Splenic marginal zone lymphoma
Splenic marginal zone lymphoma is a rare, slow-growing type of blood cancer that mainly affects the spleen, and while it often develops gradually without symptoms, it can usually be treated effectively with modern therapies.
Table of contents
- What is splenic marginal zone lymphoma?
- Parts of the body affected
- Who is affected by this condition?
- Signs and symptoms
- How doctors diagnose the condition
- What to expect: outlook and survival
- Treatment options
- Follow-up care
- When lymphoma returns or doesn’t respond
What is splenic marginal zone lymphoma?
Splenic marginal zone lymphoma (SMZL) is a type of blood cancer that develops when white blood cells called lymphocytes (cells that help your body fight infections) grow out of control[1]. More specifically, it is a non-Hodgkin lymphoma, which means it belongs to a large group of lymphomas that are different from Hodgkin lymphoma[1].
This cancer develops from B cells, a specific type of lymphocyte, and is called a marginal zone lymphoma because it starts in a particular region at the edge of lymphoid tissues (collections of lymphocytes) called the marginal zone[1]. There are three types of marginal zone lymphoma, and SMZL is the one that mainly affects the spleen[3].
SMZL is considered a low-grade or indolent lymphoma, which means it grows slowly[4][7]. It accounts for about 1 to 2 percent of all non-Hodgkin lymphomas[6]. The cancer cells can be found in the spleen, bone marrow, blood, and sometimes in the lymph nodes near the spleen[4].
- Spleen
- Bone marrow
- Blood
- Lymph nodes (particularly those near the spleen)
Who is affected by this condition?
Splenic marginal zone lymphoma is a rare disease. It is the second most common type of marginal zone lymphoma, making up about 20% of all marginal zone lymphoma cases[7]. SMZL usually affects people aged 60 and older, and it tends to be more common in men than in women[5].
Certain factors increase the risk of developing SMZL. People with hepatitis C virus (HCV) infections are more likely to develop this condition—about 1 out of 5 people with SMZL are infected with HCV[6][9]. Autoimmune disorders may also increase risk[6]. However, most people with HCV or autoimmune conditions do not develop SMZL[6].
Having a family history of lymphoma is a notable risk factor for marginal zone lymphomas[3]. The exact cause of SMZL is not fully understood, but the cancer is thought to develop from B cells that have already matured and moved through certain developmental stages[9].
Signs and symptoms
SMZL may not always cause symptoms right away. About 1 out of 4 people don’t have symptoms, especially when the disease is still in its early stages[4][6]. Eventually, most people with SMZL develop splenomegaly, which means an enlarged spleen[6]. In fact, enlargement of the spleen is seen in nearly all people affected by SMZL[9].
Splenomegaly can cause several problems. It may lead to pain in the abdomen or left shoulder, feelings of fullness in the upper part of the abdomen, or feeling full after eating only a small amount of food[6]. It can also hurt to sleep on the left side[19].
SMZL can sometimes spread to the bone marrow, the soft tissue inside certain bones where new blood cells are made. When cancer cells crowd the bone marrow, they can push out healthy blood cells, causing cytopenia (low blood cell counts)[6]. Low numbers of blood cells appear in about 25% of cases and are often related to an overactive, enlarged spleen[4].
Some people with SMZL develop anemia, which means low levels of red blood cells. This may lead to extreme tiredness, shortness of breath, and heart palpitations[6]. SMZL can also cause thrombocytopenia, or low levels of platelets, which may lead to bleeding or bruising problems[6].
SMZL can also cause what doctors call B symptoms, which include fever, night sweats, and unexplained weight loss[5][6]. However, the presence of B symptoms or high levels of lactate dehydrogenase (LDH, a substance measured in blood tests) at diagnosis is unusual[4].
Additionally, 1 out of 5 people with SMZL develop autoimmune disorders, which are problems where the immune system attacks the body’s own tissues. Examples include autoimmune hemolytic anemia, rheumatoid arthritis, or primary biliary cirrhosis[4][6]. About one-third of patients have small amounts of a protein called monoclonal protein in their blood, usually immunoglobulin M (IgM)[4].
How doctors diagnose the condition
When diagnosing SMZL, doctors look for signs of the disease through several types of tests. Enlargement of the spleen is a requirement for the diagnosis of SMZL[9]. Doctors may begin with a physical exam that checks for an enlarged spleen in the upper left part of the abdomen[10].
Blood tests are an important part of diagnosis. They can show whether lymphoma cells are present in the blood[10]. Sometimes, circulating lymphoma cells appear in the blood and may have a distinctive appearance with short projections at the ends of the cells[9]. Blood tests can also check for infections like hepatitis C, which may increase the risk of SMZL[10].
Imaging tests, such as ultrasound, MRI, CT scans, and positron emission tomography (PET) scans, help doctors see the location and extent of the lymphoma[10]. These tests create pictures of the inside of the body.
