Non-Hodgkinís lymphomas (NHLs) are a very heterogeneous group of cancers that develop in the lymph nodes present throughout the body. There are over 25 subtypes of NHL, although most are diagnosed infrequently.
This is certainly true of splenic marginal zone lymphoma (MZL), which accounts for less than 1% of all NHLs in the United States. Splenic MZL is an indolent lymphoma. This means that it is slow growing, and patients live many years with the disease.
However, most patients are not curable. Splenic MZL was previously referred to as splenic lymphoma with villous lymphocytes, due to the characteristic appearance of the circulating lymphoma cells. Splenic MZL appears to be slightly more often diagnosed in women than in men. The average age at diagnosis is 68 years.
Risk Factors
The exact cause of splenic MZL is generally unknown. As with most cancers, a family history increases a patientís risk to some extent. Occupational exposures, notably pesticides, also increase the risk of SLL. In fact, the Midwest, where farming is prevalent, has the highest incidence of NHL in the United States. Hepatitis C infection has also been associated with the development of splenic MZL in about one-third of cases.
Signs and Symptoms
Swollen lymph nodes (lymphadenopathy) are the most common presenting sign in most patients with NHL. This is not the case with splenic MZL, in which peripheral lymphadenopathy is extremely rare. The diagnosis is often suspected when a patient presents with an enlarged spleen (splenomegaly) and is subsequently found to have circulating lymphoma cells in the blood.
The spleen is usually moderately to massively enlarged and often leads to symptoms of weight loss, early satiety with meals, and abdominal pain. 75% of patients have enough circulating lymphoma cells to result in significantly elevated lymphocyte counts in the blood. Involvement of the bone marrow is also common in splenic MZL and may lead to low red blood cell count (64% of patients), low platelet count (15% of patients), and/or low white blood cell count (5% of patients). B symptoms such as fever and night sweats are uncommon.
Diagnosis and Staging
The diagnosis of splenic MZL may be made presumptively, based upon the signs and symptoms discussed and pathologic examination of the circulating lymphoma cells or bone marrow. It may also be definitely diagnosed by performing a splenectomy. Other diseases that present similarly to splenic MZL and should be ruled-out include hairy cell leukemia, chronic lymphocytic leukemia, and mantle cell NHL.
Once the diagnosis of splenic MZL is established, patients should undergo tests to determine the extent of disease. This should include CT scans of the chest, abdomen, and pelvis, a bone marrow biopsy, a complete blood count, serum chemistries (including lactate dehydrogenase (LDH) and uric acid), and an HIV test. Testing for hepatitis B and C are also recommended. There is no formal staging system for splenic MZL.
Prognostic Factors
The overall prognosis of splenic MZL is quite good in most patients. The percentage of patients surviving 5 years from diagnosis is 65 to 75%, often even in the absence of treatment or a complete response to treatment. Many patients survive 10 years or more. The prognosis is poorer for patients with extensive bone marrow involvement and low blood counts or significantly elevated lymphocyte counts.
As with other types of indolent NHLs, splenic MZL may transform into a more aggressive histology over time. This appears to occur in about 10% of patients, and their average survival after transformation is less than 2 years.
First-Line Treatment of Splenic Marginal Zone Lymphoma
Patients without low blood counts or symptoms due to splenic MZL may simply be monitored closely, so-called watchful waiting. This is a therapeutic approach taken with other indolent lymphomas as well. Two-thirds of patients do not have symptoms at diagnosis, and up to one-third of those may never require anti-lymphoma treatment. Over 85% of asymptomatic patients survive at least 5 years.
Patients presenting with symptomatic (usually painful) splenomegaly are most often treated by removal of the spleen (splenectomy). This approach often results in a remission lasting several years. Patients who have contraindications to splenectomy may undergo splenic irradiation as an alternative. If patients have splenomegaly and are positive for hepatitis C, treatment with the anti-hepatitis drugs alpha-interferon and ribavirin may be considered and has led to responses in many patients.
Patients who have other symptoms of splenic MZL or who have low blood counts due to bone marrow involvement with lymphoma are candidates for more aggressive therapy. The most effective agent appears to be rituximab, a monoclonal antibody that specifically kills B-cell lymphomas. Treatment with rituximab in these symptomatic patients is superior to splenectomy and often leads to normalizing of blood counts and disappearance of splenomegaly.
Treatment of progressive or recurrent splenic MZL is managed similarly to other recurrent indolent lymphomas. Combination chemotherapy is preferred. This subtype of NHL responds less well to chemotherapy than other indolent lymphomas, particularly when alkylating agents such as chlorambucil or cyclophosphamide are used.
Purine analogs such as fludarabine and cladribine seem to produce higher response rates, although no standard regimen exists. Rituximab is synergistic with chemotherapy and is often added to whichever regimen is chosen.
Supportive Care Issues
Infections due to bone marrow involvement with lymphoma and/or chemotherapy immune suppression are common in splenic MZL patients. This is especially true in patients receiving rituximab as part of their therapy.
In addition, patients who have had their spleen removed are at risk for infections with encapsulated bacteria such as Salmonella and Streptococcus. Prophylaxis with antibiotics may be appropriate in some, and patients should always contact their oncologist if they develop a fever.
Although more common as a complication of CLL, autoimmune cytopenias may be present in patients with splenic MZL. This includes autoimmune hemolytic anemia (destruction of the red blood cells) and immune thrombocytopenic purpurea (ITP; destruction of platelets). In addition to treating the underlying lymphoma, treatment of these autoimmune complications usually includes corticosteroids such as prednisone and/or intravenous immune globulin.
