Marginal zone lymphoma (MZL) is a type of cancer that arises in cells of the immune system. It is a rare disease, with approximately 8,000 new cases in the United States each year. It is most commonly diagnosed in older adults.

What Is MZL?

Lymphomas can be broadly categorized into two groups: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). There are different subtypes of NHL — marginal zone lymphoma is one subtype of NHL. It is indolent (a low-grade or slow-growing disease) and makes up approximately seven percent of NHL cases. MZL arises in a type of white blood cell known as B lymphocytes or B cells and is also known as marginal zone B-cell lymphoma.

What Causes MZL?

B cells work as part of the immune system to help the body recognize and fight infection. Although primarily located in the lymph nodes, B cells are also found in the marginal zone of the spleen and are called marginal zone B cells. However, genetic mutations can occur and cause improper multiplication of marginal zone B cells, giving rise to MZL. Chronic inflammation caused by bacterial or viral infections or autoimmune conditions such as Sjögren’s syndrome have also been shown to contribute to MZL’s development.

Types of MZL

MZL can be further categorized into three distinct subtypes, depending on where the cancer forms:

• Mucosa-associated lymphoid tissue lymphoma (MALT, or extranodal MZL)
• Splenic marginal zone B-cell lymphoma (SMZL)
• Nodal marginal zone B-cell lymphoma (NMZL)

Mucosa-Associated Lymphoid Tissue Lymphoma

Mucosa-associated lymphoid tissue lymphoma (MALT), also called extranodal marginal zone B-cell lymphoma (EMZL), is the most common type of MZL — it makes up about 61 percent of all MZL cases. MALT can be further divided into two groups:

• Gastric, which is the most common type and occurs in the stomach
• Nongastric, which occurs in other tissues such as the lungs and salivary glands

The gastric form of MALT is strongly associated with Helicobacter pylori (H. pylori) bacterial infection.

Nodal Marginal Zone Lymphoma

Nodal marginal zone lymphoma (NMZL) is the second most common type of MZL, making up about 30 percent of cases. NMZL occurs in the lymph nodes and bone marrow.

Splenic Marginal Zone B-Cell Lymphoma

Splenic marginal zone lymphoma (SMZL) is the rarest form of MZL, accounting for about 9 percent of cases. It occurs primarily in the spleen and bone marrow.

Signs and Symptoms of Marginal Zone Lymphoma

Because it is a slow-growing lymphoma, many people with MZL originally show no symptoms. For those who have symptoms, however, symptoms of MZL may include:

• Swollen lymph nodes
• Chest pains or problems breathing
• Fatigue
• Abdominal pain

These symptoms are also common in many other forms of B-cell lymphoma, and are often referred to as B symptoms:

• Fever
• Night sweats
• Sudden weight loss

Additional symptoms specific to MALT lymphoma may include:

• Nausea or vomiting
• Indigestion
• Abdominal pain
• Bleeding in the stomach

Diagnosis of MZL

To explore a diagnosis of MZL, a doctor may need to perform the following tests:

• Physical exam
• Lymph node biopsy
• Blood test
• Imaging tests
• Bone marrow biopsy
• Esophagogastroduodenoscopy (EGD)

Most of these tests pertain to all subtypes of MZL, although each subtype has unique diagnostic criteria.

Physical Exam

A doctor will check externally for swollen lymph nodes during a physical exam and confirm other disease symptoms present.

Lymph Node Biopsy

A lymph node biopsy involves a doctor examining a lymph node for the presence of cancer cells. The procedure can be a surgical biopsy, which removes an entire lymph node from the body, or a needle biopsy, which removes a portion of a lymph node. Marginal zone B-cell lymphoma can be distinguished from other types of B-cell lymphomas by observing the unique shape of marginal zone B cells and cancer protein markers in the lymph node tissue.

Blood and Urine Tests

Blood tests can be used to check a person for signs of MZL, such as low counts of red blood cells, white blood cells, or platelets. A blood test also measures levels of the proteins lactate dehydrogenase (LDH), beta-2-microglobulin (B2M), and can detect evidence of infection by H. pylori, hepatitis C virus (HCV), or human immunodeficiency virus (HIV).

A urine test may also be performed to analyze kidney, liver, and bladder function.

Imaging Tests

Imaging techniques such as a CT scan, MRI, or PET scan are often used by doctors to look for internal evidence of cancer. Your doctor may use these imaging tests to check for cancer cells in swollen lymph nodes, the abdomen, and salivary glands.

Bone Marrow Biopsy

A doctor uses a needle to withdraw liquid and tissue from the bone marrow during a bone marrow biopsy. The samples are analyzed under a microscope for the presence of cancer cells. This test is generally necessary to diagnose MZL that is thought to occur in the bone marrow.

Treatments for MZL

There are several treatment options for MZL, including:

• Antibiotics and antiviral therapy
• Radiation therapy
• Chemotherapy
• Immunotherapy
• Surgery

The type of treatment recommended may vary depending on the specific subtype of MZL and the stage of the disease.

Antibiotics

Antibiotics are often the first line of treatment for people with gastric MALT-type marginal zone lymphoma due to its association with H. pylori infection. Drugs called proton pump inhibitors are generally used in combination with antibiotics to treat both the bacterial infection and cancer.

Antiviral treatments might also be effective in people diagnosed with HCV-associated MALT.

Radiation Therapy

Radiation may be recommended to people with localized cancer, in just one part of the body. Radiation may also be recommended for people with MALT who have cancer remaining after treatment with antibiotics.

Chemotherapy

Chemotherapy is a common treatment for people with MZL. Chemotherapy is most likely to be recommended to people who haven’t had a complete response with earlier treatments.

Immunotherapy

Immunotherapy is a treatment that uses the immune system to fight cancer cells. Immunotherapy medications often involve human-made versions of proteins known as antibodies that recognize specific molecules (called antigens) that are present on the surface of certain cells. As part of the immune system, antibodies can bind to foreign antigens and target those cells to be destroyed. Rituximab is an antibody-drug that has been engineered to recognize antigens on the surface of B cells so it can attack the cancer cells. Rituximab might be used alone or in combination with chemotherapy to treat MZL.

Surgery

Surgery in the form of splenectomy (removal of the spleen) was previously a primary form of treatment in people with SMZL. Surgery has since taken a back seat to treatment with rituximab or chemotherapy but may still be recommended for people who didn’t respond to initial treatments.

Prognosis for MZL

The subtypes of marginal zone lymphoma have distinct characteristics, so disease prognosis (outlook) can vary.

MALT lymphoma, the most common subtype, is generally responsive to treatment and has a high five-year survival rate at approximately 90 percent of cases. SMZL and NMZL have lower survival rates at 50 percent to 70 percent, but they are also somewhat responsive to treatment. Due to the rarity of SMZL and NMZL, more research is needed to identify more effective treatments and improve the prognosis of these diseases.

Talk With Others Who Understand

A new cancer diagnosis can be a lot to handle. It may help to have the support of others who understand what you’re going through as you face new challenges. MyLymphomaTeam is the social network for people with lymphoma and their loved ones. More than 8,000 members understand what it’s like to face lymphoma and can provide support and answers.

Are you or a loved one newly diagnosed with marginal zone lymphoma? Share your experience at MyLymphomaTeam or comment below to start a conversation.