Abstract: Background and purpose: Carcinoma showing thymus-like differentiation (CASTLE) is a rare disease. There were few reports so far. The diagnosis and treatment experience and disease cognition are still insufficient. Methods: The clinical, pathological and prognostic data of 30 patients with CASTLE who received operation at Fudan University Shanghai Cancer Center from September 1, 2007 to September 1, 2021 were analyzed retrospectively. Three cases of thyroid carcinoma and adjacent tissues were analyzed by whole genome sequencing, and MSH2 gene overexpressed cells were transfected and constructed. The effects of mutant genes on cell biological behavior were detected by Western blot, cell activity and migration experiments. Results: 66.7% (20/30) of the 30 patients had different degrees of invasion. After an average follow-up of 60.6 months, distant metastasis occurred in 2 cases, and there was no local recurrence, progression or death. CD5 and CD117 could play important role in the diagnosis of CASTLE. Exon mutations in MSH2, FBXW7 and NOTCH1 were identified by whole gene detection and sequencing. The mutation rate of MSH2 was the highest, and may be involved in promoting the proliferation and metastasis of thyroid cells. Conclusion: CASTLE usually shows low malignancy, slow progression and good prognosis. Radical surgery is the preferred treatment for CASTLE. Postoperative radiotherapy may play a role in reducing local recurrence. MSH2 gene may be involved in the occurrence and development of CASTLE.

Key words: Thyroid, Carcinoma showing thymus-like differentiation, MSH2