{"entity":{"id":"metaplasia-dysplasia-carcinoma-sequence","kind":"term","name":"Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer","aka":["dysplasia-carcinoma sequence","flat dysplasia of the gallbladder","BilIN of the gallbladder","biliary intraepithelial neoplasia"],"tldr":"Most gallbladder cancers grow out of flat, invisible changes in the lining: years of irritation from stones turn the mucosa metaplastic, then dysplastic, then into carcinoma in situ, and finally into invasive cancer, a process estimated at 10 to 15 years.","summary":"The flat pathway is the dominant carcinogenic route in the gallbladder. Metaplasia, dysplasia and carcinoma in situ were present in the mucosa adjacent to 66%, 81.3% and 69% of invasive cancers, and dysplasia unassociated with cancer was seen in about 1% of cholecystectomies for symptomatic stones; the mean ages of patients with isolated dysplasia (51.9 years), early carcinoma (56.8) and advanced carcinoma (62.9) form a gradient that puts the sequence at roughly 10 years (Roa 2006), or around 15 years in the earlier series of 84 dysplasias, 60 early and 181 advanced carcinomas (Roa 1996). In the WHO scheme these flat lesions are graded as biliary intraepithelial neoplasia (BilIN), low or high grade. Exome sequencing of co-existing low-grade BilIN, high-grade BilIN and carcinoma from the same gallbladders showed ageing as the main source of mutations, CTNNB1 as a critical early event and two evolutionary paths: the stepwise sequence, and a carcinoma that diverged early after extensive loss of heterozygosity and evolved independently of the visible precursor (Lin 2021). The raised alternative, adenoma or intracholecystic papillary-tubular neoplasm, has its own page.","asOf":"2026-09-24","links":[{"label":"Roa et al., J Surg Oncol 2006: preneoplastic lesions in gallbladder cancer","url":"https://doi.org/10.1002/jso.20527"},{"label":"Roa et al., Gastroenterology 1996: time from dysplasia to gallbladder carcinoma","url":"https://doi.org/10.1053/gast.1996.v111.pm8698204"},{"label":"Lin et al., Nat Commun 2021: co-existing neoplasia and carcinoma lesions of the gallbladder","url":"https://doi.org/10.1038/s41467-021-25012-9"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["ctnnb1","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysplasia","intracholecystic-papillary-tubular-neoplasm"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-roa-gallbladder-preneoplastic-lesions-jso-2006","paper-roa-dysplasia-to-carcinoma-interval-gastroenterology-1996","paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},"route":"/terms/metaplasia-dysplasia-carcinoma-sequence/","neighbours":{"cancer":[{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"target":[{"id":"ctnnb1","kind":"target","name":"CTNNB1","route":"/targets/ctnnb1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"term":[{"id":"dysplasia","kind":"term","name":"Dysplasia (pre-cancerous change)","route":"/terms/dysplasia/"},{"id":"intracholecystic-papillary-tubular-neoplasm","kind":"term","name":"Intracholecystic papillary-tubular neoplasm (ICPN)","route":"/terms/intracholecystic-papillary-tubular-neoplasm/"}],"paper":[{"id":"paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021","kind":"paper","name":"Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","route":"/key-papers/paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021/"},{"id":"paper-roa-dysplasia-to-carcinoma-interval-gastroenterology-1996","kind":"paper","name":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","route":"/key-papers/paper-roa-dysplasia-to-carcinoma-interval-gastroenterology-1996/"},{"id":"paper-roa-gallbladder-preneoplastic-lesions-jso-2006","kind":"paper","name":"Preneoplastic lesions in gallbladder cancer","route":"/key-papers/paper-roa-gallbladder-preneoplastic-lesions-jso-2006/"}]}}