Track

Case Reports

Abstract

Introduction

BRCA1-associated protein-1 (BAP1)-inactivated melanocytomas (BAIM) are predominantly intradermal epithelioid melanocytic proliferations with loss of nuclear BAP1 expression by immunohistochemistry (IHC), a marker for BAP1 biallelic inactivation. Loss of function mutations of MutL protein homolog 1 (MLH1), a tumor suppressor involved in DNA mismatch repair (MMR), are seen in colorectal, sebaceous, and rarely in melanocytic neoplasms exhibiting microsatellite instability (MSI). To the best of our knowledge, we report for the first time a BAIM with subclonal MLH1 loss.

Case report

A 74-year-old female with no history of Lynch or Muir-Torre syndrome presented with a pink exophytic papule on her left dorsal arm. Histological examination revealed a predominantly intradermal SOX10+/BRAF+ epithelioid melanocytic neoplasm demonstrating loss of BAP1 expression. Concerning features included cellular clusters with high N:C ratios, focal p16 loss, and focal PRAME expression. FISH testing was negative for RREB1, CDKN2A/2B, CCND1, and C-MYC copy number alterations. Targeted next-generation sequencing showed BRAF V600E and BAP1 Q392* mutations at similar allelic frequencies. It also identified a MLH1 E523* loss of function mutation at a lower allelic frequency suggestive of a somatic mutation. MMR protein IHC stains showed isolated subclonal MLH1 loss in neoplastic cells. Given the molecular alterations in the absence of overtly malignant morphological features, a diagnosis of BAP1-inactivated compound melanocytoma with atypical features was made.

Conclusion

Taken together, the mutational allelic frequency of MLH1 and the MLH1 IHC stain suggest a subclonal process that could represent molecular progression in this intermediate-grade melanocytic neoplasm and provides an avenue for further exploration.