Malt lymphoma of the salivary glands is successfully treated. MALT-lymphomas. Treatment of high-grade gastric lymphoma

Lymphoma of the stomach is a malignant tumor that is formed from the lymphoid cells of the digestive tract. Pathology is rarely detected in the early stages of the oncological process, which negatively affects the prognosis of the patient's cure.

Description and statistics

Lymphoma of the stomach is a non-leukemic neoplasm originating from lymphoid tissues located in the wall of the organ. It is characterized by slow development and similarity of symptoms with stomach cancer, but differs from the latter in a more favorable prognosis. The disease occurs in different forms, however, in all cases, cells of the lymphoid tissue and the mucous membrane of the organ are subject to malignant lesions.

The number of people with lymphomas is increasing every year. This circumstance is due to a combination of several factors - the deterioration of natural resources, the saturation of food with carcinogenic and other chemical additives, increased stress on the immune system in a metropolis.

In human blood there are lymphocytes - bodies in which substances are formed aimed at neutralizing and destroying pathogenic agents - viruses, microbes and toxins that enter the body from the external environment. Violations in the work of immunity lead to a reduction in the synthesis of lymphocytes or stimulation of their attack against their own cells - an autoimmune reaction.

Histological analysis of gastric lymphoma in the tumor tissues reveals a large accumulation of lymphocytes in the mucosa and submucosal layer of the organ. At the same time, the secretory glands of the stomach are covered with follicles from the lymphoid tissue, and therefore the digestion process suffers.

Among all oncological lesions of the stomach, 95% are adenocarcinomas or cancer of the organ, and only 5% are lymphomas. According to statistics, the disease is diagnosed in 6 people out of 100,000 healthy people. It usually occurs in men over 50-60 years of age.

ICD-10 code: C81-C96 Malignant neoplasms of lymphoid, hematopoietic and related tissues in the stomach.

The reasons

With lymphoma of the digestive organs, malignancy of the cellular structures of the epithelium occurs, that is, the tissues undergo atypical degeneration. The true factors that provoke the development of pathology are not known for certain, but experts believe that people with chronic gastritis of bacterial origin most often face the disease. The most dangerous in this regard is the atrophic form of the disease caused by the microorganism Helicobacter pylori.

Additional triggering aspects of gastric lymphoma can be the following factors:

• autoimmune problems;
• unfavorable heredity for oncology;
• persistent immunodeficiency provoked by conditions such as HIV infection, AIDS, organ transplantation, chemotherapy;
• living in an area with an overestimated radiation background.

Symptoms

The clinical picture of gastric lymphoma at first is very similar to gastritis or ulcers. There are symptoms such as frequent heartburn and nausea, flatulence, epigastric pain and stool disorders. Specific signs of oncological lesions of the organ at the initial stage either do not appear or are poorly expressed, which greatly complicates the early diagnosis of the disease.

We list the main symptoms of stomach lymphoma:

• pain in the epigastric region;
• nausea and vomiting, with the progression of the disease, streaks of blood are found in its contents;
• abdominal discomfort, flatulence, persistent bowel disorders;
• sudden weight loss, which, in the absence of adequate assistance, can cause death of a person from exhaustion;
• increased sweating at night;
• satiety with a small amount of food;
• the presence of undigested food in the feces.

If there is a suspicion of stomach lymphoma, you need to contact a gastroenterologist. The specialist will prescribe the appropriate examinations and make a diagnosis.

stages

Like all other types of malignant tumors, gastric lymphoma has four stages of development. Let's look at them in the following table.

Classification

There are several classifications of lymphomas of the digestive system. Let's consider them in more detail.

According to the form of the course of the disease, the following types of lymphomas are distinguished:

• polyploid. It is represented by a malignant tumor that has a round, cone-shaped or spherical appearance, which grows in the lumen of the stomach;
• nodal. Oncoprocess is localized on the wall of the organ. The neoplasm is represented by flattened or hemispherical nodes of a massive form, devoid of a mucous membrane;

• inintral. Possesses high aggressiveness in comparison with the previous types. Contributes to the rapid course of the disease and poor prognosis for survival.

According to the origin of the oncoprocess, the following types of gastric lymphomas are distinguished:

• primary. It is the result of the formation of a primary tumor. It usually develops against the background of chronic pathologies of the gastrointestinal tract - gastritis or ulcers. The clinical picture is similar to stomach cancer;
• secondary. It becomes a consequence of metastases, that is, the penetration into the tissues of malignant cells from primary oncofoci located in the body. Lymphoma is multicentric in nature, that is, the walls of the stomach can be affected comprehensively.

The following lymphomas are distinguished by types of oncoprocess:

• non-Hodgkin. This is a low-differential tumor that begins development and growth due to pathogenic microflora in the stomach - for example, Helicobacter pylori;

• pseudolymphoma. The pathological process begins to develop in the walls of the organ, affecting the mucous and submucosal layers. In the early stages, there are no malignant changes in the lymph nodes, however, in the absence of medical care, pseudolymphoma degenerates into a true tumor, initially not being one;
• Hodgkin's lymphoma, or lymphogranulomatosis. This oncoprocess differs from others in the spread of atypical cells from the affected lymph nodes to the tissues of the organ, and not vice versa. It is worth noting that among other types of neoplasms in the stomach, this one is the rarest.

