Splenic Lymphoma
Splenic lymphoma refers to involvement of the spleen by a cancer of the lymphatic system. The spleen is rich in lymphoid tissue and is one of the more common organs involved by systemic lymphoma; true primary splenic lymphoma is much less common. Splenic lymphoma can present as one or more masses, diffuse infiltration of the spleen, or splenomegaly with no discrete lesion. Most are non-Hodgkin lymphomas, with subtypes including splenic marginal zone lymphoma, diffuse large B-cell lymphoma, hairy cell leukemia, and others. Imaging—particularly CT, MRI, and PET/CT—and tissue diagnosis are central to evaluation.
What is it?
The spleen contains large amounts of lymphoid tissue and plays a central role in filtering blood and supporting immune function. Lymphoma is a cancer of the lymphatic system, in which abnormal lymphocytes (a type of white blood cell) grow and accumulate. Because the spleen is rich in lymphoid tissue, it is one of the more common organs involved by lymphoma. Splenic lymphoma describes involvement of the spleen by a lymphoma, regardless of whether the disease started elsewhere and spread to the spleen or—much less commonly—began in the spleen itself.
Splenic lymphoma can be broadly divided into two categories. Secondary splenic involvement by lymphoma is far more common and occurs when systemic lymphoma involves the spleen, often along with lymph nodes, bone marrow, the liver, or other organs. This is seen across many types of non-Hodgkin lymphoma and in Hodgkin lymphoma. Primary splenic lymphoma is uncommon and is defined by lymphoma that is largely confined to the spleen and immediately surrounding lymph nodes, with little or no involvement elsewhere at the time of diagnosis. Strict definitions of primary splenic lymphoma vary, and many cases involve some degree of bone marrow or other extrasplenic disease.
Specific lymphoma subtypes have particular relationships with the spleen. Splenic marginal zone lymphoma is one of the prototypical “splenic” lymphomas, often producing significant splenomegaly, characteristic blood findings, and a clinical course that can be slow over many years. Hairy cell leukemia is another condition in which splenomegaly is a prominent feature. Diffuse large B-cell lymphoma is a common aggressive subtype that can involve the spleen as part of more widespread disease. Other relevant entities include follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, T-cell lymphomas, hepatosplenic T-cell lymphoma (a rare and aggressive entity that often involves the spleen and liver), and Hodgkin lymphoma. Chronic infections such as hepatitis C have been associated with certain lymphomas involving the spleen.
The patterns of splenic involvement vary. Some patients develop one or more discrete masses or nodules within the spleen, which can range from small to large. Others show diffuse infiltration of the spleen producing significant splenomegaly without an obvious discrete lesion. Some patients have a “miliary” pattern with many tiny nodules. In patients with established systemic lymphoma, splenic involvement is often discovered during staging imaging.
Symptoms vary widely. Many patients with splenic involvement by lymphoma have systemic features such as fatigue, weight loss, fevers, drenching night sweats, and loss of appetite—the classic “B symptoms” of lymphoma. Local symptoms may include upper left abdominal pain or fullness, early fullness with meals, and discomfort that may radiate to the left shoulder. Enlargement of the liver and lymph nodes is common when systemic disease is present. Splenomegaly with low blood counts (hypersplenism) can produce anemia, fatigue, easy bruising or bleeding from low platelet counts, and frequent infections from low white blood cell counts.
Diagnosis combines clinical assessment, laboratory tests, imaging, and tissue confirmation. Blood tests typically include a complete blood count, peripheral blood smear (which can identify circulating abnormal lymphocytes in some lymphomas, including splenic marginal zone lymphoma and hairy cell leukemia), comprehensive liver function tests, LDH (often elevated in lymphoma), uric acid, and viral hepatitis testing (hepatitis B and C). HIV testing is often performed. Immunoglobulin levels and specific markers may be helpful. Imaging usually begins with ultrasound, which may show splenomegaly, masses, or diffuse changes. CT with contrast and MRI with contrast provide detailed characterization of splenic involvement and surrounding structures, as well as evaluation of lymph nodes and other organs. PET/CT is widely used for staging and for evaluating response to treatment in many lymphomas.
