LAUSR

Sir, We report the first cases of cutaneous squamous cell carcinoma in situ (SCC IS) and invasive squamous cell carcinoma (SCC) with BRCA1-associated protein-1 (BAP1) loss/inactivation in a patient known to have a BAP1 germline mutation. This expands the clinical phenotype of the BAP1 tumour predisposition syndrome, and therefore is of importance to pathologists and clinicians to enable more accurate recognition of individuals and families at risk of this recently described familial tumour syndrome. In addition, in the same patient, we document the occurrence of an unusual BAP1 deficient metastatic carcinoma that behaved in an aggressive manner. Based on careful cliniopathological correlation, the metastatic carcinoma was strongly favoured to have arisen from a cutaneous primary. This unusual case raises the distinct possibility that a subset of BAP1-associated cutaneous malignancies may be at high risk of metastasis and adverse outcomes. The BAP1 gene locus encodes a deubiquitylating enzyme that catalyses the removal of ubiquitin from protein substrates. It has been shown that BAP1 acts as a tumour suppressor gene through its involvement with numerous biological processes including regulation of the cell cycle, cell differentiation, cell death, gluconeogenesis and DNA damage response. However, complete understanding of the mechanisms of action of BAP1 are not yet fully