Classification of non-Hodgkin lymphomas

Any classification is designed to accurately define and recognize an object, phenomenon or process. The diversity and variability of tumor processes lymphatic system until now does not give medicine the opportunity to build a full-fledged comprehensive classification of non-Hodgkin's lymphomas. The current attempts to create classifications for any one criterion do not allow sufficiently accurately and unambiguously to accurately determine the specific form of the disease.

The simplest classification according to the degree of malignancy of non-Hodgkin's lymphomas. More precisely, the rate of progression of the disease, since all lymphomas are malignant.

Classification by the rate of development of the disease

Very slow lymphomas process development, long time that do not affect the state of the body - indolent lymphomas.

Lymphomas with a very rapid, sometimes lightning-fast development of the process, which has an extremely pronounced detrimental effect on the body - aggressive lymphomas.

Lymphomas with an intermediate rate of development of the process, which have a noticeable and increasing effect on the body - an intermediate form of lymphomas.

Another type of classification that is quite often used in practice is division according to the place of origin of the tumor process.

Site classification

Lymphomas arising in the lymph nodes (node \u200b\u200b- nodus) are nodal.

Lymphomas that arise outside the lymph nodes (in the stomach, bone marrow, lungs, spleen, etc.) are extranodal.

By the World Health Organization adopted for general use a unified classification for the standardization of statistical and scientific data by physicians around the world.

WHO classification of non-Hodgkin lymphomas

B-cell tumors that develop from precursors of B-lymphocytes.

T-cell and NK-cell tumors that develop from the precursors of T-lymphocytes.

T-cell lymphomas that develop from peripheral (mature) T-lymphocytes.

The division used in the WHO classification is based primarily on the structural features of pathologically altered cells. These features are revealed by careful microscopic examination using a microscope. Structural differences are very important for scientific research, but the picture of the development of the disease seems to be more important for application directly in the clinic to solve the problems of treating patients.

For clinical use, the classification adopted by the Congress of Oncologists in the American city of Ann Arbor is used. The stage of development of the disease is used as a defining feature in the Ann Arbor classification. Focusing on the stage of development of lymphoma, it is possible to more accurately develop tactics and treatment methods to combat the disease.

Ann Arbor classification of non-Hodgkin lymphomas

1st stage

Lymph nodes of one local group are affected or manifestations of lymphoma are found in one internal organ.

Stage 2

Affected groups of lymph nodes, more than one, located on one side of the diaphragm. In this case, the transition of the process to one nearby organ is possible.

Stage 3

The defeat of groups of lymph nodes on both sides of the diaphragm. Perhaps the attachment of the defeat of one nearby organ and the spleen.

Stage 4

The disease has spread beyond the lymphatic system. Defeat remotely located internal organs (liver, lungs, bone marrow, pleura, stomach, intestines).

Lymphoma stages and lesions. At stages 3 and 4, inflamed nodes appear below the diaphragm line

To clarify the clinical picture of the disease, a letter designation (A or B) is added to the serial number of the stage, characterizing the presence or absence of pronounced external signs in the patient - weight loss, severe weakness, temperature, torrential night sweat.

Some types of non-Hodgkin lymphomas

Among the lymphomas that are not related to Hodgkin's disease, there are a number of more common, or simply better known due to their unusualness, or high malignancy of the disease.

Lymphosarcoma

Lymphosarcoma is perhaps the most well-known type of non-Hodgkin lymphoma. It can occur at any age, initially affecting the lymph nodes on one side of the neck, but other localization of the tumor (tonsils, pharynx, inguinal lymph nodes, gastrointestinal tract) is not excluded. Lymphosarcoma refers to aggressive tumors characterized by rapid growth and early metastasis to other lymph nodes (mediastinum, liver, spleen, abdominal cavity). At the same time, the patient's condition deteriorates sharply, who notes a significant weight loss, fever, accompanied by a torrential night sweat.

The diagnosis of lymphosarcoma is based mainly on the data of microscopic examination of the prints of the node (cytological analysis) and biopsy material (histological examination). In this case, cytology enjoys the predominant right of initial diagnosis, since it does not require a lot of labor. The taken, dried and torn material can be ready for viewing in a couple of hours. Imprints of lymph nodes allow to establish the presence of lymphoblasts in the material and the absence of mature lymphocytes, which confirms the presence of lymphosarcoma.

Burkitt's lymphoma

A disease related (which is an exception among lymphomas) to endemic - that is, associated with a certain area of \u200b\u200bresidence. Most of the reported cases of Burkitt's lymphoma are from Central Africa. The Epstein-Barr virus is believed to be the trigger for this form of lymphoma. Being the causative agent of another dangerous disease - infectious mononucleosis, this virus affects the gene structure of lymphocytes, causing lymphoma.

Burkitt's lymphoma is characterized by a severe, rapidly progressive course with a tendency to quickly go beyond the lymphatic system and damage organs. The abdominal cavity is often affected with an increase in regional groups of lymph nodes and intestines.

Burkitt's lymphoma does not occur in our country.

To recognize lymphomas, the histological classification is based on morphological features tumor cells and structures of the affected lymph node. Many cases require clarification of the diagnosis by studies: molecular genetic, cytogenetic and immunophenotyping. With the improvement of diagnostic methods, several new nosological units were identified, including rare species.

All types of lymphomas were combined according to the principle of therapeutic expediency. Today, two classifications are used that complement each other:

1. working classification of lymphomas;
2. wHO classification of lymphomas.

They are based on the REAL classification of lymphomas (Revised European American Classification of Lymphoid Tumors). They also use the amended and revised Kiel classification of lymphomas and Rappaport's classification.

