Context.—Pancreatic cancer is one of the most deadly forms of cancer (43 140 new cases per year; 36 800 deaths), and most people with pancreatic cancer do not survive past 5 years. New therapeutic regimens are constantly being evaluated in an attempt to reduce the rapid progression of this disease. Although some patients receive neoadjuvant therapy in an attempt to make a nonresectable or borderline-resectable tumor resectable, more patients with resectable disease are being enrolled in clinical trials that provide neoadjuvant therapy. This means more pancreatic resections must be evaluated for therapy effect. Histologic grading schemes for the assessment of posttherapy response have been described, but difficulties associated with determining the histologic features of treatment effect in pancreatic cancer have not been addressed.

Objectives.—To critically review the diagnostic criteria for proposed grading schemes for pancreatic cancer treated with neoadjuvant chemoradiation therapy and to provide guidance to surgical pathologists who encounter treated pancreatic cancer resections.

Data Sources.—Published peer-reviewed literature and the personal experience of the authors.

Conclusions.—Assessment of treatment effect in pancreatic cancer is difficult. Pathologists need to be aware that some histologic features of treatment effect overlap with histologic features seen in untreated pancreatic cancer, such as tumor cell anaplasia, necrosis, and fibrosis. Careful assessment of pancreatic resections, including detailed gross examination and thorough histologic sampling, is important in accurately assessing treatment effect and improving patient outcomes.