Pancreatic cancer, autoimmune or chronic pancreatitis, beyond tissue diagnosis: Collateral imaging and clinical characteristics may differentiate them

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is developing into the 2(nd) leading cause of cancer-related death. Often, the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses, such as autoimmune pancreatitis (AIP) and mass-forming chronic pancreatitis (MFCP), making its diagnosis challenging. Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications. Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses; however, the diagnostic accuracy is imperfect. Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis. It is not unusual that after a thorough diagnostic evaluation, the clinician is confronted with a pancreatic mass with uncertain diagnosis. In those cases, a re-evaluation must be entertained, preferably by an experienced multispecialty team including radiologists, pathologists, gastroenterologists, and surgeons, looking for disease-specific clinical, imaging, and histological hallmarks or collateral evidence that could favor a specific diagnosis. Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP, PDAC, and MFCP and to highlight those disease-specific clinical, radiological, serological, and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.