The Brescia International Multidisciplinary Consensus Guidelines on the Optimal Pathology Assessment and Multidisciplinary Pathways of Non-Pancreatic Neoplasms in and Around the Ampulla of Vater (PERIPAN)

Abstract

Importance: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

Objective: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

Design: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology (SIGN), including the Delphi methodology and the AGREEII tool for quality assessment and external validation.

Results: The 38 consensus questions and 51 recommendations provide guidance on the following key aspects: I. More specific anatomic criteria for the definition of what qualifies as "ampullary" neoplasms, their distinction from duodenal and common bile duct tumors, and clinicopathologic characteristics of anatomic subsets; II. Avoidance of the confusing term "periampullary" for final classification; III. Refined definitions of intestinal, pancreatobiliary and mixed subtypes, and introduction of rare histologic subtypes; IV. The use and limitations of immunohistochemical and molecular profiling; V. Biopsy acquisition; VI. Clinical information required for accurate pathology assessment of biopsies and ampullectomy specimens; VII. Key items to be included in pathology reports of endoscopic specimens.

Conclusions and relevance: Recognition of the Brescia PERIPAN guidelines will allow a more accurate classification of true ampullary cancers and their differentiation from other "periampullary" tumors. This will have significant implications for endoscopic interpretation and management, staging, pathologic diagnosis and therapeutic evaluation as well as oncologic treatment of various anatomic and histologic subsets of ampullary tumors. This will enhance the quality of both clinical care and future research in this complex medical field.

Keywords: ampulla of Vater; bile duct tumor; classification; consensus; duodenal tumor; guidelines; neoplasm; pancreatobiliary; periampullary.

FIGURE 1

Multidisciplinary workflow. The schematic figure represents the multidisciplinary workflow for neoplasms in the periampullary region, as it is practiced in most countries. It includes radiologists, surgeons, oncologists, gastroenterologists and pathologists. All arrows indicate the transfer of information, tissue biopsy, or surgical specimen. All multidisciplinary recommendations are related to one of the arrows in the figure. Optimal Multidisciplinary workflow is essential for patient treatment and care.

FIGURE 2

Periampullary region. The ampulla refers to the area where the common bile duct and the main pancreatic duct meet, forming a channel known as the intra‐Oddi compartment (IOC), as well as the papilla of Vater, that is, the area where the channel opens to the duodenum. Cancers that have their (epi)center in this region are regarded as ampullary cancer (AC). Indicated in the figure are the regions in which non‐ampullary duodenal cancers (NADC), distal common bile duct cancers (DCBC) and pancreatic ductal adenocarcinomas (PDAC) have their (epi)center.

FIGURE 3

Carcinoma of ampullary origin. Tumors arising on the wall of the very distal tips (intra‐Oddi components) of the CBD and pancreatic duct (left), and tumors arising from the duodenal surface of the ampulla, which typically engulf the ampullary orifice eccentrically (right), are referred to as of ampullary‐ductal origin.

FIGURE 4

Intra‐ampullary papillary tubular neoplasm (IAPN). From an endoscopist's (duodenal luminal) perspective, the ampulla shows a mucosa‐covered bulge (left), which is due to an adenomatous neoplasm within the ampulla (i.e., IAPN). The picture on the right illustrates the cut section of the ampulla with a tan beige polypoid mass filling the very distal (intraampullary) ends of the CBD and pancreatic duct. On histological examination, a microscopic focus of invasive carcinoma was identified.

FIGURE 5

Carcinoma of ampullary‐duodenal origin. Ampullary cancer of ampullary‐duodenal origin is characterized by an ulcero‐vegetating mass in the region of the ampulla that is readily identified on endoscopy (left). The ampullary orifice is engulfed eccentrically in this lesion. A cut section of the ampulla illustrates that both the CBD and pancreatic duct open into the lesion (right), with tumor surrounding the orifices of both ducts in the ampullary duodenum.

FIGURE 6

Non‐ampullary duodenal cancer. Probes inserted into the common bile duct (CBD) and pancreatic duct demonstrate that the ampullary orifice in the duodenum is completely spared. The tumor is located more than 1 cm away from the ampulla, confirming its classification as non‐ampullary. It is staged as a duodenal, not ampullary, carcinoma. Compare with Figure 5.