According to the etiology of the disease, the following types of lymphomas are distinguished:

• MALT-lymphoma. The basis of the disease is the defeat of the lymphoid tissue associated with the mucosal epithelium. This process is characterized by the development of single tumors limited from each other and the absence of specific symptoms characteristic of malignant changes - inflammation of the lymph nodes, bone marrow damage, etc. It belongs to the group of non-Hodgkin's lymphomas;
• B-cell or extranodal lymphoma. The tumor is formed from primitive cellular structures prone to rapid uncontrolled division. The disease is extremely aggressive. Oncologists believe that B-cell lymphoma is a complication of MALT lymphoma;
• T-cell or T-blast lymphoma. Consists of immature T-lymphocytes that are transmitted to humans genetically; Usually, the oncoprocess in this case has a low degree of malignancy and does not differ in an aggressive course;
• diffuse non-Hodgkin's lymphoma. Atypical cells grow and spread rapidly. The tumor can grow into all internal organs. With timely treatment, there is a chance to extend a person's life by 5-10 years;
• false lymphoma. Has the most favorable prognosis. In the gastric mucosa, an infiltrative neoplasm of a lymphoid nature develops. Pathology does not make itself felt for a long time, without causing any clinical manifestations. Malignancy of the infiltrate and the progression of the disease does not always occur, so the patient may never know until the end of his days about the presence of a precancerous condition in his stomach.

According to the symptoms of the oncological process, the following forms of lymphomas are distinguished:

• gastritis-like or erosive. During endoscopic examination, changes in the form of erosions are found in the mucosa of the organ. The disease, as a rule, is a consequence of chronic untreated gastritis;

• ulcerative. One of the most dangerous forms of gastric lymphomas, which quickly leads to the destruction of the walls of the organ and early numerous metastases;
• mixed. This oncoprocess can combine signs of gastritis-like and ulcerative lymphoma, as well as such types of neoplasms as nodes, plaques, and erosions. Malignant changes occupy a significant part of the stomach;
• flat infiltrative. On the walls of the affected organ, infiltrative folds are formed, unevenly thickened in area, which can be covered with fibrin or have erosive and ulcerative changes;
• plaque lymphoma. In the mucous layer of the stomach, single or multiple flattened neoplasms appear, having characteristic depressions at the top, which makes them look like plaques. The base of the tumor has a soft elastic consistency, but as it grows, the mucous membrane covering the altered tissues breaks.

Diagnostics

You can detect stomach lymphoma with the help of a comprehensive examination - laboratory tests and instrumental techniques. Consider what will be the list of diagnostic measures in practice:

• general and biochemical analysis of blood. The growth of ESR and microcytic anemia raise the suspicion of a malignant process in the body. Metabolic abnormalities, such as elevated creatinine, phosphate, and lactate dehydrogenase, confirm a high risk of lymphoma;
• test for tumor markers. A malignant lesion of the lymphoid tissue leads to the accumulation of specific substances, in response to which the body synthesizes certain antibodies aimed at combating atypical particles. In gastric lymphoma, β2-microglobulin becomes the main oncomarker. According to its concentration in the blood, the doctor draws conclusions about the stage and prevalence of the disease;
• endoscopic examination. Allows you to detect even minor changes in the gastric mucosa, invisible to the human eye. During endoscopy, it is important for a specialist to differentiate the lymphoma of an organ from gastritis and ulcers, as well as other diseases that are not related to oncology;

• x-ray. Effective, but not the only way to confirm the diagnosis. It is used infrequently, since in the obtained images, lymphoma has many similarities with gastric carcinoma, which means that other studies are required;
• CT scan. Gives a complete picture of the tumor and the general condition of the human body. With its help, the degree of the malignant process is determined, the presence of metastases outside the stomach;
• deep biopsy and subsequent histology of tumor samples. It is carried out using a diagnostic laparotomy. The collected material is subjected to laboratory study. The final diagnosis is based on the results of the last analysis.

Only an integrated approach allows developing an individual treatment protocol, which will consist of measures aimed at combating the disease.

Treatment

Therapy of gastric lymphoma is carried out by classical methods generally accepted in oncology. These include surgical removal of the tumor, chemotherapy, and radiation exposure. As a rule, doctors prescribe an integrated approach in the fight against this disease, necessarily taking into account the general condition of the patient and the stage of the oncological process.

Early stage gastric lymphoma. Usually surgical treatment is applied. It consists in the surgical excision of altered tissues in the fullest possible extent. After surgery, doctors carefully examine the condition of the remaining lymph nodes and neighboring organs, such as the small intestine or lungs. This allows them to draw conclusions about the general picture of the lesion and spread of malignant cells with blood and lymph flow.

The second stage of the disease. As a rule, a gastrectomy or complete removal of the stomach is performed. Unfortunately, the effectiveness of surgical treatment barely reaches 75% even at the very beginning of the pathology, therefore, after the operation, specialists prescribe methods of radiation exposure to the body and chemotherapy. In the case of the latter, such cytostatics as "Doxorubicin", "Vincristine" and "Cyclophosphamide" are used, it is these drugs that are successfully used for oncological lesions of the gastrointestinal tract. They affect the entire digestive tract, but most of them settle in the stomach.

Third and fourth stages of lymphoma. In this case, an urgent resection of the organ is performed with an additional course of cytostatics. If the patient is inoperable, for example, due to a severe general condition or damage to the main large vessels, palliative treatment is prescribed at this stage.