Classification of lymphoid leukemias and lymphomas

CLASSIFICATION				Chromosome abnormalities	Origin%
REAL	Working	Kiel	Rappaport
LOW-DEGREE MALIGNANCES
Chronic lymphocytic leukemia, small lymphocyte lymphoma, prolymphric leukemia	A: Small lymphocyte lymphoma		Diffuse highly differentiated lymphocytic lymphoma	IN	Trisomy on the 12th chromosomes 1-11; 14; t-14; 19; t-9; 14
Chronic T-cell leukemia, T-cell prolymphocytic leukemia	A: Small lymphocyte lymphoma. E: Diffuse small cell lymphoma with split nuclei	Chronic lymphocytic leukemia, Prolymphocytic leukemia	Diffuse highly differentiated lymphocytic lymphoma	T	-
Large granular lymphocyte leukemia	A: Small lymphocyte lymphoma. E: Diffuse small cell lymphoma with split nuclei	Chronic lymphocytic leukemia, Prolymphocytic leukemia	Diffuse highly differentiated lymphocytic lymphoma. Diffuse poorly differentiated lymphocytic lymphoma	T	-
Hairy cell leukemia	-	Hairy cell leukemia	-	IN	-
Follicle center cell lymphoma (grade I)	B: follicular lymphoma of small cells with split nuclei		Diffuse poorly differentiated lymphocytic lymphoma	IN	t (14; 18); deletion on chromosome 6
Follicular center cell lymphoma (grade II)	C: Follicular lymphoma mixed, of small cells with split nuclei and large cells	Centroblast-centrocytic lymphoma	Nodular lowdifferentiated lymphocytic lymphoma	IN	t (14; 18); deletion in the 2nd chromosome; trisomy on chromosome 8
Lymphomas from cells of the marginal zone (lymph nodes and spleen / MACH lymphoma)	-	Monocytoid lymphoma, immunocytoma (lymph nodes and spleen or extranodal)	Nodular mixed cell lymphoma (lymphocytic-histiocytic)	IN	-
Fungal mycosis	-	Small cell lymphoma with cerebriform nuclei (fungal mycosis)	-	T	-
HIGH DEGREE MALIGNANCES
Follicle center cell lymphoma	D: Large cell follicular lymphoma	Follicular centroblastic lymphoma	Nodular histiocytic lymphoma	-	t (14; 18); trisomy on the 7th chromosome
Mantle cell lymphoma	E: Diffuse small cell lymphoma with split nuclei	Centrocytic lymphoma	Diffuse poorly differentiated lymphocytic lymphoma	-	t (11; 14)
Diffuse B - large cell lymphoma	F: Diffuse small cell and large cell lymphoma	Centroblastic lymphoma	Diffuse mixed cell lymphoma (lymphocytic-histiocytic).	IN	t (14; 18) / IGH - BCL2. t (3; 22) / B CL6. t (3; 14). t (2; 3); trisomies on the 4th, 7th and 21st chromosomes; deletions on chromosomes 6, 8 and 13
Primary large cell lymphoma of the mediastinum (thymic)	G: Diffuse large cell lymphoma	Mediastinal centroblastic lymphoma with sclerosis	Diffuse histiocytic lymphoma	IN	-
Peripheral T-cell lymphoma	F: Diffuse lymphoma mixed, from small and large cells G: Diffuse lymphoma from large cells. H: Large cell lymphoma, immunoblastism	Lymphoepithelioid lymphoma, polymorphic (small, medium or large cells)		T	t (14; 14) (q11; q32) / TRA - TCL1A. inv (14) (q11; q13). t (8; 14) (q24; q1). tq24; q (t (14; 14) (q11; q32) / TRA-TCL1A. inv (14) (q11; q32). t (8; 14) (q24; q11). t (10; 14)
T - cell angioimmunoblastic lymphoma	-	Angioimmunoblastic lymphoma	-	T	-
T - cell leukemia lymphoma in adults	-	Polymorphic lymphoma (from small, medium or large cells carrying the genome of T - human lymphotropic virus type 1)	-	T	-
Angiocentric lymphoma	-	-	Diffuse histiocytic lymphoma	T	-
Primary T-cell lymphoma of the small intestine	-	-	Polymorphic lymphoma (small, medium, or large cells)	T	-
Anaplastic large cell lymphoma	H: Large cell lymphoma, immunoblastic	Large cell anaplastic lymphoma (Ki1 +)	-	T (70) 0 (30)	t (2; 5)
B and T - lymphoblastic lymphomas	I: Lymphoblastic lymphoma	I: Lymphoblastic lymphoma	Diffuse lymphoblastic lymphoma	T (90) B (10)	-
Acute B - and T - lymphoblastic leukemias	-	-	-	B (80) T (20)	At - B-cell: t (9; 22), t (4; II), t (I; 19). T - cellular: 14qII or 7q34. B - cellular: t (8; 14), t (2; 8), I (8; 22)
Burkitt's lymphoma	J: Small cell lymphoma with non-cleaved Burkitt-type nuclei	Burkitt's lymphoma	Diffuse undifferentiated lymphoma	B (95) T (5)	t (8; 14), t (2; 8), t (8; 22)

0 - 0 - cellular immunophenotype; B - B - lymphocytes; T - T - lymphocytes.

Lymphoma in brief

The working classification of lymphomas includes the most common types of lymphoma. Rare - in the WHO and REAL classification, since it compares lymphoma cells with normal lymphoid cells. The WHO and REAL are based on immunophenotyping and cell ownership analysis, so they are more reproducible. High, medium and low grade cancers were included in the working classification, since there is not enough clarity between these categories. But from a clinical point of view, it was necessary to create a separate group from the formations of low malignancy. Malignant lymphomas would then include masses of medium to high malignancy. REAL - classification based on immunophenotyping makes it possible to accurately determine the belonging of cells to cell lines and divide lymphomas into separate nosologies, including those that are not included in the Working Classification.

Malignant lymphomas are lymphatic pathogenic diseases that occur in any organ. But can lymphoma be benign? Yes maybe.

Reactive processes give rise to simple lymphomas, consisting of a limited infiltration of lymph cells. Their light centers of reproduction are somewhat pronounced and morphologically identical to lymph follicles.

Stage 1 lymphoma - tumor detected:

• in one lymph node of one organ;
• lymphatic pharyngeal ring;
• thymus gland;
• spleen.

