SWI/SNF Complex-deficient Undifferentiated Carcinoma of the Gastrointestinal Tract: Clinicopathologic Study of 30 Cases With an Emphasis on Variable Morphology, Immune Features, and the Prognostic Significance of Different SMARCA4 and SMARCA2 Subunit Deficiencies.

Undifferentiated carcinoma of the gastrointestinal tract has variable rhabdoid features. Expression of switch/sucrose nonfermenting (SWI/SNF) complex subunits is reportedly lost in a portion of cases; however, the prognostic significance of this loss remains unknown. Herein, 30 undifferentiated carcinoma cases were assessed for the expression of 4 SWI/SNF complex subunits (SMARCB1, SMARCA2, SMARCA4, and ARID1A). Tumor origin sites comprised stomach (40.0%), large intestine (20.0%), small intestine (16.7%), lower esophagus and stomach fundus (13.3%), ileocecal junction (3.3%), rectum (3.3%), and pancreas (3.3%). The tumors were composed of epithelioid neoplastic cells arranged in diffuse solid or discohesive sheets, nests, cords, poor cohesive pseudoglandular, and trabecular patterns. Rhabdoid tumor cells were identified in 66.7% (20/30) of cases. In total, 29/30 (96.7%) showed complete loss of at least 1 SWI/SNF subunit: SMARCA4-/SMARCA2- (11), isolated SMARCA4- (2), SMARCA4-/SMARCA2 unknown (6), isolated SMARCA2- (7), SMARCA2-/ARID1A- (1), and isolated ARID1A- (2). Negative or decreased expression (≤10% positive) of pan-cytokeratin was observed in 58.6% (17/29) of cases. In addition, 66.7% (20/30) of patients were late-stage (III or IV), and 65.2% (15/23) of stage IIB to IV patients succumbed to the disease at a mean clinical follow-up of 12.7 months. Specifically, patients with loss of SMARCA4 expression had the worst overall survival (P=0.028) and disease-free survival (P=0.006) rates, compared with those with SMARCA4 expression. The loss or decreased expression of epithelial markers is thus common in SWI/SNF complex-deficient undifferentiated carcinoma of the gastrointestinal tract, and loss of SMARCA4 correlates with poor prognosis.