Radiation therapy. In case of malignant lesions of the stomach, it is used infrequently due to the proximity to the oncocenter of vital organs. Recently, a certain dose of radiation has been purposefully used only in relation to the localization of the tumor, that is, complete immobility of the patient on the operating table is ensured, the rest of the body is covered with a special protective screen, and the impact falls exclusively on the affected stomach. The course lasts no more than 2 weeks. After that, a repeat of chemotherapy is recommended.

Can be used in the fight against lymphomas. With a decrease in protective forces, the body is not able to produce antibodies, so it needs external help. Immunomodulators destroy lymphoma cells, stopping the aggressive growth of the tumor, and activate the natural immunity of a person. Most often, for this purpose, "Interferon" is prescribed, which contains monoclonal antibodies synthesized artificially. Of course, immunotherapy cannot be the only treatment for lymphoma, but it can improve the effectiveness of other measures.

Self-medication in the fight against malignant processes in the body should be strictly prohibited. Various folk recipes that can be easily found on the Internet are not recommended to be used on their own without consulting a doctor. Their effectiveness has not been proven by official medicine, which means that their use in practice is doubtful.

Recovery process after treatment

During the rehabilitation period, the main attention is paid to the organization of proper nutrition. A therapeutic diet will help restore the digestive tract, normalize the patient's well-being and speedy recovery.

Malignant lesions of the stomach lead to the fact that a person refuses food due to severe discomfort in the digestive tract, nausea and repeated vomiting, severe problems with the absorption of any products. These factors cause chronic nutritional deficiencies, dramatic weight loss up to cachexia or exhaustion. Of course, these processes negatively affect the state of the immune system and the patient's strength, which he needs to fight the disease.

Therefore, the rehabilitation period is an important part of medical care for a person after treatment on the stomach. Parenteral nutrition, a balanced easily digestible diet of permitted products, outdoor walks, psychotherapy, exercise therapy methods can successfully support the patient at the stage of recovery.

Diet

Both before surgical treatment and after it during rehabilitation, properly organized nutrition is important for gastric lymphoma. With such a diagnosis, dietary correction becomes a vital necessity, and here you can not do without the help of a professional.

As mentioned above, all persons with malignant lesions of the stomach have no appetite, which negatively affects the intake of nutrients. Therefore, experts strongly recommend for this disease to reduce the amount of animal protein in the diet, increasing the amount of fermented milk drinks, fruits and vegetables.

All products must be carefully processed thermally. Food is prepared by boiling or steaming. All dishes are served to the table in pureed or liquid form. Food should not be cold or hot, the recommended optimum temperature is 37 degrees.

The basic principles of nutrition before and after treatment are as follows:

• fractional food intake - 6 times a day in small portions;
• refusal to overeat;
• exclusion of carcinogenic products stuffed with GMOs and other chemical fillers;
• a ban on other methods of cooking, except for boiling.

The course and treatment of the disease in children, pregnant women and the elderly

Children. In young patients, gastric lymphoma is a rather rare occurrence, about 1 in 100,000. The disease is more often diagnosed in boys. Its causes in children have not yet been elucidated. The main signs of trouble: pathological proliferation of lymph nodes, night sweats, poor appetite, thinness, fatigue. Chemotherapy and radiation exposure to the body are mainly used as treatment, with invasive tumor growth and complications in the gastrointestinal tract - surgical intervention. With the timely detection of pathology and the fight against it, the survival rate approaches almost 100%.

Pregnancy. In the primary diagnosis of gastric lymphoma during pregnancy, an individual treatment protocol is used for each patient. It is determined by the gestational age, the clinical picture of the disease, the prevalence of the malignant process. The desire of the woman herself to keep the child is also taken into account. Gastric lymphoma does not adversely affect the course of pregnancy, so sometimes doctors take expectant management up to 32 weeks and perform delivery, provided that the disease is detected no earlier than the second trimester.

Advanced age. This malignant disease is more often detected in the elderly, mainly in men over 50 years of age. Treatment of this group is difficult due to the characteristics of the immune system and concomitant diseases. Even with successful complex treatment, remission is achieved only in 37% of older people. As a rule, the emphasis is on chemotherapy, namely the drug "Rituximab", which almost 3 times increases the average survival rate among patients.

Treatment of stomach lymphoma in Russia and abroad

Despite the variety of lymphomas, many of them successfully respond to modern therapy, provided that the disease is not neglected. We offer to find out how they deal with this pathology in different countries.

Treatment in Russia

Compared to other diseases, the diagnosis of lymphoma is difficult and requires close attention from specialists. If a malignant process is detected, treatment should be started as soon as possible. The basis of therapy in Russian cancer centers and clinics is surgery, chemo- and radiation effects on the body. The treatment protocol for each patient is selected individually, depending on the stage of the oncological process and the general condition of the patient.

Further tactics of therapy depend on the course of the pathology. When remission is achieved every six months for 5 years, the patient is prescribed an endoscopic examination of the stomach stump to determine the fact of infection with Helicobacter pylori and study changes in the organ. In case of recurrence or signs of metastases, a course of chemotherapy is necessary.

Consider in the following table the cost of gastric lymphoma treatment in Russia using the example of the MedicaMente Center for Oncology and Oncosurgery in Moscow.

Which clinics in Moscow and St. Petersburg can be treated?

• Russian Cancer Research Center. Blokhin, Moscow.
• City clinical oncological dispensary, St. Petersburg.

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Svetlana, 46 years old. “With gastric lymphoma of the 2nd stage, we managed to get a referral to the Cancer Center. Blokhin. Very satisfied with both diagnosis and treatment. Illness behind.

