LAUSR

To the Editor, Primary hepatic lymphoma (PHL) is quite rare, accounting for only 0.016% of all cases of non-Hodgkin lymphoma. Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is even more scarce, comprising only 2% to 4% of all PHLs. Here we report a rare case of primary hepatic MALT lymphoma accompanied with hepatocellular carcinoma (HCC). A 67-year-old female patient was accidentally found to have liver cirrhosis during a routine health check-up in 2011. She underwent a liver biopsy in a local hospital in Shanghai, and was pathologically diagnosed as having autoimmune hepatopathy (AIH). In light of her clinical manifestations and laboratory results, including positive antinuclear antibodies (ANA) and negative results for hepatitis B (HBV) and C virus (HCV) infections, the patient was diagnosed with AIHrelated cirrhosis. She was given no treatment until upper gastrointestinal bleeding occurred several months after the diagnosis. She then received a transjugular intrahepatic portosystemic shunt (TIPS) and recovered after the operation. She was then regularly followed up without receiving therapy. The patient visited our hospital for routine health checkup in January 2019. She reported no discomfort, fever, weight loss, or emaciation. Her physical examination was unremarkable, and there was no superficial lymphadenopathy. A liver function test showed the levels of alanine aminotransferase (ALT) of 34 U/L (normal range 0-75 U/L), aspartate aminotransferase (AST) of 56 U/L (normal range 0-40 U/L), total bilirubin of 34.6 μmol/L (normal range 3.4-17.1 μmol/L), direct bilirubin of 16.8 μmol/L (normal range 0.1-5 μmol/L), and γ-glutamyltranspeptidase of 190 U/L (normal range 11-50 U/L). An abdominal ultrasonography showed chronic hepatopathy with many hypoechoic masses, and a computed tomography angiography of the upper abdomen revealed hepatic cirrhosis, splenomegaly, portal hypertension, a left lateral lobe mass and a slightly low density of the right posterior lobe of the liver. She then received an orthotopic liver transplantation in March 2019. Liver atrophy and severe cirrhosis with mixed nodules were observed during the operation. One mass was found at the left lateral lobe (approximately 1 cm in size), while the other was located at the right lobe (3 cm × 2.5 cm × 2.5 cm in size). Pathology of the mass at the left lateral lobe revealed an abnormal proliferation of lymphocytes. Immunohistochemical staining was positive for CD20, CD79α, Bcl-2 (partial) and CD21 (follicular dendritic cells), but negative for CD3, CD10 and cyclin D1. The Ki67 index was approximately 20%. The gene rearrangement of the proliferating lymphocytes was positive for an immunoglobulin heavy chain. Interphase fluorescent in situ hybridization examination of t(11;18)(q21;q21) was not detected. The pathology of the other mass showed grade II HCC. Immunohistochemical staining of the HCC cells was positive for CK8 and hepatocytes, and negative for glypican (GPC)-3, α-fetoprotein (AFP) and CK19 (Figure 1). The patient was admitted to our Department of Hematology in July 2019 for the management of the MALT lymphoma. Her blood cell counts and serum biochemical tests, including ALT, lactate dehydrogenase (LDH), renal function, protein electrophoresis, were unremarkable at admission. Differential counts with a peripheral smear did not reveal any atypical cells. Serological examinations were negative for infections with human immunodeficiency virus, HBV and HCV, Epstein–Barr virus (EBV), cytomegalovirus and Helicobacter pylori (H. pylori). Tumor biomarkers, including AFP, carbohydrate antigen 19-9 (CA199) and carcinoembryonic antigen (CEA) were unremarkable. Serum β2 microglobulin was elevated (3.56 mg/L [normal range 0.7-1.8 mg/L]). AIH-related markers were negative except ANA (1:1280). Bone marrow biopsy showed trilineage maturation with no evidence of lymphoma. A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/ CT) showed no sign of increased uptake of FDG, enlargement of lymph nodes or the spleen. The patient was diagnosed with primary hepatic MALT lymphoma with HCC, combined with autoimmune hepatitis and liver cirrhosis. She received triple-drug immunosuppressive therapy including cyclosporin A 75 mg twice daily, prednisone 5 mg once daily and enteric-coated mycophenolate sodium 360 mg twice daily. She remained disease-free throughout the 8-month follow-up (up to the time of writing this report). PHL originates from intrahepatic lymphoid tissue or residual hematopoietic tissue, and initially does not involve lymph nodes. PHL represents 0.016% of all non-Hodgkin lymphoma, 0.4% of all extranodal lymphomas, and only 0.1% of liver tumors. The diagnostic criteria for PHL are: (a) symptoms caused mainly by liver involvement at presentation; (b) absence of distant lymphadenopathy, palpable clinically at presentation or detected during staging radiological studies; and (c) absence of leukemic blood involvement in the peripheral blood smear. Therefore, the diagnosis of PHL requires pathological Received: 17 February 2020 Revised: 15 May 2020 Accepted: 23 June 2020