Primary Hepatic Lymphoma: A Rare Form of Diffuse Large B-Cell Lymphoma of the Liver

Primary hepatic lymphoma (PHL) is a rare, malignant lymphoma of the liver. It differs from the predominantly lymph nodal or splenic involvement associated with other types of lymphoma. It is usually detected incidentally on imaging examination, commonly computed tomography (CT), for nonspecific clinical presentation. However, it has important clinical implications for early diagnosis and treatment as indicated in our case.

Case Presentation

An 84-year-old man presented to the emergency department for evaluation of upper back pain. The patient had a history of hypertension, diabetes mellitus, and was a former smoker. He had normal vital signs, an unremarkable physical examination, and a body mass index of 25. His laboratory studies showed a normal blood cell count and serum chemistry, including serum calcium level and α-fetoprotein, but mildly elevated liver function tests.

The patient’s chest CT angiography showed no evidence of thoracic aortic dissection, penetrating atherosclerotic ulceration, or pulmonary artery embolism. Besides emphysematous changes in the lung, the chest CT was within normal limits.

Liver CT demonstrated several subtle, relatively low-density, space-occupying lesions in both lobes of his liver, the largest in the right lobe, measuring nearly 8 cm with a prominent, contrast-enhanced vessel at the periphery (Figure 1).

Abdominal magnetic resonance imaging (MRI) showed hepatomegaly (the liver measured up to 19.3 cm in craniocaudal length) and multiple, large intrahepatic space-occupying lesions, the largest measuring 9.9 cm × 9.5 cm in the right lobe, as well as multiple lesions in the inferior right and left lobe with enhancing capsules surrounding the hepatic lesions (Figure 2).

The kidneys, pancreas, spleen, and biliary ducts showed no abnormalities.

An ultrasound-guided core needle biopsy of the liver was performed. Flow cytometry showed a monoclonal B-cell population that was mostly intermediate to large based on forward scattered light characteristics. Immunohistochemical staining was positive for CD20, BCL2, BCL6, and CD45 in the neoplastic cells. Anaplastic lymphoma kinase (ALK), CD15, CD30, and CD10 were negative, as were cytokeratin AE1/AE3 and pan-melanoma. CD3 highlighted background T cells. Ki-67 highlighted a proliferative index of approximately 75%, and the MYC stain demonstrated 50% positivity. This was consistent with diffuse large B-cell lymphoma (DLBCL). However, there was insufficient tissue on the MUM1-stained slide; therefore, it was inconclusive to distinguish a nongerminal center derived from germinal center–derived DLBCL.

Two weeks after the initial CT examination, the patient’s condition quickly deteriorated, and he was admitted for severe weakness with evidence of severe hypercalcemia, hyperuricemia, and renal insufficiency (Table).

His lactate dehydrogenase (LDH), a nonspecific marker of tissue turnover, was severely elevated at 1027 IU/L (reference range, 105-333 IU/L). The patient received calcitonin, zoledronic acid, IV fluid for hypercalcemia and acute renal insufficiency, and rasburicase for severe hyperuricemia.

To get additional tissue for further tumor characterization, a repeat liver biopsy was performed along with other diagnostic tests, including head MRI, bone marrow biopsy, and fluorodeoxyglucose (FDG) full-body positron emission tomography (PET). Repeat liver biopsy showed only necrotic debris with immunostaining positive for CD20 and negative for CD3. B-cell lymphomas tend to retain CD20 expression after necrosis, so the presence of CD20 staining was consistent with a necrotic tumor. Again, there was insufficient tissue on the MUM1-stained slide. Head MRI showed no evidence of tumor involvement. Full-body PET showed abnormally elevated standardized uptake value (SUV) of radioactive tracers in several areas: multifocal, large area uptake within both right (SUV, 19) and left (SUV, 24) hepatic lobe (Figure 3A), retroperitoneal lymph node (SUV, 3.9), and a right lateral pleural-based nodule (SUV, 17.9) (Figure 3B).

There was no uptake in the spleen, bone, mediastinum, or other parts of the lung. Attenuation CT obtained with PET again detected those lesions in the liver but also a new, right lateral subpleural-based mass (11 mm) that was not present on the initial CT obtained a month earlier. Bone marrow biopsy showed normocellular marrow without dysplasia nor morphologic or immunophenotypic evidence of lymphoma/leukemia.

The diagnosis was primary DLBCL of the liver with retroperitoneal lymph nodes and right lung metastasis. The patient was started on systemic chemotherapy of R-CHOP (rituximab with reduced cyclophosphamide, doxorubicin, vincristine, and prednisone).