Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples

Abstract

Background. Gallbladder diseases, especially cholelithiasis, are extremely frequent in Chile, and an increasing frequency of gallbladder carcinoma has been observed during the last decades. Hyperplastic and atypical epithelial lesions of gallbladder epithelium have been considered potential precursors of invasive carcinoma. The current study was designed to study the frequency, distribution, extension, and probability of routine detection of potentially preneoplastic changes of gallbladder epithelium. Methods. Epithelial changes were histologically studied by mapping gallbladders obtained at elective cholecystectomy for lithiasis in 162 Chilean patients. Results. Antral‐type metaplasia was found in 95.1% of the cases, intestinal metaplasia in 58.1%, hyperplasia in 46.9%, dysplasia in 16%, and carcinoma in situ in 2.5%. A significant association of intestinal metaplasia with hyperplasia, intestinal metaplasia with dysplasia, and hyperplasia with dysplasia was found. Hyperplasia and dysplasia were also present in four cases with carcinoma in situ. Mean extension of the lesions (percentages of the sections in which the change was observed) was antral‐type metaplasia (62.7%), intestinal metaplasia (25.3%), hyperplasia (24.1%), dysplasia (15.5%), and carcinoma in situ (9.7%). Antral‐type and intestinal metaplasia were more extensive and more severe in patients older than 50 years of age. Hyperplasia was more extensive in cases in which it was associated with dysplasia and carcinoma in situ. Conclusions.The extension of metaplasia seems to depend in part on the age of the patients. The association of intestinal metaplasia with hyperplasia and dysplasia agrees with the findings of other authors that relate metaplasia to gallbladder cancer. The epithelial lesions are focal or partially confluent, thus a single random histologic section will detect less than one third of the hyperplasias, dysplasias, and carcinomas insitu.

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition

“…Within them, dysplasia is thought to be a premalignant lesion because it is found rarely in the mucosa of gallbladder resected for cholecystlithiasis and chronic cholecystitis [237][238][239]. Molecular biological analysis also indicates the existence of metaplasia-dysplasia-carcinoma sequence [240,241].…”

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma

“…Additionally, metaplastic changes have been implicated as an even earlier potential precursor in gallbladder carcinoma. 4,5 Risk factors for the development of biliary tract carcinoma include race (increased risk in native and Hispanic Americans), cholelithiasis, abnormal junction of the pancreatic and biliary duct for gallbladder carcinoma, and primary sclerosing cholangitis and choledochal cyst for carcinoma of the extrahepatic bile ducts. The frequent advanced nature of disease on presentation, as well as limited knowledge of causative molecular factors underlying biliary tract carcinoma, has limited the therapeutic options for patients with this cancer.…”

Seek and ye shall find: the importance of careful macroscopic examination and thorough sampling in 2522 cholecystectomy specimens

“…Dysplasia and carcinoma may be focal, and can be missed if a suboptimal sampling protocol is used -a single random section will identify less than 30% of significant epithelial lesions [16]. When examination of initial tissue blocks reveals dysplasia, authors disagree as to whether the entire remainder of the organ or only selected sections from it need then be examined [17][18][19].…”