Stage is subdivided into stages: I and IE.

Stage II lymphoma is divided into stages II and IIE:

1. Stage II: Cancer cells are found in two or more LNs on either side of the diaphragm (the thin muscle between the lungs, it facilitates breathing and separates the chest from the peritoneum).
2. Stage IIE: Cancer cells are found in one or more groups of LNs under or above the diaphragm, as well as outside the LN in a nearby organ or muscles of the body. At stage 2, the prognosis will be favorable in the absence of risk factors:

• the tumor in the sternum has reached 10 cm;
• tumor in the LU and in the organ;
• erythrocytes in the blood are deposited at a high rate;
• affected by cancer cells 3 or more;
• the presence of symptoms: fever, hot flashes, weight loss.

Stage 3 lymphoma - divided into three stages: III, IIIE, IIIS and IIIE, S. Affected by the LN on both sides of the diaphragm, the organ and / or the spleen are affected.

1. Stage III: The tumor has spread to groups of lymph nodes under and above the diaphragm, is located at the top abdominal cavity.
2. Stage IIIE: The cancer has spread to groups of lymph nodes below and above the diaphragm. In addition, abnormal cells are found outside the lymph nodes in the nearest organ or body area, in the LN located along the aorta in the pelvis.
3. Stage IIIS: Cancer cells are found in LN clusters under and above the diaphragm and in the spleen.
4. Stage IIIE, S: Abnormal cells are found in groups of lymph nodes below and above the diaphragm, outside the lymph nodes in a nearby organ or body region, and in the spleen.

At stage 3, the prognosis is favorable in the absence of risk factors:

• male gender;
• age over 45;
• decreased levels of albumin or hemoglobin in the blood;
• an increased level of leukocytes in the blood (15,000 or higher);
• decreased level of lymphocytes (below 600 or less than 8% of the number of leukocytes).

The prospect of recovery with adequate treatment was noted in 10-15%, life expectancy of 5 years or more - in 80-85% of patients.

Stage 4 lymphoma is characterized by the following symptoms:

• the tumor has spread outside the lymph nodes and has affected one or more organs; malignant cells are located in the lymph nodes near these organs;
• pathology is found outside the lymph nodes in one organ and spreads beyond this organ;
• cancer cells are found in distant organs: cerebrospinal fluid, lung, bone marrow, liver.

At stage 4, a five-year survival rate was observed in 60% of patients.

TNM system classification - general rules

General rules of the TNM system

The TNM system was adopted to describe the anatomical spread of the lesion. It is based on three main components.

By them you can find out:

• T is the spread of the primary tumor;
• N - the absence or presence of metastases in regional lymph nodes and the degree of their damage;
• M - absence or presence of distant metastases.

To determine the spread of the malignant process, numbers are added to these three components: T0. T1. T2. T3. T4. N0. N1. N2. N3. M0. M1.

General rules for tumors of all localizations:

• All cases must be histologically confirmed at diagnosis. If there is no confirmation, then such cases are described separately.
• Each localization is described by two classifications:

1. Clinical classification TNM (or cTNM) is applied before starting treatment. It is based on data from clinical, X-ray, endoscopic studies of biopsy, surgical methods of research and a number of additional methods.
2. Pathological classification (post-surgical, pathologic classification), denoted - pTNM. It is based on data obtained before starting treatment, but supplemented or changed based on information received during surgical intervention or examination of the operating material.

In pathological assessment of the primary tumor (pT), a biopsy (or) resection of the primary tumor is performed to assess the highest pT grade.

To assess the pathology of regional LNs (pN), they are adequately removed and the absence (pN0) is determined or the upper limit of the pN category is estimated.

Pathological assessment of distant metastases (pM) is performed after their microscopic examination.

• After determining the T, N, M and / or pT, pN and pM categories, the stages are grouped. The established degree of spread of the tumor process through the TNM system or by stages in medical records do not change. Clinical classification helps to select and evaluate treatment methods, pathological - to obtain accurate data for predicting and evaluate long-term treatment results.
• If there is any doubt about the correctness of the definition of categories T. N or M - choose the lowest (less common) category and grouping by stages.
• If there are multiple synchronous malignant tumors in the same organ, the classification is based on the assessment of the tumor with the highest T category. Additionally, indicate the number of tumors (their multiplicity) - T2 (m) or T2 (5).

In the presence of synchronous bilateral tumors of paired organs, each of them is classified separately. In the presence of thyroid (8), liver and ovarian tumors, multiplicity is the T category criterion.

• TNM-defined categories or stage groupings are used for clinical or research purposes until the classification criteria are changed.

Non-Hodgkin lymphomas - classification

The main and common ones are:

• B-cell tumors from B-lymphocytes:

1. B-lymphoblastic lymphoma (B-cell acute lymphoblastic leukemia);
2. lymphocytic lymphoma (B-cell chronic lymphocytic leukemia)
3. B-cell prolymphocytic leukemia (B-cell lymphoma from small lymphocytes);
4. lymphoplasmacytic lymphoma;
5. lymphoma of the marginal zone of the spleen (spleen lymphoma) with or without villous lymphocytes;
6. hairy cell leukemia;
7. plasma cell myeloma / plasmacytoma (plasmablastic lymphoma);
8. lymphoma extranodal B-cell marginal zone type MALT;
9. follicular lymphoma;
10. B-cell lymphoma of the marginal zone with monocytic B-lymphocytes;
11. lymphoma from cells of the mantle zone (mantle cell lymphoma);
12. large cell lymphoma: anaplastic, mediastinal and diffuse large B-cell lymphoma (B-cell lymphoma);
13. mediastinal lymphoma - diffuse large B-cell;
14. primary exudative lymphoma;
15. burkitt leukemia / lymphoma;
16. anaplastic large cell lymphoma.