Nina, 55 years old. “In St. Petersburg, I had a stomach lymphoma removed in the city oncology dispensary. Everything went well. Now I follow a strict diet, regularly visit a doctor and undergo examinations. Recovery is progressing slowly but surely."

Treatment in Germany

Treatment of gastric lymphoma in German clinics is mainly conservative, that is, courses of chemotherapy, immuno- and radiotherapy are carried out. Their application corresponds to the latest achievements of oncology. The need for surgical intervention depends on the spread of the malignant process, the scale of the operation is determined by endoscopic examination using laparotomy.

Consider the prices for diagnostics and treatment in German clinics.

Which clinics can I contact in Germany?

• Essen University Hospital, Essen.
• Clinic "Stuttgart", Stuttgart.

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Marina, 58 years old. “My husband was diagnosed with stomach lymphoma. The forecasts turned out to be unfavorable, and we decided to turn to foreign specialists. The clinic "Stuttgart" employs real professionals. The treatment was long, 6 cycles of chemotherapy, surgery and recovery, so many worries and doubts, but, fortunately, the disease has receded. 2 years have passed since the trip, there are no relapses.

Julia, 26 years old. “Mom was treated for gastric lymphoma in Germany, at the Nordwest clinic. The operation was not done, the help was exclusively conservative, since the stage turned out to be early. Six months have passed since the discharge, the tests are good, we hope that the issue of oncology will no longer arise in our family and my mother will live a long and healthy life.”

Treatment of stomach lymphoma in Israel

In this country, gastric lymphoma is treated very successfully. According to statistics, 80% of patients achieve stable remission. These figures also apply to children.

Surgery and combined chemotherapy in combination with targeted, immune and radiotherapy are becoming a common method of fighting the disease. All this increases the chances of a complete cure for the patient. The protocol is selected taking into account the type of lymphoma, the stage of pathology, the response of the malignant process to the ongoing activities and the general condition of the patient. In addition to recovery, specialists are focused on reducing the toxicity of therapeutic procedures and reducing side effects.

With an aggressive form of lymphoma, doctors may resort to stem cell transplantation as the only chance for long-term remission.

Consider the approximate prices for diagnostics and treatment in Israel. They may vary depending on the status of the clinic and the characteristics of the patient's disease.

Where can you get treatment in Israel?

• Ichilov State Hospital, Tel Aviv.
• Institute of Oncology "Hadassah", Jerusalem.

Consider reviews of the listed medical institutions.

Natalia, 38 years old. “Treatment in Israel is significantly more expensive than in Russia, but I do not regret that in 2014 I turned to the Assuta clinic with my disease. I had a stomach lymphoma removed, had a course of targeted therapy and rehabilitation. I am very happy that the disease has receded.

Irina, 46 years old. “In the oncology center of Perm, she underwent treatment for lymphoma, but after 7 months the pathology returned. With a recurrence of a tumor in the stomach, I turned to the Hadassah clinic, where I received the necessary specialized assistance. I am very grateful to the doctors."

Complications

Lymphoid tissue is a structural component of immunity, therefore, tumors from its cells lead to the development of persistent immunodeficiency or autoimmunization of the body. As a result, susceptibility to various kinds of infections increases, and the general condition of the patient worsens.

Complications arise not only from the disease itself - damage to the lymphoid tissue, but also as a result of ongoing medical procedures. For example, against the background of chemotherapy, a person may complain of constant weakness, fatigue, lack of appetite. After radiation exposure, many patients experience hair loss, deterioration of the skin, dysfunctional disorders of the internal organs. All this requires the help of medical personnel.

Common complications of any type of lymphoma are:

• obstruction of the digestive tract;
• the development of inflammatory infiltrates - not only in the gastrointestinal tract, but also in other organs - the lungs, salivary glands, central nervous system, etc .;
• blood pathologies - persistent leukocytosis, lymphocytosis, thrombocytosis;
• damage to vital systems - hepatic, vascular, renal failure.

Relapses

6 months after treatment, the first relapses of lymphoma occur. Usually they are more aggressive than the original tumor, their detection requires a change in the chemotherapy regimen, and in some cases, the use of radiation exposure to the body.

To prevent the occurrence of relapses, until the stage of stable remission is reached, the patient is recommended to visit an oncologist once every 3 months to undergo a comprehensive diagnosis and follow the instructions of a specialist. Detection of a secondary tumor focus at an early stage has a favorable outcome.

Forecast

Positive results from the treatment performed directly depend not only on the stage of the oncological process, but also on the following factors:

• patient's age;
• the presence of concomitant pathologies;
• state of the immune system.

Consider in the following table the estimated prognosis for 5-year survival in adult patients.

It is important to note that in the presence of metastases, the prognosis worsens significantly. But if the patient adheres to all medical recommendations and reconsiders his lifestyle, even at this stage a person can be saved.

Prevention

Preventive measures for gastric lymphoma are exactly the same as for carcinoma. It is impossible to prevent a malignant process by 100%, but it is possible to avoid the factors that provoke the disease.

A healthy balanced diet, timely treatment of any pathologies of the gastrointestinal tract, annual rest in an ecologically clean area, elimination of stress and increased immune defense - all this is the prevention of oncological lesions of the body.

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Incidence

Mucosa-associated marginal zone lymphoma (MALT) accounts for ~7% of all non-Hodgkin's lymphomas. The process can occur in any extranodal areas, but most (one third of all cases) are gastric lymphomas. The exact incidence for Europe is not exactly known due to differences in the classification systems used in different countries.

