Adenosquamous and squamous carcinoma of the gallbladder

Squamous differentiation arises through metaplasia in the chronically inflamed gallbladder lining. A tumour is called adenosquamous when the squamous component exceeds 25 percent (Gasparello 2026); pure squamous cell carcinoma has no glandular component. In the National Cancer Database analysis of 13,158 patients, the 703 adenosquamous tumours (5 percent) were larger, more often poorly differentiated and more often stage III or IV (75 versus 69 percent), and overall survival was worse both overall and after curative-intent resection; adjuvant chemoradiation was associated with benefit (Murimwa 2021). A SEER series identified 388 patients between 1975 and 2018 and found surgery, node dissection, radiotherapy and chemotherapy each associated with better cancer-specific survival (Fang 2023). In a Chinese surgical series of 411 gallbladder cancers, 10 squamous and 24 adenosquamous tumours were all T3 or T4, with more T4 disease (61.8 versus 34.0 percent) and more node involvement (58.8 versus 39.0 percent) than adenocarcinoma; only complete (R0) resection gave one-year survivors (30 percent) (Song 2015). A 2026 molecular study of 25 European cases found PD-L1 positivity (combined positive score above 1) in 96 percent and claudin 18.2 expression in 28 percent (Gasparello 2026).

What differs in treatment: staging, surgery and chemotherapy follow the adenocarcinoma pathway (Cancer Research UK: treated in the same way as adenocarcinomas), but the expectation is of bulkier, more invasive disease, so complete resection is harder to achieve, and the high PD-L1 expression is a reason to study immunotherapy in this subtype specifically. No approved treatment is specific to it.