P6401 - SMARCA4 and SMARCA2 Co-Deficiency: A Rare Case of Gastric SMARCA4 and SMARCA2-Deficient Undifferentiated Malignancy as a Source of GI Bleed

Omar Zuhdi, MD, Amanda Rigdon, MD, Zein Barakat, DO, Camila Villacreses, DO, Hassan Hasanein, MD
Lakeland Regional Health Medical Center, Lakeland, FL

Introduction: Deficiency in either SMARCA4 or SMARCA2 has been identified as a source of tumorigenesis in a wide variety of neoplasms. However, co-deficiency in both SMARCA4 and SMARCA2 is remarkably rare resulting in aggressive and rapidly growing forms of cancer.

Case Description/

Methods: The patient is a 51-year-old male, with no significant past medical history, who presented due to fatigue, abdominal pain, and recurrent tarry stools for the past year. CT scan showed mediastinal/parenchymal masses and lymphadenopathy, solid mass of the right axilla, pathologic lymph nodes in the peripancreatic region with abnormal pancreatic head, and a mesenteric mass along the gastrocolic ligament. Endoscopy was performed and showed a large ulcerated mass in the proximal gastric body measuring approximately 5 x 10 cm. Biopsy of the gastric mass was positive for SWI/SNF complex (SMARCA2-SMARCA4) deficient undifferentiated neoplasm. PET scan showed pleural, mediastinal, axillary, and gastric hypermetabolic masses. The patient presented with significant blood loss anemia requiring numerous blood transfusions, however, the patient was not a good candidate for treatment endoscopically or through angiography/embolization. The patient started his first round of his chemotherapy regimen of carboplatin and paclitaxel with plans to start pembrolizumab. However, due to progression of the cancer and worsening of the patient’s status, the patient was transitioned to hospice care.

Discussion: SMARCA4 and SMARCA2 act as catalytic subunits of the SWItch/Sucrose Non-Fermentable complex (SWI/SNF complex) which are involved in chromatin remodeling. While deficiency in one of these catalytic subunits has been known to result in a wide variety of neoplasms, deficiency in both SMARCA4 and SMARCA2 has very rarely been reported in the literature. Co-deficiency in SMARCA4 and SMARCA2 has most commonly been reported in SCCOHT (small-cell carcinoma of the ovary, hypercalcemic type) but has also been reported in aggressive and poorly differentiated neoplasms of lung, gastrointestinal, and uterine origin. Due to the rarity of this co-deficiency, there is limited information regarding these forms of cancer, however, they have been associated with poor patient outcomes. Currently, treatment modalities being studied for treatment of SCCOHT (small-cell carcinoma of the ovary, hypercalcemic type) are also being researched to be applied to other SMARCA4 and SMARCA2 co-deficient cancers including immunotherapy, CDK4/6 inhibitors, and EZH2 inhibitors.

Disclosures:
Omar Zuhdi indicated no relevant financial relationships.
Amanda Rigdon indicated no relevant financial relationships.
Zein Barakat indicated no relevant financial relationships.
Camila Villacreses indicated no relevant financial relationships.
Hassan Hasanein indicated no relevant financial relationships.

Omar Zuhdi, MD, Amanda Rigdon, MD, Zein Barakat, DO, Camila Villacreses, DO, Hassan Hasanein, MD. P6401 - SMARCA4 and SMARCA2 Co-Deficiency: A Rare Case of Gastric SMARCA4 and SMARCA2-Deficient Undifferentiated Malignancy as a Source of GI Bleed, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.