Diagnosis

Clinically, MALT-lymphoma of the stomach is manifested by non-specific symptoms, leading the patient to endoscopic examination. EGDS usually determines nonspecific gastritis or ulcerative mucosal defect with solid structures atypical for a simple peptic ulcer.

The diagnosis is established on the basis of an immunomorphological study of the gastrobiopt material. The presence of an active Helicobacter pylori infection should be confirmed by immunohistochemistry or by a urease breath test.

To identify patients with an unlikely response to antibiotic therapy, in addition to the standard immunomorphological study, it is desirable to additionally determine t(11;18) using the FISH method.

The initial diagnosis should include endoscopy with multiple biopsies of the gastric mucosa, duodenum, gastroesophageal junction, and any suspicious sites.

Ultrasound is indicated to rule out regional lymph node involvement and gastric wall infiltration.

A comprehensive examination should include a complete blood count with calculation of the formula, a biochemical blood test with the determination of the level of LDH and beta2-microglobulin, computed tomography of the chest, abdomen and pelvis, as well as a study of aspirate and bone marrow trephine biopsy.

Positron emission (PET) has little diagnostic value and the need for the method is questionable (IV,D).

Treatment

Eradication anti-Helicobacter antibiotic therapy is considered the standard first-line therapy for local (limited to the stomach) H. Pylori-positive MALT-lymphomas. It is possible to use any eradication regimen with proven effectiveness. If the primary eradication anti-Helicobacter therapy fails, it is possible to use complicated three- and four-component regimens, including antibiotics and proton pump inhibitors.

H. pylori eradication may promote lymphoma regression and long-term disease control in most patients. The time to remission can range from a few to 12 months. Thus, in patients who achieve clinical and endoscopic remission, along with H. pylori eradication, but who have residual histological evidence of lymphoma, it makes sense to wait at least 12 months before switching to another therapy. The persistence of monoclonal B-lymphocytes after complete histological regression of lymphoma has been shown in many studies monitoring patients after antibiotic therapy. In such cases, watchful waiting is recommended, and active anticancer therapy (see below) should be reserved for symptomatic or progressive forms of the disease.

In H. Pylori negative cases, and also in the absence of the effect of primary antibiotic therapy, depending on the stage of the disease, the use of radiation or systemic chemotherapy is indicated. The surgical method has not been shown to be superior to more conservative methods in several studies. At I-II stages in H. Pylori-negative situations and with the persistence of a lymphoma clone after eradication antibiotic therapy, radiation monotherapy (SOD 30-40 Gy, 4 weeks) on the stomach and perigastric region is highly effective.

For patients with advanced disease, systemic chemotherapy and/or immunotherapy (using therapeutic anti-CD20 monoclonal antibodies) is indicated. Only a few individual drugs and regimens have been tested specifically for MALT lymphoma.

Oral alkylating agents (cyclophosphamide and chlorambucil) as well as nucleotide analogues (fludarabine and cladribine) have been shown to be highly effective in disease control. The antitumor activity of rituximab has been proven in phase II studies and the efficacy of the drug in combination with chlorambucil is being investigated, and is currently in randomized trials. At the moment, there is not enough evidence in the literature for the benefit of one or another drug or regimen, however, it should be borne in mind that therapy with purine analogs is associated with an increased risk of developing secondary meilodysplasia. Aggressive anthracycline-containing regimens are recommended for use only in cases of disease with an aggressive course and a large tumor mass.

Diffuse B-cell lymphoma of the stomach should be treated according to the guidelines developed for primary diffuse B-cell lymphomas of other sites.

Evaluation of the effectiveness of treatment and observation

The observation is based on a rigorous regular endoscopic examination of the stomach with multiple biopsies. Unfortunately, the interpretation of the quality of residual lymphoid infiltrates is very difficult, since there are currently no clear histological criteria for morphological remission. The first EGDS should be performed 2-3 months after the end of therapy to confirm eradication of H. Pylori; further, to monitor histological regression of lymphoma, the study should be repeated at least twice a year for the first 2 years.

MALT-lymphoma of the stomach is characterized by a limited ability to distant metastasis and histological transformation. Transient local recurrences are possible, tending to self-limitation (self-limiting), especially in the absence of H. Pylori reinfection.

In cases of persistent but stable residual disease or histological recurrence (without the presence of distant metastases and/or endoscopically distinct tumor), watch-and-wait may be used. Patients, however, must be closely monitored and regularly undergo endoscopic and general clinical (ultrasound, x-ray, blood tests) at least once a year.

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 present 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 infection. Helicobacter pylori (H. pylori) in the stomach or Hashimoto's thyroiditis in the thyroid gland. The presence of an autoimmune process or an infectious agent 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 intense multiple division, during which DNA breakdowns occur with the subsequent development of lymphoma. Thus, an abnormal clone arises against the 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's malignant lymphomas, ranking third in prevalence after diffuse large B-cell and follicular lymphomas. The source of MALT lymphoma is the postgerminal B cell of the marginal zone.

MALT-lymphoma of the stomach occurs more often in the elderly (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 are manifested by persistent painless enlargement of peripheral lymph nodes. In the case of a generalized increase in lymph nodes, it is necessary to exclude infections - bacterial, viral (infectious mononucleosis, cytomegalovirus, HIV infection), protozoal (toxoplasmosis). A solid lymph node >1 cm in size 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, an increase in lymph nodes is often replaced by a transient spontaneous decrease in them.

