Primary Hepatic Hodgkinʼs Lymphoma (HL) Masquerading as Drug-induced Liver Injury (DILI)

Abstract

Purpose: A 76-year-old man with history of diabetes mellitus, hypertension, and hyperlipidemia presented at an outside hospital with 3 days of acute onset right and left upper abdominal pain and fever. He also reported a 10-pound weight loss over the last 8 months. He was compliant with all his medications, metformin, glimperide, simvastatin, ramipril, nebivolol. Physical examination was significant for scleral icterus, mild tenderness in the right and left upper quadrants, enlarged liver that was firm but non-tender, and 4 cm below the right costal margin. No lymphadenopathy was palpated. Initial labs: total bilirubin 10.5 (0.3-1.2 mg/dl), indirect bilirubin 8.4 (0-0.45 mg/dl), alkaline phosphotase 305 (42-133 IU/l), SGOT 283 (15-41 IU/l), SGPT 181(7-40 u/l), Hgb 13.1 (14-18 g/dl), WBC 8.3 (4.8-10.8 thou/cmm), PLTS 62 (130-400 tho/cmm) and INR 1.37. All laboratory data from one month prior was normal. CT scan of abdomen and pelvis revealed cholelithiasis, hepatomegaly, and heterogenous lesions in an enlarged spleen; MRCP did not show choledocholithiasis. Hepatitis A, B and C, HIV, CMV, EBV, ANA, smooth muscle antibody, ceruplasmin, hemochromatosis gene analysis, and anti-mitochondrial antibody CA19-9 and CEA were all negative. Initial liver biopsy report suggested DILI, and a second pathology opinion was requested. All hepatotoxic medications were discontinued. His clinical status was stable, but no improvement in his LFTs for the next 20 days. He then presented with slurred speech and right-sided weakness due to acute/subacute infarct of left middle cerebral artery. There was no improvement in his liver tests at this admission. The liver biopsy second opinion reported expanded portal tracts with predominantly lymphocytic infiltrate and histocytes. Large atypical cells with irregular nuclear contours and prominent nucleoli were noted to be CD30, PAX5 and CD20 positive and negative for CD15, CD45, and ALK. These findings are consistent with HL. In view of the HL chemotherapy complication risks and the continued clinical deterioration, the patient's family decided to transition care to hospice. HL has a bimodal presentation with second peak at >55. Most patients with HL develop hepatic complications late in the disease course and have other extra-hepatic HL involvement. Our case represents the rare occurrence of primary HL of the liver, which was initially attributed to DILI. The elderly are at the greatest risk of DILI, due to factors such as poly-pharmacy, co-morbidities, and nutritional status, but it is important to consider other etiologies.