Cholestasis: A Paraneoplastic Syndrome

Abstract

Hodgkin's lymphoma(HL) must be included as a differential in cases of fever of unknown origin and idiopathic cholestasis with non specific hepatitis on liver biopsy. Early bone marrow examination in such cases may allow timely therapy and improve morbidity and mortality. A 60-year-old African American man presented with a two month history of recurrent high grade fever and progressive jaundice. He was treated multiple times with empiric antibiotics. Past history was significant for hypertension, alcohol and tobacco use. He denied any history of travel, new medication intake or prior malignancy. Examination revealed pale, emaciated and weak old man with no lymphade-nopathy and normal chest, cardiovascular and abdominal examination. Initial lab results revealed mild normochromic anemia and cholestatic pattern of hepatic injury with normal hepatitis serology. Elevated 5-Nucleotidase levels confirmed alkaline phosphatase to be of hepatic origin. MRCP showed normal hepatobiliary system. Enhanced CT chest and abdomen revealed small confluent lymphadenopathy with calcifications in subcarinal and peri-hilar regions. On liver biopsy we found nonspecific chronic hepatitis with mild portal fibrosis and no steatosis or granulomas with no features suggestive of autoimmune hepatitis, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis or viral hepatitis. On further evaluation, bone marrow biopsy revealed hypercellular marrow with fibrohistiocytic infiltrates and large atypical cells suggestive of lymphoma. Immuno-staining of marrow confirmed large atypical cells to be Reed-Sternberg cells (CD 30+, CD15+, CD 45-, CD20-) confirming classical HL. Patient was started on chemotherapy and following two cycles, LFTs started to improve and normalized. Patient initially tolerated chemotherapy well until he developed septic shock and multiorgan failure and eventually passed away. HL has bimodal incidence affecting ages 15-35 and >50 years. It is associated with a diverse array of paraneoplastic syndromes ranging from complex neurological syndromes to rare entities like vanishing bile duct syndrome and idiopathic cholestasis. However, other etiologies of intrahepatic cholestasis should be ruled out like alcohol, viral, drug induced, PBC and PSC. Mortality can be as high as 65% from liver involvement. Intrahepatic cholestasis is an uncommon presentation of HL (3-13% of cases), and even more so rare are cases with negative liver biopsy despite clinical picture consistent with a cholestatic pattern of liver injury. Thus, liver biopsy may not necessary reflect the underlying etiology as highlighted by our case. Although treatment of underlying HL results in normalization of liver enzymes, however, its prognostic value remains undetermined.