Most primary gastric lymphomas develop from mucosal lymphoid tissue (MALT-lymphomas). Epidemiological studies in Europe have shown that in areas with a high incidence of gastric lymphoma H. pylori detected more frequently than in low-incidence areas. Moreover, patients with gastric lymphoma are more likely than the control group to have antibodies to H. pylori. Carcinogenic effect H. pylori not fully explored. 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 indications, the appearance of lymphoid tissue in the stomach and the occurrence of MALT-lymphoma are closely related to long-term 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 gastric lymphoma remains to be established. The relationship between this pathogen and lymphomas of other localizations was not revealed.

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

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

MALT-lymphomas are detected mainly in the second half of life (mean 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 proceeds locally - approximately 70% of patients with MALT-lymphoma are diagnosed in the early, that is, stages I and II. In most cases, the factor that stimulates chronic inflammation is H. pylori. This microorganism is detected in more than 90% of biopsies of the gastric mucosa in patients with 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 prolonged 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 the 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 t(11;18) translocation is detected, which is not noted in other types of lymphomas. Translocation results in the formation and expression of a chimeric fusion gene product AP12-MLT. AP12(apoptosis inhibitor-12) is located on chromosome 11, and MLT(MALT lymphoma translocation) - on chromosome 18. In the chimeric product of the translocation, the sections AP12 necessary to suppress apoptosis are always preserved. The MLT protein fragment preserved during translocation plays an important role in the subcellular localization and stability of the chimeric product. It can be said that translocation leads to the appearance of a stable chimeric protein, which has an anti-apoptotic effect. MALT-lymphomas are characterized by low proliferative activity; therefore, the main pathogenetic mechanism of these tumors is a defect in apoptosis. Translocation t(11;18) is associated with a more aggressive course of MALT lymphoma. According to some authors, in the presence of this translocation, tumor remission after destruction H. pylori not possible with antibiotics. Translocation t(11;18) is a valuable marker that allows choosing the right therapy in patients with MALT-lymphomas. Secondary oncogenic disorders in MALT lymphomas are associated with myc, p53, and p16 oncogenes. The myc oncogene may be important in the early stages of MALT-lymphoma development and is detected in both mature-cell and aggressive variants.

Characteristic of MALT-lymphomas is also a violation 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) there is a violation of the function of the gene MALT1. Despite the fact that these translocations affect different genes, they all lead to the activation of NF-κB (nuclear factor-kappa B), which is a key regulator of the expression of genes responsible for the proliferation and apoptosis of lymphocytes. The transcription factor NF-κB consists of two subunits, p50 and p65, and exists as a complex with the inhibitory subunit NF-κB (IκB) protein in an inactive form. Activation of the IκK component results in NF-κB phosphorylation followed by IkB cleavage. In doing so, NF-κB translocates to 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. Most often there is episodic aching pain in the epigastric region, often not associated with food intake, dyspepsia, heartburn, belching, vomiting, and gastric bleeding.

Diagnosis of MALT-lymphoma of the stomach is based on endoscopic examination, in which it is not always possible to identify disorders characteristic of the tumor. As a rule, changes in the mucous membrane occur that are characteristic of chronic gastritis or peptic ulcer disease, 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 from each suspicious area. The remaining studies help to 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. It is obligatory to study the blood for the main clinical and biochemical parameters, including the determination of the level of lactate dehydrogenase and β 2 -microglobulin.

Carry out: serological test for H. pylori(if not yet confirmed), fecal analysis - antigen test for H. pylori(if not yet confirmed), computed tomography of the chest, abdomen and pelvis, bone marrow aspiration biopsy is performed. In addition, immunohistochemical and cytogenetic studies are used by FISH or polymerase chain reaction. The role of positron emission tomography in this pathology is controversial and has insignificant clinical significance, due to the indolent properties of the disease. The most common 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 cells of the marginal zone, 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" and not as "aggressive MALT lymphoma" and completely different approaches to treatment should be used. No specific immunohistochemical markers were found in this variant of lymphoma, since the typical phenotype of a tumor cell in non-Hodgkin's lymphomas of the marginal zone is presented as follows: there is a reaction only with common markers of B-lymphocytes - 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 from small lymphocyte, mantle cell, 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, 3 stages of the disease are distinguished:

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

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

I2 stage - goes to the muscle layer, subserous and / or serous layer;

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

II1 stage - paragastric lymph nodes are involved;

II2 stage - distant lymph nodes are involved (mesenteric, paraaortic, paracaval, small pelvis, iliac);

• Stage III - penetration into neighboring organs and tissues;
• Stage IV - diffuse or disseminated lesion of one or more extralymphatic organs or lesion of the gastrointestinal tract with involvement of the supradiaphragmatic lymph nodes.

Leading Proof H. pylori in the etiopathogenesis of MALT-lymphoma of the stomach 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 similar drugs that suppress secretion, colloidal bismuth subcitrate. Gastric MALT lymphoma thus appears to be the only non-Hodgkin's malignant lymphoma whose regression is fundamentally possible even without special antitumor treatment with cytostatics. However, 20-30% of patients with gastric MALT-lymphoma still do not respond to eradication therapy, who are then indicated for surgery, radiation therapy (if they are feasible) or cytostatic therapy due to the risk of transition to aggressive forms of the disease. Approximately 10% of cases of gastric MALT lymphoma develop in the absence of H. pylori.

