S4147 SMARCA4 Deficient Undifferentiated Gastric Carcinoma with Metastasis

Introduction: SMARCA4 deficient carcinomas are classically described in the thoracic cavity. Gastric SMARCA4 deficient undifferentiated carcinomas are uncommon. We present a rare case of SMARCA4 deficient undifferentiated gastric carcinoma with metastasis to local lymph nodes. Case Description/Methods: A 50-year-old man with past medical history type 2 diabetes, hypertension, hyperlipidemia presented with worsening epigastric pain with associated nausea, vomiting and night sweats. Patient revealed no significant family history. He smoked one pack per day since his teens and drank 2 alcoholic drinks per month. Admission vitals were stable. Physical exam was notable for an abdomen that was tender to palpation in all 4 quadrants. Labs were significant for leukocytosis of 13.5 B/L. Computed tomography (CT) of the abdomen and pelvis demonstrated an 8 x 5.4cm gastrohepatic mass with gastrohepatic, paraceliac, and cardiophrenic lymphadenopathy and small volume ascites. Subsequent endoscopic gastroduodenoscopy (EGD) demonstrated a large cratered, ulcerated gastric mass located at the gastroesophageal juncture extending along the lesser curvature in the region of the gastric cardia and fundus. Biopsies were ulcerated and necrotic, exhibiting limited immunohistochemical staining weakly positive for EMA, Ber-EP4 and MOC-31. Tumor cells were negative for pankeratin, CK7, CK20, p40, CD20, CD56, CEA, Melan A and S-100. Further examination with BRG-1 immunostain determined biopsies were positive for SMARCA4 deficient, poorly undifferentiated carcinoma. Patient was agreeable to trial a combination of paclitaxel, carboplatin and pembrolizumab. The patient continues to be followed closely on this regimen (Figure 1). Discussion: Isolated case reports of SMARCA4 deficient gastric carcinoma have been reported without defined incidence or prevalence. SMARCA4 is a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) ATP-dependent chromatin remodeling complexes. SMARCA4 deficient gastric carcinomas may represent a true SMARCA4 deficient neoplasm, however, may be secondary to the collapse of ARID1A, another SWI/SNF protein. Nonetheless, SMARCA4 deficient tumors are highly aggressive with poor prognosis. Loss of BRG1 nuclear staining signifies inactivation of SMARCA4, aiding in diagnosis. Platinum-based chemotherapy has proven effective however specific regimens have not been defined. While the patient's current regimen is satisfactory, the standard of care regarding SMARCA4 deficient gastric carcinoma needs additional elucidation.Figure 1.: A. 20X H&E - BRG1-deficient poorly differentiated carcinoma - Cells in this ascitic fluid are reminiscent of large cell lymphoma cells with high nuclear cytoplasmic ratio, open chromatin pattern and prominent nucleoli. Apoptotic cells are also present (smaller cells with condensed pink cytoplasm and pyknotic nuclei). B. 40X H&E - BRG1-deficient poorly differentiated carcinoma (higher power of same area). C. 20X CD45 - CD45 stains background lymphocytes. Tumor cells are negative. D. 20X CAM5.2 - Mesothelial cells positive while tumor cells are negative. High molecular weight cytokeratin was also negative (not shown). E. 20X NUT1 - NUT1 immunostain is negative. NUT1 carcinoma is a rare aggressive tumor with a similar undifferentiated appearance, although it tends to have areas of abrupt keratinization/squamous differentiation. F. 20X Kappa light chain (by immunohistochemistry) - Kappa light chain shows negative expression. G. 20X H&E - Lambda light chain (by immunohistochemistry). Interestingly this tumor was positive for lambda light chain. This is likely an expression of cancer derived immunoglobulin (immunoglobulin originating from cancer cells, not lymphoid or plasma cells). Cancer derived immunoglobulin functions in pro-tumorigenic mechanisms. H. 20X H&E - Tumor cells also expressed vimentin. In the previous gastric biopsy, there was patchy variable expression of Ber-EP4 and pankeratin. Additional immunostains (performed at Mayo Clinic [on the gastric biopsy specimen]) showed expression of OSCAR keratin, CK7 (subset) and rare expression of mucicarmine. BRG-1 stain (performed on the gastric biopsy) showed obvious negative staining (this was further confirmed by molecular testing of the ascites material which demonstrated an inactivation mutation of the SMARCA4 gene). Photos courtesy of Dr. Jenni Davis, MD.