Skin Basal Cell Carcinosarcoma in a Trichoblastic Guise-Molecular Characterization of a Novel Entity Mimicking a Pyoderma Gangrenosum.

Abstract

Basal cell carcinosarcomas (BCCSs) are rare, aggressive biphasic epithelial-mesenchymal neoplasms typically occurring in elderly patients. Their nonspecific clinical presentation may mimic inflammatory disorders, necessitating histopathological examination. We characterize a novel cutaneous BCCS with prominent trichoblastic differentiation, clinically mimicking ulcerative pyoderma gangrenosum. Although morphologically resembling trichoblastic carcinosarcoma (TBCS), the tumor retained a BCC-associated genetic signature, supporting a basal cell rather than a primary trichoblastic lineage. We therefore propose the provisional designation "basal cell carcinosarcoma with divergent trichoblastic differentiation (BCCS-DTB)", suggesting acquired follicular lineage plasticity within a Hedgehog-driven, UV-mutagenized BCC clone. Shared molecular alterations across epithelial and sarcomatous components support monoclonality and an inside-out epithelial-mesenchymal transition (EMT) model, with progressive acquisition of trichoblastic and sarcomatous features. The patient's young age, unusual tumor location, and development during the COVID-19 pandemic raise the hypothesis of additional environmental influences. Detection of associated spike protein and Snail expression is hypothesis-generating given their reported association with EMT. Further cases are required to validate the molecular profile for diagnostic and therapeutic relevance involving Hedgehog, FGFR2, and mTOR signaling.