Thus, in recent years, the understanding of malignant lymphomas in general and MALT lymphomas in particular has 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 have been determined on diagnostic criteria, prognostic factors and principles of treatment for each nosological form. MALT-lymphomas, according to most researchers, represent a clearly defined group of lymphoid tumors with 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

1. Johnson R.M., Brown E.J. (2000) Cell-mediated immunity in host defense against infectious diseases. Principles and Practices of Infectious Disease. 5th ed. Philadelphia, Pa: Churchill Livingstone: 131–134.

2 . Greer J.P., Macon W.R., McCurley T.L. (1999) Non-Hodgkin lymphoma. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Lippincott, Williams & Wilkins: 2471–2473.

3 . Bufo P. (1999) Academic lesson. The MALTomas.

4. Santacroce L. (1997) Academic lesson. Anatomy, physiology and surgical pathophysiology of the MALT.

5 . De Vita V., Hellman S., Rosenberg S. (2008) Cancer. Principles and Practices of Oncology. Philadelphia: 2098–2143.

6. Ming-Quing Du. (2007) MALT lymphoma: recent advances in aetiology and molecular genetics. J.Clin. Exp. Hematopathol., 47: 31–42.

7. Farinha P., Gascoyne R. (2005) Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma. J.Clin. Oncol., 23: 6370–6378.

8. Morgner A., ​​Schmelz R., Christian Thiede C. et al. (2007) Therapy of gastric mucosa associated lymphoid tissue lymphoma. World J. Gastroenterol., 13(26): 3554–356.

9 . Zucca E., Dreyling M. (2010) Gastric marginal zone lymphoma of MALT type: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 21: 175–176.

10 . Hoffmann M., Kletter K., Becherer A. et al. (2003) 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for staging and follow-up of marginal zone B-cell lymphoma. Oncology, 64: 336–340.

11. Jaffe E., Harris N., Stein H. et al. (2001) World Health Organization classification of tumours: Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press: 157–160.

12 . Hyung Soon Park, Yu Jin Kim, Woo Ick Yang et al. (2010) Treatment outcome of localized Helicobacter pylori- negative low-grade gastric MALT lymphoma. World J. Gastroenterol., 16(17): 2158–2162.

13 . Cohen S., Petryk M., Varma M. (2006) Non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue. The Oncologist, 11: 1100–1117.

14 . Rohatiner A., ​​d'Amore F., Coiffier B. et al. (1994) Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann. Oncol., 5: 397–400.

15 . Psyrril A., Papageorgiou S., Economopoulos T. (2008) Primary extranodal lymphomas of stomach: clinical presentation, diagnostic pitfalls and management. Ann. Oncol., 19: 1992–1999.

MALT-lymphoma: causes of blame, pathogenesis, classification, clinical picture

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

National Institute of Cancer, Kyiv

Summary. Extranodal lymphoma of the marginal zone, which is due to lymphoid tissue associated with mucous membranes (MALT), is characterized by specific pathogenetic, histological and clinical signs. Important criteria for the diagnosis of MALT-lymphoma, factors for the prognosis and the special treatment of patients with a diseased nosological form have been pointed out.

Keywords: extranodal lymphoma of the marginal zone, associated with mucous membranes (MALT), primary lymphoma of the duct, infection of the duct, associated with Helicobacter pylori, Wotherspoon score, 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. Lomonosov, 33/43
National Cancer Institute,
Email: [email protected]

Another name for this disease is malt (malt) lymphoma of the stomach. Pathology is characterized by a slow course and resembles gastric cancer in symptoms, although it differs from the latter in a more favorable prognosis.

The disease can occur in various forms: in all cases, the lymphoid tissue of the stomach is affected, as well as the mucous membrane of the organ. Recently, doctors in developed countries have noticed a trend towards a general increase in the number of gastric lymphomas, although in general this form of malignant ailments is among the rare ones.

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What it is

Every year the number of patients with malignant lymphomas increases. This circumstance is explained by several factors - the deterioration of the ecological situation on the planet, the use of food saturated with chemical additives, and the excessive load on the immune system of a modern person.

It is in lymphocytes that antibodies are formed that are responsible for the destruction or neutralization of pathogenic factors and agents that enter the body from the outside. Malfunctions of the immune system lead to the fact that antibodies are either produced in small quantities or begin to attack the cells of their own body.

Histological studies of gastric lymphomas reveal pathological accumulations of lymphoid tissue in the gastric mucosa and its submucosal layer. In this case, the glands of the stomach are infiltrated by lymphoid follicles, causing dysfunction of the digestive process.

Primary lymphoma of the stomach almost never gives metastases to the bone marrow and does not cause damage to the peripheral nodes of the lymphatic system.

The reasons

The exact cause of lymphomas is not known to medicine.

The following factors increase the risk of this disease:

• hereditary predisposition;
• the presence of autoimmune diseases;
• transferred organ transplant operations (kidney, bone marrow transplantation);
• infection with the bacterium Helicobacter;
• living in regions with high radiation levels;

excess ultraviolet exposure;

• irrational nutrition (and especially the use of vegetables with pesticides);
• suppression of the immune system as a result of the use of certain drugs or in patients with AIDS;
• contact with carcinogenic compounds.

An additional risk factor is age over 50 years and male gender.

