Marginal Zone Lymphoma

Marginal zone lymphoma is a slow-growing type of cancer that affects the body’s immune system, typically diagnosed in people over age 60, and can often be treated successfully with various approaches depending on where the disease develops.

Table of contents

• What is marginal zone lymphoma?
• Types of marginal zone lymphoma
• Affected areas of the body
• Causes and risk factors
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• Outlook and prognosis

What is marginal zone lymphoma?

Marginal zone lymphoma (MZL) is a type of cancer that affects the lymphatic system, which is part of the body’s defense network against infections and disease. The lymphatic system includes organs, glands, tube-like vessels, and clusters of cells called lymph nodes that work together to protect your body from germs^[1].

This cancer is classified as a non-Hodgkin lymphoma, which is one of two main categories of lymphoma. Marginal zone lymphoma gets its name from where it starts: in the marginal zone, which is a specific part of the immune system where infection-fighting white blood cells called B cells (also known as B lymphocytes) live^[1].

In marginal zone lymphoma, changes occur that turn these B cells into cancer cells. The cancer cells can grow in various parts of the body, including the lymph nodes, bone marrow, stomach, spleen, and other organs^[1]. Marginal zone lymphoma is considered an indolent or slow-growing type of cancer, which means it typically develops gradually over time^[4].

This type of lymphoma accounts for approximately eight percent of all non-Hodgkin lymphoma cases. It usually affects people aged 60 and older, and tends to be slightly more common in women than in men^[4][2].

Types of marginal zone lymphoma

There are three main types of marginal zone lymphoma, classified based on where in the body the cancer develops^[1][2]:

Extranodal marginal zone lymphoma (MALT lymphoma)

Extranodal marginal zone lymphoma, also known as mucosa-associated lymphoid tissue (MALT) lymphoma, is the most common type of marginal zone lymphoma. It accounts for about two-thirds of all MZL cases. The term “extranodal” means that this type develops outside of the lymph nodes^[4].

MALT lymphoma most commonly develops in the stomach, which is known as gastric MALT lymphoma. It is often linked to ongoing inflammation caused by infections, especially infection with a bacteria called Helicobacter pylori (H. pylori)^[1][2].

This type can also develop in other parts of the body outside the stomach, which is called nongastric MALT lymphoma. These locations include the lungs, breasts, thyroid, salivary glands, small intestine, skin, eyes, and bowels^[4][2].

Splenic marginal zone lymphoma

Splenic marginal zone lymphoma is a rare type that primarily affects the spleen, blood, and bone marrow. It comprises about 20 percent of marginal zone lymphoma cases diagnosed each year. This type has been associated with hepatitis C virus (HCV) infection^[4].

Nodal marginal zone lymphoma

Nodal marginal zone lymphoma (sometimes called monocytoid B-cell lymphoma) develops within the lymph nodes and accounts for about 10 percent of all MZL cases. It can also appear in the bone marrow^[4][2].

Affected areas of the body

• Lymph nodes
• Bone marrow
• Spleen
• Stomach
• Lungs
• Skin
• Thyroid gland
• Salivary glands
• Eyes (ocular adnexa)
• Breasts
• Small intestine
• Blood

Causes and risk factors

Marginal zone lymphoma is distinctive because many cases are associated with ongoing stimulation of the immune system. This stimulation often comes from chronic inflammation that accompanies certain infections or autoimmune diseases^[5].

In general, people with marginal zone lymphoma often have a family history of lymphoma, frequent infections, or autoimmune diseases^[2].

Causes by subtype

MALT lymphoma causes include bacterial infections, specifically H. pylori infections that affect the stomach. It can also be linked to autoimmune diseases like Hashimoto’s disease (a thyroid condition) or Sjӧgren’s syndrome (a condition affecting moisture-producing glands), or having a family history of lymphoma^[2].

Splenic marginal zone lymphoma is linked to hepatitis C virus infection and autoimmune diseases^[2].

Nodal marginal zone lymphoma is associated with hepatitis C virus infection^[2].

The main risk factors for developing marginal zone lymphoma include having a family history of lymphoma and having certain infections and autoimmune disorders^[2].

Signs and symptoms

Marginal zone lymphoma typically grows very slowly. Because of this, you may have this condition without experiencing any symptoms at all. When symptoms do occur, they vary depending on which type of marginal zone lymphoma you have and where in the body it develops^[2].

General symptoms

In general, marginal zone lymphomas can cause the following symptoms^[2]:

• Fever
• Night sweats
• Unexplained weight loss

MALT lymphoma symptoms

Symptoms of extranodal marginal zone lymphoma vary based on where the lymphoma is located. For example, MALT lymphoma in the stomach may cause^[2]:

• Nausea and vomiting
• Belly pain
• Feeling full even when you haven’t eaten much

Non-gastric MALT lymphoma symptoms may include changes in the eye’s surface (conjunctiva) or tear (lacrimal) glands^[2].

