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Adeno‐endocrine cancer of the gallbladder

Cancer of the gallbladder is an uncommon malignancy that often presents with advanced disease and carries a poor prognosis. Adenocarcinoma arising in biliary epithelium accounts for 90% of all gallbladder cancers while papillary, mucinous, squamous and adenosquamous subtypes also occur and account for a further 9% of cases. Carcinoid tumours (or neuroendocrine tumours) also occur within the gallbladder and are thought to arise from neural crest cells that migrate to sites within the gastrointestinal tract during embryonal development rather than from biliary epithelia. However, there have been a total of 19 reported cases of a mixed tumour 1 composed of elements of adenocarcinoma and neuroendocrine carcinoma (adeno-endocrine cancer), indicating that these tumours might arise from a common epithelial stem cell or be the result of simultaneous malignant transformation in two different cell types. A 68-year-old woman presented to our service with a history of 2 months of aching pain in the right lower quadrant. There were no associated symptoms of diarrhoea, constipation, palpitations, sweats or flushing. Her past medical history was significant for a left mastectomy with axillary lymph node dissection and immediate reconstruction for invasive ductal cancer 3 years previously. Examination was unremarkable apart from a palpable fullness in the right iliac fossa. Full blood count, urea and electrolytes, and liver function tests were within normal range. She was investigated with a gastroduodenoscopy and colonoscopy, which were unremarkable. Magnetic resonance scan of the abdomen showed multiple intra-abdominal masses and a distended gallbladder. Fine needle biopsy of one of the abdominal masses showed neuroendocrine carcinoma. A 24-h urine collection showed a 5-hydroxyindole acetic acid (5HIAA) concentration of 13 μ mol (normal <50 μ mol). A bone scan showed no metastatic lesions. The patient then presented acutely with severe right sided abdominal pain and anaemia. At laparotomy 1500cc of blood stained ascites was found with a bleeding point localized to a mass in the right paracolic gutter. Extensive debulking of the intra-abdominal disease was undertaken. The gallbladder was also noted to be distended and open cholecystectomy was performed because of the concern of an infected mucocele. Macroscopic examination of the gallbladder revealed at fullness in the fundus although there was no sign of invasive malignancy. On opening the gallbladder a fluid filled cystic tumour in the fundus was observed. Sections of this tumour showed a multilocular cystic neoplasm with multiple cysts lined with mucin secreting epithelial cells (Fig. 1a). A significant part of the neoplasm was also composed of sheets of malignant cells and several acinar clumps. There was transmural penetration but no macroscopic invasion of the liver bed. Postoperatively the patient made a satisfactory recovery from surgery and was discharged from hospital on day 8. The final histology was of an adeno-endocrine tumour of the gallbladder (Fig. 1b) with peritoneal metastases. Systemic etoposide and 5-fluorouracil/leucovorin was commenced 6 weeks postoperatively, however, the patient died of progressive disease 6 months later.