A Case of Vanishing Bile Duct Syndrome in a Patient with T-Cell Leukemia/Lymphoma of the Liver

Abstract

Vanishing bile duct syndrome (VBDS) is a rare entity which may be caused by a multitude of etiologies like idiopathic, drug-induced, Hodgkin's disease, chronic rejection and after liver transplant. VBDS is characterized by destruction of intra-hepatic bile ducts and patients usually present with symptoms of jaundice and pruritus. Patients with lymphoma can develop jaundice on the basis of infiltrative involvement of the liver and spleen. To our knowledge, we are reporting the first case of a gamma delta T-cell Leukemia/lymphoma (T-LGL) resulting in VBDS. In this case, 78 year old female with a history of myelodysplastic syndrome diagnosed 8 months prior to presentation, developed a 2 week and clay colored stools. She was noted to have hepatosplenomegaly on physical examination. Laboratory workup revealed elevated alkaline phosphatase and bilirubin levels as well as an ANA + at 1:80. CBC showed WBC 5with 23% neutrophils and 71% lymphocytes and severe anemia. Further work up with MRCP showed non-visualization of the intra-hepatic bile ducts. A liver biopsy revealed an atypical sinusoidal lymphoid infiltrate, portal cholangitis, pericholangitis and paucity of bile ducts consistent with VBDS and periportal and lobular hepatitis. Immunotyping on the liver biopsy and flow cytometry of the peripheral blood revealed the atypical lymphoid cells to be consistent with T-LGL with a predominant CD8 (T suppressor) phenotype (CD3+, CD4 focal. CD8+, CD2+, CD7+, CD 57+). PCR demonstrated a monoclonal TCR gamma gene rearrangement. On review of peripheral blood smear, increased large granular lymphocytes were seen. According to latest (WHO) classifications, T-LGL is characterized by a persistent increase in peripheral blood large granular lymphocytes, represents 2–3% of cases of small lymphocytic leukemia, and is synonymous with T-cell CLL. The disorder typically involves the peripheral blood bone marrow, liver and spleen but rarely lymph nodes.The disease usually follows an indolent course. The common variant of T-LGL has an immunoprofile of CD3+ CD4+, CD8+, TCR alpha beta+, however a rare variant and TCR gamma delta+ is recognized. Our case appears to represent this rare variant of T- LGL. To our knowledge, VBDS has never been reported in any case of T cell leukemia/Lymphoma, including TLGL and cases with hepatic involvement by T cell leukemia/lymphoma, thus the first reported case of VBDS associated with-cell Leukemia/lymphoma (T-LGL).