S4459 SMARCA4-Deficient Gastroesophageal Carcinoma: A Case Study of a Rare Entity

Introduction: SMARCA4 is a gene located on chromosome 19p13.2 and encodes for BRG1 protein which regulates gene transcription via alteration of chromatin structure. Loss of function of this gene can lead to SMARCA4-deficient carcinoma, a rare and aggressive malignancy, with less than 40 cases existing in the literature. Notably, the age of these patients has ranged from 45 to 82 years. We present a case here of a 29-year-old woman who developed SMARCA4-deficient esophageal cancer and outline points to consider in regards to the diagnosis. Case Description/Methods: A 29-year-old woman with a past medical history of anxiety and depression presented with severe left upper quadrant abdominal pain alongside 6 weeks of reflux symptoms, night sweats and an unintentional 10-pound weight loss. Her family history was notable for a paternal grandfather with gastric cancer. Computed tomography of the chest, abdomen, and pelvis demonstrated asymmetric soft tissue thickening of the distal esophagus and stomach involving the gastrohepatic ligament alongside extensive liver lesions. Esophagogastroduodenoscopy was performed which demonstrated a large, fungating, infiltrative and ulcerated mass extending from 37-42 cm from the incisors extending along the cardia with oozing of blood. Pathological assessment of the mass revealed SMARCA4-deficient undifferentiated carcinoma. Immunohistochemistry was notable for PD-L1 combined positive score of ∼5% and claudin positivity. She was treated with 2 cycles of FOLFOX with the addition of immunotherapy using nivolumab and zolbetuximab. Unfortunately, she developed worsening hepatic and skeletal metastases during cycle two of therapy and died just two months after her diagnosis. Discussion: SMARCA4-deficient esophageal carcinoma is a recently emerging entity and exceedingly rare, comprising less than 1% of all gastroesophageal carcinomas. As of 2025, there were a total of 32 published cases. This is the first documented case affecting an individual less than 30 years of age. Unfortunately, the average survival following diagnosis is uniformly grim at 2.35 months. There are no chemotherapy regimens demonstrating effectiveness. A few cases have seen some success in treatment with PD-1 inhibitors, however, immunotherapy has only yielded anecdotal evidence. Future research is needed to better understand this class of carcinoma and design treatment options.