Neuroendocrine carcinoma of the gallbladder

Gallbladder neuroendocrine carcinomas were characterised in 2026 from 31 cases among 636 gallbladder cancers: 7 pure small cell, 2 pure large cell and 22 mixed with an adenocarcinoma component (the neuroendocrine part averaging 80 percent of the tumour). The female to male ratio was 5.2 to 1 and median age 58, seven years younger than ordinary gallbladder cancer; high-grade glandular dysplasia was present in 15, six arising in intracholecystic papillary neoplasms. Median Ki-67 was 70 percent, lymphovascular invasion was seen in 74 percent and perineural invasion in 56 percent; 72 percent were pT3 or pT4 against 26 percent of ordinary cancers. Synaptophysin was positive in 95 percent, chromogranin in 75 percent and CD56 in 90 percent; the pRB/p16 pathway was inactivated in 83 percent and p53 was mutant-pattern in 89 percent. Median survival was 6.1 months, with a few unexpectedly long survivors (Reid 2026). In SEER (287 cases, 1975 to 2016) the incidence was 1.6 percent of gallbladder carcinomas, the male to female ratio 1 to 2, median survival 7 months, and one, two, three and five-year overall survival 36.6, 17.8, 13.2 and 7.3 percent; serum chromogranin A was proposed as a marker (Cai 2022). Cancer Research UK lists small cell (oat cell) carcinoma and neuroendocrine tumours among the rare types and notes they are not necessarily treated like adenocarcinoma.

What differs in treatment: these are managed as poorly differentiated neuroendocrine carcinomas of the digestive tract, with platinum and etoposide chemotherapy rather than gemcitabine and cisplatin, and surgery for the minority with localised disease; a population-based analysis found surgery and adjuvant chemotherapy each associated with better survival (Khan 2023, J Pers Med, doi 10.3390/jpm13061009). Mixed tumours are treated according to the higher-grade neuroendocrine component. Well-differentiated neuroendocrine tumours of the gallbladder are a separate, far less aggressive group covered on the neuroendocrine pages.