Chronic Lymphocytic Leukemia-Associated Cholangiopathy

Abstract

1University of Birmingham Medical School, Birmingham, United Kingdom; 2Department of Pathology, Calgary Laboratory Services; 3Division of Hematology and Hematological Malignancies; 4Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta Correspondence: Dr Mark G Swain, Division of Gastroenterology, Health Research Innovation Center, Room 4AA20, 3280 Hospital Drive, Northwest, Calgary, Alberta T2N 4Z6. Telephone 403-220-3719, fax 403-210-9146, e-mail swain@ucalgary.ca Received for publication May 9, 2011. Accepted May 16, 2011 CASE PRESENTATION A 41-year-old woman with untreated low-grade B-cell chronic lymphocytic leukemia (CLL), diagnosed by peripheral blood flow cytometry nine months previously (white blood cell count 14.7×109/L; lymphocytes 10.4×109/L), was referred to the University of Calgary Liver Unit (Calgary, Alberta) with abnormal serum levels of liver enzymes: alkaline phosphatase 138 U/L to 204 U/L (normal lower than 115 U/L); aspartate aminotransferase 42 U/L (normal lower than 32 U/L); alanine aminotransferase 53 U/L (normal range 1 U/L to 40 U/L); and gamma-glutamyl transferase 115 U/L to 187 U/L (normal lower than 35 U/L). She was asymptomatic and her medical history consisted only of hypothyroidism treated with thyroxine. She was taking no other regular medications or herbal supplements. She consumed one to two standard alcoholic beverages per week. The physical examination was normal (body mass index 21 kg/m2). A screen for metabolic liver diseases was negative, as were tests for viral hepatitis. Antinuclear antibody was positive at a titre of 1:5210, with a speckled homogeneous pattern (NSP1). Rheumatoid factor was also positive (85 kU/L; normal lower than 20 kU/L). Anti-smooth muscle, antineutrophil cytoplasmic antigen, immunoglobulin A antitransglutaminase and antimitochondrial antibodies were negative. Serum immunoglobulin levels were all normal. Ultrasound of the liver was normal. Percutaneous liver biopsy was performed. The biopsy core (2 cm) included 17 portal areas; seven were expanded by a monotonous infiltrate composed predominantly of small lymphocytes. There was no parenchymal infiltrate. Bile ducts within lymphocyte-infiltrated portal spaces were pushed toward the periphery (Figure 1). Of note, four bile ducts showed distinct lymphocytic infiltration within the biliary epithelium (cholangiopathy), resulting in a significant narrowing of the bile duct lumen (Figures 2 and 3). The lymphocytic infiltrate was further characterized by immunohistochemical staining for the following: CD3, CD5, CD10, CD20, CD23, Bcl-2, cyclin-D1 and Ki67. The results of the immunological staining profile were classical for CLL (the Bcl-2 staining is shown in Figure 4).