Extranodal Marginal Zone Lymphoma of Mucosal-Associated Lymphoid Tissue: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Aleksandra Paliga MD FRCPC
April 21, 2026

Extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue — also called MALT lymphoma, or EMZL — is a slow-growing (indolent) blood cancer that starts in B cells, the white blood cells that help the body fight infections. The word “extranodal” means that the lymphoma arises outside the lymph nodes, in the tissues of various organs. “Marginal zone” refers to the specific compartment within normal lymphoid tissue from which the lymphoma cells originate. “Mucosal-associated lymphoid tissue” (MALT) describes the small clusters of immune cells that are normally present in the lining (mucosa) of many organs — particularly the stomach, intestines, lungs, salivary glands, and other mucosal surfaces — and that form the starting point for this lymphoma. MALT lymphoma is one of the most common types of lymphoma and can arise in many different organs throughout the body. Despite being classified as cancer, most cases grow very slowly and remain localized for many years, and treatment — which depends on the site and cause — is often highly effective. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

Where in the body is MALT lymphoma found?

MALT lymphoma can arise in almost any organ that contains mucosal or glandular tissue. The most common sites are the stomach, the tissues surrounding the eye (ocular adnexa), the salivary glands, the lung, the thyroid gland, the skin, the breast, and the thymus. Less commonly, MALT lymphoma arises in the small intestine, colon, bladder, liver, and other sites. The stomach is the single most common location, accounting for approximately 30–40% of all cases worldwide. The specific site of origin matters because the causes, treatment approach, and prognosis can differ substantially between locations.

What are the symptoms of MALT lymphoma?

Many people with MALT lymphoma have no symptoms at the time of diagnosis, and the lymphoma is found incidentally — by accident — during imaging, endoscopy, or surgery performed for another reason. When symptoms do occur, they depend on the organ involved.

In the stomach, symptoms often resemble those of chronic gastritis or peptic ulcer disease: upper abdominal pain or discomfort, a burning sensation, nausea, early satiety, or occasionally bleeding. Because these symptoms are common and non-specific, many patients are initially treated for H. pylori gastritis before lymphoma is identified on biopsy.

In the ocular adnexa (the soft tissues surrounding the eye, including the conjunctiva, lacrimal gland, and orbit), MALT lymphoma typically presents as a slowly enlarging, painless mass, a visible salmon-colored patch on the conjunctiva, mild proptosis (forward protrusion of the eyeball), or double vision. It is often found on routine eye examination.

In the salivary glands, patients typically notice a slowly enlarging swelling in the cheek or below the jaw, which may be confused with a benign salivary gland condition, particularly in people with Sjögren’s disease.

In the lung, MALT lymphoma is frequently asymptomatic and discovered as a nodule or consolidation on imaging. When symptomatic, it can cause cough, shortness of breath, or recurrent respiratory infections that do not fully resolve.

In the thyroid gland, it presents as an enlarging thyroid mass, often in the context of known Hashimoto’s thyroiditis.

General symptoms such as fever, drenching night sweats, and significant weight loss — called B symptoms — are uncommon in MALT lymphoma because of its characteristically indolent behavior, and their presence should prompt evaluation for a more aggressive disease or transformation.

What causes MALT lymphoma?

MALT lymphoma is caused by prolonged chronic inflammation in a particular organ. Normally, the mucosal surfaces of the body contain very few permanent immune cells. When a site becomes repeatedly or persistently stimulated — by an infection or an autoimmune process — the immune system builds up a population of reactive B cells at that site. Over many years, these repeatedly stimulated B cells accumulate additional genetic changes and eventually transform into lymphoma cells. The specific trigger for this process varies by location.

In the stomach, Helicobacter pylori (H. pylori) infection is the dominant cause, present in approximately 70–80% of gastric MALT lymphoma cases. H. pylori is a bacterium that colonizes the stomach lining and causes chronic gastritis. The persistent immune response it provokes drives the B cell expansion that eventually becomes lymphoma. The most clinically important implication of this relationship is that eradicating H. pylori with antibiotics can cause the lymphoma to regress — sometimes achieving complete remission without chemotherapy or radiation.

In the ocular adnexa, Chlamydophila psittaci — a bacterium transmitted by birds — has been identified as a potential triggering infection in some geographic regions, particularly in Europe. Similar to H. pylori in the stomach, treating the infection with doxycycline has led to lymphoma regression in some cases, though the association is less consistent than H. pylori in gastric disease.

In the salivary glands and thyroid gland, autoimmune conditions are the dominant predisposing factor. Sjögren’s disease (an autoimmune condition in which the immune system attacks the salivary and lacrimal glands) substantially increases the risk of salivary gland MALT lymphoma, and Hashimoto’s thyroiditis (an autoimmune condition affecting the thyroid) is strongly associated with thyroid MALT lymphoma. In both cases, the prolonged autoimmune-driven inflammation provides the chronic B cell stimulation that drives lymphoma development.

