metastasizing to the infant, as well as cases of skin metastases from malignant gestational trophoblastic disease.