Gallbladder Lymphoma in Primary Sclerosing Cholangitis
Article Outline
A 74-year-old man with long-term primary sclerosing cholangitis and ulcerative colitis had a soft-tissue mass in the gallbladder that was detected during a semiannual magnetic resonance imaging surveillance examination in March 2006. That study (Figure A; coronal enhanced fat-suppressed, T1-weighted image) revealed uniform enhancement in the thickened gallbladder wall (long arrow), and mild dilatation of the intrahepatic ducts (small arrows) with more central effacement indicated underlying primary sclerosing cholangitis. Serum hepatobiliary tumor marker levels for α-fetoprotein, carbohydrate antigen 19-9, and carcinoembryonic antigen all were within the normal range. Regional lymph nodes appeared clinically normal during open cholecystectomy, and the patient had no ascites. The gallbladder measured 4.5 × 4.0 cm and contained multiple gallstones. The gallbladder wall was 0.8 cm thick and contained compact aggregates of morphologically abnormal, nonpolarized lymphoid follicles that permeated the wall of the gallbladder (Figure B; H&E: original magnification, 20×). The lymphoid follicles and extrafollicular lymphocytes were positive for CD10 (Figure C; CD10 immunostain: original magnification, 100×), CD20, and BCL-6, indicating a follicular center cell origin. The lack of germinal center BCL-2 oncoprotein expression (often negative in extranodal follicular lymphomas) and the lack of BCL-2–immunoglobulin H fusion with the presence of B-cell clones (detected by polymerase chain reaction for immunoglobulin H gene rearrangement) were consistent with a B-cell lymphoma of extranodal origin. No lymphocytic or plasma cell periportal infiltrates were identified to suggest autoimmune cholangitis, and the liver biopsy findings were most consistent with biliary cirrhosis.
The development of cholangiocarcinoma is the most feared complication of primary sclerosing cholangitis, with a lifetime risk of 7% to 15%, but it is not necessarily associated with the severity of liver disease. A study reviewing the pathologic findings of 102 patients with primary sclerosing cholangitis who underwent cholecystectomy identified gallbladder neoplasms in 14.1 Of these 14 patients, 8 had cholangiocarcinoma and 6 had benign disease. The investigators concluded that gallbladder neoplasms in patients with primary sclerosing cholangitis have a high likelihood of malignancy (usually cholangiocarcinoma). Therefore, the finding of a follicular cell lymphoma in our patient's gallbladder was unexpected.
The gastrointestinal tract is the most common location for the development of extranodal lymphomas; the highest-frequency site of lymphomas is the small intestine, followed by the large intestine and stomach.2, 3 Lymphoma of the gallbladder is rare, and most reported cases describe secondary involvement of the gallbladder for patients with systemic lymphoma. Subtypes of primary non-Hodgkin lymphoma of the gallbladder include mucosa-associated lymphoid tissue lymphoma, high-grade B-cell lymphoma, T-cell lymphoblastic lymphoma, small lymphocytic lymphoma, follicular lymphoma, and Burkitt lymphoma. Although extranodal lymphomas are defined as being restricted to a solitary site (with or without involvement of adjacent lymph nodes), of the cases reported in the literature, only 3 (including our patient) have disease that was confined to the gallbladder.
Primary follicular lymphoma of the gallbladder generally is symptomatic. We report a case of primary follicular lymphoma of the gallbladder in an asymptomatic patient with primary sclerosing cholangitis. The patient has done well postoperatively and remains free of recurrence 18 months later.
References
- In primary sclerosing cholangitis, gallbladder polyps are frequently malignant. Am J Gastroenterol. 2002;97:1138–1142
- . Follicular lymphoma of the gallbladder and extrahepatic bile ducts. Virchows Arch. 2003;442:136–140Epub 2002 Dec 18
- Primary follicular lymphoma of the gastrointestinal tract: a clinical and pathologic study of 26 cases. Am J Surg Pathol. 2002;26:216–224
PII: S1542-3565(08)00836-7
doi:10.1016/j.cgh.2008.08.007
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
