Gallbladder FISH: An Unusual Case of Early Detection and Cure of Gallbladder Cancer

Abstract

Introduction: This is a case report of early diagnosis of gallbladder malignancy using fluorescence in situ hybridization (FISH) that led to surgical resection and cure from a malignancy, which otherwise has a very poor prognosis. Case Description: A 66-year-old Caucasian man with a 12-year history of ulcerative colitis (UC) was evaluated because of abnormal liver function tests and suspected primary sclerosing cholangitis (PSC). He had an abdominal CT scan that showed mildly dilated intrahepatic ducts with no other biliary ductal or gallbladder abnormalities. His Ca 19.9 was elevated at 80 units/mL. He underwent an endoscopic retrograde cholangiography (ERC) that showed irregularity in the distal common bile duct (CBD) and stricturing in the right hepatic duct (RHD) consistent with PSC. Brushing for cytology and FISH were obtained from the CBD and the RHD. Cytology showed reactive cellular atypia and acute inflammation and FISH showed 5 cells with gains of two or more chromosomes, 3(D3Z1), 7(D7Z1), and 17(D17Z1), and greater than 10 cells with gains of a single chromosome, 7(D7Z1). These results were consistent with malignancy. An endoscopic ultrasound was performed showing asymmetric gallbladder wall thickening and no evidence of a mass. The distal CBD was also mildly thickened. He was planned to undergo colectomy for colonic dysplasia in the setting of longstanding UC so he underwent a concomitant cholecystectomy based on our recommendations. Pathology showed a well-differentiated 2.2 cm gallbladder carcinoma with perimuscular invasion but no extension beyond the serosa or into the liver and no malignant adenopathy (stage T2 N0 M0). The patient has been followed-up closely for 2 years with multiple MRIs and ERCs with cytology and FISH being performed. These have been consistently negative for malignancy. He has no other clinical findings suggestive of cholangiocarcinoma. Discussion: While the molecular pathogenesis of adenocarcinoma of the biliary tree remains poorly understood, evidence suggests that there is a field carcinogenic effect in patients with PSC putting them at an increased risk of both cholangiocarcinoma and gallbladder cancer. A positive FISH in our patient with no clear evidence of cholangiocarcinoma prompted a careful examination of the gallbladder with findings suspicious enough to lead to cholecystectomy. This thorough evaluation led to early detection and long-term cure from gallbladder cancer, which otherwise has a very poor prognosis unless detected incidentally on cholecystectomy done for a different etiology.