Standardized cytopathology reporting for the pancreas: The time is right

“Atypical,” “atypical epithelial cells,” “mucinous epithelial cells,” and “findings consistent with cyst” are a few random examples of interpretations provided in cytopathology reports of fine-needle aspirations (FNAs) of the pancreas. The clinician who seeks guidance for patient management finds herself or himself at a loss to interpret this language, and frequently will call the cytopathologist to obtain clarification. This may or may not be forthcoming, but regardless the report remains, and is not a very effective way to document cytological findings or clearly communicate information to guide patient management. The recently recommended standardized terminology and nomenclature guidelines from the Papanicolaou Society of Cytopathology1 are long overdue. Over the last 20 years, there has been a steep increase in the use of cross-linear imaging. This, coupled with improvements in the resolution of both computed tomography and magnetic resonance imaging, has resulted in an explosion in the incidental discovery of lesions throughout the body. The pancreas has not been exempt, and large numbers of solid and cystic lesions are being identified in patients who otherwise have no symptoms related to the pancreas. Because pancreatic malignancies, and in particular ductal adenocarcinoma, are among the deadliest cancers, such a discovery may be perceived as a welcome finding. After all, identifying these tumors at an earlier phase should lead to earlier treatment and a better chance of cure. The problem is that the overall prevalence of these pancreatic “incidentalomas” is approximately 2% and increases with age to the point that 10% of individuals aged > 70 years will have such findings. This prevalence is at least 100 times greater than that of all pancreatic malignancies combined, and therefore the vast majority of these incidental lesions are innocuous. Furthermore, the preemptive removal of these lesions is accomplished with pancreatic resection, which even in expert centers has a mortality rate of 2% to 5% and a morbidity rate of 40% and higher. Clinical guidelines and algorithms for the management of cystic lesions of the pancreas have helped physicians in the care of these patients (incidentally discovered solid lesions are far less common). Initially, these guidelines relied heavily on clinical data and information from imaging studies. After excluding inflammatory cysts and some cystic neoplasms with very characteristic epidemiology and/or imaging features, the bulk of the remaining cystic lesions of the pancreas are thought to be branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). The management of BD-IPMNs continues to be in a state of flux, but the most recent guidelines now recommend the use of endoscopic ultrasound (EUS) and FNA to characterize those lesions measuring > 2 cm in diameter.2 We and others have for many years used pancreatic cyst cytology coupled with cyst fluid measurements of carcinoembryonic antigen and amylase, and more recently molecular testing for mutations in KRAS and GNAS genes, to refine the differential diagnosis among the different cystic neoplasms and to determine the degree of dysplasia of BD-IPMNs.3 This is still an imperfect science, but the hope is that this one day will lead to more accurate preoperative diagnosis and less overtreatment of these lesions. However, to the best of our knowledge, there is no universal agreement that EUS with cytology and fluid analysis is useful (in Japan and Korea, for example, cyst fluid aspiration is very rarely used), and many centers have used FNA of pancreatic cysts routinely but have found the interpretation of cytology to be inconsistent or unreliable. Because EUS is proliferating, and new guidelines are recommending its use, it is quite likely that it will be used in an increasing number of patients with pancreatic cysts. Having standardized nomenclature will provide a framework for pathologists to follow for the uniform interpretation of cyst fluids that will be more clearly understood by the clinician treating the patient. Although less of a problem than pancreatic cysts, the incidental detection of small solid lesions in the pancreas has also created a challenge. Although a small minority are indeed early ductal adenocarcinomas, the vast majority are small, nonfunctioning neuroendocrine tumors, many of which measure < 1 cm in size. The potential for growth and malignant spread among these lesions is uncertain and, accordingly, their management is also in a state of flux, with some clinicians advocating resection and others making a case for observation alone based on the finding that these lesions are observed in 1% of autopsy studies. EUS-guided FNA is very effective in establishing the diagnosis of a pancreatic neuroendocrine tumor. From a clinician's standpoint, I am relieved to see that this diagnosis does not by default go into a “malignant” category, but rather into a “neoplastic, other” grouping. Convincing a patient that doing nothing is appropriate when a report states a malignant tumor is present is virtually impossible. No specific funding was disclosed. The author made no disclosures. Dr. Carlos Fernández-del Castillo was born and raised in Mexico City, Mexico, where he also attended medical school and completed his residency. In 1989, he came to the Massachusetts General Hospital as a research fellow in the Pancreatic Biology Research Laboratory of Dr. Andrew Warshaw, and in 1991 joined the Division of General and Gastrointestinal Surgery. He is currently the director of the Pancreas and Biliary Surgery Program and codirector of the Tucker Gosnell Center for Gastrointestinal Cancers at the Massachusetts General Hospital, as well as a professor of surgery at Harvard Medical School. He has authored over 190 original articles and 90 book chapters and reviews, mostly on topics related to surgical diseases of the pancreas. He is a member of many medical associations, and currently holds leadership positions in the American Pancreatic Association and the International Association of Pancreatology.

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