Definition

A destinctive melanocytic tumor which may arise sporadically or less often represent a germline mutation in the tumor-suppressor gene BRCA1-associated protein-1 (BAP1). The latter is associated with an increased risk of devloping mesothelioma, uveal melanoma, cutaneous melanoma, Merkel cell carcinoma, basal cell carcinoma, meningioma & renal cell carcinoma

Alternative nomenclature

•BAP1-inactivated melanocytic tumors (BINT)

•Wiesner’s nevus

•Melanocytic  BAP1-mutated atypical intradermal tumor (MBAIT)

•Epithelioid atypical Spitz tumor

•Spitz nevus with halo-like reaction

•BAP1-negative atypical Spitz tumor

•BAP1-inactivated Spitzoid nevus

•Spitzoid tumor of uncertain malignant potential (STUMP)

Clinical features

•Pedunculated orange-brown or erythematous dome-shaped nodules

•0.5-1.0 cm diameter

•Head, neck, trunk & limbs

•Mostly 2-3^rd decade

Histological features, immunohistochemistry and molecular studies

•Spitzoid

•Rhabdoid

•Nevoid (don’t misdiagnose as nevoid melanoma)

•BAP1 loss in blue nevus-like melanoma (GNAQ & GNA11 mutations)

•Lacks acanthosis, clefting, Kamino bodies and spindle cells as seen in Spitz nevus

•May be a pure population (rare) or biphasic in association with banal or congenital nevus-like component

•Lymphocytic infiltrate

•Large epithelioid (sometimes Spitzoid or rhabdoid) cells with ground-glass cytoplasm

•Nuclear pseudoinclusions

•Few mitoses & variable pleomorphism

•Perinuclear clumps (Gammon)

•SOX10, S100, Melan-A, PRAME (often positive)

•BAP1 almost invariably negative (nuclear) however see abstract below

•BRAF p.V600E (67-89%) mutation in all tumor cells, loss of BAP1 in epithelioid cells

•BAP1 gene product is a nuclear located deubiquitinase and affects transcription, differentiation and DNA damage response through the Ataxia Telangiectasia (ATM) pathway

•Possible role in apoptosis through Ca2+flux

•(Zhang A. et al J Cut Pathol, 2019;46:965-972)