SWI/SNF complex alteration and dMMR in primary small bowel undifferentiated tumor: a rare case further complicated by synchronous low-grade endometrioid adenocarcinoma

The 2019 World Health Organization Classification of Digestive Tumors recognizes undifferentiated rhabdoid tumors, driven by switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex alterations such as SMARCA4, SMARCA2, SMARCB1, and ARID1A under the undifferentiated carcinoma category. SMARCA4 -mutated undifferentiated tumors, first described in thoracic sites, are increasingly recognized in extrathoracic locations including the gastrointestinal tract. These tumors are high-grade epithelial neoplasms characterized by loss of differentiation and SMARCA4 expression. We report a 53-year-old woman presenting with severe anemia secondary to heavy vaginal bleeding. Imaging revealed a large ileal mass with hepatic hypodensities. She underwent ileocolic and hepatic wedge resections and hysterectomy. Histopathology revealed two separate tumors: a low-grade, mismatch repair (MMR) intact endometrioid endometrial carcinoma and a SMARCA4 -mutated undifferentiated ileal neoplasm with epithelioid/rhabdoid morphology and liver metastasis. The ileal tumor was positive for vimentin and showed p53 overexpression with preserved SMARCB1 expression. It displayed microsatellite instability (MSI). Next-generation sequencing detected loss-of-function variants in SMARCA4 and ARID1A . The endometrial carcinoma differed in morphology and MMR status, supporting two independent primaries. SMARCA4 -mutated undifferentiated tumor of the small intestine is exceedingly rare. To our knowledge, concurrent SMARCA4 and ARID1A mutations with MSI have not been documented in a primary ileal tumor. This case underscores the diagnostic challenges of SWI/SNF-mutated tumors, particularly in distinguishing synchronous primaries from metastatic carcinoma with rhabdoid tumor-like evolution. SWI/SNF assessment in undifferentiated small bowel tumors, especially with rhabdoid morphology, is warranted. Future studies should explore predictive value for immunotherapy and targeted approaches in MSI-high, ARID1A -deficient tumors.