Trichoblastic carcinosarcoma with panfollicular differentiation (panfollicular carcinosarcoma) and CTNNB1 (beta‐catenin) mutation

Abstract

We present a case of trichoblastic carcinosarcoma with panfollicular differentiation. An 80‐year‐old man presented with a lesion on the left ear, which had been present for several months. Histopathology revealed a well‐demarcated neoplasm in the dermis composed of intimately intermingled malignant epithelial and mesenchymal cells. The epithelial component showed multilineage follicular differentiation toward all of the elements of a normal hair follicle. Molecular analysis revealed identical molecular aberrations in both epithelial and mesenchymal components including CTNNB1 and SUFU mutations. To the best of our knowledge, this is the first report of panfollicular carcinosarcoma and of the presence of a CTNNB1 mutation in trichoblastic carcinosarcoma.

Trichoblastic carcinosarcoma in a 34‐year‐old woman with histopathologic and molecular analysis, including re‐demonstration of a CDKN2A p.(R58*) mutation

“…The immunohistochemical profiles of these tumors remain to be fully characterized. Previous reports, as in our case, showed a sharp distinction between the epithelial and stromal components on cytokeratin staining 6,9,10,12,13 . The epithelial component of our case demonstrated positive staining for BerEP4.…”

“…The protein regulates expression of genes involved in cell cycle arrest, apoptosis, senescence, DNA repair, and changes in metabolism. TP53 is the most frequently mutated gene in cancer, 19 and variants in this gene were detected in five of the six cutaneous carcinosarcoma cases reported by Paniz‐Mondolfi et al 16 ; the variant TP53 p.Y205N was found in the recently reported case of trichoblastic carcinosarcoma 13 …”

“…Ultraviolet‐induced sun‐damage has been shown to play an important role in the pathogenesis of cutaneous carcinosarcomas, including with the frequent presence of TP53 mutations seen across a number of studies 1,15‐17 . These studies have also shown that in the majority of cases the epithelial and stromal components of cutaneous carcinosarcomas appear to originate from a single clone, with similar underlying molecular alterations seen in both components 13,15‐17 …”

“…Our molecular analysis found two pathogenic variants TP53 p.(R158C), TP53 p.(R273P), a likely pathogenic variant CDKN2A p.(R58*) and a variant of unknown significance MET p.(T1010I). Only a small number of studies have examined genetic variants in cutaneous carcinosarcomas (Table 3), including one other recent case report of trichoblastic carcinosarcoma 13 …”

“…Features that have been described as discriminatory include the presence of a distinct trichoblastic stroma, with a sharp demarcation between the epithelial and stromal components 4 . In addition, reported trichoblastic carcinosarcomas have been predominantly dermal‐based 13 …”