In the skin, Borrelia burgdorferi — the bacterium that causes Lyme disease — has been identified as a potential cause in some European cases.

In cases with no identifiable infectious or autoimmune trigger, the chronic inflammatory stimulus may be unknown. MALT lymphoma is not caused by lifestyle factors, and no dietary or environmental cause has been consistently identified.

How is the diagnosis made?

The diagnosis of MALT lymphoma requires tissue examination and cannot be made on imaging alone. A biopsy of the affected site is required, and the method depends on the location. For gastric MALT lymphoma, biopsies are taken during upper endoscopy — a procedure in which a flexible camera is passed through the mouth into the stomach, and small tissue samples are taken from the stomach lining. Multiple biopsies from different areas of the stomach are recommended to maximize the likelihood of detecting the lymphoma and to test for H. pylori. For ocular adnexal disease, an excisional or core needle biopsy of the involved tissue is performed. For salivary gland, thyroid, lung, or other sites, biopsy is tailored to the anatomical location.

The pathologist examines the biopsy tissue under the microscope and performs immunohistochemistry (IHC) to confirm the diagnosis and distinguish MALT lymphoma from other B cell lymphomas — particularly follicular lymphoma, CLL/SLL, and mantle cell lymphoma — that can look similar. For gastric MALT lymphoma, H. pylori testing is performed on the biopsy material as well, using special stains or immunohistochemistry.

In gastric and some other cases, FISH (fluorescence in situ hybridization) testing for specific chromosomal translocations — particularly t(11;18) — is performed because this result directly affects treatment planning (see the FISH section below). Once the diagnosis is established, CT or PET/CT imaging, blood tests, and occasionally bone marrow biopsy are used to determine the extent of disease and confirm that the lymphoma is localized.

What does MALT lymphoma look like under the microscope?

Under the microscope, MALT lymphoma has several characteristic features, though the appearance varies somewhat by site. The tumor is composed of small to medium-sized B cells with moderately abundant pale cytoplasm and slightly irregular nuclei. Pathologists describe these cells as having a centrocyte-like (resembling a type of normal germinal center B cell) or monocytoid appearance (resembling monocytes, with a characteristic clear, spacious cytoplasm).

The most diagnostically important microscopic feature is the lymphoepithelial lesion — a finding in which groups of three or more lymphoma cells infiltrate and partially destroy the epithelial structures of the organ (the lining cells of the stomach, salivary gland ducts, bronchial glands, or other glandular structures). When the pathologist identifies lymphoepithelial lesions, this is one of the strongest microscopic indicators of MALT lymphoma. The presence and number of lymphoepithelial lesions is often specifically noted in the pathology report.

A second important feature is follicular colonization — a process in which the lymphoma cells invade and fill the germinal centers of reactive lymphoid follicles (the normal immune structures present in the tissue), giving the appearance of lymphoma cells growing within what look like normal follicles. This can occasionally be confused with follicular lymphoma, and IHC is essential to distinguish the two.

Plasma cells (mature B cells that produce antibodies) are often seen at the edges of the tumor and sometimes in large numbers, because MALT lymphoma cells can undergo partial maturation toward a plasma cell-like state. Plasmacytic differentiation is particularly common in salivary gland and thyroid MALT lymphoma.

The background tissue typically contains reactive lymphocytes, scattered plasma cells, and sometimes eosinophils, reflecting the chronic inflammatory environment in which the lymphoma developed.

Immunohistochemistry results

Immunohistochemistry (IHC) is a laboratory test performed on the biopsy tissue. It uses specially prepared antibodies that attach to specific proteins in the cells and produce a visible color change under the microscope, allowing the pathologist to detect which proteins a cell is making. In MALT lymphoma, IHC serves two important purposes: it confirms that the lymphoma cells are B cells (rather than T cells or another cell type), and it compares the protein profile of the cells against other B cell lymphomas — such as follicular lymphoma, CLL/SLL, and mantle cell lymphoma — that can look similar under the microscope but require different treatment. Each result is reported as positive (the protein is present) or negative (the protein is absent). The combination of positive and negative results together establishes the diagnosis. The characteristic protein profile of MALT lymphoma is described below.

