Metatypical basal cell carcinoma with diffuse PRAME expression

Summary: Preferentially Expressed Antigen in Melanoma (PRAME) is a nuclear receptor and transcriptional activator in the cancer/testis antigen family. Aberrant overexpression of PRAME is typically associated with melanoma but has been found in various non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC). In this case study, we describe a 70 year old male presenting with a lobulated and superficially ulcerated nodule on his left dorsal forearm. A shave biopsy showed a nodular and cystic BCC with focal areas of clear cell and squamoid differentiation. The lesional cells were positive for BerEp4, CK7, CK5/6, and CK19 on immunohistochemical staining. PRAME showed diffuse, strong nuclear positivity in >90% of the cells of interest. PRAME expression in NMSC represents a potential diagnostic pitfall, and variable immunoreactivity with PRAME has been described in squamous cell carcinoma, Merkel cell carcinoma, sebaceous carcinoma, and other cutaneous neoplasms. Regarding BCC, one study found that 59.4% of cases demonstrated nuclear PRAME staining, typically with low intensity staining and with accentuation of the peripheral palisade cells. Our case highlights a subset of BCCs with diffuse, high-intensity nuclear staining with PRAME. It is crucial to recognize the staining patterns of PRAME in BCC to avoid a potential misdiagnosis of melanoma.