Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting

Abstract

Background: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs).

Design: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations.

Results: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic).

Conclusions: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

Figure 1

A branch duct IPMN manifesting as a cyst without any significant dilation of the main pancreatic duct. Papilla formation is not evident grossly.

Figure 2

Main duct IPMN involving the entire pancreatic duct (star), filled with friable papillary projections and sticky mucin. Note the adjacent normal common bile duct (CBD).

Figure 3

Ductal (tubular)-type invasive carcinoma arising in IPMN (left) is virtually indistinguishable from ordinary pancreatic ductal adenocarcinomas, characterized by atypical cells forming irregular, often complex, tubular or glandular structures, usually accompanied by dense stroma. In contrasts, colloid carcinoma (right) is characterized by the muconodular pattern composed of distinct pools of mucin that contain scanty clusters of carcinoma cells, floating within the mucin (hematoxylin and eosin stain).

Figure 4

In IPMNs, rupture of the ducts can lead to extrusion of mucin into the stroma, which can be difficult to distinguish from true invasive colloid carcinoma (hematoxylin and eosin stain).

Figure 5

A) Gastric type IPMN shows relatively simple and typically short papillae and often have pyloric-like glandular elements at their base in the cyst wall. The epithelial lining is highly similar to gastric foveolar epithelium. B) Intestinal type IPMN typically has a villous growth pattern and reveals pseudostratified columnar cells with a basophilic appearance and apical mucin. C) Oncocytic type IPMN reveals arborizing papillae lined by 2–5 layers of cuboidal cells with oncocytic cytoplasm and prominent, eccentric nucleoli as well as intraepithelial lumina. D) Pancreatobiliary type IPMN has complex arborizing and interconnecting papillary configurations with delicate fibrovascular cores and is composed of cuboidal cells with enlarged nuclei and little mucin production (hematoxylin and eosin stain).