S2679 An Unusual Suspect for Cholestatic Liver Injury

Abstract

Introduction: Vanishing Bile Duct Syndrome (VBDS) and idiopathic cholestasis (IC) have been associated with lymphoma in rare cases. In VBDS, the defining feature on liver biopsy is ductopenia, while in IC there is canalicular cholestasis and mixed inflammatory changes. Existing literature reports a few cases of paraneoplastic cholestasis with pathological features of either VBDS or IC. We describe an unique case of severe cholestasis as the presenting sign of Hodgkin’s lymphoma in the absence of bile duct loss or inflammatory changes. Case Description/Methods: 60-year-old man with no past medical history presented to the ED with increasing fatigue and jaundice that started five months earlier. He underwent cholecystectomy and intraoperative liver biopsy four months earlier which showed bland lobular cholestasis and mild lobular injury with no fibrosis, inflammatory changes, abnormal lymphocytic infiltration, or evidence of bile duct loss. An MRI/MRCP 6 weeks before presentation showed multiple small hepatic cysts and no biliary obstruction or ductal dilatation. Ursodiol 14 mg/kg/d was started 2 weeks later but he developed hypotension and presented to the ED. In the ED, vital signs were normal. Physical exam showed jaundice and hepatomegaly. Labs revealed ALP 1002 U/L, AST 81 U/L, ALT 90 U/L, total bilirubin 10.8 mg/dL, and direct bilirubin 8.1 mg/dL. Further work up showed negative AMA, ANA, ASMA and vasculitis serologies, normal ceruloplasmin, and negative viral studies including hepatitis A, B, C, HSV, CMV, HIV and COVID-19. EBV PCR was 69,697 copies/mL with positive IgG suggestive of reactivation of previous infection. Lyme and Ehrlichia serologies were negative. Repeat MRI/MRCP showed normal bile ducts but extensive retroperitoneal lymphadenopathy. Lymph node core needle biopsy revealed classic Hodgkin’s lymphoma. He was started on chemotherapy and liver enzymes improved. Discussion: Hodgkin’s lymphoma can present with cholestatic liver injury as shown in our patient who was on no medications and had no other identifiable causes of cholestasis. In the existing literature, VBDS and IC have been described as the pathological features for these patients where either ductopenia or canalicular cholestasis and mixed inflammatory changes are seen. Our case is unique because our patient had neither of these features. Bland cholestasis associated with lymphoma should be kept in the differential in someone with otherwise unexplained cholestatic liver injury.Figure 1.: Panel A: High power view of liver biopsy (200x, H&E). Yellow-green bile can be seen in dilated canaliculi. There is no significant lobular inflammation, steatosis, or other alterations. Panel B: High power view of liver biopsy (400x, H&E). Pale yellow-green watery bile can be seen in dilated canaliculi (yellow arrows). There is no significant lobular inflammation, steatosis, or other alterations. Panel C: High power view of lymph node (200x, H&E). The lymph node shows loss of normal architecture with replacement by fibrosis and an atypical lymphohistiocytic infiltrate. Scattered large cells with irregular nuclear contours and hyperchromasia are seen suggestive of Hodgkin cells. Panel D: Immunoperoxidase studies show the Hodgkin Reed-Sternberg (HRS) cells are positive for CD15 and CD30. PAX-5 is weakly expressed in the large cells in comparison to the background small B cells. CD20 stains background small B cells but is negative in the HRS cells. The immunophenotype is consistent with classic Hodgkin lymphoma.