Malt lymphoma of the salivary glands is successfully treated. MALT lymphoma: causes, treatment methods and prognosis

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Symptoms of MALT lymphoma of the stomach: treatment methods and prognosis

MALT lymphoma of the stomach is a tumor that affects the lymphoid tissues of the gastric mucosa. It is a non-painful neoplasm that arises in the stomach and spreads to the gastrointestinal tract and lymph nodes. The abbreviation MALT stands for mucosa-associated lymphoid tissue - lymphoid tissue associated with the mucous membrane.

MALT lymphoma is a type of non-Hodgkin lymphoma, and accounts for about 8% of cases of this type of formation.

Women are most susceptible to this disease. The average age of patients is 61 years.

Symptoms

In the early stages of development, MALT lymphoma of the stomach shows few symptoms, or they are similar to the manifestations of peptic ulcer disease or gastritis.

The patient may exhibit the following symptoms:

• rare pain in the stomach (aching);
• belching, heartburn, vomiting;
• stomach bleeding;
• rapid onset of satiety when eating;
• increased body temperature, sweating in the evening and at night;
• psychophysiological exhaustion;
• weight loss;
• an increase in the size of the lymph nodes in the armpits, neck, and groin.

Enlarged lymph nodes initially retain mobility and elasticity, and the nodes merge into a conglomerate. MALT lymphoma of the gastric mucosa may be similar in its manifestations to gastric cancer.

Symptoms indicating a tumor neoplasm are quite rare.

Diagnostics

Nonspecific symptoms of MALT lymphoma warrant investigation. Often the first step is endoscopic examination. It reveals foci of ulcers, erosions, edema, hyperemia - changes in the mucous membrane typical for peptic ulcers and gastritis.

Suspicion of MALT lymphoma arises when solid structures that are atypical for other diseases of the gastric mucosa are identified. In this case, a biopsy is performed. Biological material is subject to immunomorphological examination.

Then an additional examination of the gastrointestinal tract is performed using fibrogastroduodenoscopy. During this procedure, biological material is collected from all areas of the stomach, gastroesophageal junction, duodenum and any other area that causes suspicion.

An endoscopic ultrasound examination is performed to visually assess the lymph nodes, as well as determine the extent of damage to the stomach walls by lymphoma.

Laboratory research methods include biochemical and clinical blood tests, including tests to determine the level of lactate dehydrase and β2-microglobulin; serological test for Helicobacter pylori; stool analysis for Helicobacter pylori.

This gastric lymphoma is also diagnosed using computed tomography and magnetic resonance imaging of the pelvic organs, abdomen and chest.

As additional studies, cytogenetic and immunohistochemical analysis is carried out using fluorescence in situ hybridization and polymerase chain reaction.

It is necessary to carry out differential diagnosis with gastritis associated with Helicobacter pylori. Gastric lymphoma is characterized by a high-density lymphoid infiltrate, which occupies a significant part of the collected biological material; significant lymphoepithelial lesions; lymphoid cells with moderate cellular atypia.

Stages

MALT lymphoma on the gastric mucosa has 4 stages of development:

Stage 1. The tumor process occurs in the gastrointestinal tract, and it is limited to the mucous layer. Then it is transferred to the serous, subserous and muscular layers.

Stage 2. In addition to the stomach, the process spreads to neighboring organs and abdominal, paragastric lymph nodes.

Stage 3. The pathological process affects the mesenteric, paracaval, para-aortic, iliac and pelvic lymph nodes. Penetration of the process into neighboring tissues and organs.

Stage 4. Damage to extralymphatic organs of a diffuse or disseminated nature. Damage to the gastrointestinal tract with involvement of the supradiaphragmatic lymph nodes in the pathological process.

Treatment

In the case of the initial stages of malt lymphoma and the presence of Helicobacter pylori, the main therapy is aimed at eradicating the bacterium. According to clinical studies, remission of lymphoma occurs in 80% of clinical cases (at stage 1 of development). Long-term observation of patients showed that 90% of them overcome the five-year survival barrier; 80% had complete remission. Relapse of the disease occurred in only 3% of clinical cases. At the second stage of the disease, remission occurs in 40% of patients.

The choice of a specific eradication scheme is made in each case individually, taking into account the sensitivity of the bacterial strains and the patient’s sensitivity to the drugs used. The following drugs are used to combat the bacterium: proton pump inhibitors, Amoxicillin, Clarithromycin, Josamycin, Nifuratel, Furazolidone, Bismuth tripotassium dicitrate, Metronidazole, Tetracycline, Rifaximin.

In case of negative tests for Helicobacter pylori (approximately 10% of cases of malt lymphoma), as well as in the absence of a positive result after undergoing antibiotic therapy, the following methods are used:

• surgical intervention;
• radiation therapy;
• chemotherapy.

