Splenic marginal zone lymphoma (SMZL) is a type of non-Hodgkin lymphoma (NHL). About 1 percent to 2 percent of all NHL cases are splenic marginal zone lymphoma. This type of cancer is considered low-grade, which means that it grows slowly. People with SMZL often have good outlooks and may live for many years. SMZL doesn’t always need to be treated right away.

What Is Splenic Marginal Zone Lymphoma?

Lymphoma is a type of cancer that develops from immune cells called lymphocytes. These cells help the body fight infection. SMZL is a type of marginal zone lymphoma (MZL) that develops from lymphocytes called B cells.

MZL develops in tissues of the lymphatic system, in an area called the marginal zone. There are three types of MZL. These subtypes are defined by which tissues they are located in:

• Nodal marginal zone lymphoma begins in the lymph nodes (glands that filter out waste and germs).
• Mucosa-associated lymphoid tissue (MALT) lymphoma, also called extranodal MZL, develops outside of the lymph nodes, in tissues such as the lungs, skin, and digestive system.
• Splenic marginal zone lymphoma usually affects the spleen and blood.

People with SMZL have many cancer cells inside the spleen. The spleen is an organ in the upper part of the abdomen, on the left side. This organ helps kill germs, make new blood cells, and get rid of old or damaged blood cells.

Risk Factors for SMZL

People with hepatitis C virus (HCV) infections are more likely to develop SMZL. About 1 out of 5 people with SMZL are infected with HCV. Autoimmune disorders may also increase risk. However, most people with HCV or autoimmune conditions don’t develop SMZL.

Splenic Marginal Zone Lymphoma Symptoms

SMZL may not always cause symptoms right away. About 1 out of 4 people don’t have symptoms, especially when SMZL is still in its early stages. Eventually, most people with SMZL develop splenomegaly (an enlarged spleen). Splenomegaly can cause:

• Pain in the abdomen or left shoulder
• Feelings of fullness in the upper part of the abdomen
• Feeling full after eating a small amount of food

SMZL can sometimes spread to the soft tissue inside of certain bones, called the bone marrow. Cells in the bone marrow make new blood cells. If cancer spreads to the bone marrow, it can crowd out the body’s healthy blood cells, causing cytopenia (low blood cell counts).

Some people with SMZL develop anemia (low levels of red blood cells), which may lead to extreme tiredness, shortness of breath, and heart palpitations. SMZL can also cause thrombocytopenia (low levels of platelets), which may lead to bleeding or bruising problems.

SMZL can also cause B symptoms, which include fever, night sweats, and weight loss. Additionally, 1 out of 5 people with SMZL develop autoimmune disorders (problems with the immune system) such as autoimmune hemolytic anemia, rheumatoid arthritis, or primary biliary cirrhosis.

Diagnosis of SMZL

When diagnosing SMZL, doctors may look for abnormalities with blood tests, bone marrow tests, and laboratory tests. Occasionally, surgery is involved in finding the right diagnosis. These tests help confirm you have SMZL and rule out other types of B-cell lymphoma that cause similar symptoms like:

• Follicular lymphoma (FL)
• Diffuse large B-cell lymphoma (DLBCL)
• Mantle cell lymphoma (MCL)
• Chronic lymphocytic leukemia (CLL)

Blood Tests

SMZL diagnosis often includes a complete blood count (CBC), in which the levels of each type of blood cell are measured. Other blood tests can help determine how well the kidneys and liver are working. Additionally, doctors may want to measure the blood levels of certain molecules that may serve as signs of cancer, including lactate dehydrogenase (LDH) and beta-2 microglobulin.

Bone Marrow Tests

Looking inside the bone marrow can help doctors determine whether lymphoma has spread in that area. To analyze the bone marrow, doctors may perform a bone marrow biopsy, in which they remove a small sample of bone tissue, or a bone marrow aspiration, in which they take out a sample of fluid. A doctor will look at this sample under a microscope. People with SMZL can have villous lymphocytes — abnormal B cells that look like cobblestones.

Surgery

Some people may have their spleen surgically removed (splenectomy) before they get an official diagnosis of SMZL. In the case of splenectomy, doctors will typically use pieces of the spleen for further laboratory testing and diagnosis.

Laboratory Tests

Samples from the bone marrow or spleen are sent to a laboratory so that the cells can be further studied. Laboratory tests include histology and other tests such as flow cytometry. These tests help doctors see what the bone marrow or spleen cells look like, determine whether the cells are cancerous, and figure out the type of lymphoma. Additionally, tests that look for certain gene changes can help doctors tell SMZL apart from other types of lymphoma.

Other Tests

Doctors may also recommend additional tests to gather more information about lymphoma or the various health conditions that SMZL can cause. These tests may include:

• Tests to look for a hepatitis C virus infection
• Tests to look for an abnormal antibody made by immune cells (serum protein electrophoresis or quantitative immunoglobulin levels)
• Tests to screen for autoimmune disorders

Staging

After diagnosis, doctors determine how far the lymphoma has spread (lymphoma stage). Knowing the lymphoma stage helps doctors plan treatments and estimate prognosis. Doctors stage SMZL using the above tests as well as imaging tests like CT scans.