• T and NK - cell tumors from precursors of T-lymphocytes:

1. T-lymphoblastic lymphoma;

• T-cell lymphoma from peripheral (mature) T-lymphocytes:

1. T-cell prolymphocytic leukemia;
2. T-cell leukemia from large granular lymphocytes;
3. Aggressive NK cell leukemia;
4. Adult T cell lymphoma / leukemia (HTLV1 +) or peripheral T cell lymphoma;
5. Extranodal NK / T cell lymphoma, nasal type;
6. T-cell lymphoma associated with enteropathy;
7. Hepatolienal T-cell lymphoma;
8. T-cell panniculitis-like lymphoma of the subcutaneous tissue;
9. Fungal mycosis / Sesari's syndrome;
10. Anaplastic large cell lymphoma, T / 0-cell, with primary skin involvement;
11. Peripheral T-cell lymphoma, not specified;
12. Angioimmunoblastic T-cell lymphoma;
13. Anaplastic large cell lymphoma, T / 0-cell, with primary systemic involvement.

Non-Hodgkin's lymphoma is divided into 2 types: tumors B and T are cellular.

Treatment for them is different, because they are:

• aggressive - rapidly growing and progressive, manifested by many symptoms. Their treatment is started immediately. This gives a chance to completely get rid of oncological tumors;
• indolent lymphomas are chronic, benign or with a low degree of malignancy. Their condition requires constant monitoring and periodic treatment.

Diffuse large B cell tumors - these are aggressive forms of oncology that arise in any organ, but more often in the lymph nodes of the neck, armpits and groin. Rapid progress does not prevent the tumor from responding well to treatment.

Marginal - non-aggressive forms of oncological tumors. There are varieties of them and are found in the spleen, lymph nodes or other organs that do not belong to the lymphatic system. They appear more often in men after 60 years.

Lymphoblastic Is a type of T-cell lymphoma. T-lymphoblastic are malignant neoplasmscomposed of immature T-lymphocytes. They are inherited.

Anaplastic - belong to the aggressive forms of T-cell lymphomas. Normal ones must fulfill the function of the body's defense. But these cancer cells are underdeveloped. They cluster and increase in size in the groin, neck and armpit.

Mediastinal form b-cells and are found in the mediastinal region of women 30-40 years of age.

Small cell diffuse lymphoma (small cell lymphoma) is a type of non-Hodgkin B-cell lymphoma. They grow slowly and are difficult to treat.

Angioimmunoblastic lymphomas of T cells poorly perceive treatment and give poor prognosis.

Extranodal lymphomas characteristic malignant development in internal organs, including the brain, intestines, stomach.

Intestinal lymphomas are more often secondary and are manifested by nausea, abdominal pain, blood in feces.

Lymphomas in the abdominal cavity found in children and older people. Hodgkin's tumors and non-Hodgkin's types b and t affect the peritoneum.

Malignant cutaneous are rare and are characterized by multiple neoplasms, itching and skin inflammation.

Mediastinal lymphoma more often it appears as a B-cell non-Hodgkin primary tumor of indolent aggressive forms, are rare.

Bone lymphoma: primary and secondary occurs in the joints of the spine, ribs and pelvic bones. It is a consequence of metastasis.

Kidney lymphoma is a secondary form of cancer with the accumulation of cancer cells in the organ.

Liver lymphoma occurs in 10% of all confirmed lymphomas. It manifests itself as nonspecific heartburn and pain in the right hypochondrium or signs of jaundice, which complicates the confirmation of the diagnosis.

Thyroid lymphoma refers to a non-Hodgkin secondary tumor. They are rare due to the metastasis of the LN in the neck.

CNS lymphoma over the past 10 years, it has been more common due to AIDS. The tumor affects the brain and spinal cord.

Inguinal lymphoma LU meet in 3% of all cases of oncology. Oncology is aggressive and difficult to treat.

Lymphoma eyeball, as a type of non-Hodgkin's lymphoma, it is rare in patients over 30 years of age.

Mantle lymphoma grows from the cells of the mantle region. For men over 60, the prognosis is not encouraging.

Plasmablastic lymphoma is rare, but it is particularly aggressive: hemoglobin and platelets in the blood decrease, leukocytes grow sharply.

Retroperitoneal lymphoma affects the LN and metasizes to the stomach area, provoking secondary cancer.

Hand lymphoma occurs as a secondary cancer, when the vessels or veins are compressed by enlarged lymph nodes. This causes swelling of the hand.

Burkitt's lymphoma occurs when it appears in children's body herpes virus of 4 degrees. Isolated cases were registered on the territory of Russia.

How long do people live with lymphoma?

Let's dwell on the most famous types of lymphomas:

Hodgkin's lymphoma or lymphogranulomatosis. It differs from other types by the appearance of tumor tissue from giant B-lymphocytes in the lymph nodes. The tissue consists of special cells called Berezovsky-Sternberg-Reed.

With timely and adequate treatment, the body gives a positive response. Hodgkin's lymphoma - the prognosis at stages 1-2 gives 90% and higher, at 3-4 stages - 65-70%. With relapses, 50% or more of patients are cured. After 5 years of remission, lymphoma is considered cured, but patients are registered and monitored for the rest of their lives, since relapse can occur after 10-20 years.

- life expectancy depends on the form of oncological tumor, stage and complex therapy... The most aggressive forms most often give a favorable prognosis after chemotherapy in combination with folk remedies: medicinal herbs and mushrooms. Non-Hodgkin's lymphoma - life expectancy over 5 years and cure rate in 40% of patients.

If viewed from non-Hodgkin spleen lymphoma - the prognosis is favorable and is 95% before the stage of the spread of malignant cells. Late stages are characterized by splenomegaly - an abnormal enlargement of the organ. With the penetration of malignant lymphocytes into the bone marrow, circulatory system and "storage" in the body of lymphoid tissue for 5 years, only 10-15% of patients survive.

Small lymphocyte lymphoma: the prognosis is the same as chronic lymphocytic leukemia. These tumors are almost identical, since only the degree of involvement of peripheral blood in the oncological process is different for them.

