Case-series of SWI/SNF Deficient Malignant Tumors of the Gastrointestinal Tract

Introduction
Switch/sucrose nonfermentable (SWI/SNF)-deficient carcinomas are rare, aggressive malignancies recently recognized in the gastrointestinal tract (GIT). They result from SMARCB1 or SMARCA4 inactivation, key components of the chromatin-remodeling SWI/SNF complex. Accurate diagnosis is crucial given emerging therapeutic implications (EZH2-inhibitors, immunotherapy).
Methods
We retrospectively reviewed all SWI/SNF-deficient GIT carcinomas diagnosed at our institution from 2015 to 2025. Tumors were identified by complete loss of SMARCB1 or SMARCA4 protein expression in tumor cells, with intact internal controls.
Results
Six cases were identified: three SMARCB1-deficient and three SMARCA4-deficient carcinomas. Median age was 33.7 years, with a male-to-female ratio of 1:2. Tumor sites included the stomach (n=3), gallbladder (n=2), and pancreas (n=1). One patient had an unresectable tumor, and three had distant metastases. Three underwent surgery. Median tumor size was 9 cm. Histology revealed high-grade undifferentiated carcinoma, with rhabdoid (n=3), yolk sac-like (n=1), and glandular (n=1) features. One case had multiseptate, empty vacuoles. All tumors expressed keratins, and three each showed complete loss of SMARCB1 or SMARCA4. Mismatch repair proteins were retained; PD-L1 CPS scores were <3. One patient was lost to follow-up. With a median follow-up of 8 months, four progressed on palliative chemotherapy, and one died of disease.
Conclusions
SWI/SNF-deficient GIT carcinomas are rare, aggressive, and have poor outcomes. Key histologic clues include undifferentiated, rhabdoid, and yolk sac-like morphology. Immunohistochemistry is essential for diagnosis and guiding trial enrollment.