Dysplasia and carcinoma of the gallbladder: pathological evaluation, sampling, differential diagnosis and clinical implications

Abstract

Pathological evaluation of gallbladder neoplasia remains a challenge. A significant proportion of cases presents as clinically and grossly inapparent lesions, and grossing protocols are not well established. Among epithelial alterations, pseudo‐pyloric gland metaplasia is ubiquitous and of no apparent consequence, whereas goblet cell metaplasia and a foveolar change in surface cells require closer attention. Low‐grade dysplasia is difficult to objectively define and appears to be clinically inconsequential by itself; however, extra sampling is required to exclude the possibility of accompanying more significant lesions. For high‐grade dysplasia (‘high‐grade BilIN’, also known as ‘carcinoma in situ’), a complete sampling is necessary to rule out invasion. Designating in‐situ or minimally invasive carcinomas limited to muscularis or above as early gallbladder carcinoma (EGBC) helps to alleviate the major geographical differences (West/East) in the criteria for ‘invasiveness’ to assign a case to pTis or pT1. Total sampling is crucial in proper diagnosis of such cases. A subset of invasive GBCs (5–10%) arise from the intracholecystic neoplasm (ICN, ‘adenoma‐carcinoma sequence’) category. Approximately two‐thirds of ICNs have invasive carcinoma. However, this propensity differs by subtype. True ‘pyloric gland adenomas’ (> 1 cm) are uncommon and scarcely associated with invasive carcinoma. A distinct subtype of ICN composed of tubular, non‐mucinous MUC6+ glands [intracholecystic tubular non‐mucinous neoplasm (ICTN)] forms a localised pedunculated polyp. Although it is morphologically complex and high‐grade, it appears to be invasion‐resistant. Some of the invasive carcinoma types in the gallbladder have been better characterised recently with adenosquamous, neuroendocrine, poorly cohesive and mucinous carcinomas often being more advanced and aggressive.

Incidental Gallbladder Neoplasms: A Growing Global Burden

“…The studies have shown its incidence ranging from 0.2%-3.3%. [ 1 , 4 , 9 - 11 , 24 ]. Out of the total who received cholecystectomies during the study period, 11 GBC (11/1253; 0.87%) were diagnosed incidentally in our study, which was in accordance with the published literature.…”

“…Gallstones are the major co-morbid risk factors seen in 70-98% of GBC cases with an incidence of GBC related to cholelithiasis ranging from 0.3% to 12%. [ 2 , 4 , 7 , 11 , 17 - 19 ]. Estrogen causing increased cholesterol super-saturation in the bile has been attributed to the gallstone-mediated GBC pathogenesis [ 20 ].…”

“…GB malignancies and dysplastic lesions pose a big diagnostic dilemma both clinically and radiologically. They have overlapping features with benign conditions and about 0.2%-3.3% of them are diagnosed incidentally, either intraoperatively or on histopathological examination [ 4 , 9 - 11 ].…”

A nomogram‐based model and ultrasonic radiomic features for gallbladder polyp classification

“…Clinical characteristics, laboratory parameters, and pathological diagnoses were collected retrospectively from electronic medical records. The pathological diagnosis was made by professional pathologists in keeping with relevant pathological guidelines, 18 and the results were classified in Table S1. Tumor markers such as alpha‐fetoprotein, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 were included 19 .…”

Precursor Lesions of Gallbladder Carcinoma: Disease Concept, Pathology, and Genetics

“…Details are not given on why, among the grossly visible preneoplastic lesions of the gallbladder, only PGA was placed outside of the ICPN in WHO 2019. However, one possible reason may be that PGA is relatively well-characterized as a neoplastic precursor gallbladder lesion and is more innocuous in behavior compared to other tumors categorized under ICPN [ 15 ], hence it is treated as an independent entity.…”