Radiation therapy is an effective treatment for malt lymphoma. It provides local control of tumor growth and potential cure in the initial stages. However, the disadvantage of the procedure is that a large area is exposed to radiation. When carrying out radiation therapy, effects on the kidneys and liver should be excluded. According to research statistics, gastric lymphoma responds positively to radiation treatment. Radiation therapy shows a positive effect in more than 90% of clinical cases.

Chemotherapy is indicated in cases resistant to antibacterial and radiation therapy. This therapy uses various regimens: with alkylating agents (cyclophosphamide, melphalan, chlorambucil), with anthracyclines (daunomycin, idarubicin, doxorubicin), with prednisolone and mitoxantrone, with purine nucleoside analogs (cladribine, fladarabine). Gastric lymphoma at the first stage of development can be treated with chemotherapy in more than 80% of cases, at the fourth stage - in 50-60% of cases.

Surgery is not considered an effective treatment for malt lymphoma. Previously, it was the standard method used for these lymphomas. However, more than 50% of those operated on experienced complications after surgery (including death), and the survival rate within 5 years after the procedure was only 60%. Surgery is necessary in case of extensive tissue damage. Gastric resection may be required. Initiation of therapy at subsequent stages shows lower survival rates.

Drug monotherapy with the drug Rituximab is also used. Studies have shown that this remedy gives a positive effect in 70% of cases, and complete remission in 45% of cases among patients in the initial stages of the disease and without Helicobacter pylori.

You should not treat lymphoma yourself with folk remedies, as this can be fatal.

Forecast

An unambiguous prognosis for malt lymphoma is impossible. The result of therapy depends on the stage of development of the formation, the individual characteristics of the patient’s body and the correct choice of course of therapy.

When treatment is started in the first stages of the disease, the prognosis is favorable in most cases. Drug treatment, radiation and chemotherapy show more than 90% survival rate in the five-year period after therapy. Delayed initiation of treatment reduces the chances of a positive effect and remission.

After completing the course of therapy, it is necessary to regularly undergo endoscopic examination of the stomach with the collection of biomaterial for research. The first such examination should be 2-3 months after the end of therapeutic measures. Subsequently, endoscopic examinations should be performed twice a year for several years.

Experts identify many types of lymphomas. They differ not only in the degree of malignancy, but also in localization and further prognosis. One form of the disease is malt lymphoma, which most often affects the gastric mucosa.

General information about the disease

Malt lymphoma belongs to a class of malignant diseases in which the pathological process affects the cells of the lymphatic system. The pathology is also called maltoma.

Inflammation is most often found in the stomach area, but can also be localized in other parts of the body. Based on research results, it has been established that the disease is diagnosed more often in elderly patients, mainly in women. Among all non-Hodgkin's lymphomas, maltoma ranks third.

But, despite many studies, specialists were unable to obtain complete information about the disease and its molecular genetic features.

The danger of the disease is that the pathological process can quickly spread to neighboring and distant organs. Diagnosis in the initial stages is difficult, since there are practically no signs of pathology.

Classification

Malt lymphoma is divided depending on the location of the pathological process. The disease is also classified according to the stage of development of the disease.

Stage 1

Inflammation affects only one area or organ. Located outside the nodes of the lymphatic system.

Signs of pathology are practically absent, which greatly complicates the diagnosis.

Stage 2

The pathological process affects only one organ or area, the lymph nodes on one side of the diaphragm.

Symptoms of the disease become more intense, which forces patients to consult a specialist.

Stage 3

The pathological process affects tissues located on both sides of the diaphragm. It can also spread to distant lymph nodes and the spleen.

Stage 4

It is the most dangerous stage of disease development. Signs of pathology are clearly expressed, patients complain of pain.

It is difficult to cure the disease at stage 4. To achieve remission, complex treatment is used.

Localization

Maltoma most often affects the stomach tissue. This localization of inflammation is observed in more than half of the cases of lymphoma.

But the pathological process can affect the thyroid gland, liver tissue, lungs, conjunctival area, respiratory tract and chest. Symptoms appear depending on the location of the inflammation.

Causes

The exact causes of maltoma have not been established. It is believed that the main cause of the development of the pathological process in the stomach area is bacteria of the Helicobacter pylori type.

Experts have also identified a number of unfavorable factors that influence the occurrence of the disease. These include exposure to chemicals and toxic substances, smoking, drinking alcohol, and infectious diseases. Maltoma can be caused by stomach diseases such as ulcers and gastritis.

Genetic predisposition is of particular importance. Many patients had close relatives who also suffered from similar diseases.

Clinical picture

The intensity of symptoms depends on the stage of development of the pathology. In addition, signs appear in accordance with the localization of the pathological process.

Most often, patients complain of pain in the stomach, spleen, liver or upper respiratory tract. Usually they are aching in nature.

Common symptoms also include vomiting, belching, increased body temperature, and increased sweating, mainly at night. There is a rapid onset of a feeling of fullness when eating.

As the pathological process spreads, gastric bleeding may occur, and patients experience psycho-emotional exhaustion.

