metastatic gallbladder carcinoma

Adenocarcinoma Clinical Most early gallbladder carcinomas are detected by a pathologist after cholecystectomy for cholecystitis. In spite of an occasional early is identified, metastases often are already present. Jaundice in a setting of cancer generally implies spread to lymph nodes adjacent to extrahepatic bile ducts. An occasional gallbladder carcinoma invades the liver, necroses, and becomes infected, and the patient presents with a liver abscess.
A rare gallbladder carcinoma results in afetoprotein secretion. Immunostaining detects overexpression of p53 protein in most gallbladder cancers and overexpression appears directly related to increasing carcinoma grade. Ultrasonography screening of a high-risk population is occasionally proposed to detect
early gallbladder carcinomas, but such a practice is not common. Even if detected early, prognosis is generally poor. Compared to normal ducts, patients with a congenital anomalous pancreaticobiliary junction are at increased risk for developing gallbladder cancer (sphincter of Oddi anomalies are discussed in the earlier Congenital Abnormalities section).
An association of gallbladder cancer with chronic cholecystitis is well known. Likewise, because of the high risk for cancer, detection of a porcelain gallbladder is generally deemed an indication for elective cholecystectomy. Patients with chronic Salmonella typhi infection are at increased risk for several hepatobiliary cancers, including gallbladder carcinoma. A possible association between actinomycosis and gallbladder carcinoma is suggested. An increased prevalence of gallbladder carcinoma is found in a setting of sclerosing cholangitis, although the much higher risk of primary bile duct carcinoma overshadows gallbladder involvement. Synchronous primary gallbladder and extrahepatic bile duct carcinomas are uncommon. Often differentiation of separate primaries from metastases is difficult.
Pathology Carcinoma-in-situ implies a tumor limited to the epithelium and is usually detected by the pathologist after cholecystectomy for cholelithiasis. Most in-situ carcinomas discovered after laparoscopic cholecystectomy do not manifest lymphatic, venous, or perineural invasion and thus are potentially curable. A diagnosis of early gallbladder carcinoma is rarely made outside of Japan. Japanese investigators divide these early tumors into superficial flat and superficial elevated types. The superficial flat carcinomas are not detected by imaging and are difficult to identify even by a pathologist. Sessile cancers are more common than pedunculated ones. Histologic variants include papillary, mucinous, and an occasional clear cell carcinoma, although most are simply reported as adenocarcinomas. They range from well differentiated to anaplastic. A number of tumors contain more than one subtype, thus complicating the histologic subdivision. Papillary carcinomas tend to grow intraluminally, and some have a cauliflower-like appearance. Most gallbladder carcinomas, however, infiltrate early and extensively. Detection A number of studies confirm that a preoperative diagnosis of gallbladder cancer is achieved in only 30% to 40% of patients. In particular, stages 0 to II are diagnosed either at surgery or, more often, at histology. Imaging detection of a solitary gallstone, a gallstone elevated because of focal wall thickening, an intraluminal or invasive tumor, and discontinuity of the mucosal echo pattern suggests a carcinoma. Gallbladder wall thickening is found with both benign and malignant disease. An asymmetric or irregular wall thickening, however, is more common with a cancer. Also, a large polyp or an infiltrating tumor replacing most or all of the gallbladder lumen or invading adjacent structures suggests a cancer, regardless of whether or not gallstones are present. Nevertheless, a not uncommon scenario is a thickened gallbladder wall detected by CT or US, believed to represent chronic cholecystitis, containing a gallbladder cancer.
A necrotic, perforated gallbladder cancer mimics acute cholecystitis both clinically and by imaging. Some tumors contain hypodense regions, signifying necrosis.Viable tumor tends to enhance postcontrast. Currently the primary role of both CT and MR is in staging rather than diagnosis. A rare mucus-secreting gallbladder carcinoma develops sufficient intratumoral calcifications to be visible by CT or even with conventional radiography.
Ultrasonography reveals either focal gallbladder wall thickening or an inhomogeneous, hyperechoic, fungating, broad-based tumor within the lumen with little acoustic shadowing. With invasion of surrounding tissues quite often the gallbladder is not recognized and US simply identifies a poorly marginated, heterogeneous mass. Associated gallstones are common. Most authors agree that endoscopic US detects more and earlier gallbladder tumor than conventional US, yet concomitant cholecystitis or stones often prevent tumor identification. Color Doppler US of a carcinoma reveals color signals both in intraluminal tumors and gallbladder wall. The presence of a high-resistance index is uncommonly detected but is suggestive of a malignancy. Gallbladder carcinomas most often are hypointense on T1- and hyperintense on T2- weighted images. Postcontrast MRI of carcinomas reveals early and irregular enhancement, in distinction to the delayed wall enhancement found in chronic cholecystitis. The usual threelayer gallbladder wall MR appearance is destroyed by a carcinoma but tends to be preserved with inflammatory disease. In most instances cholangiography is not helpful in detecting a gallbladder cancer because of concurrent cystic duct obstruction. Not uncommon is hepatic duct invasion due to metastasis. Occasionally US-guided percutaneous transhepatic fine-needle aspiration cytology from a tumor provides a diagnosis, although a malignant focus in an adenoma is readily missed.
image
This is radiology images of Hepatic duct obstruction (arrow) secondary to metastatic gallbladder carcinoma. Other metastases can have a similar appearance.

