Updated 20 January 2006

1 Clinico-pathologic Considerations

It is important to note that biopsy tracts are readily seeded, and biopsy should be undertaken only if the tumor is clearly unresectable.

Gallbladder cancers are usually locally advanced at the time of presentation. Only 10% are confined to the gallbladder wall at diagnosis, and fewer than 30% have potentially resectable disease. Early cancers are generally detected incidentally at the time of cholecystectomy. Increasingly, early cancers are being recognized in the resection specimens of laparoscopic cholecystectomy.

2 Diagnostic Pathology

The most common histology is adenocarcinoma. Rarer histologies include small cell carcinoma, squamous cell carcinoma, lymphoma and sarcoma. Gallbladder cancer can appear infiltrative, nodular, papillary or a combination. Papillary carcinoma carries a more favorable prognosis.

Gallbladder cancers often progress from dysplasia to carcinoma in-situ before becoming invasive, usually over a period of fifteen years.

Adenomatous polyps may represent a premalignant lesion although this is unclear. Larger polyps are more likely to contain foci of invasive carcinoma. However, unlike invasive gallbladder cancer, gallbladder polyps occur frequently in patients without cholelithiasis and do not appear with a background of chronic inflammation.

Adenocarcinomas originate in the mucosa of the gallbladder. They invade the gallbladder wall as they grow. There appears to be early vascular, lymphatic and neural invasion. Gallbladder cancer is frequently found outside the gallbladder and can invade adjacent organs, particularly the liver.

3 Diagnostic Imaging

The majority of gallbladder cancers are actually diagnosed intra-operatively. Thus, many patients do not have pre-operative imaging specifically for gallbladder cancer.

Ultrasound is the most common diagnostic modality used to investigate patients with cholelithiasis. The sensitivity of trans-abdominal ultrasound for detecting gallbladder cancer is only 38%. The sensitivity for detecting nodal metastases is only 50%. The findings on abdominal ultrasound suggestive, but not diagnostic, of gallbladder malignancy include a solitary or displaced stone, an intraluminal or invasive mass, mural thickening, mural calcification, loss of the interface between the gallbladder and the liver or direct liver infiltration. Cholecystectomy should be considered for all polyps greater that 1 cm (seen on ultrasound) because carcinoma is found in about ¼ (23%) of them.

Endoscopic ultrasound is more accurate for imaging the gallbladder. The sensitivity, specificity, positive predictive value and negative predictive value for gallbladder cancer for endoscopic ultrasound are 92%, 88%, 76% and 97% compared to 54%, 54%, 54% and 95% for trans-abdominal ultrasound. Endoscopic ultrasound is superior to trans-abdominal ultrasound in assessing the depth of tumor invasion into the gallbladder wall and also in defining lymph node metastases and involvement of the portal and peripancreatic regions. In addition, one can obtain a bile sample from endoscopic ultrasound to assess for cytology. The sensitivity of bile analysis for malignancy is 73%.

Endoscopic ultrasound, if available, is the preferred imaging modality for patients who have gallbladder polyps, thickened gallbladder wall, jaundice, or elevated bilirubin and alkaline phosphatase and for whom there is a suspicion of gallbladder cancer.

CT scanning is useful to determine the extent of tumor growth within the gallbladder or bile duct.