Gastric SMARCA4-Deficient Undifferentiated Carcinoma: A Report of 4 Patients and Literature Review.

SMARCA4-deficient undifferentiated carcinoma (SMARCA4-DUC) of the stomach is a rare gastric tumor that has been receiving increased attention in recent years. With its varied pathological presentations, accurate diagnosis can be challenging. In order to improve our understanding of this aggressive neoplasm, we have carefully documented and analyzed 4 patients with gastric SMARCA4-DUC, adding to the overall knowledge of this uncommon malignancy. The patients were all men, with an average age of 69 years (range 57-76 years). The tumors were located in the gastric antrum (2 patients), the gastric body (1 patient), and the cardia (1 patient). Microscopically, the 3 surgical specimens exhibited similar morphological features: large to medium sized tumor cells, round, irregular to epithelioid undifferentiated cells in solid sheets or discohesive nests, with no obvious stromal reaction. In one patient, short spindle cells arranged in reticular, pseudopapillary, and disorderly patterns were observed amidst extensive interstitial edema. Some areas displayed a lymphoma-like starry sky phenomenon. The biopsy specimens showed large cells diffusely distributed in the submucosa, presenting pale pink cytoplasm, fine chromatin, and prominent large red nucleoli resembling melanoma. All 4 patients demonstrated BRG1 (SMARCA4) loss, INI1 (SMARCB1) retention, and focal positivity for epithelial markers (AE1/AE3 or epithelial membrane antigen). Three patients had clinically advanced (stages IIIC-IV) disease. Follow-up revealed that 1 patient deceased within 4.8 months. This article expands the morphological spectrum of this cancer, providing new insights for accurate cancer diagnosis.