Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent, or slow-growing, type of non-Hodgkin lymphoma (NHL). It originates outside the lymph nodes and is the most common form of marginal zone lymphoma, often developing in the lining of various organs. This slow growth is reflected in its favorable long-term outcomes.
Defining MALT Lymphoma and Associated Risk Factors
MALT lymphoma develops from B-cells within the mucosa-associated lymphoid tissue, a collection of immune cells that forms in response to chronic inflammation. It is classified as an extranodal lymphoma because it starts in the tissue lining organs rather than in the lymph nodes. The stomach is the most frequent location, known as gastric MALT lymphoma, but it can also affect the lungs, salivary glands, thyroid, skin, and tissues around the eye.
The development of MALT lymphoma is strongly linked to chronic immune stimulation, often caused by persistent infections or autoimmune conditions. The most established example is the association between gastric MALT lymphoma and the bacterium Helicobacter pylori (H. pylori). This bacterium causes long-term inflammation in the stomach lining, which creates the necessary environment for the lymphoma to develop.
Other infectious agents and autoimmune diseases are implicated in MALT lymphomas at non-gastric sites. For instance, Borrelia burgdorferi, the bacterium responsible for Lyme disease, has been linked to MALT lymphoma of the skin. Autoimmune disorders such as Sjögren’s syndrome and Hashimoto’s thyroiditis are associated with MALT lymphoma in the salivary glands and thyroid, respectively. The chronic inflammation these conditions produce acts as a persistent stimulus, promoting the uncontrolled growth of B-cells.
The Diagnostic Process and Disease Staging
Diagnosis of MALT lymphoma typically begins with a tissue biopsy from the affected organ, often obtained via endoscopy for the stomach lining. Pathologists examine the biopsy using specialized techniques like immunohistochemistry to confirm the presence of characteristic B-cells and rule out other types of lymphoma. A specific finding in gastric MALT is the “lymphoepithelial lesion,” where the malignant lymphocytes invade the epithelial lining of the glands.
Once the diagnosis is confirmed, the extent of the disease must be determined through staging. The Lugano Classification, a modification of the Ann Arbor staging system, is commonly used to assess the spread of the lymphoma. Staging procedures involve imaging tests, such as computed tomography (CT) or positron emission tomography (PET) scans, of the chest, abdomen, and pelvis. An endoscopic ultrasound may also be performed for gastric MALT to determine the depth of the tumor’s invasion into the stomach wall.
The staging system categorizes the disease from Stage I, representing localized disease within a single extranodal site, up to Stage IV, indicating widespread disease involving distant organs or multiple sites. For gastric MALT lymphoma, staging often uses a modified classification that specifies the depth of involvement, such as whether the disease is limited to the mucosa and submucosa (Stage IE1) or has extended to regional lymph nodes (Stage IIE1). Determining the stage is important because localized disease typically responds better to less intensive treatments and carries a better prognosis.
Primary Treatment Modalities
Treatment for MALT lymphoma is individualized and depends primarily on the site of origin, the stage, and whether an underlying infection is present. For localized gastric MALT lymphoma that tests positive for H. pylori, the first line of therapy is antibiotic eradication of the bacterial infection. Successful elimination of H. pylori can lead to complete remission of the lymphoma in the majority of early-stage cases.
For cases that do not respond to antibiotics, are not associated with an infection, or involve non-gastric sites, localized therapy is often employed. Radiation therapy (RT) is highly effective for localized MALT lymphoma, including cases in the stomach, orbit, and salivary glands. This approach uses a moderate dose of radiation, often around 30 Gray, which is well-tolerated and achieves a high rate of local control and cure.
Systemic therapy is generally reserved for more advanced stages (Stage III or IV), widespread disease, or cases that have relapsed after local treatment. This typically involves immunotherapy, often using a monoclonal antibody like rituximab, which targets the CD20 protein on B-cells. Chemotherapy, sometimes combined with immunotherapy, may be used for patients with more aggressive features or for those with advanced, symptomatic disease. In very localized, asymptomatic cases, particularly in non-gastric sites, a “watchful waiting” approach may be used due to the disease’s indolent nature.
Understanding Survival Rates and Prognostic Factors
MALT lymphoma is characterized by one of the most favorable outlooks among all non-Hodgkin lymphomas due to its high responsiveness to treatment. The 5-year overall survival (OS) rate for MALT lymphoma patients is generally very high, often exceeding 85% to 90%. Studies focusing on gastric MALT lymphoma, for instance, have reported 5-year overall survival rates as high as 97.7%.
The prognosis is often measured using the 5-year relative survival rate, which compares the survival of MALT lymphoma patients to that of the general population. Data indicates that many subgroups, particularly those with localized (Stage I) disease of gastric or skin origin, have a survival rate nearly comparable to that of the age-matched healthy population. This prognosis is supported by the low lymphoma-specific mortality rate, which has been observed to be around 4% at 10 years.
Several specific factors influence an individual’s long-term outcome. The stage at diagnosis is a primary element, with limited-stage disease (Stage I or II) having a significantly better prognosis than advanced-stage disease. Age also plays a role, as older patients are more likely to die from non-lymphoma causes, which can lower the overall survival statistics.
The site of the lymphoma is another major factor; gastric MALT lymphoma has a better outcome due to the high success rate of antibiotic eradication therapy. Specific genetic markers, such as the translocation t(11;18), are associated with resistance to antibiotic treatment and may indicate a less favorable course, though this primarily affects the choice of initial therapy. The MALT-IPI (International Prognostic Index) is a tool that incorporates factors like age, stage, and elevated lactate dehydrogenase (LDH) levels to help predict the risk of a less favorable outcome.