MALToma

What is MALToma?

Marginal zone B-cell lymphomas are cancers that occur when a certain type of white blood cell, known as B cells, start to grow uncontrollably in a specific area of the lymph tissue, called the marginal zone. Sometimes, these B cells can grow out of control in areas that are not typically associated with lymph tissue, like the lining of various organs in the body. This condition is called mucosa-associated lymphoid tissue (MALT) lymphoma, or more commonly, MALToma.

The stomach is most often affected by MALToma, but it can happen in other parts of the body, including the gastrointestinal tract, thyroid, salivary and lacrimal glands, lungs, lining of the joints and brain, breasts, skin, and eyes. MALToma appears equally in both men and women. However, it usually shows up in the gastrointestinal tract, kidneys, and skin in men, while it tends to occur in the thyroid, soft tissues, and skin in women.

What Causes MALToma?

The marginal zone, an area in our body’s immune system, contains special B cells that are changing due to exposure to germs. Sometimes, the body’s immune system can become overactive due to infection- or autoimmune disease-related reasons. This can lead to the creation of MALTomas, a kind of tumor related to the immune system. The basic idea behind the creation of these tumors is that constant inflammation concentrates B cells – a kind of white blood cell – in one area.

At first, it’s just a small number of cells that grow due to chronic inflammation. But over time, these cells start to multiply and change due to genetic mutations, shifting from a pattern of a single type of cell to a mixture of different types. This causes the creation of abnormal B cells in the marginal zone.

There are common genetic changes seen in MALTomas, such as:

* t(14;18)(q32;q21)
* t(11;18)(q21;q21)
* t(3;14)(p13;q32)
* t(1;14)(p22;q32)

Many of these genetic changes turn on a feature in the cell called nuclear factor-kappa B (NF-ΚB). NF-ΚB is like a survival switch for these abnormal B cells in the marginal zone, helping them to live longer.

Risk Factors and Frequency for MALToma

Marginal zone lymphoma is a type of non-Hodgkin lymphoma that is usually found outside the lymph nodes. This condition is quite uncommon, making up around 8% of all non-Hodgkin lymphoma cases. It typically affects adults, with the average age being 66 years at the time of diagnosis. The most common place for this lymphoma to be found outside the lymph nodes is the stomach. There are about 3.8 cases per 1,000,000 people per year. Meanwhile, the overall incident rate for this condition outside the lymph nodes is 18.3 per 1,000,000 people per year. Research has shown that the Black population tends to have this condition less frequently than the non-Hispanic white population.

• Marginal zone lymphoma is a rarer type of non-Hodgkin lymphoma that usually shows up outside the lymph nodes, making up about 8% of all non-Hodgkin lymphoma cases.
• The average age for those diagnosed with this condition is 66.
• The most common place for this type of lymphoma to occur outside the lymph nodes is in the stomach.
• The incidence rate in the stomach is around 3.8 cases per 1,000,000 people per year, and the overall rate for the condition occurring outside of the lymph nodes is 18.3 cases per 1,000,000 people per year.
• Studies have shown that this condition is less common among the Black population compared to the non-Hispanic white population.

Signs and Symptoms of MALToma

MALTomas, or Mucosa-associated lymphoid tissue lymphomas, are a type of cancer that can affect multiple organs. The symptoms people display can depend on which organs the disease has impacted. Here are just a few examples:

• Skin MALTomas: These can lead to the development of bumps or small rounded growths (nodules and papules) on the skin.
• Pulmonary (lung) MALTomas: This form could cause repeated respiratory infections.
• Stomach MALTomas: These might result in acid reflux, upset stomach, and hidden internal bleeding in the digestive tract.
• MALTomas in the small intestine: Symptoms can include occasional diarrhea, abdominal pain, and difficulty absorbing nutrients from food (malabsorption).
• Eye MALTomas: People may experience red eyes, excessive tearing, or vision impairment.
• Salivary gland MALTomas: These can cause one-sided or two-sided swelling of the salivary glands.

Moreover, some people may experience general symptoms such as low-grade fever, night sweats, fatigue, abdominal pain, and weight loss. However, these are not specific to MALTomas and occur in less than 5% of cases.

Testing for MALToma

Laboratory tests, like complete blood count and metabolic tests, are common parts of the evaluation process in diagnosing diseases, although they can’t provide a definitive diagnosis on their own. For cases possibly concerning splenic MALT (a type of cancer), testing for hepatitis B and C is crucial, since having these conditions can affect the course of the disease and its management.

Echocardiography, or a heart ultrasound, might be necessary in certain cases to monitor heart health, especially if the treatment plan includes chemotherapy medication that could potentially affect the heart. It’s also important for women of childbearing age to have a pregnancy test and to be given advice about fertility, as this is a key part of a comprehensive healthcare approach.

