Critical issues in pathologic evaluation of pancreatic ductal adenocarcinoma resected after neoadjuvant treatment: a narrative review

Background and Objective: Preoperative neoadjuvant therapy (NAT) is increasingly used in the treatment of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Because NAT often induces heterogeneous tumor response and extensive fibrosis both in tumor and adjacent pancreatic tissue, pathologic assessment of posttherapy pancreatectomy specimens is challenging. A limited number of studies examined the optimal grossing and sampling methods, tumor response grading (TRG), and the prognostic value of posttherapy tumor (ypT) and lymph node (ypN) stages of treated PDAC patients. In this review, we will provide an overview of the current status and critical issues in pathologic evaluation of PDAC resected after NAT. Methods: In PubMed, Google Scholar and Web of Science, we reviewed existing English literature (published up to December 2021) highlighting the most recent ones using electronic databases and authors’ experience to outline the challenging aspects and new perspectives on pathologic assessment of the treated PDAC. Key Content and Findings: The recent recommendations from the Pancreatobiliary Pathology Society (PBPS) provide the much-needed guidelines for systematic and standardized pathologic evaluation and reporting of treated PDAC for optimal patient care. For treated PDAC, tumor size measured by gross and radiology is not reliable. Histologic validation of tumor size on consecutive mapping sections is recommended for accurate ypT stage. A tumor size of 1.0 cm seems to be a better cutoff for ypT2 for treated PDACs. The published data suggested that the MD Anderson Cancer Center (MDA) TRG system is easy to use, has a better interobserver agreement and better correlation with patient prognosis compared to the College of American Pathologists (CAP) and Evans grading systems and may be used as an alternative TRG system for the CAP cancer protocol. Conclusions: Systemic and standardized grossing and sampling are essential for accurate pathologic evaluation and reporting for optimal care of PDAC patients who received NAT. Future studies on optimal sampling and integration of histopathology with artificial intelligence (AI), molecular and immunohistochemical markers are needed for better and personalized care of treated PDAC patients.