Splenic Marginal Zone Lymphoma Treatment

Doctors don’t have one standard treatment plan that is always used to treat splenic marginal zone lymphoma. SMZL is rare, which makes it hard to study. However, researchers have found that treatments like surgery, chemotherapy, and targeted therapies can help people have better outcomes. Doctors often recommend different treatment plans based on a person’s symptoms and their overall health.

Watch and Wait

If SMZL is not causing symptoms, treatment may not be needed. People with asymptomatic SMZL can often live for many years without being treated. Delaying treatment can help people avoid unpleasant side effects. During this time, it is important to have regular follow-up visits with doctors to make sure that the lymphoma is not getting worse.

Surgery

Doctors sometimes use a splenectomy to treat SMZL. A splenectomy can quickly relieve many SMZL symptoms. However, a splenectomy won’t remove all of the lymphoma cells because SMZL usually spreads to the bone marrow. Medications are increasingly becoming more successful at treating SMZL, so doctors don’t use splenectomies to treat SMZL as often as they once did.

Targeted Therapy

Rituximab (Rituxan) is a first-line targeted therapy most commonly used to treat SMZL. Targeted therapy drugs attack tumor cells while largely leaving the body’s normal cells alone. Rituximab is a monoclonal antibody drug designed to specifically target B cells. Many doctors recommend rituximab because it is less toxic and leads to fewer side effects than chemotherapy.

There are two main ways rituximab helps treat SMZL:

• Rituximab monotherapy, meaning the drug is given on its own
• Rituximab combination therapy given with chemotherapy drugs like bendamustine (Treanda)

A newer class of medications called Bruton’s tyrosine kinase (BTK) inhibitors is also used for SMZL. B cells use the BTK protein to grow and divide uncontrollably. Blocking it with a BTK inhibitor helps prevent lymphoma spread. You may receive a BTK inhibitor if you have relapsed/refractory (R/R) SMZL. This means your cancer has returned or stopped responding to previous treatments. Examples of BTK inhibitors include:

• Acalabrutinib (Calquence)
• Ibrutinib (Imbruvica)
• Zanubrutinib (Brukinsa)

Chemotherapy

SMZL can be treated with several different combinations of chemotherapy drugs. Since these medications are more toxic than targeted therapies, doctors don’t use them very often anymore.

Chemotherapy options include:

• CVP — Cyclophosphamide, vincristine, and prednisone
• CHOP — Cyclophosphamide, doxorubicin, vincristine, and prednisone
• FC — Fludarabine and cyclophosphamide

Antiviral Drugs

People with SMZL who have a hepatitis C infection often take antiviral drugs to help kill the virus. Direct-acting antiviral (DAA) drugs specifically target enzymes that viruses use to replicate themselves. Studies show that taking DAAs to treat hepatitis C also successfully treats SMZL. Most DAAs come in combination tablets to target multiple enzymes at once. Examples include:

• Glecaprevir/pibrentasvir (Mavyret)
• Ledipasavir/sofosbuvir (Harvoni)
• Sofosbuvir/velpatasvir (Epclusa)

Splenic Marginal Zone Lymphoma Prognosis

SMZL is indolent lymphoma, meaning it grows slowly. People with this condition often have a good outlook. The five- and 10-year overall survival rates with this cancer are 77 percent and 60 percent, respectively. This means that five years after SMZL diagnosis, 77 percent of people are still alive. At 10 years, 60 percent are still alive.

Is Splenic Marginal Zone Lymphoma Aggressive?

Most cases of SMZL are indolent, meaning they’re slow-growing and not aggressive. However, sometimes SMZL can lead to worse outcomes. About 3 out of 10 people with SMZL develop aggressive lymphoma that grows more quickly. People with this faster-growing type live an average of four years after diagnosis. Additionally, SMZL sometimes transforms into diffuse large B-cell lymphoma (DLBCL), a more aggressive type of lymphoma.

Factors Associated With Poor Outlook

Certain prognostic factors increase the chances that a person with SMZL will have a poor outlook:

• Older age
• Lymphadenopathy (enlarged lymph nodes)
• SMZL cells in parts of the body outside of the spleen and bone marrow
• Certain gene mutations within SMZL cells
• Lymphocytosis (high white blood cell counts)
• Low red blood or platelet cell counts
• High levels of beta-2 microglobulin
• Presence of monoclonal protein or M protein (an abnormal antibody made by plasma cells)
• Poor overall health and inability to carry out daily activities

Can Splenic Marginal Zone Lymphoma Be Cured?

At this time, SMZL can’t be cured. Many people are successfully treated with available treatments like rituximab and chemotherapy. Since it grows slowly, most people live with SMZL for several years. However, the lymphoma tends to relapse over time. Newer treatment options like BTK inhibitors are now helping improve the outlook for those with R/R SMZL.

Talk to your healthcare team if you would like to know more about your prognosis. Your doctors can help you understand what to expect from splenic marginal zone lymphoma.

Talk With Others Who Understand

A lymphoma diagnosis can be difficult, but it may be made easier by connecting with others who share a similar experience. MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 21,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Are you living with splenic marginal zone lymphoma? Share your experiences in the comments below, or start a conversation by posting on MyLymphomaTeam.