title: Combined BRAF(V600E)-positive melanocytic lesions with large epithelioid cells lacking BAP1 expression and conventional nevomelanocytes.
abstract: Recently a group of spitzoid melanocytic proliferations with loss of BAP1 expression has been reported. The lesions may occur sporadically or as part of a familial cancer syndrome. They have distinct histopathologic features characterized by a nevus-like silhouette and cytologic composition of large epithelioid melanocytes with oval vesicular nuclei, distinct nucleoli, and abundant cytoplasm with well-defined cytoplasmic borders. A characteristic immunohistochemical finding is loss of nuclear labeling for BAP1. In contrast to classic Spitz nevi, the lesions carry the BRAF mutation. They may present as a pure large epithelioid cell proliferation or as a combined lesion in association with a conventional nevus. Here we report a series of 8 combined melanocytic lesions, in which a dominant large epithelioid cell proliferation with loss of BAP1 expression was associated and intimately admixed with a BAP1-positive conventional nevus. These biphenotypic lesions were from 6 patients, 3 female and 3 male, ranging in age from 16 to 59 years. Immunohistochemical analysis for BAP1 showed loss of nuclear labeling confined to the large epithelioid melanocyte subpopulation. The conventional melanocytes retained BAP1 expression. Both large epithelioid and conventional melanocytes were immunoreactive with the monoclonal antibody VE1, which recognizes the protein encoded by mutant BRAF. In 6 cases the conventional nevus component was a compound nevus of small "type B" melanocytes. In 2 cases, the nevus remnant was entirely intradermal. The lesions described herein may represent a peculiar combined melanocytic nevus variant. However, longer follow-up and more studies are needed to determine the biological potential of the BAP1-negative melanocyte proliferations.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. busamk@mskcc.org
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Joanne
authors.initials: J
authors.lastname: Sung
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiesner
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Achim
authors.initials: A
authors.lastname: Jungbluth
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015622:Epithelioid Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000378:metabolism / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000172:deficiency* / Q000378:metabolism; D055815:Young Adult
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D043222:Ubiquitin Thiolesterase