Splenic marginal zone lymphoma symptoms

Splenic marginal zone lymphoma may cause^[2]:

• Fatigue (extreme tiredness)
• Enlarged spleen
• Night sweats
• Unexplained weight loss

Nodal marginal zone lymphoma symptoms

Nodal marginal zone lymphoma symptoms may include^[2]:

• Fever
• Night sweats
• Unexplained weight loss

How is it diagnosed?

Marginal zone lymphoma diagnosis often begins with a physical exam. Your healthcare provider will check for swollen lymph nodes in your neck, underarms, and groin, as well as check for an enlarged spleen^[8]. They will also ask questions about your symptoms, your medical history, and your family medical history^[2].

Blood tests

Blood tests can sometimes show whether lymphoma cells are present in your blood. Blood tests can also check for infections that may increase the risk of marginal zone lymphoma, such as hepatitis C^[8].

Tests may include^[2]:

• Complete blood count (CBC)
• LDH test (a test that measures an enzyme in the blood)
• Beta-2 microglobulin, a tumor marker for blood cancers
• Liver function tests
• Kidney function tests

Imaging tests

Imaging tests create pictures of the inside of your body. They can show the location and extent of marginal zone lymphoma. Tests might include ultrasound, MRI (magnetic resonance imaging), CT (computed tomography), and PET (positron emission tomography) scans^[8].

Biopsy procedures

Your healthcare provider may suggest a lymph node biopsy to look for cancer cells. A biopsy is a procedure to remove a sample of tissue for testing in a laboratory. A lymph node biopsy involves removing all or part of a lymph node. In the lab, tests can show whether you have marginal zone lymphoma^[8].

Bone marrow aspiration and biopsy are procedures to collect cells from the bone marrow for testing. Bone marrow is the soft matter inside bones where blood cells are made. The samples are typically taken from the hip bone and sent to a lab for testing. In marginal zone lymphoma, this procedure is done to help determine how much the cancer has spread^[8].

Endoscopy

An upper endoscopy is a procedure to look at the inside of the esophagus (food pipe), stomach, and first part of the small intestine. A thin tube with a camera is used to view these areas. This test may be done if doctors suspect MALT lymphoma in the stomach^[8].

Treatment options

Treatment for marginal zone lymphoma depends on the type, the stage and location of the disease, your age and overall health, and any lymphoma-related signs or symptoms^[7]. Because marginal zone lymphoma is often a slow-growing disease, doctors may initially adopt a “watch and wait” or “active surveillance” approach for people without symptoms. With this strategy, your overall health and disease are monitored through regular checkup visits and various tests. Active treatment is started if you begin to develop lymphoma-related symptoms or there are signs that the disease is getting worse^[7].

Treatment for gastric MALT lymphoma

Since gastric MALT lymphoma is often the result of an infection with H. pylori bacteria, the initial treatment is antibiotic therapy, usually combined with proton pump inhibitors (PPIs). PPIs are medications that reduce the production of stomach acid to help prevent or heal ulcers. This treatment is typically given for two weeks^[7].

In about 90 percent of cases, these lymphomas go away following antibiotic and PPI treatment, although this may take several months. If the lymphoma comes back after antibiotic therapy or does not respond to treatment, there are many additional treatment options available, including rituximab (Rituxan), radiation therapy, and surgery^[7].

Treatment for non-gastric MALT lymphoma

Non-gastric MALT lymphoma can appear in a variety of areas throughout the body. Therefore, treatment is usually based on the exact location and how far the disease has spread. When treatment is necessary, it typically includes surgery for certain sites (such as lung or breast) or radiation therapy. More advanced disease is usually treated with immunotherapy (treatment that helps your immune system fight cancer) and chemotherapy (drugs that kill cancer cells)^[7].

Common initial treatments include bendamustine (Treanda) combined with rituximab, and R-CHOP (a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)^[7].

Antibiotic therapy such as doxycycline has been shown to be effective in MALT lymphoma that affects the area around the eye (ocular adnexal lymphoma), which has been associated with infection^[7].

Treatment for nodal and splenic marginal zone lymphoma

Since nodal and splenic marginal zone lymphoma are most often slow-growing diseases, doctors may adopt an active surveillance approach for people without symptoms^[7]. When treatment is needed, options may include chemotherapy, immunotherapy, radiation therapy, targeted therapy (drugs that target specific features of cancer cells), and bone marrow transplant (also called bone marrow stem cell transplant)^[1].

Outlook and prognosis

Marginal zone lymphoma is a slow-growing type of cancer with an excellent prognosis. Healthcare providers can treat and sometimes cure some types of MZL^[2]. However, the disease generally remains incurable, and the majority of patients will need repeated therapy for disease control over the course of their lifetime^[10].

One of the most distinctive features of marginal zone lymphoma is that many cases associated with certain infectious pathogens can be cured by treatment directed at the infections causing or associated with the disease^[5]. This is particularly true for gastric MALT lymphoma related to H. pylori infection.

Nodal marginal zone lymphoma carries a somewhat worse long-term outcome than the other subtypes. Any of the MZL subtypes may progress in a low percentage of cases to a more aggressive lymphoma, particularly diffuse large B-cell lymphoma^[5].