From small lymphocytes and chronic lymphocytic lymphoma: symptoms initially do not appear, then nonspecific loss of weight and appetite appears. The second stage is characterized by bacterial complications against the background of hypogammaglobulinemia, as well as autoimmune hemolytic anemia, autoimmune thrombocytopenia, lymphadenopathy and gelatosplenomegaly.

The survival rate after treatment is 4-6 years. When these tumors transform into more aggressive ones, as in prolymorphic leukemia or diffuse large B cell lymphoma, the survival rate is 1 year.

Follicular lymphoma - the prognosis is impossible, since the tumor differs in chromosomal translocation t (14:18) and the lymphoma is considered incurable. The prognosis index by doctors from leading countries has not yet been clarified. If defined by three risk groups, then the first is the most benign. With long-term remission, patients live for more than 20 years. Older people after 50 years live only 3.5-5 years.

The most unfavorable for the prognosis is considered large cell lymphoma, prognosis depends on the stage. At stages III-IV, a low life expectancy was noted due to extranodal foci, general condition and the presence of serum lactate dehydrogenase (LDH).

More often people get sick after 40-50 years. The lesions are located in the LU of the neck, peritoneum, as well as extranodally in the testes, gastrointestinal tract, thyroid gland, salivary glands, bones, brain and skin. Tumors appear in the lungs, kidneys, and liver. Five-year survival rate is up to 70% -60% (1-2 stages) and 40% -20% (3-4 stages).

In diffuse large B-cell lymphosarcomas, infiltrating growth is characteristic, therefore, vessels grow, airways and nerves, bones are destroyed, the bone marrow is affected even at the beginning of the disease (10-20%). Metastases are detected in the central nervous system, in the later stages the bone marrow is especially affected and leukemization occurs. It is difficult to predict with this course of the disease.

Young women often have mediastinal lymphoma, prognosis recovery in patients up to 80%, if the processes are localized at stages 1-2. The tumor can grow into surrounding tissues and organs, but metastases are rare. Extranodal mediastinal lymphoma manifests itself in 30% of cases in the lymphatic pharyngeal ring, gastrointestinal tract, paranasal sinuses nose, bones or central nervous system. In 25% of cases, the tumor affects the bone marrow, which can be detected at stages 1-2. At 3-4 stages, the 5-year survival rate is 30-40%.

Informative video

Non-Hodgkin's lymphomas are a heterogeneous group of diseases characterized by monoclonal proliferation of malignant lymphoid cells in the lymphoreticular areas, including lymph nodes, bone marrow, spleen, liver, and gastrointestinal tract.

The disease usually presents with peripheral lymphadenopathy. However, in some forms, there is no enlargement of the lymph nodes, but there are abnormal lymphocytes in the circulating blood. Unlike Hodgkin's lymphoma, the disease is characterized by dissemination of the process at the time of diagnosis. The diagnosis is based on a lymph node or bone marrow biopsy. Treatment includes radiation and / or chemotherapy, and stem cell transplantation is usually performed as salvage therapy for incomplete remission or recurrence of the disease.

Non-Hodgkin's lymphoma is more common than Hodgkin's lymphoma. It is the 6th most common cancer in the United States, and about 56,000 new cases of non-Hodgkin's lymphomas are reported annually across all age groups. However, non-Hodgkin's lymphoma is not a single disease, but an entire category of lymphoproliferative malignant diseases. The incidence increases with age (median age is 50 years).

ICD-10 code

C82 Follicular [nodular] non-Hodgkin's lymphoma

C83 Diffuse non-Hodgkin's lymphoma

Causes of non-Hodgkin lymphomas

The majority of non-Hodgkin's lymphomas (80 to 85%) originate from B cells, in the rest of the cases, the source of the tumor is T cells or natural killer cells. In all cases, early or mature progenitor cells are the source.

The cause of non-Hodgkin's lymphomas is unknown, although, as with leukemia, there are strong indications of a viral nature of the disease (eg, human T-cell leukemia / lymphoma virus, Epstein-Barr virus, HIV). Risk factors for the development of non-Hodgkin's lymphomas are immunodeficiency (secondary post-transplant immunosuppression, AIDS, primary immune diseases, dry eye syndrome, RA), infection Helicobacter pylori,exposure to certain chemicals, previous treatments for Hodgkin's lymphoma. Non-Hodgkin's lymphomas are the second most common cancer in HIV-infected patients, and AIDS is defined in many primary patients with lymphoma. Rearrangement S-tuscharacteristic of some AIDS-associated lymphomas.

Leukemias and non-Hodgkin lymphomas have many common features, since in both pathologies, lymphocytes or their precursors proliferate. For some types of non-Hodgkin lymphomas clinical picture, similar to leukemia with peripheral lymphocytosis and bone marrow involvement, occurs in 50% of children and 20% of adults. Differential diagnosis can be difficult, but usually in patients with many lymph nodes (especially mediastinopic) involvement, a small number of circulating abnormal cells and blast forms in the bone marrow (

Hypogammaglobulinemia, caused by a progressive decrease in immunoglobulin production, occurs in 15% of patients and can predispose to the development of severe bacterial infections.

Symptoms of non-Hodgkin lymphomas

In many patients, the disease manifests itself as asymptomatic peripheral lymphadenopathy. The enlarged lymph nodes are elastic and mobile, later they merge into conglomerates. In some patients, the disease is localized, but in the majority there are multiple lesions. Mediastinal and retroperitoneal lymphadenopathy can cause compression symptoms in various organs. Extranodal lesions may dominate the clinical picture (eg, gastric involvement may mimic cancer; bowel lymphoma may cause malabsorption syndrome; CNS is often affected in HIV patients).

Skin and bones are initially affected in 15% of patients with aggressive lymphomas and in 7% of patients with indolent lymphomas. Sometimes in patients with a pronounced process in the abdominal or chest cavity, chyle ascites or pleural effusion caused by obstruction of the lymphatic ducts develops. Weight loss, fever, night sweats, and asthenia indicate disseminated disease. Patients may also have splenomegaly and hepatomegaly.