CD20 — Positive. Confirms B cell lineage. Also the target of rituximab, the antibody used in treatment.
CD79a and PAX5 — Positive. Additional pan-B cell markers confirming B cell origin.
IRTA1 and MNDA — Positive in approximately 75% of cases. These are markers that are relatively specific to marginal zone B cells and help confirm the marginal zone origin of the lymphoma. Their positivity helps distinguish MALT lymphoma from follicular lymphoma and other B cell lymphomas when morphology is ambiguous.
CD5 — Negative. CD5 is expressed in CLL/SLL and mantle cell lymphoma but not in MALT lymphoma. Its absence helps exclude both of those diagnoses.
CD10, BCL6 — Negative. CD10 and BCL6 are germinal center B cell markers expressed in follicular lymphoma. Their absence in MALT lymphoma is important for distinguishing MALT lymphoma from follicular lymphoma, particularly when follicular colonization creates a follicular-like pattern.
CD23 — Negative. Helps exclude CLL/SLL, which is characteristically CD23-positive.
Cyclin D1 — Negative. Cyclin D1 is the defining marker of mantle cell lymphoma and is absent in MALT lymphoma. Its absence excludes mantle cell lymphoma.
SOX11 — Negative. Another mantle cell lymphoma marker absent in MALT lymphoma.

FISH and molecular testing

FISH (fluorescence in situ hybridization) is a molecular test performed on the biopsy tissue that looks for specific changes in the chromosomes — the structures inside cells that carry DNA. Each cell normally has 46 chromosomes arranged in pairs. Sometimes a piece of one chromosome breaks off and attaches to a different chromosome, bringing two genes that are normally separate into an abnormal partnership; this is called a translocation. Translocations can permanently switch genes on or produce an abnormal protein that drives cancer cell growth. In MALT lymphoma, FISH is used to detect specific translocations that have been found in some cases. The results are clinically important because certain translocations directly affect which treatment is most likely to work, particularly whether antibiotic therapy alone is sufficient for gastric MALT lymphoma. Chromosomal changes detected by FISH are clinically important in MALT lymphoma, particularly for gastric disease. The most important translocation to test for is:

t(11;18)/API2-MALT1 — This is the most common chromosomal translocation in MALT lymphoma, present in approximately 15–40% of gastric cases and a higher proportion of pulmonary MALT lymphoma. It fuses two genes — API2 (also called BIRC3) on chromosome 11 and MALT1 on chromosome 18 — creating an abnormal protein that drives lymphoma cell survival independently of chronic antigen stimulation. The critical clinical implication is that gastric MALT lymphomas carrying this translocation almost never respond to H. pylori eradication therapy alone, even when H. pylori is successfully eliminated. A positive t(11;18) result in a gastric MALT lymphoma means that antibiotic therapy will not cure the lymphoma, and alternative treatment — typically radiation therapy or rituximab — will be required. For this reason, FISH for t(11;18) is routinely performed in gastric MALT lymphoma at most centers.

Other translocations that occur less frequently in MALT lymphoma include t(14;18)/IGH-MALT1, t(1;14)/BCL10-IGH, and t(3;14)/FOXP1-IGH. These are found in various sites and affect different organs with different frequencies. Complex karyotypes or multiple chromosomal abnormalities are rare in MALT lymphoma and, when present, may suggest a higher risk of transformation.

What is the difference between MALT lymphoma and nodal marginal zone lymphoma?

Despite their similar names, extranodal marginal zone lymphoma (MALT lymphoma) and nodal marginal zone lymphoma are distinct diseases that arise from the same cell type but in different locations and with different behaviors. MALT lymphoma arises in the tissues of organs (the stomach, salivary glands, lungs, etc.) and typically remains localized to its site of origin for many years. Nodal marginal zone lymphoma arises primarily within lymph nodes, tends to involve multiple lymph node groups, and is generally managed differently. Both are indolent lymphomas, but MALT lymphoma — particularly gastric MALT lymphoma — has the unique feature that it can sometimes be cured by treating the underlying infection, with no need for chemotherapy or radiation. This antibiotic-responsive behavior is specific to MALT lymphoma and does not apply to nodal marginal zone lymphoma.

Staging

MALT lymphoma is staged using the Lugano classification (modified Ann Arbor system), which is applied to the specific organ involved. Staging is based on CT or PET/CT imaging and is important for guiding treatment decisions. Most patients present with localized (stage I or II) disease, which is one of the reasons outcomes are generally excellent.

Stage I — The lymphoma is limited to a single extranodal site (one organ) without involvement of regional lymph nodes.
Stage II — The lymphoma involves one extranodal site with involvement of regional lymph nodes on the same side of the diaphragm, or extends to adjacent structures beyond the primary organ.
Stage III — Lymph node involvement on both sides of the diaphragm, with or without extranodal involvement.
Stage IV — Disseminated extranodal disease, or involvement of a distant organ such as the bone marrow or liver in addition to the primary site.

