Cholestatic Jaundice as a Paraneoplastic Presentation of Hodgkinʼs Lymphoma

Abstract

Purpose: A 21 year old female was transferred to our hospital for the management of hyperbilirubinemia in the setting of a recent diagnosis of Hodgkin's disease. Upon initial assessment, laboratory workup revealed cholestasis with elevated transaminases, alkaline phosphatase, and no coagulopathy. The rest of the workup was negative. Abdominal imaging was negative. Her bilirubin continued to rise, and a liver biopsy showed pericentral cholestasis and mild non-specific lobular inflammation. She was started on prednisone with a gradual taper. Six weeks into treatment, her jaundice resolved. Hodgkin's disease-related cholestasis has multiple pathophysiologic mechanisms. The differential diagnosis of jaundice in a lymphoma patient includes the more common etiologies of sepsis, drugs, viral infections and hepatic metastasis. These diagnoses can usually be ruled out with an extensive initial workup. However, liver involvement in Hodgkin's disease (HD) can be a more subtle finding that requires a prompt and a more invasive workup. The three main causes of intrahepatic cholestasis in association with lymphomas are hepatic lymphoma, vanishing bile duct syndrome (VBDS) and a paraneoplastic phenomenon. Secondary hepatic lymphoma is almost always an end-stage manifestation of the disease that can rapidly progress into fulminant hepatic failure. Primary hepatic lymphoma, on the other hand, occurs in the absence of extrahepatic disease. It has an extremely dismal prognosis. VBDS is another cause of cholestasis that has been associated with HD. Histologically, this entity is characterized by the absence of bile ducts in the portal triads. Treatment with steroids, ursodeoxycolic acid and IVIG has been described with not enough evidence to advocate the use of either therapy. The last mechanism is due to a paraneoplastic effect. Stauffer described a syndrome of nonmetastatic nephrogenic hepatic dysfunction in association with renal cell carcinoma. Later on a similar paraneoplastic cholestatic entity has been described in association with multiple malignancies including lymphoma. The proposed mechanism for this rare entity could be overexpression of IL-6 by the tumor cells, and hence the reported literature on the improvement of the cholestasis after treating the malignancy. Conclusion: In conclusion, the possibility of hepatic lymphoma, VBDS or a paraneoplastic mechanism should be considered in every case of jaundice and HD. This can be a life threatening complication that can progress to fulminant hepatic failure short of early and appropriate intervention.