Often none until late; many cancers are found by the pathologist after a gallbladder is removed for stones (NHS; Soreide 2019)
Aching or dragging pain in the right upper tummy, sometimes sharp; feeling or being sick; loss of appetite or unexplained weight loss (NHS)
Yellow whites of the eyes or skin (jaundice), which may be harder to see on brown or black skin, with itchy skin, dark urine and pale stools: seek urgent help the same day (NHS)
A high temperature, a lump in the tummy, or a swollen tummy not related to eating (NHS)
Half of English cases are diagnosed after an emergency presentation, so new or worsening symptoms should not wait for a routine check (CRUK)
How it is confirmed
GP examination and blood tests (liver function, sometimes CA 19-9 and CEA); NICE NG12 asks for an urgent direct-access ultrasound if there is an upper abdominal mass consistent with an enlarged gallbladder
A needle biopsy is usually avoided when the mass looks resectable; surgeons rely on imaging and intraoperative frozen section, and biopsy when the disease is unresectable and drug treatment is planned (Chan 2022; Banh 2024; NHS)
ERBB2 (HER2) amplification: 8-10% (8% amplification alone plus 1.5% amplification with a mutation among 260 patients (Mondaca 2024))
ERBB2 (HER2) activating mutation (s310f/y hotspot): 4-8% (4% mutation alone, 1.5% with amplification and 0.4% fusion among 260 patients (Mondaca 2024))
ERBB2 (HER2) proteinoverexpression (ihc): 9-31% (31.3% HER2-positive among 80 resected Japanese gallbladder carcinomas scored by the gastro-oesophageal guideline (Hiraoka 2020))
ERBB3 (HER3) mutation (amplification rarer): 7-12% (11.8% of 57 (Li 2014, a significantly mutatedgene))
PIK3CA mutation : 11% (Mutation in 26 of 244 samples, 10.7%, in cBioPortal gbc_mskcc_2022 and 11 of 103, 10.7%, in gbc_msk_2018)
CDKN2B deep deletion (with cdkn2a): 14% (Deep deletion in 34 of 244 samples, 13.9%, in cBioPortal gbc_mskcc_2022 and 12 of 103, 11.7%, in gbc_msk_2018)
ARID1A mutation (loss of function): 13-25% (13% of 85 (Javle 2016))
SMAD4 mutation or deletion : 21-38% (38% in Chile, 36% in Japan and 27% in the United States among 81 patients, with worse survival (10 versus 25 months)
CTNNB1 mutation (wnt activation): 6% (Mutation in 15 of 244 samples, 6.1%, in cBioPortal gbc_mskcc_2022 and 6 of 103, 5.8%, in gbc_msk_2018)
EGFR amplification or mutation : 1-3% (Amplification in 8 of 244 samples, 3.3%, and mutation in 3 of 244, 1.2%, in cBioPortal gbc_mskcc_2022)
MDM2 amplification : 12% (Amplification in 29 of 244 samples, 11.9%, in cBioPortal gbc_mskcc_2022 and 12 of 103, 11.7%, in gbc_msk_2018)
BRAF mutation : 3% (Mutation in 7 of 244 samples, 2.9%, in cBioPortal gbc_mskcc_2022 and 5 of 103, 4.9%, in gbc_msk_2018)
IDH1 / IDH2 mutation : 0.4% (IDH1 mutation in 1 of 244 samples, 0.4%, and no IDH2 mutation in cBioPortal gbc_mskcc_2022)
Tumour mutational burden tmb (mutations per megabase): 1-12% (Median 4.1 non-synonymous mutations per megabase, with 28 of 244 samples, 11.5%, at 10 or more on the MSK-IMPACT panel (cBioPortal gbc_mskcc_2022))
BRCA1 / BRCA2 mutation (somatic or germline): 1-5% (BRCA2mutation in 13 of 244 samples, 5.3%, and BRCA1 in 3 of 244, 1.2%, in cBioPortal gbc_mskcc_2022)
ATM mutation : 7-16% (Mutation in 16 of 244 samples, 6.6%, in cBioPortal gbc_mskcc_2022 and 16 of 103, 15.5%, in gbc_msk_2018)
PALB2 mutation : 1.6% (Mutation in 4 of 244 samples, 1.6%, in cBioPortal gbc_mskcc_2022)