Kinds

There are several types of lymphomas according to the form of the course:

• polypoid, which is an exophytic tumor growing into the lumen of the stomach;
• nodular, forming a primary tumor node on the gastric mucosa;
• ulcerative (infiltrative), characterized by the greatest aggressiveness.

Lymphomas of the stomach are also classified according to the histological structure.

There are the following varieties:

• lymphogranulomatosis of the stomach - more often a secondary disease that begins in the cervical and supraclavicular lymph nodes;
• non-Hodgkin's lymphoma of the stomach : the development of this pathology is associated with the activity of the bacterium Helocobacter (the primary focus is a differentiated tumor with varying degrees of malignancy);
• pseudolymphoma - a disease that begins as a benign lesion of the gastric mucosa, but has a high probability of transition to a malignant form with damage to the lymphoid tissue.

More often diagnosed are secondary gastric lymphomas resulting from metastasis from foci in other organs. Some researchers consider primary lymphomas to be a malignant complication of gastric pathologies such as chronic gastritis and peptic ulcer.

Symptoms of stomach lymphoma

As mentioned above, the clinical signs of lymphoma resemble gastric cancer.

Most patients at the onset of the disease have the following symptoms:

• dull and aching pain in the epigastrium;
• fast satiety after a small amount of food;
• nausea, vomiting;
• lack of appetite;
• aversion to certain types of food (in particular, to fatty meat);
• weight loss;
• fever (a sign is especially characteristic of diffuse lymphoma);
• increased night sweats.

The development of the disease and the spread of the malignant process lead to various complications - gastric stenosis (progressive narrowing of its lumen, which causes a decrease in the amount of food consumed and further weight loss), bleeding due to tumor perforation.

Diagnostics

Identification of the disease begins with a preliminary conversation between the doctor and the patient, during which a detailed history of the disease is compiled, an external examination of the patient is performed, and palpation of the abdominal cavity.

Diagnostic procedures for suspected gastric lymphoma are as follows:

• a blood test that allows you to assess the erythrocyte sedimentation rate (with lymphoma it is increased), as well as to identify specific proteins - cancer markers and microcytic anemia;
• endoscopy of the stomach allows you to make a visual examination of the mucous membrane of the organ, however, this diagnosis cannot be called indicative, since it is rather difficult to distinguish the picture of gastritis, ulcers from malignant lymphoma;
• tumor tissue biopsy and biopsy examination in the laboratory (a procedure to confirm the initial diagnosis);
• diagnostic laparotomy (minimally invasive surgery, during which tumor tissue can be taken for histological examination);
• cytological examination of biomaterial;
• x-ray examination;
• computed tomography: allows you to assess the size of the primary tumor, the degree of its spread beyond the walls of the stomach;
• MRI (allows you to find secondary lesions - metastases).

A competent diagnosis allows you to develop the most adequate treatment tactics. According to statistics, in half of the cases, lymphoma is detected at stages 1 and 2, which increases the likelihood of a favorable outcome.

Treatment

During the operation, nearby lymph nodes and organs are examined to determine the extent of their damage. If necessary, a complete gastrectomy is performed - resection of the stomach. The resectability of tumor foci at stage 1 reaches 75%.

Postoperative (adjuvant) therapy with chemotherapy drugs and radiation is prescribed regardless of the stage of the disease. The use of adjuvant therapy significantly improves the results of treatment and prolongs the period of remission.

Chemotherapy uses drugs such as:

• "Cyclophosphamide";
• "Vincristine";
• "Doxorubicin";
• "Prednisolone".

The entire abdominal cavity is irradiated, but the stomach area is more intense. Stages 3 and 4 also require combination therapy with gastric resection and subsequent enhanced course of drug treatment. In case of inoperable types of tumor (germination into large blood vessels, a serious condition of the patient), palliative treatment is performed.

In general, lymphoma responds well to chemotherapy without surgery, but the duration of remission depends on the degree of spread of the malignant process through the lymphatic system.

In some cases, chemotherapeutic treatment is performed first, and then gastric resection. Preliminary aggressive drug treatment helps to reduce the size of the tumor, which allows surgery to be performed if it was previously difficult.

Forecast

The prognosis of survival depends on many concomitant factors - the age of the patient, the state of his immune system and the presence of other diseases of the internal organs.

Survival for 5 years or more in stage 1 gastric lymphoma reaches 95%. In the second stage, the survival rate is -75%. At the stage of metastasis, the prognosis is less favorable, but with adequate treatment, out of 100 patients, 40-50 patients overcome the five-year period.

Unlike gastric cancer, lymphoma develops more slowly and metastasizes later (if at all). In some cases, the defeat of distant organs does not occur at all - the tumor spreads only to nearby tissues and organs. All these circumstances improve the prognosis and give a good chance of complete healing.

Diet

During treatment and during the recovery phase after surgery, proper nutrition is essential. It is recommended to correct the menu and radically change the diet. At this stage, the help of a qualified dietitian is needed.

Most patients have impaired appetite and persistent or intermittent stomach pain that makes it difficult to eat. All this leads to a decrease in the amount of nutrients consumed and further depletion of the body.

Properly selected diet helps to solve the problem of lack of appetite.

Menu examples for lymphoma

Menu #1

1. First breakfast. Meatballs from dietary meat with rice. Green tea.
2. Lunch. Shredded cottage cheese.
3. Dinner. Soup puree from boiled vegetables. Boiled fish (lean).
4. afternoon tea. Fresh vegetable or fruit juice.
5. Dinner. Well-boiled cereal porridge, boiled chicken.