Evidence for Wnt/β-Catenin-Activated Rosette-Forming Carcinoma Arising in Rb-Inactivated Bowen Disease

Wnt/β-catenin-activated nonpilomatrical rosette-forming carcinoma is a recently described skin neoplasm with a distinct morphology and pathogenic profile involving mutations in the APC/CTNNB1 and RB1 genes. We report a Wnt/β-catenin-activated, invasive, rosette-forming carcinoma surrounded by Bowen disease on the leg of a 90-year-old woman. Pathogenic mutations in RB1 and APC with allelic frequencies of 83.5% and 53.92%, respectively, were detected by NGS. The invasive tumor showed a predominantly peripheral basaloid component forming rosettes and a poorly differentiated squamoid component and exclusively the former arose multifocally in the Bowen disease. Heterogeneous synaptophysin, chromogranin, BerEp4, and CK7 immunostaining were present in the invasive tumor but not in Bowen disease. Diffuse nuclear β-catenin and Rb loss were found in both invasive components. In Bowen disease, there was also diffuse Rb loss but only some variably sized spots of nuclear β-catenin immunostaining. CDX2 immunoreactivity varied among the three components. It was more extensive in poorly differentiated areas and showed an inverse correlation with the proliferation rate. Our histopathologic, immunohistochemical and genetic findings provide further evidence that Bowen disease may act as a precursor for the rosette-forming component of the Wnt/β-catenin-activated carcinoma and that there is an inverse correlation between CDX2 expression and the proliferation rate.