Histopathological and genetic landscape of pancreatic ductal adenocarcinoma and its variants

Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease where proper pathologic evaluation ensures appropriate clinical management. This review article summarizes literature regarding problematic, uncommon, and new challenges in PDAC evaluation and highlights recent molecular advancements. Microscopically, the morphologies of PDAC are diverse, and certain features, such as foamy gland morphology, large duct pattern of invasion, cancerization of ducts, and neoadjuvant therapy effects, are important to recognize and distinguish from mimickers. Immunohistochemistry can be useful in select settings for distinguishing malignant from benign pancreatic epithelium. Morphologic subtypes of PDAC have their own distinct clinical, histologic, and molecular features that provide insight into disease mechanisms and therapy. Finally, therapies targeting molecular alterations can significantly impact some patients, and molecular subtyping of PDAC has rapidly advanced in the last decade through detailed transcriptomic evaluation.