Two signs are typical in NHL and are rare in Hodgkin's lymphoma: hyperemia and edema of the face and neck may occur due to compression of the superior vena cava (superior vena cava syndrome or superior mediastinal syndrome), compression of the ureter by the retroperitoneal and / or pelvic lymph nodes disrupts flow of urine through the ureter and can lead to secondary renal failure.

Anemia initially occurs in 33% of patients and gradually develops in most patients. Anemia can be due to the following reasons: bleeding with gastrointestinal lymphoma with or without thrombocytopenia; hypersplenism or Coombs-positive hemolytic anemia; infiltration of bone marrow with lymphoma cells; myelosuppression caused by chemotherapy or radiation therapy.

T-cell lymphoma / leukemia (associated with HTLV-1) has an acute onset, violent clinical course with skin infiltration, lymphadenopathy, hepatosplenomegaly and leukemia. Leukemia cells are malignant T cells with altered nuclei. Hypercalcemia often develops, associated more with humoral factors than with bone damage.

Patients with anaplastic large cell lymphoma have rapidly progressive skin lesions, adenopathy, and damage to the visceral organs. This disease can be mistaken for Hodgkin's lymphoma or metastases of undifferentiated cancer.

Staging of non-Hodgkin lymphomas

Although localized non-Hodgkin's lymphomas are sometimes found, the disease is usually disseminated at the time of diagnosis. Tests for staging are CT scans of the chest, abdomen and pelvis, PET, and bone marrow biopsy. The definitive staging of non-Hodgkin's lymphomas, as in Hodgkin's lymphoma, is based on clinical and histological findings.

Classification of non-Hodgkin lymphomas

The classification of non-Hodgkin's lymphomas continues to evolve, reflecting new knowledge of the cellular nature and biological basis of these heterogeneous diseases. The most common is the WHO classification, reflecting the immunophenotype, genotype and cytogenetics of cells; there are other classification of lymphomas (for example, the Lyon classification). The most important new types of lymphomas included in the WHO classification are lymphoid tumors associated with mucous membranes; lymphoma from cells of the mantle area (previously diffuse from small cleaved cells lymphoma) and anaplastic large cell lymphoma, a heterogeneous disease, in 75% of cases originating from T cells, in 15% from B cells, in 10% of cases - unclassified. However, despite the variety of types of lymphomas, their treatment is often the same, except for certain types of T-cell lymphomas.

Lymphomas are usually classified as indolent and aggressive. Indolent lymphomas progress slowly and respond to therapy, but are incurable. Aggressive lymphomas progress rapidly but respond to therapy and are often curable.

In children, non-Hodgkin's lymphomas are almost always aggressive. Follicular and other indolent lymphomas are very rare. Treatment of aggressive lymphomas (Burkitt, diffuse large B-cell and lymphoblastic lymphoma) requires special approaches due to the involvement of such areas as the gastrointestinal tract (especially in the terminal ileum); meninges and other organs (such as the brain, testes). It is also necessary to take into account possible development side effects therapy such as secondary malignant tumors, cardiorespiratory complications, and the need to maintain fertility. Currently research work are aimed at solving these issues, as well as studying the development of the tumor process at the molecular level, prognostic factors for lymphoma in children.

Subtypes of non-Hodgkin's lymphoma (WHO classification)

B cell tumors

T- and NK-cell tumors

From precursors of B cells B-lymphoblastic leukemia / B-cell precursor lymphoma From mature B cells B-cell chronic lymphocytic leukemia / small cell lymphocytic lymphoma. B-cell prolymphocytic leukemia. Lymphoplasmacytic lymphoma. B-cell lymphoma from cells of the marginal zone of the spleen. Hairy cell leukemia. Plasma cell myeloma / plasmacytoma. Extranodal B-cell lymphoma of the marginal zone of lymphoid tissue (MALT lymphoma). Nodal B-cell lymphoma from cells of the marginal zone. Follicular lymphoma. Lymphoma from cells of the mantle zone. Diffuse large B-cell lymphomas. (including mediastinal large B-cell lymphoma, primary exudative lymphoma). Burkitt's lymphoma

From precursors of T cells T-lymphoblastic leukemia / lymphoma from precursor T cells. From mature T cells T-cell prolymphocytic leukemia. T-cell leukemia from large granular leukocytes. Aggressive NK cell leukemia. Adult T cell leukemia / lymphoma (HTLV1-positive). Extranodal 1MCD-cell lymphoma, nasal type. Hepatosplenic T-cell lymphoma. Subcutaneous panniculitis-like T-cell lymphoma. Fungal mycosis / Sesari's syndrome. Anaplastic large cell T / NK cell lymphoma, primary cutaneous type. Peripheral T-cell lymphoma, nonspecific. Angioimmunoblastic T-cell lymphoma

MALT is lymphoid tissue associated with mucous membranes.

NK are natural killers.

HTLV 1 (human T-cell leukemia virus 1) - human T-cell leukemia virus 1.

Aggressive.

Indolent.

Indolent, but rapidly progressing.

Diagnosis of non-Hodgkin lymphomas

Non-Hodgkin's lymphoma is suspected in patients with painless lymphadenopathy or when mediastinal adenopathy is found on routine chest x-ray. Painless lymphadenopathy can result from infectious mononucleosis, toxoplasmosis, cytomegalovirus infection or leukemia.

Radiographic findings may be similar to lung cancer, sarcoidosis or tuberculosis. Less commonly, the disease is detected in connection with lymphocytosis in the peripheral blood and the presence of nonspecific symptoms. In such cases differential diagnosis is performed with leukemia, Epstein-Barr virus infection and Duncan syndrome.

A chest x-ray is performed if it has not been previously performed, as well as a lymph node biopsy if lymphadenopathy is confirmed on a CG or PET scan. In the presence of enlarged mediastinal lymph nodes, the patient needs to perform a biopsy of the lymph node under the control of CG or mediastinoscopy. The following examinations are performed as standard: general analysis blood, alkaline phosphatase, renal and hepatic function tests, LDH, uric acid. Other tests are done based on preliminary findings (eg, MRI for symptoms of spinal cord compression or CNS abnormalities).