Tissue diagnosis is essential for definitive subtyping and treatment planning. In patients with accessible lymph nodes or bone marrow disease, biopsy of those sites is often the preferred approach. Image-guided biopsy of the spleen is performed in selected cases but carries some risk of bleeding. Splenectomy is occasionally needed both for diagnosis and treatment, particularly in patients with isolated splenic disease, large splenic masses, or in specific subtypes such as splenic marginal zone lymphoma. Bone marrow biopsy is commonly performed and helps both establish the diagnosis and assess the extent of disease.
Important to Know
Treatment of splenic lymphoma is driven by the specific lymphoma subtype, the stage of disease, the patient’s overall health, and any associated conditions such as chronic viral hepatitis or immunosuppression. Care is typically coordinated by hematologists/oncologists with lymphoma expertise, working with hepatobiliary or general surgeons (when splenectomy is considered), infectious disease specialists, hepatologists, interventional radiologists, and palliative care providers.
For aggressive lymphomas involving the spleen—such as diffuse large B-cell lymphoma—chemoimmunotherapy regimens that include rituximab (an antibody targeting CD20) combined with chemotherapy form the standard backbone of treatment. Other B-cell lymphomas, T-cell lymphomas, and Hodgkin lymphomas have their own subtype-specific regimens. Targeted therapies, immune-based treatments (such as bispecific antibodies and chimeric antigen receptor [CAR] T-cell therapy in selected cases), and other novel agents are increasingly important options for certain lymphoma subtypes and in relapsed or refractory disease. Radiation therapy is used in selected situations.
For more indolent lymphomas such as splenic marginal zone lymphoma, treatment is highly individualized. Asymptomatic patients with limited disease may be observed without immediate treatment. Patients with significant symptoms or progressive cytopenias may benefit from rituximab alone or in combination with chemotherapy, or—in selected patients—splenectomy, which can provide durable control. Hepatitis C infection, when present, is often treated as part of the overall plan, as antiviral therapy alone can lead to lymphoma regression in some hepatitis C–associated marginal zone lymphomas. Hairy cell leukemia is treated with specific chemotherapy regimens such as cladribine, which is highly effective in many patients.
Stem cell transplantation—autologous or allogeneic—plays a role in selected patients, typically in relapsed or specific high-risk lymphomas. Treatment plans are highly individualized.
Management of associated conditions is important. Patients with chronic hepatitis B or C require careful coordination with hepatology, both for direct treatment of the viral infection and to prevent hepatitis B reactivation during immunosuppressive therapy (often with prophylactic antiviral medications). Patients with immunosuppression, HIV, or transplant-related lymphomas require integrated care for their underlying condition.
Splenectomy is considered in selected patients—for example, those with significant symptomatic hypersplenism, certain primary splenic lymphomas (especially splenic marginal zone lymphoma), specific subtypes where splenectomy provides effective control, or as part of diagnostic evaluation when other approaches have been inconclusive. Patients undergoing splenectomy require specific attention to infection prevention, including vaccinations against encapsulated bacteria (such as pneumococcal, meningococcal, and Haemophilus influenzae type b vaccines), antibiotic prophylaxis in selected patients, education about prompt evaluation of fevers, and consideration of travel-related risks.
Tumor lysis syndrome—a metabolic complication that can occur when fast-growing lymphomas are treated—requires preventive measures and close monitoring at the start of therapy.
Supportive and palliative care play important roles throughout the course of disease. Pain management, nutritional support, mental health support, transfusion support, treatment of infections, and family-centered care planning are essential. Early integration of palliative care, even alongside active treatment, is associated with improved quality of life.
Care is best provided in centers with experience in lymphoma. Imaging and laboratory findings are interpreted alongside the patient’s symptoms, examination, and broader clinical context rather than in isolation.
Red flag symptoms include sudden severe upper left abdominal pain (especially after trauma to the abdomen), lightheadedness or fainting, rapid heart rate, cool clammy skin or signs of shock, high fever with rigors or signs of severe infection, easy bruising or bleeding with severe symptoms, severe fatigue with confusion, severe shortness of breath, sudden change in mental status, or rapid worsening of known symptoms. These warrant prompt or urgent medical evaluation, as they may indicate splenic rupture, severe infection, hematologic complications, or other serious conditions.