Bone marrow tests are frequently used in diagnosis. Doctors use special needles to collect samples of both the liquid and solid parts of bone marrow, usually from the hip bone. The samples go to a lab for testing[10]. The bone marrow is often involved in patients with SMZL, showing a pattern with cells that look similar to what is seen in lymph nodes near the spleen[9].
Sometimes, a biopsy of the spleen or other tissue may be needed. This involves removing a sample of tissue for examination in a lab. Tests on the tissue sample can show whether lymphoma cells are present and what type they are[10].
Lab tests look at specific markers on the surface of the cancer cells. For SMZL, the cancer cells typically test positive for certain markers (like CD20 and CD79a) and negative for others (like CD5, CD10, and CD23)[9]. These patterns help doctors distinguish SMZL from other types of lymphoma that can look similar.
What to expect: outlook and survival
People with SMZL often have good outlooks and may live for many years[6]. Three-quarters of patients survive five or more years, and more than half of patients with SMZL survive more than a decade after diagnosis[9].
The disease typically has an indolent, or slow-growing, course[4]. However, some patients may have a more aggressive disease. Patients who have a hemoglobin level (a measure of red blood cells) of less than 12 g/dL, a lactate dehydrogenase level higher than normal, or blood serum albumin levels (a protein in blood) of less than 3.5 g/dL are likely to have a more aggressive disease and a shorter survival[9]. Still, even high-risk patients have even odds of living for five years after diagnosis[9].
Sometimes SMZL can change, or transform, into a more aggressive type of lymphoma called diffuse large B-cell lymphoma (DLBCL)[7]. If this happens, the lymphoma is treated like DLBCL[7].
Treatment options
Treatment for SMZL depends on several factors, including the stage of the disease, whether symptoms are present, the patient’s age, and overall health[14]. Because SMZL is a rare disease with no large randomized trials, there is no single standard treatment[4].
If SMZL is linked with a hepatitis C virus (HCV) infection, treating the infection with antiviral drugs is usually the first step. Treating the HCV can sometimes reduce the symptoms of SMZL, and additional cancer treatment may not be needed[7][15].
Watchful waiting
If SMZL is growing slowly and not causing any symptoms, doctors may recommend watchful waiting, also called active surveillance[7][15]. With this approach, the healthcare team uses tests to carefully monitor the disease during regular checkups. When symptoms appear or there are signs that the disease is getting worse, other treatments are started[7].
Targeted therapy
Targeted therapy uses drugs that target specific molecules on or inside cancer cells. These drugs stop the growth and spread of cancer cells while limiting harm to normal cells[7]. Targeted therapy can be used alone or combined with chemotherapy or immunotherapy.
The most common targeted therapy drug used to treat SMZL is rituximab (brand names include Rituxan)[7][15]. Rituximab is often well tolerated, though some patients may have reactions during the first treatment, such as dizziness, low blood pressure, high heart rate, or numbness[19].
If SMZL comes back after treatment (relapses) or stops responding to treatment (refractory disease), other targeted therapy drugs may be used. These include ibrutinib (Imbruvica), zanubrutinib (Brukinsa), or lenalidomide (Revlimid)[7][15].
Chemotherapy
Chemotherapy uses drugs to destroy cancer cells. It is often combined with rituximab to treat SMZL[7][15]. Common drug combinations include:
- BR – bendamustine (Treanda, Benvyon, Esamuze) and rituximab
- R-CHOP – rituximab, cyclophosphamide (Procytox), doxorubicin, vincristine, and prednisone
- R-CVP – rituximab, cyclophosphamide, vincristine, and prednisone
- Chlorambucil (Leukeran) and rituximab
- Cyclophosphamide and rituximab
Studies have shown that bendamustine and rituximab (BR) can be very effective as a first-line treatment for symptomatic SMZL[12].
Surgery
Surgery to remove the spleen, called a splenectomy, may be offered for SMZL[7][15]. Splenectomy has been done for many years to control the disease[4]. It is done to improve red blood cell or platelet counts, or to relieve discomfort if the spleen is very large and putting pressure on other organs[7][15]. However, it is not encouraged as a first-line treatment anymore because newer therapies like rituximab are as effective with less risk[4].
Follow-up care
After treatment for SMZL, regular follow-up care is important. This usually includes regular checkup visits with the healthcare team. During these visits, doctors monitor the patient’s overall health and watch for any signs that the lymphoma may be returning[7].
Follow-up may include blood tests and imaging tests such as PET scans to check how well the treatment worked and whether the disease has responded completely[19]. If tests show that the lymphoma is in remission (meaning no signs of cancer can be found), patients continue with regular monitoring[19].
When lymphoma returns or doesn’t respond
Sometimes SMZL comes back after treatment (called relapsed lymphoma) or does not respond to treatment (called refractory lymphoma). When this happens, additional treatment options are available[7].
For relapsed or refractory SMZL, doctors may use different targeted therapy drugs such as ibrutinib, zanubrutinib, or lenalidomide[7][15]. Other chemotherapy combinations may also be tried.
Research is ongoing to find new and better treatments for SMZL. Patients with relapsed or refractory disease may be able to join clinical trials, which are research studies that test new treatments[14].
