A 71-year-old Japanese man was admitted with new onset jaundice, leg swelling, abdominal distention, pruritus, multiple ecchymotic lesions, and mild behavioral changes. He reportedly had history of easy bruising, epistaxis, and bright red blood per rectum, which worsened around 3 days prior. He reported recent intake of 1600 mg of ibuprofen and 4 g of acetaminophen, taken over a period of 3 days, about 8 days prior to presentation. In addition, patient reported a 20-year history of alcohol abuse. On examination, patient was icteric, with multiple ecchymotic lesions.
Labs showed severe thrombocytopenia and moderate neutrophilic leukocytosis. He had elevated total bilirubin (9.7 mg/dL), Aspartate Transaminase (AST) of 645 U/L, Alanine Transaminase (ALT) of 175 U/L, and Alkaline Phosphatase (ALP) of 834 U/L. Prothrombin time (PT)/International Normalized Ratio (INR)/activated partial thromboplastin time (APTT) were 13.6/1.29/43 seconds, respectively. Toxicology screen was negative. Creatinine was 5.33 mg/dL, estimated glomerular filtration rate 11 mL/min, sodium 124 mmol/L, and blood urea nitrogen 42 mg/dL. Ammonia was <10 umol/L, ceruloplasmin level was normal at 39.9 mg/dL. Hepatitis panel, Quantiferon tuberculosis gold assay, and Human Immunodeficiency Virus antibodies were negative. Cytomegalovirus (CMV) IgG Ab was 2.5 U/mL, Epstein Barr Virus (EBV) capsid Ag IgG Ab was 225 U/mL, and EBV Nuclear Ag Ab titer was 224 U/mL. Autoimmune markers were within normal limits.
Computed tomography (CT) scan of the abdomen showed hepatomegaly with mild diffuse hepatic fatty change and mild anasarca characterized by small volume ascites and small bilateral pleural effusions. Magnetic resonance (MR) imaging of the abdomen showed hepatomegaly without evidence of diffuse infiltrative process or hepatic mass, but there was nonspecific peri-portal edema, which was favored to be secondary to hepatitis. Computed tomography of the chest did not show any visible lymphadenopathy but showed small bilateral pleural effusions.
Drug induced liver injury and alcoholic cirrhosis were initial considerations. Over the course of hospitalization, patient's condition deteriorated with worsening coagulopathy, neutropenia, and anemia requiring multiple transfusions of blood products including factor concentrates. Progressive renal failure required hemodialysis.
A liver biopsy was performed and pathology revealed an atypical proliferation of small/medium-sized lymphoid cells involving the hepatic parenchyma (Figure 1). Immunohistochemical studies (IHC) showed a marked predominance of atypical CD20-positive B-cells consistent with B-cell lymphoma (Figure 2). The lesional cells were predominantly distributed within sinusoids with expansion and forming medium-sized atypical aggregates involving portal tracts, evidenced by intact bile ducts centered within the aggregates (Figure 3). There was no evidence of large nodules or sheets of large cells. Additional IHC studies showed aberrant co-expression of BCL6 and fluorescence in situ hybridization (FISH) studies positive for t(14; 18) most consistent with follicular lymphoma, grade 1 to 2. A bone marrow biopsy showed significant involvement by lymphoma. Epstein Barr Virus in situ hybridization studies were negative. The background liver showed features of obstructive cholestasis. There was no evidence of peripheralized lymphoma by flow cytometry.
He received a total of 4 weeks course of rituximab and 2 weeks course of melfalan chemotherapy. Adriamycin was not started due to significant hyperbilirubinemia. During hospital stay, total bilirubin was elevated up to 48.9 mg/dL which slightly improved after commencement of chemo, in addition to reduction in transaminases. He remained coagulopathic with INR of 2.03, APTT of 126 seconds, and PT of 21.4 seconds. Lactic acid increased up to 16.3 mmol/L. He also developed increasing ascites and paracentesis showed elevated polymorph nuclear cell count of >250 cells/mm3. Because of this, appropriate treatment for spontaneous bacterial peritonitis was initiated.
Our patient died 40 days after admission due to septic shock, atrial flutter, acute renal failure, and eventual hypoxic respiratory failure.