In the past, doctors used to rely on barium contrast studies, which is a type of X-ray, to detect MALTomas or cancers in the digestive tract. But this method wasn’t very reliable. Today, a newer technique called PET-CT (positron emission tomography–computed tomography) is often used. According to a particular study, this method was able to correctly identify MALToma in its early stages 42% of the time and was 100% effective for detecting it in the later, more advanced stages.

Still, for a definitive diagnosis of MALToma, a biopsy, which is a procedure where a small sample of tissue is removed and examined, is necessary. The biopsy helps doctors look for certain features that suggest MALToma, such as irregular cells that disrupt the normal structure of tissues. Immunophenotyping, a process that identifies and examines specific types of cells, is also done. It found that cells from MALTomas are usually positive for certain B-cell markers but negative for others.

Genetic analysis can also be carried out, revealing specific genetic changes that further confirm a MALToma diagnosis. Additionally, testing for H pylori, a bacterium linked with stomach ulcers and cancer, is important, particularly when stomach MALToma is suspected. This information helps decide on the best course of treatment. H pylori testing can be done through a biopsy during an endoscopy or with non-invasive tests like stool antigen testing or urea breath tests.

Treatment Options for MALToma

If you’ve been diagnosed with a specific type of tumor known as MALToma, the kind of treatment you’ll receive will depend on whether the tumor is located in your stomach (called gastric MALToma) or elsewhere (non-gastric MALToma).

For stomach-related MALToma that isn’t linked to a specific genetic condition – signified as “t(11;18)-negative” – and is caused by an H. pylori infection, antibiotics are the first course of treatment. However, if the MALToma is linked to the genetic condition, not caused by H. pylori infection, or antibiotics didn’t work, then radiotherapy or medical therapies may be recommended instead.

We know from studies that for H. pylori-caused stomach MALToma, a whopping 80% of patients completely respond to antibiotics. Radiotherapy treatments can often achieve an even higher rate of success but come with a higher risk of long-term side effects. Surgery to remove part or all of the stomach is typically only used if the tumor is causing complications like bleeding, a hole in the stomach, or blockages. However, surgery comes with higher risk of problems and potential for the tumor to come back compared to radiotherapy.

For MALTomas located outside of the stomach, the preferred treatment is usually up-front radiotherapy. However, if a chronic bacterial infection – like Chlamydia psittaci – is suspected to be the cause of the MALToma (in cases where the tumor is affecting the tissue near the eye, for example), antibiotics may be the first course of treatment. Over 90% of patients have seen their non-stomach MALTomas completely respond to radiotherapy. When radiotherapy might cause unacceptable side effects or the disease is advanced, medical treatments may be recommended. Some patients may be treated with rituximab, a medication which works by affecting the immune system, alone or in combination with chemotherapy.

Combining rituximab with chemotherapy may improve treatment outcomes for some patients but doesn’t always increase overall survival, and can increase side effects. Patients with less severe symptoms might be started on rituximab alone. If the disease doesn’t respond, or for patients with severe symptoms or larger tumors, or for those who want to delay the need for further treatment as long as possible, combining treatments may be an option. Common treatment combinations with rituximab include rituximab plus bendamustine or rituximab plus a combination of chlorambucil, vincristine, and prednisone. In rare cases, surgery might be recommended for MALTomas affecting certain areas like the small bowel, lung, breast, and thyroid.

What else can MALToma be?

When doctors are making a diagnosis for a disease known as MALToma, they need to consider several other potential conditions that might seem similar. These include:

• Reactive lesions: These are different because they typically maintain normal organization in the cells of the organ’s lining.
• Splenic marginal zone lymphoma: This could be the diagnosis if there are similar types of tumors which have spread to involve the spleen.
• Nodal marginal zone lymphoma: This is another possibility when similar types of tumors have spread to involve the lymph nodes in a widespread way.
• Mantle cell lymphoma: This condition is also a type of tumor originating in B cells, the white blood cells that make antibodies, but it expresses a marker called CD5, differentiating it from MALToma.
• Follicular lymphoma: This is another type of tumor originating in B cells, but it expresses a marker called CD10 and has changes in the 14th and 18th chromosomes involving the BCL2 gene.
• Diffuse large B-cell lymphoma: Both diffuse large B-cell lymphoma and MALToma are types of tumors originating in B cells, but the former often grows more quickly and has a worse prognosis. Doctors can usually tell it apart from MALToma by observing the size of the tumor cells, as they have larger cell size and their nuclei are about twice the size of a small lymphocyte (a type of white blood cell).

These possible conditions are all factors the doctor will take into consideration when conducting tests and making a final diagnosis for MALToma.

Surgical Treatment of MALToma

MALTomas are a type of cancer that can develop in different organs like the thyroid, lung, colon, small bowel, and breast. The main treatment for MALTomas is usually not surgery; instead, doctors typically rely on other methods like radiation treatment or chemotherapy. However, in certain instances and for some types of MALTomas, surgery might be considered. The decision to choose surgery isn’t just about treating the disease; it can also help in diagnosing the condition.

