Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B-cell non-Hodgkin lymphoma that belongs to the group of extranodal marginal zone lymphomas (EMZL).

MALT lymphoma can develop in many organs and tissues outside the lymph nodes. The stomach is the most common site, while other common locations include the ocular adnexa, salivary glands, lungs, thyroid, and skin.

Most MALT lymphomas grow slowly, and some remain stable for long periods. Treatment depends on the location and stage of the lymphoma, symptoms, and whether the disease is affecting organ function.

Helicobacter pylori Infection

Gastric MALT lymphoma is strongly associated with Helicobacter pylori (H. pylori) infection.

Long-term H. pylori infection can cause chronic inflammation in the stomach and stimulate the growth of lymphoid tissue. In some patients with gastric MALT lymphoma, the lymphoma may regress after H. pylori is successfully eradicated.

Other Infections

Some non-gastric MALT lymphomas have also been associated with certain infections. For example, Chlamydia psittaci has been linked to some cases of ocular adnexal MALT lymphoma, and hepatitis C virus has been associated with certain MALT lymphomas.

These associations vary by geographic region, and many patients have no identifiable infection.

Autoimmune Conditions

Certain autoimmune conditions may increase the risk of MALT lymphoma in specific organs. Examples include:

• Sjögren syndrome and salivary gland MALT lymphoma

• Hashimoto thyroiditis and thyroid MALT lymphoma

Long-term inflammation and immune stimulation may contribute to the development of the disease.

Symptoms of MALT lymphoma depend largely on where the lymphoma develops. Because the disease often grows slowly, some patients may have few or no symptoms at first.

Gastric MALT Lymphoma

Symptoms of gastric MALT lymphoma are often nonspecific and may include:

• Upper abdominal discomfort or pain

• Indigestion

• Bloating

• Acid reflux

• Nausea

• Loss of appetite

• Less commonly, gastrointestinal bleeding such as black stools

Systemic B symptoms such as fever, drenching night sweats, and significant weight loss are less common.

Non-Gastric MALT Lymphoma

Symptoms of non-gastric MALT lymphoma vary by the organ involved. Examples include:

• Ocular adnexa: swelling around the eye, bulging of the eye, double vision, or eye discomfort

• Salivary glands: painless swelling in the salivary gland area

• Lungs: cough, shortness of breath, or chest discomfort, although some patients have no symptoms

• Thyroid: a neck or thyroid mass that may affect swallowing or breathing if large

• Skin: one or more papules, nodules, or plaques

Diagnosis of MALT lymphoma depends primarily on a tissue biopsy and pathological examination. Once the diagnosis is confirmed, laboratory and imaging tests may be used to determine the extent of the disease and guide treatment.

Biopsy

A tissue biopsy is essential for diagnosing MALT lymphoma.

Tissue from the affected area is examined by a pathologist, often with immunohistochemistry, to confirm MALT lymphoma and distinguish it from other lymphomas or inflammatory conditions.

For gastric MALT lymphoma, multiple biopsies are often obtained during upper endoscopy because the disease can be patchy and may look similar to gastritis or a stomach ulcer.

H. pylori Testing

Patients with gastric MALT lymphoma are tested for H. pylori infection.

Testing may include biopsy-based methods, a urea breath test, or a stool antigen test. If H. pylori is not found on biopsy, additional testing may sometimes be used.

Blood Tests

Blood tests can measure red blood cells, white blood cells, and platelets and assess liver and kidney function, lactate dehydrogenase (LDH), and other markers.

Testing for infections such as hepatitis B, hepatitis C, or HIV may also be performed depending on the clinical situation.

Imaging Tests

CT scans may be used to determine whether lymphoma involves other organs or lymph nodes and to help stage the disease.

MRI or PET/CT may also be used depending on the location of the lymphoma and the individual situation. Because MALT lymphoma can show variable activity on PET imaging, PET/CT is not required for every patient.

Bone Marrow Tests

A bone marrow aspiration and/or biopsy may be performed in selected patients to determine whether the lymphoma involves the bone marrow.

Bone marrow testing is not routinely required for every patient and depends on the stage, other test results, and the treatment plan.

Genetic and Molecular Testing

Chromosomal and molecular testing may be performed in selected patients to provide additional information about the biological features of MALT lymphoma.

For example, some gastric MALT lymphomas have a t(11;18) chromosomal translocation. These findings may provide useful information about the disease and its potential response to treatment.

MALT lymphoma usually grows slowly. Treatment depends on whether the lymphoma is gastric or non-gastric, whether it is localized or widespread, whether symptoms are present, whether an associated infection is identified, and whether organ function is affected.

Not everyone with MALT lymphoma needs systemic treatment right away. Depending on the situation, treatment may include infection eradication, localized radiation therapy, active surveillance, or systemic therapy.

Gastric MALT Lymphoma: H. pylori Eradication

For H. pylori-positive gastric MALT lymphoma, eradication of H. pylori is usually the first treatment.

Treatment generally includes acid suppression and antibiotics. The specific antibiotic regimen depends on local resistance patterns, previous antibiotic exposure, and other individual factors.

After treatment, testing is used to confirm that H. pylori has been eradicated, and follow-up endoscopy with biopsies is performed to monitor the lymphoma.

Histologic regression of MALT lymphoma can take several months or longer. If the infection has been successfully eradicated and the lymphoma remains stable without progression, some patients with residual lymphoma on biopsy can continue to be monitored rather than starting another treatment immediately.

Active Surveillance

For selected patients who have no significant symptoms, slowly progressing disease, and no immediate threat to organ function, active surveillance may be appropriate.

Follow-up may include physical exams, blood tests, imaging, or endoscopy depending on the location of the lymphoma.

Radiation Therapy

MALT lymphoma is generally sensitive to radiation therapy.

For patients with localized gastric MALT lymphoma that progresses after H. pylori eradication, or H. pylori-negative disease that requires treatment, localized radiation therapy is an important option.

Radiation therapy can also provide effective local disease control for selected patients with localized non-gastric MALT lymphoma, including lymphoma involving areas such as the ocular adnexa or salivary glands.

Systemic Therapy

Systemic treatment may be considered for patients with widespread disease, significant symptoms, threatened organ function, or disease that is not suitable for local treatment.

Anti-CD20 monoclonal antibodies such as rituximab may be used alone or in combination with other medications. Some patients may receive immunochemotherapy or other systemic therapies.

Additional targeted treatments may also be available for selected patients with relapsed marginal zone lymphoma. The choice depends on previous treatments, disease characteristics, and overall health.

Non-Gastric MALT Lymphoma

Treatment for non-gastric MALT lymphoma is individualized and does not simply follow the same approach used for gastric disease.

Localized disease may be treated with radiation therapy or, in selected cases, monitored with active surveillance. Widespread or symptomatic disease may require systemic treatment.

For a small number of patients with a clearly associated infection, treatment of that infection may be considered. However, antibiotic therapy is not a universal first-line treatment for non-gastric MALT lymphoma.

Surgery

With advances in diagnosis, radiation therapy, and systemic treatment, surgery is generally not a routine treatment for MALT lymphoma.

Surgery may still be used in selected situations, such as obtaining diagnostic tissue, when a lesion has already been completely removed for another reason, or when the location of the disease creates a specific clinical problem. Further treatment depends on the pathology, stage, and site of the lymphoma.