[SMARCA4-deficient primary thoracic sarcoma:a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological characteristics of SMARCA4- deficient thoracic sarcomas. Methods: The clinical features and CT scans of SMARCA4-deficient thoracic sarcomas (n=5) diagnosed at Fudan University Cancer Hospital from December 2016 to October 2018 were reviewed. Hematoxylin-eosin staining, immunohistochemistry and targeted next generation sequencing were performed in available cases along with a literature review. Results: All 5 patients were males with age ranging from 32 to 65 years (average 54 years; median 61 years). Four patients were smokers except one with unknown smoking history. The average maximum diameter of tumor was 5.6 cm. Tumor primary sites included thoracic wall,thoracic cavity,lung and mediastinum. Histologically,tumor cells formed solid sheets or anastomosing islands with brisk mitotic figures accompanying with large areas of necrosis. Three cases focally exhibited rhabdoid morphology and vesicular chromatin. Immunohistochemically, SMARCA4, SMARCA2 and Claudin-4 were negative in all cases and all tumors demonstrated SOX2 and SMARCB1 nuclear positive staining. Among 3 cases analyzed by targeted next generation sequencing, concurrent SMARCA4 and p53 mutation was detected in all three cases. Mutations of STK11, ERBB4, NF2, GNAS, MTOR,MET and FGFR1 amplification were also detected among the three cases. The follow-up information was available in all 5 cases. Two patients died of the tumor. One relapsed multiple times after surgeries but was alive with disease. Two patients received radical excisions without relapse. Conclusions: SMARCA4-deficient thoracic sarcoma is a rare but highly-aggressive tumor with dismal prognosis. The tumor is featured by rhabdoid morphology histologically and distinctive immunohistochemical and molecular phenotype.