Cytology and small biopsy diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths, accounting for over 90 % of pancreatic cancer cases. Accurate diagnosis is crucial, but often challenging. It typically relies on minimally invasive procedures, such as endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and small biopsy samples. These small biopsies may be the only tissue diagnosis made before embarking on neoadjuvant therapy, major surgery, or transition to comfort care, depending on clinicoradiologic factors. This paper reviews important diagnostic strategies and criteria for cytologic and small biopsy samples, highlighting cytomorphologic characteristics, histologic patterns, and the role of immunohistochemical and molecular diagnostics. PDAC cytology often shows hypercellular aspirates with disorganized glandular fragments, significant nuclear atypia, prominent nucleoli, and a necrotic background. In contrast, small biopsy samples typically reveal invasive glandular structures surrounded by desmoplastic stroma and nuclear pleomorphism. However, biopsies are often scant and there are a variety of difficult histologic subtypes and mimics that complicate these cases. Although there is a lack of sensitive or specific markers for PDAC, immunohistochemical markers, such as P53, and SMAD4, can be useful for supporting a diagnosis of PDAC over chronic pancreatitis/tumor mimics. Molecular alterations in KRAS, TP53, BRCA1/2, and others may aid in diagnosis, prognostication, and the selection of targeted therapeutic options. By systematically integrating clinicoradiologic, cytological, histological, immunophenotypic, and molecular data, pathologists can effectively differentiate PDAC from benign or reactive lesions and metastatic neoplasms, ensuring accurate diagnoses that are essential for optimal patient management.