Question: A 74-year-old woman with compensated Child-Pugh A cirrhosis (Model for End-Stage Liver Disease score of 8) secondary to autoimmune hepatitis on azathioprine monotherapy was evaluated for abdominal bloating and intermittent right upper quadrant abdominal pain. She endorsed a 5-lb unintentional weight loss over the past 4 months associated with anorexia. On physical examination, she was well-appearing with a soft abdomen and no abdominal tenderness, distension, or ascites. The pertinent serology revealed an aspartate aminotransferase of 76 U/L, a total protein of 8.3 g/dL, albumin of 3.4 g/dL, hemoglobin of 12.2 g/dL, white blood cells of 3.1 × 109/L, platelets of 96,000, lactate dehydrogenase of 290 U/L, and alpha fetoprotein of 4.25 ng/mL. An abdominal ultrasound examination revealed a new hypoechoic lesion measuring 2.5 cm × 2 cm × 1.5 cm with minimal flow by Doppler. Triple phase magnetic resonance imaging (MRI) of the liver revealed a lobular 3.5 cm × 3.0 cm mass in hepatic segments 2 and 3 (Figures A and B, red arrows) as well as a 3.9 cm × 3.1 cm mass in segment 7, each T1 hypointense and T2 hyperintense with peripheral enhancement and washout including marked diffusion restriction favoring multifocal hepatocellular carcinoma with an atypical enhancement pattern. Imaging was negative for extrahepatic disease. Outside of the Milan criteria, the patient was referred to surgical oncology for further evaluation and management. The mass in segment 3 seemed to be larger via intraoperative ultrasound examination (5 cm) and was therefore resected. The mass in segment 7 underwent microwave ablation to preserve the liver parenchyma. Pathology revealed a sheetlike proliferation of large, pleomorphic, atypical vesicular lymphoid cells (Figure C) with mitotic figures and apoptotic bodies (Figure D). Immunohistologic staining was diffusely and strongly positive for CD20 (Figure E), CD10, and BCL6. Workup for viral serologies was negative (hepatitis B virus, hepatitis C virus, HIV, and Epstein–Barr virus stain from liver tissue). What is the next step in evaluation and management? What is the most likely diagnosis? Look on page 1942 for the answer and see the Gastroenterology website (www.gastrojournal.org/) for more information on submitting your favorite image to Clinical Challenges and images in GI. A referral to hematology/oncology was made for the initiation of rituximab-based chemotherapy. This patient has diffuse large B-cell lymphoma (DLBCL), germinal center B-cell type. The pathology from the resected liver segments revealed DLBCL, germinal center B-cell subtype, without double or triple-hit features after fluorescence in situ hybridization analysis. Positron emission tomography with computed tomography scans confirmed no evidence of active disease and final staging was deemed to be stage IEA with a National Comprehensive Cancer Network International Prognostic Index score of 4 (high to intermediate) secondary to age, extranodal disease, and elevated lactate dehydrogenase. Three short cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was recommended. Echocardiogram revealed a normal ejection fraction. Unfortunately, she developed neutropenic fever during cycle 1 with extended spectrum beta lactamase urinary tract infection, urinary retention, and anasarca requiring granulocyte colony stimulating factor, antibiotics, and adjustment of diuretics. Additional chemotherapy was not advised, and she will follow-up with positron emission tomography with computed tomography scans in 2 months. DLBCL is the most common aggressive non-Hodgkin lymphoma (NHL).1Shibata J. Kurahashi S. Naito T. et al.Diffuse large B cell lymphoma primarily presenting as acute liver failure in a surviving patient.J Community Hosp Intern Med Perspect. 2019; 9: 135-139Crossref PubMed Google Scholar DLBCL may manifest as a primary hepatic lymphoma (PHL) in the late stage of disease. PHL is exceedingly rare, estimated to be present in 0.4% of extranodal NHL and 0.016% of all NHL cases.2Zhang K.J. Chen S. Chen J.L. et al.Complete response to comprehensive treatment of a primary hepatic diffuse large b cell lymphoma: a case report.Oncol Lett. 2015; 9: 1557-1660Crossref PubMed Scopus (3) Google Scholar Contributing factors include chronic viral infections (hepatitis B and C, Epstein–Barr virus, HIV), cirrhosis, autoimmune disease, and chronic use of immunosuppressants. R-CHOP is the gold standard of therapy. Chronic azathioprine use increases the risk of lymphoma; however, the association with PHL has not been reported. Imaging characteristics suggestive of PHL on MRI may consist of signal restriction in the diffusion-weighted imaging and a lower apparent diffusion coefficient.3Colagrande S. Calistri L. Grazzini G. et al.MRI features of primary hepatic lymphoma.Abdom Radiol. 2018; 43: 2277-2287Crossref PubMed Scopus (17) Google Scholar Clinicians should consider hepatic lymphoma in cirrhotic patients if there is a history of autoimmune disease, immunosuppressant use such as azathioprine, atypical enhancement pattern on MRI, and a normal alpha fetoprotein.
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Oct 1, 2024
Ji-Ye Kim + 4