Histological criteria for biopsy are a violation of the normal structure of the lymph node and invasion of the capsule, as well as the detection of characteristic tumor cells in the adjacent adipose tissue. Immunophenotyping determines the nature of cells, identifies specific subtypes and helps to determine the prognosis and management of the patient; these studies should also be performed on peripheral blood cells. The presence of the panleukocyte antigen CD45 helps to exclude metastatic cancer, which is often found when differential diagnosis undifferentiated types of cancer. Determination of total leukocyte antigen and gene rearrangement (documenting B- or T-cell clonality) is necessarily performed on fixed tissues. Cytogenetic studies and flow cytometry require fresh biopsies.

Treatment for non-Hodgkin lymphomas

Treatment for non-Hodgkin's lymphoma varies greatly depending on the cell type of lymphoma, and there are many treatment programs that do not allow us to dwell on them in detail. Fundamentally different approaches to the treatment of localized and disseminated stages of lymphoma, as well as aggressive and indolent lymphomas.

Localized non-Hodgkin's lymphoma (stages I and II)

Indolent lymphoma is rarely diagnosed at the stage of localized lesion, but in the presence of such a lesion, regional radiation therapy can lead to long-term remission. However, more than 10 years after radiation therapy, the disease may recur.

About half of patients with aggressive lymphomas are diagnosed in the stage of localized lesions, in which polychemotherapy in combination with or without regional radiation therapy is usually effective. Patients with lymphoblastic lymphomas or Burkitt's lymphoma, even with localized lesions, should be treated with intensive chemotherapy regimens with the prevention of central nervous system damage. Supportive therapy (for lymphoblastic lymphoma) may be required, but full recovery is possible.

Common form of non-Hodgkin's lymphoma (stage III and IV)

There are various approaches to the treatment of indolent lymphomas. A watch-and-wait approach, therapy with one alkylating drug or a combination of 2 or 3 chemotherapy drugs, can be used. The choice of treatment strategy is based on a number of criteria, including age, general status, prevalence of the disease, tumor size, histological variation, and expected treatment efficacy. Rituximab (anti-CD20 antibodies to B cells) and other biological drugs that are used in combination with chemotherapy or as monotherapy are effective. Recent reports of the use of antibodies conjugated to radioisotopes are promising. Although the survival rate of patients can be calculated in years, the long-term prognosis is poor due to the occurrence of late relapses.

For patients with aggressive B-cell lymphomas (eg, diffuse large B-cell lymphoma), the standard combination is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Complete regression of the disease occurs in more than 70% of patients and depends on the risk category (determined by the MFI). More than 70% of patients with a complete response to treatment recover, relapses 2 years after completion of treatment are rare.

The effectiveness of the use of autologous transplantation in the first line of therapy is being studied. In accordance with the MPI, patients at high risk can be selected for therapy with dose intensification regimens. It is currently being studied whether such treatment tactics chances of a cure. Individual patients with mantle cell lymphoma may also be candidates for this type of therapy.

Recurrence of aggressive lymphoma

The first relapse after the first line of therapy is almost always treated with autologous hematopoietic stem cell transplantation. Patients must be younger than 70 years of age with a satisfactory general status, respond to standard chemotherapy, and have the required number of collected CD34 + stem cells (collected from peripheral blood or bone marrow). Consolidation myeloablative therapy includes chemotherapy with or without radiation therapy. The feasibility of using immunotherapy (eg, rituximab, vaccination, IL-2) after the completion of chemotherapy is being investigated.

In allogeneic transplantation, stem cells are harvested from a compatible donor (brother, sister, or a compatible unrelated donor). Allogeneic transplantation provides a double effect: restoration of normal hematopoiesis and a "graft versus disease" effect.

Recovery is expected in 30-50% of patients with aggressive lymphomas undergoing myeloablative therapy. In indolent lymphomas, recovery from autologous transplantation is questionable, although remission may be achieved more frequently than with palliative therapy alone. The mortality rate of patients after the use of the myeloablative regimen ranges from 2 to 5% after autologous transplantation, and about 15% after allogeneic transplantation.

Consequences of standard and high-dose chemotherapy are secondary tumors, myelodysplasias, and acute myeloid leukemia. Chemotherapy in combination with radiation therapy increases this risk, although the incidence of these complications does not exceed 3%.

Non-Hodgkin lymphoma prognosis

The prognosis for patients with T-cell lymphoma is generally worse than for patients with B-cell lymphomas, although new intensive treatment programs are improving the prognosis.

Survival also depends on many factors. The International Prognostic Index (IPI) is often used for aggressive lymphomas. It is based on 5 risk factors: age over 60, poor general status [by ECOG (Eastern Cooperative Oncology Group)], increased LDH, extranodal lesions, stage III or IV. The effectiveness of treatment decreases with an increase in the number of risk factors; the actual survival rate also depends on the cell type of the tumor, for example, in large cell lymphoma, the 5-year survival rate in patients with 0 or 1 risk factor is 76%, while in patients with 4 or 5 risk factors it is only 26%. Usually, patients with\u003e 2 risk factors should receive more aggressive or experimental treatment. For indolent lymphomas, the Modified International Follicular Lymphoma Prognostic Index (FLIPI) is used.

It is important to know!

The diagnostic assessment of benign and malignant lymphoproliferative skin diseases is a very difficult task for the pathologist. In recent decades, significant progress has been made in this direction, associated with the success of immunology.

- neoplastic diseases of the lymphatic system, represented by malignant B- and T-cell lymphomas. The primary focus may arise in the lymph nodes or other organs and subsequently metastasize by the lymphogenous or hematogenous route. The clinic of lymphomas is characterized by lymphadenopathy, symptoms of damage to one or another organ, and febrile intoxication syndrome. Diagnostics is based on clinical and radiological data, results of hemogram examination, biopsy of lymph nodes and bone marrow. Antineoplastic treatment includes courses of polychemotherapy and radiation therapy.

