[SMARCB1-deficient sinonasal adenocarcinoma: clinicopathological and molecular genetic characteristics of four cases].

Objective: To investigate the clinicopathological and molecular genetic characteristics of SMARCB1-deficient sinonasal adenocarcinoma. Methods: A retrospective analysis was performed on 51 cases of poorly differentiated adenocarcinoma, yolk sac tumor, and SMARCB1-deficient carcinoma, diagnosed in the Eye, Ear, Nose and Throat Hospital of Fudan University between January 2016 and December 2024. Four cases of SMARCB1-deficient sinonasal adenocarcinoma were identified. The histological features, immunophenotypes and molecular characteristics were analyzed, and relevant literatures were reviewed. Results: Among the 4 patients, 2 were male and 2 female, with age of 75, 52, 47 and 59 years, respectively. The clinical manifestations included nasal obstruction, epistaxis, and specific symptoms associated with the affected sites. Imaging studies revealed a mass lesion in the nasal cavity and ethmoid sinus, with invasion into surrounding structures. Histologically, the tumor demonstrated glandular, nested, trabecular, and cribriform patterns. The tumor cells displayed moderate to abundant eosinophilic cytoplasm with epithelioid or plasmacytoid features, while a few showed basaloid characteristics. Three cases showed a yolk sac tumor-like differentiation, including case 1 with Schiller-Duval body, case 4 characterized by a cribriform structure, and case 2 consisting of areas of basaloid cells and reticular/microcystic yolk sac tumor-like component. SMARCB1 protein was absent in all cases. SMARCA2 was detected in 3 cases, of which 2 cases (cases 1 and 4) were loss of expression. SMARCA4, ARID1A, and ARID1B proteins were retained. CK7 and CK19 immunoreactivity was variable. CDX2, SALL4 and Glypican-3 were predominantly present in the yolk sac tumor-like region, but not limited to this area. Only case 1 demonstrated focally positive for CK20, whereas S-100 and SOX-10 were negative in all cases. The Ki-67 index was 30% to 50%. Three cases (cases 1, 3 and 4) underwent FISH and next-generation sequencing analyses. Two cases demonstrated SMARCB1 deletion, whereas case 3 was negative. Tumor mutation burden ranged from 0.2 to 3.2 Muts/Mb. Follow-up data were available for 3 cases (excluding case 1), with durations of 29, 20, and 7 months, respectively. Case 2 died, and case 3 and case 4 were alive. Conclusions: SMARCB1-deficient sinonasal adenocarcinoma is a rare tumor, characterized by various degree of glandular differentiation and/or yolk sac tumor-like structures. It should be differentiated from other tumors with similar morphology, particularly intestinal-type and non-intestinal adenocarcinomas as well as yolk sac tumors. To avoid misdiagnosis, SMARCB1 immunohistochemistry should be routinely applied in the diagnosis and differential diagnosis of high-grade sinonasal malignant tumors.