Role of single-nucleotide pleomorphism microarray in the classification of BAP1-inactivated melanocytic tumours.

Aims: BAP1-inactivated melanocytic tumours (BIMTs) occur sporadically and in association with a familial tumour predisposition syndrome involving germline mutations in the BRCA1-associated protein-1 (BAP1) gene. Here we report the clinical features, histopathologic findings, and chromosomal copy number data of 19 BAP1-inactivated melanocytomas (BIMs) and compare their features to those of five BAP1-inactivated melanomas.

Methods: We retrospectively searched the Department of Pathology archives and EMERSE (Electronic Medical Record Search Engine) for BIMTs that had undergone single-nucleotide polymorphism (SNP) microarray testing. Clinical history/follow-up data, detailed histopathologic features, and SNP microarray results were recorded.

Results: Overall, four patients (4/13) with BIMs and available clinical history had features suspicious for a germline BAP1 aberration. In BIMs (19 cases), the BAP1-inactivated component showed variable cytologic features, including epithelioid (predominant), rhabdoid, plasmacytoid, and nevoid morphologies. Sentinel lymph node biopsy was negative in all (6/6) patients in which this procedure was performed. No patient diagnosed with a BIM with available clinical follow-up (18/19; mean 38 months) experienced an adverse event. While the histologic appearances of the five melanomas varied, one case resembled a BIM. The median mitotic count was 1/mm² (range 0-6 mm²) in BIMs compared to 3/mm² (range 1-4/mm²) in melanomas (P = 0.04). The median number of copy number alterations (CNAs) was two (range 0-6) in indolent cases versus seven (range 6-10) in melanomas (P = 0.0005). The most common molecular aberration after loss of 3p21 was heterozygous loss of the CDKN2A locus, which unlike homozygous loss has not been associated with melanoma.

Conclusion: While most BIMs appear to have a favourable prognosis, even those with multiple CNAs, they deserve careful integration of all clinical and pathologic findings. Although not fully diagnostic, a mitotic count of ≥3/mm² and ≥6 CNAs in the appropriate context is supportive of a diagnosis of BAP1-inactivated melanoma.