Reflux-Associated Cholecystopathy: Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma

• Published in: The American journal of surgical pathology Vol. 41; no. 9; pp. 1167 - 1177
• Main Authors: Muraki, Takashi, Memis, Bahar, Reid, Michelle D, Uehara, Takeshi, Ito, Tetsuya, Hasebe, Osamu, Okaniwa, Shinji, Horigome, Naoto, Hisa, Takeshi, Mittal, Pardeep, Freedman, Alexa, Maithel, Shishir, Sarmiento, Juan M, Krasinskas, Alyssa, Koshiol, Jill, Adsay, Volkan
• Format: Journal Article
• Language: English
• Published: United States Copyright Wolters Kluwer Health, Inc. All rights reserved 01-09-2017
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Common Bile Duct - abnormalities; Female; Gallbladder - pathology; Gallbladder Diseases - etiology; Gallbladder Neoplasms - diagnosis; Humans; Hyperplasia - diagnosis; Japan; Male; Middle Aged; Pancreatic Ducts - abnormalities; Pancreatic Juice; Sphincter of Oddi; United States; Young Adult
• ISSN: 0147-5185; 1532-0979
• DOI: 10.1097/PAS.0000000000000882

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common includingpyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as “reflux-associated cholecystopathy.” Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.