Lymph nodes enlarge in the armpits, groin and neck. Pain may occur during palpation examination. The affected lymph nodes are elastic and mobile in the initial stages.

It is noted that in the last stages of development of maltoma, in which the lesion affects the tissues of the stomach, the disease is similar in its symptoms to cancerous damage to the organ.

There are practically no signs that indicate the presence of a neoplasm. As a result, patients turn to a specialist late.

Diagnostic methods

If the development of maltoma is suspected, the doctor conducts an examination and studies the patient’s medical history. In order to establish an accurate diagnosis and determine the course of therapy, instrumental and laboratory research methods are prescribed.

A blood test allows you to get a complete picture of the pathology. The study is prescribed to determine changes in the composition and presence of tumor markers.

The patient is also prescribed MRI, CT, and ultrasound. The techniques allow us to establish the localization and extent of spread of the pathological process.

A biopsy is also used to obtain images of changed tissue. The biopath is sent for cytological examination, which makes it possible to determine the presence of cancer cells.

Treatment methods

When maltoma is diagnosed, treatment is primarily aimed at eliminating bacteria such as Helicobacter pylori. According to studies, it has been established that the probability of remission after therapy is about 80%.

If treatment was started at the first stage of development of the pathology, only in 5% of cases is there a recurrence of the pathological process.

When malt lymphoma is detected, patients are prescribed antibacterial drugs. Nifuratel, Amoxicillin, Tetrazikin or Rifaximin are popular. If the drugs do not bring a positive effect, surgical intervention is prescribed.

But the operation is used only in 5% of cases. Typically, patients are prescribed complex treatment, which includes the use of radiation or chemotherapy.

Radiation therapy

The impact on the affected tissue is carried out by radioactive radiation. The technique allows you to slow down or completely stop the growth of the tumor and eliminate the occurrence of complications.

According to research results, it has been established that radiation therapy brings positive results in 90% of cases. The disadvantage of the method is the high risk of side effects, since radioactive radiation also has a negative effect on healthy tissue.

Chemotherapy

The use of chemotherapy drugs can improve the prognosis. The duration of the course of therapy is determined by the attending physician and depends on the stage of development of the pathology. Medicines are selected by a specialist taking into account research results.

According to experts, most often malt lymphoma at stages 1 and 2 can be treated with chemotherapy without difficulty.

Chemotherapy drugs, when the disease is at stage 3 or 4, help slow down the process of mutation of tissue cells in half of the cases.

Possible complications

Lack of therapy causes complications to develop. Patients experience stomach bleeding and severe pain.

As the pathological process spreads, disruption of the functioning of many organs and systems is observed. Metastatic lesions may also develop over time.

The most dangerous consequence is death. Death occurs as a result of complications.

Forecast

When malt lymphoma is diagnosed, the prognosis is ambiguous. It depends on many features of the disease, the correct choice of course of therapy and the capabilities of the patient’s body.

If treatment was started at the first or second stage, the prognosis is most often favorable. With the help of drugs and chemotherapy, a survival rate of more than 90% can be achieved within five years.

When the pathology is at stage 3 or 4, the chance of recovery decreases. Patients should undergo regular medical examination, including endoscopic examination.

Prevention

There are no special measures to prevent malt lymphoma, since the exact causes of the disease have not been established. Experts recommend following general rules:

1. Right eat. The diet should include vegetables and fruits, as they contain many vitamins. You also need to reduce the amount of fatty, salty and fried foods.
2. Live a healthy lifestyle life. Patients should give up bad habits such as smoking and drinking alcohol.
3. Treat in a timely manner infectious diseases. According to scientists, they are the causes of the development of pathology.
4. Take place regularly examinations. Timely diagnosis improves the prognosis.

Compliance with preventive measures will reduce the risk of developing maltoma and complications associated with the disease.

Malt lymphoma is a type of malignant lesion. The pathological process most often affects the tissues of the stomach, but can also affect internal organs.

The danger of the disease is that in the initial stages it is difficult to diagnose the pathology. This is due to the absence of obvious signs. Treatment is carried out in accordance with the stage of development and characteristics of the disease.

Both drugs and other therapies are used to destroy cancer cells. But even after completing the course, patients should visit their doctor regularly to reduce the risk of relapse.

Gastric lymphoma is a type of malignant neoplasm that affects this organ. This tumor is quite rare; according to medical statistics, it accounts for no more than 5% of all gastric cancers.

However, in recent decades there has been an increase in the number of cases of this pathology. For example, in the United States over two decades, the number of gastric lymphomas has increased by almost 60%. Most often, this pathology affects older people; the disease is usually found in people over 50 years of age; it occurs more often in men than in women.

In simple terms, gastric lymphoma is an oncological disease of the lymphoid tissue of this organ. This tumor is non-leukemic in nature and can be malignant or become malignant. This disease is classified as a low-grade B-cell neoplasm.

