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

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.

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.

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.

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.