Cytopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors in serous effusion

Abstract

Objective: To investigate the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors, and the diagnostic value of the cells in serous effusion. Methods: Eleven cases of SMARCA4-deficient tumor were collected from the Affiliated Hospital of Hebei University, China from January 2018 to July 2023, which were diagnosed using cell block of serous effusion. The clinical, histopathological, immunohistochemical and molecular genetic features were reviewed, along with related literature. Results: All the 11 patients were males with ages ranging from 54 to 77 years (median 64 years). Nine patients were smokers and two had an unknown smoking history. Most of them complained of cough and dyspnea with pleural effusion. The primary tumor sites included lung (9 cases), thoracic wall (1 case), and mediastinum (1 case), while 3 patients had a history of lung surgery. Histologically, tumor cells were large and pleomorphic, with increased nuclear-cytoplasmic ratio. They also showed round nuclei, conspicuous nucleoli, and basophilic cytoplasm in serous effusion. Immunohistochemically, tumor cells in all cases were negative for SMARCA4/BRG1, CKpan and CK7, but positive for SMARCB1/INI1. Some of the cases were positive for CD34 (7/11), synaptophysin (4/11) and SALL4 (2/11). Histologically, monotonous tumor cells formed solid sheets or anastomosing islands with poor cell adhesion and rhabdoid morphology. Brisk mitotic figures were accompanied by large areas of necrosis. Some cases focally exhibited syncytia, and some had bright cytoplasm and vesicular chromatin. The immunohistochemical profiles in the tumor tissues were consistent with those of cytology. Six cases were negative for PD-L1 (22c3). Among the 6 cases analyzed by targeted next generation sequencing, concurrent SMARCA4 and TP53 mutations were detected in all 6 cases. Some of the 6 tumors showed mutations of STK11, CDKN2A, and MET, and amplification of ERBB2, exon deletion of BRCA2, etc. Follow-up information was available in all cases and ranged from 2 to 24 months. The patients showed metastases to various sites, including lymph node, liver, kidney, adrenal gland, brain, bone and other sites. Four patients died of the tumor. The survival time of 4 patients who underwent radical resection or radiofrequency ablation was more than 13 months. Conclusions: SMARCA4-deficient thoracic sarcoma is a rare but highly aggressive tumor with dismal prognosis and rhabdomyoid features. It is difficult to diagnose this disease using only serous effusion samples. This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.