The disease is very similar to stomach cancer and is quite difficult to diagnose, but there is good news: the treatment prognosis for lymphoma is much more favorable than for cancer.

Already from the name of this pathology it becomes clear that the disease is associated with the lymphatic system of the stomach. And more precisely, with the lymphoid tissue that is located in the mucous membrane of this organ. One type of lymphoma is the so-called Malt-lymphoma of the stomach (mucosa-associated lymphoid tissue).

This disease has not been studied very well, and the causes that cause it have not been precisely established. Doctors believe that the main reason for the development of this pathology is infection with the bacterium Helicobacter pylori. There are no lymphoid follicles in the mucous membrane, but they appear in chronic gastritis caused by Helicobacter pylori.

Malt lymphoma of the stomach is associated with inflammatory processes, which are accompanied by increased proliferation of lymphoid tissue. In most cases, the cause that stimulates this chronic inflammation is Helicobacter pylori.

Another proof of this theory is the fact that Helicobacter pylori was detected in the majority of patients with gastric lymphoma (90-100%).

There are other causes of this disease. The main ones are the following:

• heredity;
• previous organ transplant operations;
• autoimmune diseases.

In addition, the likelihood of developing lymphoma is influenced by factors: increased levels of radiation, frequent consumption of foods containing carcinogenic substances.

Another factor is long-term use of medications that suppress the immune system.

Types of disease

There are many types of this disease. Several classifications have been developed for them.

Lymphoma of the stomach is:

• primary;
• secondary.

The primary form of the disease is very similar to stomach cancer. It is very rare; this form accounts for less than 15% of all malignant diseases of the stomach and no more than 2% of all lymphomas of this organ. It should be noted that the stomach is the most common site of development of primary lymphomas after the lymph nodes.

This form of lymphoma is similar to cancer when examined endoscopically: it can have a polypoid, ulcerative and infiltrative form. The infiltrative diffuse form of primary lymphoma completely affects the mucous membrane and its submucosal layer.

If you conduct a histological examination, you can see the accumulation of lymphoid tissue in the mucosa and submucosa, as well as the infiltration of the gastric glands with cells of lymphoid follicles.

Primary lymphoma is non-leukemic, meaning it does not affect the bone marrow or peripheral lymph nodes. However, regional lymph nodes are affected, as well as nodes located in the chest.

The secondary form of gastric lymphoma is characterized by more significant damage to the walls of the organ.

There are other types of lymphomas, these include:

• B-cell lymphoma of the stomach;
• pseudolymphoma or lymphatosis;
• lymphogranulomatosis or Hodgkin's disease;

B-cell lymphoma of the stomach consists of B-lymphocytes with a low degree of differentiation. This type of disease belongs to non-Hodgkin lymphoma. Malt lymphoma of the stomach belongs to this type of disease; it is considered a B-cell lymphoma with a low degree of malignancy. At the moment, it has been practically proven that about 90% of cases of this pathology are associated with infection with the bacterium H. pylori.

Pseudolymphoma or lymphatosis is a benign neoplasm that develops in the stomach. It penetrates the walls of the stomach, usually into its mucous and submucosal layer, but does not metastasize. However, there is always a threat of degeneration of lymphatosis into a malignant neoplasm. Therefore, such tumors are recommended to be removed surgically.

Lymphogranulomatosis or Hodgkin's disease is a type of cancer that begins in the lymph nodes and then spreads to the stomach tissue. It is extremely rare.

Malt lymphoma of the stomach

Extranodal B-cell lymphoma of the marginal zone, which develops in the mucous membranes, or Malt-lymphoma of the stomach is one of the “youngest” types of lymphomas; it was described by British scientists Isaacson and D. Wright only in 1983.

Previously, such a pathology was considered one of the types of pseudolymphomas, that is, a benign neoplasm. Only after the monoclonality of this pathology was proven, that is, its origin from a single cell, was it classified as an oncohematological pathology.

Malt lymphoma on endoscopy.

Most often, this disease occurs due to an inflammatory process, usually stimulated by Helicobacter pylori.

The gastric mucosa normally does not contain lymphoid tissue, but under the influence of a permanent infection the situation changes. Clonal proliferation of B lymphocytes occurs, which leads to the formation of lymphoid tissue. Moreover, under the influence of constant antigenic stimulation from Helicobacter pylori, genetic aberrations accumulate in B lymphocytes, which affect genes responsible for cell apoptosis. This is one of the most important mechanisms of antitumor defense of the body and is inherent in all cells.

In addition, the activity of a pathogenic microorganism causes the activation of certain oncogenes in lymphocytes.

Stages of the disease

Gastric lymphoma, like other types of this disease, has four stages. Each of them differs in severity and clinical picture. The first stage is the easiest; if the disease is detected at it, then the prognosis for treatment is almost one hundred percent positive. The situation is worst at the fourth stage of the pathology.

