Preneoplastic lesions in gallbladder cancer

Abstract

From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years.

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

“…(Grade 2, evidence level C) Statement: Adenoma and dysplasia have been regarded as a precancerous lesion of the gallbladder and intestinal metaplasia seems to be the pathway through which the epithelial dysplasia is produced [26,27]. Several reports showed that polypoid lesion is highly likely to be cancerous if it is sessile and/or solitary, its diameter is equal to or greater than 10 mm, patient's age is equal to or greater than 60 years old, and/or it grows rapidly [28][29][30][31][32].…”

Asymptomatic Gallstones (AsGS) – To Treat or Not to?

“…Risk of GBC has been reported to increase with increasing size of GS and with increasing number of stones [20,21] -especially if the stones occupy a significant volume of the GB [22]. Progressive changes in GB wall from chronic cholecystitis, hyperplasia, metaplasia, dysplasia, carcinoma in situ to invasive cancer have been reported from Chile -the time course of which lends credence to a gradual progression from chronic inflammation to dysplasia to invasive carcinoma [42]. The incidence of GBC is also reported to be higher in patients with xanthogranulomatous cholecystitis and Mirizzi's syndrome -both associated with long-standing GS disease [43][44][45].…”

Estrogen-dependent gallbladder carcinogenesis in LXRβ −/− female mice

“…Gallbladder cancer is preceded by a sequence of molecular and histopathological alterations evolving to cancer over a long period, estimated to be approximately 15 y (26). This multistage pathogenesis starts from chronic inflammation, often associated with cholesterol gallstones, and progresses to dysplastic flat-epithelial changes characterized by high cell density, hyperchromasia, and elongated nuclei (27,28). Subsequently, the atypical epithelium undergoes increased stratification leading to the high-grade premalignant lesion called carcinoma in situ (27,28).…”

“…This multistage pathogenesis starts from chronic inflammation, often associated with cholesterol gallstones, and progresses to dysplastic flat-epithelial changes characterized by high cell density, hyperchromasia, and elongated nuclei (27,28). Subsequently, the atypical epithelium undergoes increased stratification leading to the high-grade premalignant lesion called carcinoma in situ (27,28). Besides this most frequent evolution, a small number of gallbladder carcinomas seems to evolve from preexisting adenomas (29).…”