MALT Lymphoma of the Stomach: Understanding Your Pathology Report

Editor de sección: David Driman
11 de noviembre.

MALT lymphoma of the stomach is a slow-growing cancer and a type of no linfoma de Hodgkin. It starts in the stomach and develops from immune cells called Células B. Its full name is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, and MALT is short for mucosa-associated lymphoid tissue. Your report may use either name, and some reports call it gastric MALT lymphoma.

The stomach is the most common site for MALT lymphoma to develop. In many people, the lymphoma is linked to a long-lasting stomach infection with a bacterium called Helicobacter pylori (H. pylori). When this infection is treated with antibiotics, the lymphoma often shrinks and disappears. This article explains what MALT lymphoma of the stomach is, how it is diagnosed, and what the findings in your pathology report mean.

MALT lymphoma can also start in other parts of the body, such as the eye area, lung, salivary gland, or thyroid. For lymphoma in those places, see our article on extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

What causes MALT lymphoma of the stomach?

Most cases of MALT lymphoma of the stomach start with a long-lasting H. pylori infection. The healthy stomach lining normally contains very few immune cells. When H. pylori infects the stomach, the body sends large numbers of immune cells, including B cells, into the lining to fight the bacteria. This causes Gastritis por Helicobacter, a type of long-lasting inflamación.

Over many years, the constant stimulation from the bacteria can cause one B cell to develop genetic changes and grow out of control. In the early stages, these lymphoma cells still depend on bacteria-triggered signals to keep growing. This is why removing the infection with antibiotics can make the lymphoma go away. About two out of three cases are linked to H. pylori. In the remaining cases, the lymphoma cells have developed genetic changes that allow them to grow without the bacteria.

What are the symptoms of MALT lymphoma of the stomach?

The symptoms of MALT lymphoma of the stomach are often mild and similar to those of gastritis or a stomach ulcer. Some people have no symptoms, and the lymphoma is found during an endoscopy done for another reason.

Indigestion or upper abdominal pain. This is the most common symptom and often lasts for months before diagnosis.
Nausea or feeling full quickly. Some people feel full after eating only a small amount of food.
Hemorragias y anemia. The lymphoma can cause slow bleeding from the stomach lining, which can lead to anemia y cansancio.
Pérdida de peso. Weight loss, fevers, and night sweats are uncommon because the lymphoma grows slowly.

¿Cómo se hace el diagnóstico?

MALT lymphoma of the stomach is usually diagnosed after an upper endoscopy. During this procedure, a doctor passes a thin, flexible tube with a camera through the mouth to look at the inside of the stomach. The lymphoma may look like gastritis, an erosión, un úlcera, thickened folds, or a small mass. Because the lymphoma can be patchy, the doctor usually takes many biopsias from both abnormal and normal-looking areas.

A patólogo then examines the tissue under a microscope. The diagnosis usually needs additional tests, including immunohistochemistry and sometimes molecular testing. These tests help distinguish MALT lymphoma from the large numbers of normal immune cells present in gastritis.

What does MALT lymphoma of the stomach look like under the microscope?

Under the microscope, MALT lymphoma of the stomach is made up of sheets of small to medium-sized B cells. These cells fill the lámina propia, the tissue that supports the glands in the stomach lining, and push the normal glands apart. Some lymphoma cells have pale cytoplasm, and others resemble Células de plasma. Normal-looking immune cell clusters with centros germinales are often scattered among the lymphoma cells.

A key feature that pathologists look for is the lymphoepithelial lesion, which forms when lymphoma cells invade and damage the glands of the stomach lining. These lesions are an important clue because they are much more common in lymphoma than in gastritis.

In some cases, the lymphoma grows deeper into the stomach wall, reaching the submucosa o el muscular propia. A small biopsy usually shows only the lining, so clinicians often measure the lymphoma’s depth with an endoscopic ultrasound rather than from the pathology report.

Inmunohistoquímica

Inmunohistoquímica is a test that uses antibodies to show which proteins are present in cells. For MALT lymphoma of the stomach, it confirms that the abnormal cells are B cells and helps rule out other types of lymphoma. Your report may describe the following results.

CD20, CD79a, and PAX5. The lymphoma cells are positive for CD20, CD79a, y PAX5. These markers confirm that the cells are B cells.
CD3. CD3 highlights the normal las células T mixed in with the lymphoma. The lymphoma cells themselves are negative for this marker.
CD5, CD10, and cyclin D1. The lymphoma cells are negative for CD5, CD10, y ciclina D1. These results help rule out other small B cell lymphomas, such as mantle cell lymphoma and follicular lymphoma.
Cytokeratins. A cytokeratin stain highlights the glands of the stomach lining, making lymphoepithelial lesions easier to see.
Kappa and lambda. Each B cell makes only one type of antibody light chain, either kappa or lambda. When most plasma cells make only one type, the result is called light chain restriction, which supports a diagnosis of lymphoma.
Ki-67. Ki-67 shows how many cells are dividing. It is usually low in MALT lymphoma because the lymphoma grows slowly.

Helicobacter pylori

Pathologists look for H. pylori in every biopsy showing MALT lymphoma of the stomach because the result guides first-line treatment. The bacteria can sometimes be seen on routine slides, but many pathologists also use a mancha especial or an immunohistochemistry test to make the bacteria easier to find. If no bacteria are seen in the biopsy, your doctor may order a breath test, stool test, or blood test to check for the infection in another way.