When looking at past data, there wasn’t any noticeable difference in the survival rates after 10 years among patients who had had surgery and patients who had had radiation or chemotherapy treatments for their gastric MALTomas (a type of MALToma that affects the stomach). As for non-gastric MALTomas (those that occur in other organs outside the stomach), the evidence supporting surgery is mostly derived from individual patient stories and small groups of cases.

In retrospective analyses—looking back at previous patients’ records—patients with MALTomas in the lungs that were treated with surgery alone had a 97% remission rate, meaning that their cancer had improved or disappeared. Similarly, surgery on thyroid MALTomas showed very high relapse-free survival rates of over 95% in a Japanese patient group. This means that the likelihood of the cancer coming back was very low and compared well with those treated with radiation therapy to the specific site of the disease.

However, because these findings come from a relatively small number of patients, researchers recognize the need for additional studies to confirm these results.

What to expect with MALToma

People diagnosed with a type of cancer called MALToma often live more than 10 years after their diagnosis. There’s a new tool called MALT-IPI that healthcare professionals use to predict how likely the disease is to get worse. They consider three important factors: whether a patient is 70 years old or older, if a specific enzyme in the blood called lactate dehydrogenase is higher than normal, and if the disease is at stage III or IV. The more a patient has of these risk factors, the lower their likelihood of survival.

If a person doesn’t have any of these risk factors, they have approximately a 99% chance of living for 5 more years. One risk factor means that they are at an intermediate risk and have around a 93% chance of surviving for 5 more years. Two or more risk factors mean that they are at a high risk and their chance of surviving for 5 more years is around 64%. The patient’s age and overall health can also affect their prognosis.

Sometimes, MALToma gets worse and changes into a more aggressive form of cancer known as high-grade lymphoma. Factors that influence this progression include the cancer spreading to more than 4 lymph nodes, unusually high levels of lactate dehydrogenase, and if the cancer doesn’t go away completely after initial treatment. Patients whose cancer has transformed generally have a lower chance of surviving for 5 more years.

Prognosis also depends on how advanced the cancer is. People with lower-grade tumors can often live a long time. However, curing patients with advanced MALToma can be harder. It’s estimated that between 77% to 80% of MALToma patients will stay free of disease. For patients with a type of cancer called marginal zone lymphomas, those in stage I have around an 80% 5-year survival rate. Stage II patients have about a 75% survival rate. Stage III patients have a greater than 50% survival rate, and those in stage IV have approximately a 65% survival rate.

Possible Complications When Diagnosed with MALToma

The complications from MALToma, a type of lymphoma, are usually specific to each organ it affects. About 30% of patients with MALToma in the stomach, and half of the patients with MALToma outside of the intestines, might have the disease occurring in another organ. This could result in the disease coming back after initial treatment.

In some instances, MALTomas may develop into a more aggressive type of lymphoma known as diffuse large B-cell lymphoma, which can lower the chances of recovery and survival.

Complication of MALToma:

• Usually specific to the organ it affects
• Possible occurrence in more than one organ
• Potential for the disease to return after treatment
• Possible transformation into a more aggressive type of lymphoma
• Lower chances of recovery and survival due to possible transformation

Preventing MALToma

For patients with a type of stomach tumor called gastric MALTomas, regular check-ups are essential. People who originally tested positive for a bacteria called H pylori, it’s very important to make sure the bacteria has been completely eradicated or destroyed. Doctors can test this by using a non-invasive method four weeks after the patient’s antibiotic treatment is completed. The methods used include a stool antigen test or a test that measures the amount of urea in your breath.

Most of the time, patients get rid of the H pylori bacteria after a single treatment. However, a small amount of people may need a second treatment regimen to completely get rid of the infection without showing signs of lymphoma, a type of cancer. Usually, a procedure called an endoscopy, which uses a small camera to view inside the body, along with a biopsy, is performed at 3 months. In some cases, if symptoms persist, this evaluation may need to be done earlier.

A complete healing from the therapy could happen as early as 3 months, but it might take up to 18 months. If patients show signs that the disease is getting worse at any stage, or if symptoms persist with the disease even after 12 to 18 months, they should be evaluated for another course of therapy. Regular scanning is usually not necessary unless the doctor recommends. According to guidelines from the National Comprehensive Cancer Network (NCCN), it’s usually recommended that these patients should have follow-ups every 3 to 6 months for the first 5 years after treatment, then once a year, regardless of the H pylori status.

For patients with MALTomas that are not in the stomach, the ideal frequency of follow-ups isn’t well-defined. As these tumors can sometimes come back after a long time, it’s recommended to monitor them for several years, ideally throughout their lifetime. As with gastric MALTomas, the NCCN guidelines suggest follow-ups every 3 to 6 months for the first 5 years, switching to once a year afterwards. These follow-up visits might involve physical examinations, scans, and diagnostic tests.