S3628 A Marker-Negative Malignancy: The Diagnostic Pitfall of Pancreatic Ductal Adenocarcinoma

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy often diagnosed at an advanced stage. Carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are commonly utilized tumor markers in the diagnostic and prognostic evaluation of PDAC. However, their absence does not exclude the presence of malignancy. We present a case of pancreatic tail adenocarcinoma with negative CA 19-9 and CEA, underscoring the diagnostic limitations of these tumor markers and the pivotal role of imaging and histopathological assessment. Case Description/Methods: A 72-year-old man with a history of controlled type 2 diabetes and hyperlipidemia, compliant with all recommended screenings, presented to the emergency department with left lower quadrant abdominal pain rated at 6/10, persisting for 1 week. He denied fever, chills, or changes in bowel habits but reported early satiety and a 30-pound weight loss over the past year, which he attributed to a carbohydrate-controlled diet. He had no history of smoking, alcohol use, or illicit drug use. A computed tomography scan of the abdomen and pelvis revealed a 4.8 cm mass in the pancreatic tail. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) was performed, and histopathology confirmed invasive ductal adenocarcinoma. Notably, both CA 19-9 and CEA were negative, highlighting the diagnostic challenge when relying solely on tumor markers for pancreatic cancer detection. Discussion: CA 19-9 is elevated in approximately 80% of pancreatic adenocarcinomas; however, its sensitivity and specificity are not absolute. Notably, individuals with the Lewis α-β- genotype (approximately 5–10% of the White population) do not express CA 19-9, leading to false-negative results. Additionally, CA 19-9 can be elevated in benign conditions such as pancreatitis and obstructive jaundice, further complicating its diagnostic utility. The absence of elevated tumor markers necessitates a high index of clinical suspicion. Imaging modalities, particularly EUS-FNA, are crucial for the detection and characterization of pancreatic masses, providing tissue diagnosis when serological markers are inconclusive. Clinicians should consider comprehensive diagnostic approaches, including advanced imaging and histopathological evaluation, in patients presenting with unexplained gastrointestinal symptoms and weight loss.