Stable disease after multimodal treatment of SMARCA4-deficient undifferentiated tumor concurrently involving the stomach and mediastinum: a case report.

We report a clinically rare SMARCA4-deficient undifferentiated tumor concurrently involving the stomach and mediastinum. A 54-year-old man presented with a 1-month history of left upper abdominal pain radiating to the anterior chest and back. Contrast-enhanced computed tomography of the chest and abdomen showed thickening and abnormal enhancement of the gastric wall along the greater curvature, multiple enlarged lymph nodes along the lesser curvature, and a posterior inferior mediastinal mass. Biopsies of both the gastric body lesion and the mediastinal mass revealed a poorly differentiated/undifferentiated malignant tumor, and additional immunohistochemistry supported SMARCA4/BRG1-deficient undifferentiated tumor at both sites. The similar undifferentiated morphology and loss of SMARCA4/BRG1 expression support a possible biological relationship between the two lesions but do not establish the primary site, direction of spread, or a shared clonal origin. Because paired molecular profiling, clonality analysis, and phylogenetic analysis were not performed, three possibilities cannot be reliably distinguished: a gastric primary with mediastinal metastasis; a mediastinal primary with gastric involvement or metastasis; and two independent primary tumors of the stomach and mediastinum. The symptomatic mediastinal lesion was treated with local radiotherapy using 6-MV X-rays and image-guided radiotherapy (IGRT), with prescribed doses of 67.2 Gy in 28 fractions to GTVboost, 61.6 Gy in 28 fractions to GTV, and 50.4 Gy in 28 fractions to PTV, together with systemic therapy. Computed tomography after the 25th fraction showed marked shrinkage of the mediastinal lesion, with substantial relief of left upper abdominal and radiating chest and back pain. The patient subsequently received radiotherapy to multiple lesions and several lines of systemic treatment and remained alive with stable disease at the last follow-up. This case highlights the uncertainty in determining the primary site and relationship between lesions when a SMARCA4-deficient undifferentiated tumor concurrently involves the stomach and mediastinum. In symptomatic patients with advanced disease, local radiotherapy combined with systemic treatment may contribute to pain relief and short-term disease control.