Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1‐associated cancer susceptibility syndrome

Abstract

We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions.

Gene of the month:BAP1

“…Two of three cases showed no recurrence or metastasis after 3 and 6 years of initial excision, despite having tumour depths of 2.5 and 4.5 mm, respectively 15. BAP1, BRCA1-associated protein 1.…”

“…In terms of prognosis, BAP1 germline mutations are associated with poor prognosis in UM, CM and RCC, while in mesothelioma they are associated with less aggressive disease 14. The BAP1 -deficient atypical Spitz tumours are generally benign lesions with a very low reported risk of malignant transformation 15. The molecular mechanism responsible for the difference in disease outcomes and the cellular pathways leading to carcinogenesis of specific tumour types are not clear.…”

Histopathology of melanocytic lesions in a family with an inherited BAP1 mutation

“…Marusic et al1 described the presence of nuclear pseudoinclusions and multinucleated melanocytes within five of six nevi from this family. The lesions were mainly intradermal, composed of large epithelioid melanocytes, and showed loss of BAP1 expression by immunohistochemistry.…”

“…We read with interest the report by Marusic et al1 who expanded on the histopathological features of melanocytic neoplasms in a family with an inherited BAP1 mutation.…”

“…Recognizing this pattern of clinical and histopathological presentation is key to identifying possible carriers of a BAP1 mutation, who have a cancer susceptibility syndrome, having a particular diathesis to cutaneous and uveal melanomas,3 meningiomas,4 mesotheliomas5 and renal cell cancers 1. Nuclear pseudoinclusions can be identified in several melanocytic tumors, including benign melanocytic nevi and even some melanomas 1. Although non‐specific, they appear to be a prominent feature of melanocytic lesions from patients with a germline BAP1 mutation.…”