Primary Hepatic Lymphoma: A Rare Form of Diffuse Large B-Cell Lymphoma of the Liver
Background: Primary hepatic lymphoma is a rare, malignant lymphoma of the liver unlike the predominant lymph nodal or splenic involvement associated with other types of lymphoma. It is commonly associated with nonspecific symptoms and usually detected incidentally on imaging examination.
Case Presentation: An 84-year-old man was evaluated for upper back pain. Chest computed tomography showed multiple large lesions in the liver, leading to the diagnosis of primary diffuse large B-cell lymphoma of the liver. Within 2 weeks of detecting his liver mass, the patient developed hypercalcemia and hyperuricemia that led to rapid deterioration and admission for treatment. Further diagnostic testing was performed, and he was initiated on appropriate chemotherapy.
Conclusions: Primary hepatic lymphoma, a form of diffuse large B-cell lymphoma of the liver is a rare disease without specific clinical manifestations, biochemical indicators, or radiologic features except for space-occupying liver lesions. However, patients’ conditions can deteriorate rapidly at an advanced stage as demonstrated in this case, which highlights the importance of a high level of suspicion for early diagnosis and treatment.
Discussion
Lymphoma is a tumor that originates from hematopoietic cells typically presented as a circumscribed solid tumor of lymphoid cells.1 Lymphomas are usually seen in the lymph nodes, spleen, blood, bone marrow, brain, gastrointestinal tract, skin, or other normal structures where lymphoreticular cells exist but very rarely in the liver.2 PHL is extremely rare due to the lack of abundant lymphoid tissue in the normal liver.3 It accounts for 0.4% of extra-nodal lymphomas and 0.016% of non-Hodgkin lymphoma.4-6 The etiology of PHL is unknown but usually it develops in patients with previous liver disease: viral infection (hepatitis B and C, Epstein-Barr, and HIV), autoimmune disease, immunosuppression, or liver cirrhosis.5-7
The diagnosis of PHL can be challenging due to its rarity, vague clinical features, and nonspecific radiologic findings. The common presenting symptoms are usually vague and include abdominal pain or discomfort, fatigue, jaundice, weight loss, and fever.5 Liver biopsy is essential to its diagnosis. The disease course is usually indolent among most patients with PHL. In our case, the patient presented with upper back pain but his condition deteriorated rapidly, likely due to the advanced stage of the disease. Diagnosis of liver lymphoma depends on a liver biopsy that should be compatible with the lymphoma. The criteria for diagnosis of PHL defined by Lei include (1) symptoms caused mainly by liver involvement at presentation; (2) absence of distant lymphadenopathy, palpable clinically at presentation or detected during staging radiologic studies; and (3) absence of leukemic blood involvement in the peripheral blood smear.7 Other authors define PHL as having major liver involvement without evidence of extrahepatic involvement for at least 6 months.8 In our case, the multiple large lesions of the liver are consistent with advanced stage PHL with retroperitoneal lymph nodes and right lung metastasis. DLBCL is the most common histopathological type of lymphoma (65.9%). Other types have been described less commonly, including diffuse mixed large- and small-cell, lymphoblastic, diffuse histiocytic, mantle cell, and small noncleaved or Burkitt lymphoma.5-7
Currently, there is no consensus on PHL treatment. The therapeutic options include surgery, chemotherapy, radiation therapy, or a combination of therapies.7 Most evidence regarding treatment and tumor response comes from case series, as PHLs are rare. Surgical resection in a series of 8 patients showed a cumulative 1- and 2-year survival rate of 66.7% and 55.6%, respectively.9 Chemotherapy is the recommended treatment option for extra-nodal DLBCL, making it a choice also for the treatment of PHL.10 Page and colleagues demonstrated that combination chemotherapy regimens helped achieve remission for 83.3% of patients.11 Since PHL is chemo-sensitive, most patients are treated with chemotherapy alone or in combination with surgery and radiotherapy. The most common chemotherapy regimen is R-CHOP for CD20-positive B-cell lymphoma. The use of the R-CHOP regimen has been reported to achieve complete remission in primary DLBCL of the liver.12
Conclusions
Primary DLBCL of the liver is a very rare disease without specific clinical manifestations, biochemical indicators, or radiologic features except for space-occupying liver lesions. However, patients’ conditions can deteriorate rapidly at an advanced stage, as demonstrated in our case. DLBCL requires a high level of suspicion for its early diagnosis and treatment and should be considered in the differential diagnosis for any hepatic space-occupying lesions.
Acknowledgments
We appreciate Lynne Dryer, ARNP, for her clinical assistance with this patient and in the preparation of the manuscript.
