University of Alabama at Birmingham Heersink School of Medicine, Montgomery Regional Campus Montgomery, AL
Award: ACG Presidential Poster Award
Dharshni Ramar, MD, Jackson Reynolds, MD University of Alabama at Birmingham Heersink School of Medicine, Montgomery Regional Campus, Montgomery, AL Introduction: Peritoneal carcinomatosis, especially in patients with unknown primary sources is an aggressive condition with a median survival of 2–12 months. We present a patient who presented with abdominal discomfort and workup revealed peritoneal carcinomatosis with elevated CA 19-9 levels. Advanced AI genomic profiling helped guide the correct diagnosis.
Case Description/
Methods: A 51 year old woman presented with a three-week history of abdominal discomfort, nausea, vomiting, and watery diarrhea, along with 15lb of unintentional weight loss. She had no prior EGD/colonoscopy or family history of colon cancer. The workup revealed mildly elevated lipase and markedly elevated CA 19-9 (2700 U/mL) levels with modestly elevated CEA and CA-125 levels. Abdominal CT revealed extensive peritoneal carcinomatosis, innumerable enlarged retroperitoneal/mesenteric adenopathy, small ascites and no obvious primary source. A biopsy of the lesion revealed poorly differentiated adenocarcinoma, consistent with either a pancreatic/biliary source. However CARIS GPSai(Genomic Probability Score Artificial Intelligence) was used to delineate the primary source, which identified a CLDN18:ARHGAP26 fusion gene that guided the diagnosis of diffuse gastric cancer, as CLDN18.2 is exclusively expressed in gastric mucosal cells. The patient then started palliative chemotherapy with mFOLFOX6 (modified folinic acid,fluorouracil and oxaliplatin) following which she had symptomatic improvement. Discussion: CARIS GPSai is a molecular test that uses AI to profile a tumor's gene against a vast cancer gene database. This is particularly helpful in identifying the tumor origin in cancers of unknown origin. The CLDN18:ARHGAP26 gene fusion is a molecular hallmark of diffuse gastric cancer and is linked to poor survival due to its aggressive nature. CLDN18.2 (Claudin Isoform 2) is a junction protein found exclusively in gastric mucosal cells. In malignancies its polarity is lost, leading to its exposure on the cell surface, making it a target for immuno/chemotherapy. Zolbetuximab, a monoclonal antibody, targets this protein and has demonstrated prolonged progression-free survival in clinical trials such as SPOTLIGHT and GLOW when combined with mFOLFOX6. It is also crucial to remember that CA 19-9 can be markedly elevated in aggressive gastric tumors and is not exclusive to pancreatic tumors. In conclusion, in patients with inconclusive histopathology and unknown sources, advanced AI genomic profiling can guide us better towards diagnosis.
Disclosures: Dharshni Ramar indicated no relevant financial relationships. Jackson Reynolds indicated no relevant financial relationships.
Dharshni Ramar, MD, Jackson Reynolds, MD. P2074 - Peritoneal Carcinomatosis - Where Is the Source? Let’s Ask AI!, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
