S3953 From Infiltrates to Obstruction: A Case of Rapidly Progressive Colorectal Lymphoma in Activated PI3K Delta Syndrome

Introduction: Activated PI3K Delta Syndrome (APDS) is a rare genetic primary combined immunodeficiency caused by gain-of-function mutations in the PIK3CD gene or loss-of-function mutations in PIK3R1. These mutations lead to lymphoproliferation and increased risk of Hodgkin and non-Hodgkin lymphoma. While these malignancies may arise in any germinal center–associated tissue, colonic involvement is rare, comprising only 0.5% of colorectal neoplasms. We present a case of a patient with APDS who developed a rapidly progressive large bowel obstruction due to non-Hodgkin lymphoma. Case Description/Methods: A 25-year-old man with APDS (on leniolisib), eosinophilic esophagitis, and chronic colitis, presented to the Emergency Department with nausea, vomiting, and small-volume bloody bowel movements. A colonoscopy 3 months prior revealed pan-colitis with atypical lymphoid infiltrates, raising concern for inflammatory bowel disease (IBD), a manifestation of APDS, or malignancy. Given prior symptom improvement on prednisone and mesalamine, another course was initiated at outpatient follow up. Emergency Department evaluation revealed leukocytosis (13.0), lactic acidosis (2.7), and CT imaging demonstrated severe distension of the small and large bowel with progressive abdominal lymphadenopathy. Shortly after admission, the patient developed acute onset bright red blood per rectum, requiring transfusion of 7 units of packed red blood cells. Flexible sigmoidoscopy revealed an obstructing mass 10 cm from the anal verge that could not be traversed endoscopically. He underwent sigmoid colectomy with colostomy and inguinal lymph node biopsy for flow cytometry. On postoperative day 2, he developed Staphylococcus aureus bacteremia and Candida albicans fungemia. Due to worsening clinical status, he was transitioned to comfort care and passed away that evening. Flow cytometry of the lymph node revealed 23% abnormal B cells consistent with non-Hodgkin lymphoma. Discussion: The lymphoma risk in APDS is 13%–25% and portends a poor prognosis. While malignancy was on the differential based on prior colonoscopy findings, the patient’s rapid deterioration precluded a full oncologic evaluation. The risk of colonic lymphoma and IBD in APDS remains unclear but the PI3K-AKT-PTEN pathway is implicated in both. This case highlights the importance of early oncology evaluation and flow cytometry in patients with APDS and atypical lymphoid proliferation, with consideration of surgical or chemotherapeutic intervention to address this aggressive disease course.