Molecular comparison of concurrent components of high-grade dysplasia, adenocarcinoma, and sarcomatoid carcinoma in a case of sarcomatoid carcinoma of the gallbladder

Detailed genetic and immunohistochemical features of a sarcomatoid carcinoma of the gallbladder were reported. Studied was a resected gallbladder tumor involving the transverse colon, which was consisted of 3 histopathological neoplastic components, i.e., high-grade dysplasia, adenocarcinoma, and sarcomatoid carcinoma. The targeted amplicon sequencing showed somatic mutations in TP53 (p.S90fs) and ARID1A (c.4993 + 1G > T) in all of the 3 components. Copy numbers of CDKN2A and SMAD4 were decreased in the adenocarcinoma and the sarcomatoid component. Immunohistochemistry showed loss of expression of p53 and ARID1A in all components. p16 expression was lost in the adenocarcinoma and the sarcomatoid component, while SMAD4 expression was lost only in the latter. These results suggest that this sarcomatoid carcinoma may have developed by progression from high-grade dysplasia via adenocarcinoma with sequential accumulation of molecular aberrations involving p53, ARID1A, p16, and SMAD4. This information should serve to understand the molecular mechanism of this very intractable tumor.