SMARCA4-Deficient Carcinomas of the Small Intestine: A Systematic Review

Area of Science:

• Oncology
• Gastroenterology
• Molecular Biology

Background:

• SMARCA4-deficient carcinomas are aggressive malignancies defined by BRG1 loss.
• While typically thoracic, rare cases involve the gastrointestinal tract, specifically the small intestine.

Purpose of the Study:

• To review and consolidate literature on SMARCA4-deficient small intestine carcinomas.
• To detail their clinical, histopathological, molecular, and therapeutic characteristics.

Main Methods:

• Systematic review of PubMed up to March 2025.
• Inclusion of cases with confirmed SMARCA4/BRG1 loss via IHC or molecular testing.
• Exclusion of metastatic, non-small intestine, or molecularly uncharacterized cases.

Main Results:

• Analyzed 10 cases, predominantly affecting males (90%) with a median age of 54.
• Tumors often arose in the duodenum, presenting with nonspecific symptoms and advanced stage.
• Histology showed undifferentiated/rhabdoid features; molecular analysis revealed TP53 and CTNNB1 mutations.
• Limited response to immune checkpoint inhibitors in metastatic disease, despite PD-L1 positivity in some.

Conclusions:

• SMARCA4-deficient small intestine carcinomas are distinct, high-grade malignancies with poor prognosis.
• Early detection via SMARCA4 testing and specialized care are vital.
• Further prospective studies are needed to guide targeted therapies.