Staging
A gallbladder carcinoma spreads outside the gallbladder to adjacent liver and along the cystic duct to pericholedochal and superior pancreaticoduodenal lymph nodes. Patients with T1 tumors tend not to have lymph node involvement, but a majority of those with T2–T4 tumors have lymph node metastases, with pericholedochal and cystic lymph nodes being most often involved. Involvement of multiple nodes is common.
Similar to a number of other tumors, CT has poor sensitivity with T1 tumors. Some studies have achieved helical CT accuracies in assessing resectability of over 90%, keeping in mind that resectability differs from cure. In particular, accuracy of gauging lymph node involvement is poor even with multidetector CT. Still, CT appears helpful in treatment planning. Ultrasonography is considered inadequate in staging gallbladder cancer. Tumor spread to right and left bile duct confluence or Portal vein invasion renders a gallbladder carcinoma inoperable. In some patients percutaneous transhepatic portography and intraportal US are necessary to distinguish between vein compression and invasion.
Therapy With the exception of carcinoma-in-situ, most gallbladder cancers discovered at surgery imply a poor prognosis. Even with an early lesion a simple cholecystectomy is not necessarily curative; an extended cholecystectomy with lymph node dissection, at times combined with extrahepatic bile duct or hepatic resection, offers a possible cure. A 5-year survival of 10% to 15% is typical, with long-term survivors being stage I or II. Aggressive surgery appears to improve survival. A University of Bonn (Germany) study of patients undergoing curative resection, consisting of an extended cholecystectomy (cholecystectomy with lymphadenectomy and wedge hepatic resection), anatomic segmentectomy of segments IVa and V, or extended hepatectomy, achieved an actuarial 5-year survival rate of 55%. An endoprosthesis, placed either endoscopically or percutaneously, is useful for palliation in some patients with an unresectable carcinoma. Chemotherapy has had little impact on survival. Metastases/Recurrence Gallbladder carcinomas metastasize widely, even to bone. Spread to extrahepatic bile ducts, gastrointestinal tract, and adjacent structures is common. Occasionally a distant metastasis is the first clue to an underlying gallbladder carcinoma. An exceptional patient with extensive metastases, treated aggressively has prolonged survival.
More than most cancers, gallbladder carcinoma spreads readily along laparoscopic trocar sites.A number of patients have an unsuspected carcinoma first detected by a pathologist, with trocar site recurrence identified several months later.Even several recurrences have developed at laparoscopic ports. Peritoneal seeding also occurs, including localized seeding in the right subphrenic space.
A suspected gallbladder carcinoma probably is a contraindication to laparoscopic cholecystectomy. When a laparoscopic cholecystectomy is performed for an unsuspected carcinoma, surgical and adjuvant radiotherapy to the trocar sites appears reasonable. Computed tomography identifies port track recurrence as a homogeneous abdominal wall tumor,often directly involving adjacent omental fat. Recurrences tend to enhance markedly on postcontrast CT.
Other Primary Carcinomas/Sarcomas Both squamous and adenosquamous gallbladder carcinomas are uncommon. Often a large tumor with invasion of adjacent structures is found at initial presentation. These tumors tend to spread widely, including hematogenously. A gallbladder carcinosarcoma is rare. These tumors tend to be large when first detected. Small cell carcinomas are rare tumors spreading diffusely and having a poor prognosis. Immunochemistry reveals some of these tumors to have a neuroendocrine cell origin, and presumably they are derived from intestinal metaplasia.
Lymphoma
Primary gallbladder lymphoma is sufficiently rare that only case reports exist. Computed tomography and US detects a complex tumor confined to the gallbladder. Systemic lymphoma also uncommonly involves the gallbladder. MALT lymphomas have a propensity to involve numerous mucosal sites.Thus a 53-yearold woman with low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma underwent a total gastrectomy, developed small bowel recurrence 18 years later, underwent chemotherapy, was in clinical remission, and then was found to have gallbladder recurrence 3 years later.
Melanoma
Both primary and metastatic malignant gallbladder melanomas are reported. The presence of another obvious primary site argues for a metastasis; otherwise, a distinction between primary and metastatic melanoma is difficult. Indeed, the question can be raised: Does primary gallbladder melanoma occur? Autopsies of patients with malignant melanoma show gallbladder metastases in 15% to 20%; US reveals soft tissue tumors projecting into the lumen; an occasional one is polypoid.
Metastases to Gallbladder Aside from melanomas, metastases to the gallbladder are not common. Renal cell carcinoma and gastric carcinoma are found occasionally. A rare metastasis appears as a polyp. An occasional metastasis presents as cholecystitis. Confusing the issue, histologic differentiation of a primary clear cell gallbladder carcinoma from a metastatic renal cell carcinoma is difficult.

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