Below are the main signs for each stage of the disease:

• Stage 1: the pathological process is localized in the stomach. At stage 1a it is limited to the mucous membrane, at stage 1b it moves to deeper layers (muscular, serous).
• Stage 2: the lymph nodes lying nearby, as well as neighboring organs, are affected.
• Stage 3: distant lymph nodes are affected, and the tumor actively penetrates into neighboring organs. Lymph nodes are affected on both sides of the diaphragm.
• Stage 4: the lymph nodes located above the diaphragm are affected, as well as the lymph nodes located in the pelvis along the aorta.

At the third and fourth stages of the disease, the pathological process affects the liver, bone marrow, spleen, and other internal organs.

Symptoms of the disease and diagnosis

Diagnosing gastric lymphoma is a very difficult task. Treatment is most effective in the initial stages of the disease, but detecting pathology at this stage is very difficult. Differential diagnosis is especially difficult because gastric lymphoma is very similar to other diseases of this organ.

A 62-year-old woman with primary gastric lymphoma. CT image shows an irregular subepithelial mass in the gastric antrum.

The initial stages of lymphoma are very similar to gastritis caused by Helicobacter pylori. It is also difficult to distinguish this disease from stomach cancer. Problems also arise in the differential diagnosis of the primary and secondary forms of this disease.

The characteristic symptoms that occur with lymphoma are the following:

• frequent pain in the epigastric region, which is dull or sharp;
• loss of appetite and very rapid satiety;
• nausea and vomiting (very often with blood);
• rapid weight loss, up to anorexia;
• increased sweating at night, increased body temperature.

As you can see, such symptoms can be the result of a large number of other gastrointestinal diseases, so it is not possible to make a diagnosis based only on the clinical picture and anamnesis.

To accurately diagnose this disease, it is necessary to conduct the following studies:

• blood analysis;
• endoscopic ultrasound;
• biopsy;
• histological examination;
• CT and MRI of the stomach.

A blood test may show an increase in ESR, which is characteristic of lymphoma, and can also be detected in the blood. Endoscopic examination methods are traditional for this disease, but they cannot distinguish gastritis or ulcer from a malignant tumor, so they must be supplemented with a biopsy. It is better to carry out multiple biopsies of different parts of the stomach, this will give a more accurate picture. Histological analysis can detect lymphoma with a probability of 35 to 80%.

It is important to distinguish the primary form of pathology from the secondary one. The use of computed tomography can distinguish diffuse lesions from tumors, which usually have well-defined margins. A CT scan will also help to examine metastases.

Treatment

Treatment of this pathology depends on its type, stage and characteristics of the patient. Its success also depends on these same factors. There are three main methods of treating the disease:

• operational;
• chemotherapy;
• radiation therapy;
• drug therapy.

If the diagnosis is confirmed, the patient is initially prescribed antibacterial therapy, which should destroy Helicobacter pylori. There are several schemes for destroying this microorganism; the doctor chooses the optimal one.

At the first stage of the disease, after antibiotic therapy, surgical intervention follows. After surgery, chemotherapy is often used, the goal of which is to completely remove cancer and atypical cells.

In the second and third stages of the disease, chemotherapy and radiation therapy are first used, and only then the operation is performed. Irradiation of the abdominal cavity is used, the main effect is on the stomach. Exposure to chemotherapy and radiation significantly reduces the size of the tumor, making surgery easier and more effective.

During surgery, the doctor carefully examines the abdominal organs for the presence of metastases.

In some cases, gastric resection is performed.

If the pathological process has gone too far and the tumor has invaded large vessels and organs of the abdominal cavity, then the patient is prescribed palliative treatment, which helps reduce the symptoms of the disease and also prolongs the patient’s life.

During the course of treatment, the patient is prescribed a special diet that reduces the load on the organs of the digestive system. Usually the disease reduces appetite, the patient is haunted by pain. Therefore, the menu should be designed in such a way as to reduce the patient’s discomfort.

Proper nutrition for lymphoma usually consists of reducing the amount of fat (especially animal fat) and animal protein in the diet, while increasing plant foods.

Folk remedies

Sometimes folk remedies are also used to treat lymphomas. However, one should clearly understand the seriousness of this disease, which only highly qualified doctors can cope with.

No folk methods can replace traditional therapy. If the main treatment is not applied, then the use of such methods can only do harm.

Forecast

There is no clear prognosis for the treatment of lymphomas. Too much depends on the stage of the disease, the type of tumor, the individual characteristics of the patient and the correctness of the chosen treatment.

If you start treatment at the first stage of lymphoma, the prognosis is almost always favorable: 95% of patients live after a comprehensive course of treatment for more than five years. At the second stage, the probability of a favorable outcome is 75%. If treatment began at the third stage of the disease, then the probability that the patient will live for five years is about 25%.

Also, a lot depends on the age of the patient and his condition. Lymphoma develops more slowly than cancer, so the chance of recovery is higher. In addition, this pathology metastasizes later than stomach cancer.