Pruebas moleculares

Molecular tests look for genetic changes inside the lymphoma cells. Two tests are commonly used for MALT lymphoma of the stomach.

Testing for t(11;18). About 25% of MALT lymphomas of the stomach have a translocación called t(11;18), in which pieces of chromosomes 11 and 18 swap places. This change joins two genes, API2 y MALT1, and allows the lymphoma to grow without H. pylori. pylori. It is usually found with hibridación fluorescente in situ (FISH). Lymphomas with this change rarely respond to antibiotics alone so that doctors may move to other treatments sooner.
B cell clonality testing. Esta prueba utiliza reacción en cadena de la polimerasa (PCR) to check whether the B cells all come from a single parent cell. A single family of B cells, called a clonal population, supports a diagnosis of lymphoma. Pathologists use this test when the findings under the microscope fall between gastritis and lymphoma.

Large B cells

MALT lymphoma of the stomach is made up mostly of small cells, but a few scattered large B cells are normal for this disease. If the large cells form solid sheets, the pathologist will diagnose linfoma difuso amplio de células B, a faster-growing lymphoma that needs different treatment. It can develop from MALT lymphoma, and it can also be found at the same time in a different part of the stomach. Earlier studies found this change in about 2% to 5% of people with MALT lymphoma of the stomach.

Staging

Staging describes how far the lymphoma has spread. For lymphoma that starts in the stomach or bowel, doctors usually use the Lugano staging system. Staging is based on endoscopic ultrasound, CT or PET scans, and sometimes a bone marrow biopsy, rather than on the pathology report alone.

Estadio I. The lymphoma is found only in the stomach wall. Most people with MALT lymphoma of the stomach are diagnosed at this stage.
Estadio II. The lymphoma has spread to ganglios linfáticos in the abdomen, either near the stomach or farther away.
Etapa IIE. The lymphoma has grown through the stomach wall into a nearby organ or tissue.
Estadio IV. The lymphoma has spread to organs outside the abdomen or to lymph nodes above the diaphragm.

How is MALT lymphoma of the stomach treated?

Treatment for MALT lymphoma of the stomach depends on the lymphoma stage and whether H. pylori is present. The 2020 European Society for Medical Oncology (ESMO) guidelines recommend treating H. pylori as the first step for all people with MALT lymphoma of the stomach, regardless of stage.

Antibióticos. Treatment usually involves a combination of antibiotics and an acid-reducing medication taken for about two weeks. Your doctor will check that the infection is gone at least four weeks after treatment. About 60% to 80% of people with early-stage lymphoma and H. pylori infection have a complete response to antibiotics alone.
Terapia de radiación. Radiation is used when the lymphoma does not go away after the infection is cleared, or when H. pylori is not present. A low dose of radiation is given to the stomach over three to four weeks, and it controls the lymphoma in most people.
Medications for advanced disease. If the lymphoma has spread widely, treatment usually includes rituximab, an antibody drug that targets CD20 on the lymphoma cells. Rituximab is sometimes combined with chemotherapy for people with larger amounts of disease.
Cirugía. Surgery to remove the stomach is no longer a standard treatment for MALT lymphoma. It is now reserved for rare complications such as severe bleeding.

Follow-up biopsies after treatment

After treatment for MALT lymphoma of the stomach, you will have repeat endoscopies with biopsies to check how the lymphoma is responding. These are usually done 2 to 3 months after treatment, then at least twice a year for 2 years. Response to antibiotics can be slow, and complete remission may take a year or longer.

Many pathologists describe the findings on follow-up biopsies using the GELA grading system. GELA stands for Groupe d’Etude des Lymphomes de l’Adulte, the French lymphoma research group that developed it. Your report may use one of the following four categories.

Complete histological remission. No lymphoma is seen on biopsy, and only a few normal immune cells remain in the stomach lining.
Probable minimal residual disease. Small clusters of immune cells remain, but no lymphoepithelial lesions are seen. Doctors usually treat this result as complete remission and continue to monitor.
Responding residual disease. Lymphoma is still present, but signs suggest it is shrinking, such as empty spaces and scarring in the lining. This usually means the lymphoma is still responding, and more time may be all that is needed.
Ningún cambio. The lymphoma looks the same as it did before treatment. If this result continues over time, your doctor may recommend radiation or another treatment.

What is the outlook for a person with MALT lymphoma of the stomach?

The outlook for a person with MALT lymphoma of the stomach is very good. Most people are diagnosed early, and the lymphoma usually responds well to antibiotics, radiation, or both. Most people remain well for many years after treatment. The lymphoma can return years later, which is why regular endoscopy is important even after complete remission.

The long-lasting gastritis caused by H. pylori also slightly increases the risk of developing stomach adenocarcinoma later in life. Follow-up endoscopies help your doctors monitor this risk as well.

Preguntas para hacerle a su médico

¿Fue H. pylori found in my stomach, and how will it be treated?
Was my lymphoma tested for t(11;18), and what was the result?
Were any sheets of large B cells seen in my biopsies?
What stage is my lymphoma, and what tests are needed to find out?
How will we know if the antibiotics have worked?
When will I need my next endoscopy and biopsies?
What happens if the lymphoma does not go away after antibiotics?
Should I see a hematologist or radiation oncologist?

Linfoma MALT del estómago: cómo entender su informe de patología.