The majority of MALT lymphoma patients — approximately 70–80% — present with stage I or II disease. Advanced-stage (stage III or IV) disease is less common but does occur, particularly in salivary gland and thyroid MALT lymphoma, where bilateral involvement or multifocal spread is more frequent. Even advanced-stage MALT lymphoma often behaves indolently and may not require immediate treatment.

What is the prognosis?

The prognosis of MALT lymphoma is generally excellent, particularly for localized disease. Five-year overall survival rates exceed 85–90% for most patients, and many patients achieve complete and durable remission with treatment. Because the disease grows so slowly, many patients with advanced-stage disease who are asymptomatic can be managed with observation for extended periods without their quality of life being significantly affected.

Gastric MALT lymphoma has a uniquely favorable subset: H. pylori-positive cases without t(11;18) that are treated with antibiotic eradication therapy achieve complete histological remission in approximately 60–80% of cases, and many of these patients require no further treatment. Patients with t(11;18) or H. pylori-negative disease still have excellent outcomes with radiation or rituximab, but the antibiotic-alone approach is not effective.

The main long-term risk in MALT lymphoma is transformation to diffuse large B cell lymphoma (DLBCL) — a more aggressive lymphoma that requires intensive treatment. Transformation occurs in approximately 5–10% of patients over many years and is more likely in patients with complex chromosomal abnormalities. Transformed disease has a less favorable prognosis than de novo DLBCL, though it remains potentially treatable. If your pathology report mentions any large cell component or transformation, ask your care team what this means for your management.

What happens after the diagnosis?

Treatment for MALT lymphoma is highly site-dependent and takes into account the location, stage, H. pylori status, and the t(11;18) result where applicable.

For gastric MALT lymphoma that is H. pylori-positive and t(11;18)-negative, antibiotic eradication of H. pylori is the first treatment and can achieve complete remission without radiation or chemotherapy in the majority of patients. Standard eradication regimens use a combination of two antibiotics (typically clarithromycin and amoxicillin or metronidazole) plus a proton pump inhibitor for 10–14 days. After eradication is confirmed, repeat endoscopy with biopsies is performed at regular intervals (typically at 3 months and then every 6–12 months) to assess histological response. Full lymphoma regression can take up to 12–18 months after successful H. pylori eradication.

For gastric MALT lymphoma that is H. pylori-negative, t(11;18)-positive, or unresponsive to antibiotic therapy, involved-site radiation therapy — radiation directed at the stomach and nearby lymph nodes — is the standard approach for localized disease and achieves remission in approximately 95% of patients. Rituximab (an anti-CD20 antibody) is an alternative, particularly for patients who cannot receive radiation. Systemic chemoimmunotherapy is used for advanced-stage or refractory disease.

For ocular adnexal MALT lymphoma, low-dose involved-site radiation therapy is the standard treatment for localized disease and achieves excellent local control. In cases of Chlamydophila psittaci infection, confirmed by testing, doxycycline antibiotic therapy may be tried first. For bilateral or advanced disease, rituximab-based therapy is used.

For salivary gland and thyroid MALT lymphoma, localized disease is treated with involved-site radiation therapy or rituximab. When associated with Sjögren’s disease or Hashimoto’s thyroiditis, treating the underlying autoimmune condition does not reliably cause lymphoma regression; the lymphoma itself requires targeted treatment.

For pulmonary MALT lymphoma, localized resection (surgical removal) may be both diagnostic and curative for early-stage disease. Radiation therapy and rituximab are used for non-resectable or bilateral disease.

For advanced-stage MALT lymphoma that is asymptomatic, active surveillance (watch and wait) is often appropriate. When treatment is required, rituximab alone or in combination with mild chemotherapy (such as bendamustine-rituximab or chlorambucil) is typically well tolerated and effective.

Questions to ask your doctor

Which site does my MALT lymphoma arise from — stomach, eye, salivary gland, thyroid, lung, or another location?
Was H. pylori testing performed on my biopsy, and was the result positive or negative?
Was FISH testing for t(11;18) performed, and what was the result?
Were lymphoepithelial lesions identified in my biopsy?
What stage is my lymphoma — is it localized to the organ of origin, or has it spread?
If I have gastric MALT lymphoma and am H. pylori-positive without t(11;18), is antibiotic eradication the recommended first treatment?
If antibiotic therapy is tried, how will you monitor whether the lymphoma is responding, and how long does it take?
If radiation or rituximab is recommended, what are the expected side effects?
Is my lymphoma associated with an underlying autoimmune condition such as Sjögren’s disease or Hashimoto’s thyroiditis, and does that affect my treatment?
Is there a risk of transformation to a more aggressive lymphoma, and how will that be monitored?
How often will I need follow-up, and what tests will be done?
Are there clinical trials I should consider?