Example menu

• First breakfast. Dietary meat with rice. Tea.
• Lunch. Chopped apple.
• Dinner. Vegetable puree soup. Fruit juice.
• Afternoon snack. Homemade yogurt.
• Dinner. Macaroni with chicken or cheese.

Extranodal marginal zone lymphomas, MALT lymphomas (mucosa-associated lymphoid tissue - lymphomas from lymphoid tissue associated with mucous membranes), or maltomas, can occur in almost any organ, but more often they develop in the stomach, salivary glands and thyroid gland, then found in organs in which lymphoid tissue appears after chronic persistent inflammation. The main reason for the development of MALT lymphoma is the presence of autoreactive lymphoid tissue due to an autoimmune or inflammatory process, such as during infection Helicobacter pylori (H. pylori) in the stomach or Hashimoto's thyroiditis in the thyroid gland. The presence of an autoimmune process or infectious pathogen leads to prolonged activation of T and B cells. Constant stimulation of T cells leads to the activation of B cells with the properties of intensive multiple divisions, during which DNA breakdowns occur with the subsequent development of lymphoma. Thus, an abnormal clone arises against a background of persistent reactive proliferation. Over time, it replaces the normal B cell population and leads to the development of MALT lymphoma.

Globally, extranodal marginal zone lymphomas account for 7–8% of all non-Hodgkin malignant lymphomas, ranking third in prevalence after diffuse large B-cell and follicular lymphomas. The source of MALT lymphoma is the postgerminative marginal zone B cell.

Gastric MALT lymphoma occurs more often in older people (median 57 years). There are no differences in incidence between men and women. The clinical picture depends on the stage of the disease. In the early stages, MALT lymphoma is characterized by the absence of symptoms or minimal manifestations of dyspeptic and pain syndrome and differs little from other chronic diseases of the stomach. In ⅔ of cases, lymphomas manifest as persistent painless enlargement of peripheral lymph nodes. In the case of generalized enlargement of lymph nodes, it is necessary to exclude infections - bacterial, viral (infectious mononucleosis, cytomegalovirus, HIV infection), protozoal (toxoplasmosis). A firm lymph node measuring >1 cm in individuals without evidence of any infection that remains enlarged for more than 4 weeks should be biopsied. It should be remembered that with some lymphomas, enlargement of the lymph nodes is often replaced by a transient spontaneous decrease.

Most primary gastric lymphomas develop from mucosal lymphoid tissue (MALT lymphomas). Epidemiological studies in Europe have demonstrated that in areas with a high incidence of gastric lymphoma H. pylori detected more often than in areas with low incidence. Moreover, patients with gastric lymphoma more often than the control group have antibodies to H. pylori. Carcinogenic effect H. pylori not fully studied. The microorganism changes the physical and chemical properties of gastric mucus, which increases the susceptibility of the mucous membrane to the action of carcinogens. H. pylori reduces the secretion of ascorbic acid in the stomach, which leads to the formation of carcinogenic N-nitroso compounds. In addition, chronic inflammation can stimulate epithelial proliferation, as occurs in ulcerative colitis. According to some signs, the appearance of lymphoid tissue in the stomach and the occurrence of MALT lymphoma are closely related to prolonged antigenic stimulation of the mucous membrane.

During anti-Helicobacter therapy H. pylori and lymphoid tissue of the gastric mucosa disappear over time, that is, the substrate from which MALT lymphoma develops disappears and leads to regression of histologically confirmed low-grade MALT lymphomas. The extent to which prophylactic antibiotic therapy reduces the risk of developing gastric lymphoma remains to be determined. No relationship has been identified between this pathogen and lymphomas of other localizations.

Lymphoid tissue in MALT lymphoma is presented either in the form of diffuse infiltration or in the form of nodular accumulations lacking a closed connective tissue sheath. There is an assumption that mucous membrane-associated lymphoid tissue (MALT) forms a special secretory system in which cells synthesizing immunoglobulin A and E circulate (Table 1).

Table 1. Wotherspoon score for the differential diagnosis of gastric MALT lymphoma and H. pylori-associated gastritis

MALT lymphomas are detected mainly in the second half of life (average age 61 years). It is one of the few non-Hodgkin's lymphomas that affects women more often than men (ratio 1.1:1). Usually the disease occurs in a localized manner - in approximately 70% of patients, MALT lymphoma is diagnosed in the early stages, that is, stages I and II. In most cases, the factor stimulating chronic inflammation is H. pylori. This microorganism is detected in more than 90% of biopsy specimens of the gastric mucosa in cases of MALT lymphoma. The immunophenotype of MALT lymphomas is characterized by the expression of pan-B cell antigens (CD19, CD20 and CD79a), surface immunoglobulins, as well as CD21 and CD35, characteristic of marginal zone B cells.

