RF03: A UK case series of BRCA1-associated protein-1 inactivated melanocytic tumours from a tertiary referral centre: a marker for familial melanoma

H. Smith, E. Blakeway, A. Muinonen-Martin, B. Matthew, W. Merchant, S. Schirwan and A. Mitra

Leeds Teaching Hospitals NHS Trust, Leeds, UK

In 2012 Wiesner described a new subset of melanocytic tumours, initially thought to be atypical spitzoid neoplasms but notably demonstrating BRCA1-associated protein (BAP-1) inactivation and an epithelioid morphology. Over the last decade these lesions have been referred to as Wiesner naevi, BAPomas, naevoid melanoma-like proliferations and melanocytic BAP-1 mutated atypical tumours. Recently, the World Health Organization (Elder DE, Bastian BC, Cree IA et al. The 2018 World Health Organization classification of cutaneous, mucosal and uveal melanoma: detailed analysis of 9 distinct subtypes defined by their evolutionary pathway. Arch Pathol Lab Med 2020; 144: 500–22) described them as BAP-1-inactivated melanocytic tumours (BIMTs) encompassing a spectrum of lesions from clearly benign (naevi) to potentially malignant (melanocytomas), based on degree of atypia. They typically express BRAF somatic mutations along with loss of both BAP1 alleles, and are therefore considered intermediate tumours of uncertain malignant potential. There are also rare instances of melanomas arising within BIMTs. Although most occur sporadically, BIMTs have been identified with increased frequency in individuals with a hereditary germline mutation in BAP-1, which also endows a predisposition to cutaneous and uveal melanoma, mesothelioma, renal cell carcinoma and meningiomas. Currently, a diagnosis of any BIMT meets eligibility criteria for genetic testing (https://www.england.nhs.uk/publication/national-genomic-test-directories/). In 2020, we noted an increase in reporting of BAP-1-inactivated melanocytomas. Our aim was to better understand this phenomenon and to identify any correlations between cases. Through manual search of the Trust’s histopathology database and review of case notes, we identified 24 BIMTs in 18 patients. Nine lesions were classified as BAP-1-inactivated naevi (37%), 14 were BAP-1-inactivated melanocytomas (58%) and one was a melanoma arising within a BIMT (4%). Five patients have thus far undergone genetic testing, which revealed a BAP-1 germline mutation in three, two of whom have had multiple BMITs. The remaining patients await clinical genetics onwards referral/results. Forty per cent of BIMTs, and more specifically 69% of the melanocytomas, were diagnosed since 2019. This increase in reporting is most likely a result of enhanced histopathological identification. Follow-up data were available for 16 patients with no recurrences to date in those with BAP-1-inactivated naevi or melanocytomas. However, the patient with melanoma did develop regional lymph node recurrence at 30 months. Although preliminary evidence suggests that BIMTs follow an indolent course, follow-up so far is limited and there is little published literature regarding best management. Our multidisciplinary team currently recommends wide local excision for melanocytomas. We want to raise awareness of BMITs as improved identification will facilitate early genetic referral, with the potential for uveal and renal screening in those with confirmed BAP-1 germline mutations.