Lack of Rb and p53 Expression in a Case of CM2B4 Negative Merkel Cell Carcinoma In Situ Associated With Squamous Dysplasia

Merkel cell carcinoma (MCC) is a dermal neuroendocrine malignancy driven by inactivation of the tumor suppressors Rb and p53 either through Merkel cell polyomavirus (MCPyV) infection or ultraviolet (UV)‐induced mutations. Virus‐positive MCC exhibits pure neuroendocrine morphology, low UV‐induced mutational burden, retained Rb protein, and low p53 expression. Viral‐negative MCC includes pure neuroendocrine carcinomas and combined tumors with squamous and neuroendocrine components. These tumors typically exhibit loss of Rb expression and either overexpression of mutated p53 or a complete absence of p53. Intraepidermal, in situ MCC (MCCis) is a rare, primarily viral‐negative variant that often coexists with actinic keratosis (AK) and squamous cell carcinoma in situ (SCCis), supporting a UV‐driven pathogenesis. While MCCis is hypothesized as a potential precursor to select cases of combined MCC, its p53 and Rb expression remain largely uncharacterized. We report a CM2B4‐negative MCCis in an 87‐year‐old man associated with AK and SCCis. Compared to normal epidermis, AK and SCCis exhibited increased Rb and p53 expression, whereas MCCis demonstrated loss of expression of both tumor suppressors. These findings suggest that dual downregulation of Rb and p53 may drive select cases of MCCis in sun‐damaged skin.