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    Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.


    Tomohiko Ishikawa, Takenori Ogawa, Ayako Nakanome, Yasunari Yamauchi, Hajime Usubuchi, Masahiro Shiihara, Takuya Yoshida, Yasunobu Okamura, Kengo Kinoshita, Yukio Katori, Toru Furukawa. Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland. Virchows Archiv : an international journal of pathology. 2021 Jan 07

    PMID: 33415446

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