Cholestatic Hepatitis Due to Hepatosplenic Lymphoma

Abstract

Purpose: A 25 y/o male presented with a one month history of pharyngitis, 15 lbs weight loss and jaundice for one week. He denied other complaints or history of liver disease in self or family. He was on no medications and had no prior medical or surgical history. On physical examination he was icteric, had splenomegaly, but no hepatomegaly or lymphadenopathy (LAP). Laboratory tests: WBC 1.7 K/mm3 with 3% segs, 9% bands, 44% lymph, 21% monos, Hgb 12.8 g/dL, PLT 146 K/mm3, INR 1.3, alb 3 g/dL, AST 132 U/L, ALT 210 U/L, alk phos 162 U/L, bilirubin 5.7mg/dL, LDH 200U/L. Tests for hepatitis A, B, C, HIV, CMV, EBV, Wilson's disease, autoimmune hepatitis, and iron overload were negative. CT scan showed no adenopathy, a normal size liver and an enlarged spleen. Liver biopsy revealed atypical lymphocytes within the hepatic sinusoids positive for CD3 and CD7 and negative for CD 4, 5, 8, 20 and 56 and for EBV consistent with hepatosplenic Tcell lymphoma (HSTL). Bone marrow biopsy was consistent with non-Hodgkin's T cell lymphoma (NHL). Cytogenetics by flow cytometry was negative for clonal chromosomal abnormalities. He is currently undergoing chemotherapy and being evaluated for allogenic bone marrow transplant. Primary HSTL is a rare malignancy that constitutes only 0.016% of all cases of NHL, however, late secondary hepatic involvement is common. HSTL affects mainly young males in the second or third decades of life, and usually is associated with immunosupression as in transplant recipients, SLE, and HIV patients, or in those with a history of malaria or previous malignancy. More recently it has been reported in Crohn's patients who have been treated with biologics or immunosuppressive therapy. Patients present with fatigue, fever, nausea, and weight loss, and have significant cytopenias, and minimal or absent LAP. All patients have splenomegaly and the majority have hepatomegaly. Bone marrow involvement may be subtle but is virtually universally present. HSTL is thought to arise from γδT cells, a subset of epithelial tissue and red splenic pulp associated cytotoxic Tcells with direct antigen recognition capability, acting at the interface between innate and adaptive immunity. There is an association with the isochromosome arm 7q cytogenetic abnormality. The majority of patients initially respond to chemotherapy, but relapses are common and long-term prognosis remains poor with median survival 16 months. HSTL is a rare malignancy that can present as cholestatic liver disease due to malignant cell infiltration. It should be considered in the differential diagnosis in patients with features of cholestasis and pancytopenia. More studies are needed for better understanding and treatment of this lethal condition.