小腸のSMARCA4欠損癌：システマティックレビュー

Purpose: SMARCA4-deficient carcinomas are rare, aggressive malignancies characterized by loss of BRG1, a core component of the SWI/SNF chromatin remodeling complex. These typically arise in the chest, but recent case reports suggest rare involvement of the gastrointestinal tract, particularly the small intestine. This review aims to consolidate the available literature on SMARCA4-deficient carcinomas of the small intestine, highlighting their clinical, histopathological, molecular, and therapeutic features. Design: A systematic review of PubMed was conducted through March 2025 to identify all published cases of primary SMARCA4-deficient carcinomas of the small intestine. Inclusion criteria required immunohistochemical or molecular confirmation of SMARCA4/BRG1 loss. Studies describing metastases, non-small intestine primaries, or lacking molecular data were excluded. Ten eligible cases were analyzed in detail. Results: Patients were predominantly male (9 out of 10) with a median age of 54 years. Most carcinomas arose in the duodenum and patients frequently presented with nonspecific symptoms and advanced-stage disease. Histologically, tumors demonstrated undifferentiated or rhabdoid features with high mitotic activity and extensive necrosis. Immunohistochemistry confirmed loss of SMARCA4, while several cases also showed SMARCA2 loss. Molecular profiling revealed congruent mutations in TP53 and CTNNB1, among oncogenic drivers. While some patients with localized disease achieved prolonged survival after surgery and adjuvant chemotherapy, those with metastatic disease had limited responses to immune checkpoint inhibitors, despite PD-L1 positivity in a subset. Overall survival ranged from 2 to 29 months. Conclusions: SMARCA4-deficient carcinomas of the small intestine represent a distinct, high-grade malignancy with poor prognosis and limited therapeutic options. Prompt recognition, SMARCA4 testing, and referral to specialized centers are essential. Prospective studies are needed to guide therapy and explore targeted approaches in this challenging carcinoma subtype.