Gallbladder carcinoma is a term referring to primary epithelial malignancies arising from the gallbladder, in which the great majority (90%) are adenocarcinomas and the remainder are squamous cell carcinomas. They are more prevalent in elderly women and, in most cases, are only symptomatic when in advanced stages.
On imaging, they can present as a focal intraluminal mass, focal or diffuse gallbladder wall irregular thickening, or large mass lesion replacing the entire gallbladder. It is not uncommon to depict those tumors with some degree of invasion of adjacent structures or metastatic disease.
Although overall uncommon, gallbladder adenocarcinoma is the most common primary biliary carcinoma and the 5th most common malignancy of the gastrointestinal tract 1.
Predominantly affects older persons with long-standing cholecystolithiasis, and as such is most common in elderly women (>60 years of age, F:M ratio = 4:1) 1,3.
Early in the course of the disease, patients are invariably asymptomatic, and as such a therapeutic window is usually missed. Eventually, symptoms develop, at which time the mass is usually not resectable.
Clinical presentation depends on the direction in which the mass extends. In cases where the biliary obstruction is created then jaundice is often the first presentation. If the malignancy is located in the body or fundus of the gallbladder, then extend into the liver or adjacent colon or small bowel can lead to local pain or bowel obstruction respectively.
Other symptoms include right upper quadrant pain, weight loss and anorexia.
Over 90% of cases of gallbladder cancer are adenocarcinomas, with the majority related to chronic inflammatory metaplasia and dysplasia 15. Squamous cell carcinomas figure as the second most common histologic type of gallbladder carcinoma (representing up to 3% of all gallbladder primary malignancies) 19.
Risk factors include 1:
- chronic cholecystitis
- gallstones are seen in 70-90% of cases 3,4
- familial adenomatous polyposis syndrome (FAP)
- inflammatory bowel disease (IBD)
- porcelain gallbladder
- gallbladder polyps >1 cm that are sessile and solitary
- primary sclerosing cholangitis 13
- anomalous junction of pancreaticobiliary ducts 16
- certain ethnicities and geographical groups (e.g. Native Americans and Chileans) 16
- chronic infections including the typhoid carrier state 16
- exposure to carcinogens (e.g. lead, cadmium, chromium) 16
- obesity, diabetes, and dietary factors 17
- family history of gallbladder carcinoma 18
Gallbladder adenocarcinomas present in one of three morphologies 19:
- intraluminal mass
- diffuse mural thickening
- mass replacing the gallbladder
- presumably the end result of progression from either 1 or 2
- most common presentation
Gallstones are commonly present (60%–90%) 14.
Ultrasound can depict a focal intraluminal, wall involvement, or large mass-like lesion replacing the gallbladder. The tumor usually has irregular and sometimes ill-defined margins, with heterogeneous echotexture and predominantly low echogenicity. Hyperechoic foci with posterior acoustic shadowing may be seen within the mass, possibly reflecting gallstones or gallbladder wall calcifications - porcelain gallbladder 19.
Typically gallbladder adenocarcinomas appear as large heterogeneous masses, which may have engulfed gallstones or areas of necrosis. Patchy moderate contrast enhancement is usually seen.
Features of advanced disease include:
- intrahepatic biliary dilatation
- invasion of adjacent structures
- peritoneal carcinomatosis
- hepatic and other distant metastases
Dynamic MRI is considered useful and reliable in the staging of advanced gallbladder carcinoma. MRI combined with MRCP is sensitive in the detection of obstructive jaundice and liver invasion as well as hepatic and lymph nodal metastasis. It may be more difficult to delineate any invasion into the duodenum or to detect omental metastasis by MRI 6. Reported sensitivity rates for direct hepatic invasion and lymph node invasion on MRI can be as high as 100% and 92% respectively 7.
Treatment and prognosis
Unfortunately, due to the mostly asymptomatic nature of these tumors, the presentation is typically late with the majority of tumors being large, unresectable, with direct extension into adjacent structures or distant metastases present at diagnosis.
Curative resection is only possible for localized early disease, which is usually found incidentally. This is reflected in the dismal prognosis 4:
- 1-year survival: 80%
- 5-year survival: 1-5%
The differential will depend on the growth pattern of the tumor:
- intraluminal masses
- gallbladder polyp: see differentiating benign vs malignant gallbladder polyps
- melanoma is the most frequent 9
- other described primaries include: lung, esophagus, pancreas, colon, and kidney carcinomas 9
- mural thickening has a limited differential but is difficult to distinguish on imaging alone, possibilities include
- large tumors differentials include a number of nearby primaries with extension to the gallbladder
- hepatocellular carcinoma (HCC)
- tumors from adjacent organs (pancreas, duodenum) invading gallbladder fossa 10
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Gallbladder and biliary tract pathology
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- diffuse gallbladder wall thickening (differential)
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