In 5% of cases, activation of the oncogenic pathway is triggered regardless of infection H. pylori, for example, with long-term persistence of another infection and constant antigenic stimulation. Normally, the gastric mucosa does not contain organized lymphoid tissue, but is represented by diffuse lymphoplasmacytic infiltration of the lamina propria. Persistence H. pylori in the mucus layer stimulates clonal proliferation of B lymphocytes, which leads to the formation of organized lymphoid tissue. Over time, under the influence of antigenic stimulation, B lymphocytes accumulate the following genetic aberrations: t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21). In 30–50% of cases of mature cell MALT lymphomas, a highly specific translocation t(11;18) is detected, which is not observed in other types of lymphomas. Translocation leads to the formation and expression of a chimeric gene fusion product AP12-MLT. AP12(apoptosis inhibitor-12) is located on chromosome 11, and MLT(MALT lymphoma translocation) - on chromosome 18. In the chimeric translocation product, areas AR12, necessary to suppress apoptosis, are always preserved. The MLT protein fragment retained during translocation plays an important role in the subcellular localization and stability of the chimeric product. We can say that the translocation leads to the appearance of a stable chimeric protein that has an anti-apoptotic effect. MALT lymphomas are characterized by low proliferative activity, so the main pathogenetic mechanism of these tumors is a defect in apoptosis. The t(11;18) translocation is associated with a more aggressive course of MALT lymphomas. According to a number of authors, in the presence of this translocation, tumor remission after destruction H. pylori impossible with antibiotics. The t(11;18) translocation is a valuable marker that allows for the correct selection of therapy in patients with MALT lymphomas. Secondary oncogenic disorders in MALT lymphomas are associated with the oncogenes myc, p53 and p16. The myc oncogene may be important in the early stages of the development of MALT lymphomas and is detected in both mature cell and aggressive variants.

MALT lymphomas are also characterized by disruption of the normal activity of an important tumor suppressor gene BCL10, which is observed at t(l;14)(p22;q32). As a result of gene translocation BCL10 loses its proapoptotic activity and antitumor potential.

At t(14;18)(q32;q21) gene function is disrupted MALT1. Although these translocations affect different genes, they all lead to the activation of NF-κB (nuclear factor-kappa B), which is a key regulator of gene expression responsible for lymphocyte proliferation and apoptosis. The transcription factor NF-κB consists of two subunits - p50 and p65 - and exists as a complex with the inhibitory subunit protein NF-κB (IκB) in an inactive form. Activation of the IκK component leads to phosphorylation of NF-κB followed by cleavage of IκB. In this case, NF-κB translocates into the nucleus and activates oncogenes. Clinical manifestations of gastric MALT lymphoma in the early stages are either absent or do not differ from chronic gastritis or peptic ulcer. The most common occurrences are episodic aching pain in the epigastric region, often not associated with food intake, dyspeptic symptoms, heartburn, belching, vomiting, and gastric bleeding.

Diagnosis of gastric MALT lymphoma is based on endoscopic examination, which does not always reveal abnormalities characteristic of the tumor. As a rule, changes in the mucous membrane characteristic of chronic gastritis or peptic ulcer disease occur, that is, foci of hyperemia, edema, erosions or ulcers are formed. In this regard, the diagnosis is based on the morphological characteristics of the gastric mucosa, and the histological diagnosis of MALT lymphoma is often an unexpected finding. Fibrogastroduodenoscopy is performed with multiple biopsies from each area of ​​the stomach, duodenum, gastroesophageal junction and each suspicious area. Other studies help establish the stage of the disease or are additional. So, to visualize regional lymph nodes and determine the degree of infiltration of the stomach wall, endoscopic ultrasound is performed. A blood test for basic clinical and biochemical parameters is mandatory, including determination of the level of lactate dehydrogenase and β 2 -microglobulin.

Carry out: serological test for H. pylori(if not already confirmed), stool test - antigen test for H. pylori(if not already confirmed), computed tomography of the chest, abdomen and pelvis, bone marrow aspiration biopsy is performed. In addition, immunohistochemical and cytogenetic studies using FISH or polymerase chain reaction are used. The role of positron emission tomography in this pathology is controversial and has insignificant clinical significance, which is due to the indolent properties of the disease. Most often, the difficulty in diagnosing gastric MALT lymphoma is its differential diagnosis with H. pylori- associated gastritis. The cellular composition of extranodal marginal zone lymphoma has a diverse tumor substrate. It is represented by centrocyte-like marginal zone cells, monocytoid B lymphocytes, small lymphocytes and plasma cells. An important element characteristic of gastric MALT lymphoma, but less numerous (no more than 10%), are cells similar to centroblasts or immunoblasts. Extranodal marginal zone lymphoma is also capable of undergoing large cell transformation, when centroblasts or immunoblasts begin to predominate in the cellular composition. In this case, the diagnosis should be formulated as “diffuse large B-cell lymphoma” rather than “aggressive MALT lymphoma” and completely different treatment approaches should be used. No specific immunohistochemical markers were identified for this variant of lymphoma, since the typical phenotype of a tumor cell in marginal zone non-Hodgkin lymphoma is presented as follows: there is a reaction only with common B-lymphocyte markers - CD20, CD43, CD79 (Table 2).

