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Combined BRAFV600E-positive Melanocytic Lesions With Large Epithelioid Cells Lacking BAP1 Expression and Conventional Nevomelanocytes

Busam, Klaus J. MD*; Sung, Joanne MD; Wiesner, Thomas MD; von Deimling, Andreas MD§,∥; Jungbluth, Achim MD

The American Journal of Surgical Pathology: February 2013 - Volume 37 - Issue 2 - p 193–199
doi: 10.1097/PAS.0b013e318263648c
Original Articles

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 BRAFV600E 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 BRAFV600E. 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.

*Department of Pathology

Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center

Ludwigs Cancer Research Institute, New York, NY

Department of Dermatology, Kaiser Permanente, Walnut Creek, CA

§Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg

Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Klaus J. Busam, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065 (e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.