Table 2. Immunophenotypic characteristics of B-cell lymphomas

The reaction with antibodies to CD5, CD10 and CD23 is usually negative, which allows differential diagnosis with lymphomas from small lymphocytes, mantle cells and follicular lymphomas.

Staging of gastric MALT lymphoma is based on a system developed by the International Extranodal Lymphoma Study Group (IELSG) specifically for gastrointestinal lymphomas.

According to this classification, there are 3 stages of the disease:

• Stage I - the process is localized in the gastrointestinal tract:

Stage I1 - limited to the mucous layer with/without the submucosal layer;

Stage I2 - moves to the muscular layer, subserous and/or serous layer;

• Stage II - the process, in addition to the stomach, involves the abdominal lymph nodes and neighboring organs:

Stage II1 - paragastric lymph nodes are involved;

Stage II2 - distant lymph nodes are involved (mesenteric, para-aortic, paracaval, pelvic, iliac);

• Stage III - penetration into neighboring organs and tissues;
• Stage IV - diffuse or disseminated damage to one or more extralymphatic organs or damage to the gastrointestinal tract involving supradiaphragmatic lymph nodes.

Proof of leadership H. pylori in the etiopathogenesis of gastric MALT lymphoma is its regression in 70–80% of patients under the influence of anti-Helicobacter, in other words eradication, therapy with nitrofuran derivatives (furazolidone), drugs for the treatment of protozoal infections (metronidazole), broad-spectrum antibiotics (clarithromycin, azithromycin, roxithromycin, amoxicillin , tetracycline), histamine H2 receptor blockers (ranitidine) or drugs similar in action to them that suppress secretion, colloidal bismuth subcitrate. MALT lymphoma of the stomach, thus, seems to be the only non-Hodgkin malignant lymphoma, the regression of which is fundamentally possible without special antitumor treatment with cytostatics. However, eradication therapy is still not amenable to 20–30% of patients with gastric MALT lymphoma, who are then indicated for surgery, radiation therapy (if feasible) or therapy with cytostatics due to the risk of transition to aggressive forms of the disease. In approximately 10% of cases, gastric MALT lymphoma develops in the absence of H. pylori.

Thus, in recent years, ideas about malignant lymphomas in general and MALT lymphomas in particular have undergone significant changes. General ideas about the patterns of pathogenesis of this heterogeneous group of tumors have been established, the principles of a new classification of lymphoid neoplasia have been formulated, and important provisions on diagnostic criteria, prognosis factors and principles of treatment for each nosological form have been defined. MALT lymphomas, according to most researchers, represent a clearly defined group of lymphoid tumors that have a specific morphological picture and insufficiently studied clinical features, but they must be taken into account to develop optimal treatment programs.

List of used literature

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MALT lymphoma: causes, pathogenesis, classification, clinical picture

I.A. Kryachok, K.O. Ulyanchenko, T.V. Kadnikova, I.B. Titorenko, O.M. Alexik, A.V. Martinchik, K.S. Filonenko, E.V. Kushcheviy, O.I. Novosad, T.V. Skripets, Ya.V. Pastushenko, M.V. Inomistova

National Institute of Cancer, Kiev

Summary. Extranodal marginal zone lymphoma, which arises from mucous-associated lymphoid tissue (MALT), is characterized by specific pathogenetic, histological and clinical features. Important criteria for the diagnosis of MALT lymphoma, prognosis factors and the particular treatment of patients with this nosological form are outlined.

Key words: extranodal marginal zone lymphoma, associated with mucous membranes (MALT), primary vulcan lymphoma, vulgaris infection, associated with Helicobacter pylori, Wotherspoon scale, translocation t(11; 18).

MALT-lymphoma: etiology, pathogenesis, classification, clinical issues

I.A. Kriachok, K.O. Ulyanchenko, T.V. Kadnikova, I.B. Tytorenko, O.M. Aleksik, A.V. Martynchyk, K.S. Filonenko, E.V. Kushchevyi, O.I. Novosad, T.V. Skrypets, I.V. Pastushenko, M.V. Inomistova

National Cancer Institute, Kyiv

Summary.Extranodal marginal zone lymphoma or mucosa-associated lymphoid tissue (MALT) is the most common form of marginal zone lymphoma, which occurs outside the lymph nodes. This type of lymphoma is characterized by special pathogenetic, histological and clinical signs. Also, the diagnosis, prognostic factors, and treatment options of marginal zone lymphoma are established.

Key words:extranodal marginal zone lymphoma (MALT), Helicobacter pylori-associated primary gastric lymphoma, scale of Wotherspoon, translocation t(11;18).

Address:
Ulyanchenko Ekaterina Olegovna
03022, Kyiv, st. Lomonosova, 33/43
National Cancer Institute,
Email: [email protected]