ICD-10

C82 C85

General information

Non-Hodgkin's lymphomas (NHL, lymphosarcomas) are malignant lymphoproliferative tumors of various morphology, clinical signs and course, differing in their characteristics from Hodgkin's lymphoma (lymphogranulomatosis). Depending on the place of origin of the primary focus, hemoblastoses are divided into leukemias (tumor lesions of the bone marrow) and lymphomas (tumors of lymphoid tissue with primary extra-cerebral localization). On the basis of the distinctive morphological features, lymphomas, in turn, are subdivided into Hodgkin and non-Hodgkin; the latter in hematology include B- and T-cell lymphomas. Non-Hodgkin's lymphomas occur in all age groups, but more than half of cases of lymphosarcoma are diagnosed in people over 60 years of age. The average incidence rate among men is 2-7 cases, among women - 1-5 cases per 100,000 population. In recent years, there has been a trend towards a progressive increase in morbidity.

Causes

The etiology of lymphosarcoma is not known for certain. Moreover, the causes of lymphomas of various histological types and locations vary considerably. Currently, it is more correct to talk about risk factors that increase the likelihood of developing lymphoma, which are currently well understood. The influence of some etiofactors is significant, the contribution of others to the etiology of lymphomas is very insignificant. Such unfavorable prerequisites include:

• Infections... The greatest cytopathogenic effect on lymphoid cells is possessed by the human immunodeficiency virus (HIV), hepatitis C, and T-lymphotropic virus type 1. The relationship between infection with the Epstein-Barr virus and the development of Burkitt's lymphoma has been proven. It is known that Helicobacter pylori infection associated with gastric ulcer can cause the development of lymphoma of the same localization.
• Immunity defects... The risk of lymphomas increases with congenital and acquired immunodeficiencies (AIDS, Wiskott-Aldrich syndrome, Louis Bar, X-linked lymphoproliferative syndrome, etc.). In patients receiving immunosuppressive therapy for bone marrow or organ transplantation, the likelihood of developing NHL increases 30-50 times.
• Accompanying illnesses.An increased risk of NHL morbidity is observed among patients with rheumatoid arthritis, lupus erythematosus, which can be explained by both immune disorders and the use of immunosuppressive drugs for the treatment of these conditions. Thyroid lymphoma usually develops in the presence of autoimmune thyroiditis.
• Toxic effects... There is a causal relationship between lymphosarcomas and previous contact with chemical carcinogens (benzene, insecticides, herbicides), UV radiation, radiation therapy for cancer... Cytotoxic drugs used for chemotherapy have a direct cytopathic effect.

Pathogenesis

Pathological lymphogenesis is initiated by one or another oncogenic event that disrupts the normal cell cycle. This can involve two mechanisms - activation of oncogenes or suppression of tumor suppressors (anti-oncogenes). A tumor clone in NHL in 90% of cases is formed from B-lymphocytes, extremely rarely - from T-lymphocytes, NK-cells or undifferentiated cells. Certain chromosomal translocations are characteristic of different types of lymphomas, which lead to suppression of apoptosis, loss of control over proliferation and differentiation of lymphocytes at any stage. This is accompanied by the appearance of a clone of blast cells in the lymphatic organs. Lymph nodes (peripheral, mediastinal, mesenteric, etc.) increase in size and can disrupt the function of nearby organs. With infiltration of the bone marrow, cytopenia develops. The growth and metastasis of the tumor mass is accompanied by cachexia.

Classification

Lymphosarcomas that primarily develop in the lymph nodes are called nodal, in other organs (palatine and pharyngeal tonsils, salivary glands, stomach, spleen, intestines, brain, lungs, skin, thyroid gland and others) - extranodal. According to the structure of tumor tissue, NHL are divided into follicular (nodular) and diffuse. According to the rate of progression, lymphomas are classified into indolent (with a slow, relatively favorable course), aggressive and highly aggressive (with rapid development and generalization). If untreated, patients with indolent lymphomas live on average 7-10 years, with aggressive ones - from several months to 1.5-2 years.

The modern classification has over 30 different types lymphosarcoma. Most of tumors (85%) originate from B-lymphocytes (B-cell lymphomas), the rest from T-lymphocytes (T-cell lymphomas). Within these groups, there are various subtypes of non-Hodgkin's lymphomas. The group of B-cell tumors includes:

• diffuse large B cell lymphoma - the most common histological type of lymphosarcoma (31%). It is characterized by aggressive growth, despite this, in almost half of the cases, it can be completely cured.
• follicular lymphoma - its frequency is 22% of the number of NHLs. The course is indolent, but transformation into aggressive diffuse lymphoma is possible. The prognosis for a 5-year survival rate is 60-70%.
• small cell lymphocytic lymphoma and chronic lymphocytic leukemia - close types of NHL, which account for 7% of their number. The course is slow, but difficult to treat. The prognosis is variable: in some cases, lymphosarcoma develops within 10 years, in others, at a certain stage it turns into a fast-growing lymphoma.
• mantle cell lymphoma - in the structure of the NHL is 6%. Only 20% of patients overcome the five-year border of survival.
• B-cell lymphomas from cells of the marginal zone - are divided into extranodal (can develop in the stomach, thyroid, salivary, mammary glands), nodal (develop in the lymph nodes), splenic (localized in the spleen). They are characterized by slow local growth; in the early stages are well curable.
• B-cell mediastinal lymphoma - occurs rarely (in 2% of cases), however, unlike other types, it mainly affects young women 30-40 years old. Due to the rapid growth, it causes compression of the mediastinal organs; cured in 50% of cases.
• waldenstrom macroglobulinemia (lymphoplasmacytic lymphoma) - diagnosed in 1% of patients with NHL. It is characterized by overproduction of IgM by tumor cells, which leads to an increase in blood viscosity, vascular thrombosis, and capillary ruptures. It can have both relatively benign (with a survival rate of up to 20 years) and rapid development (with the death of the patient within 1-2 years).
• hairy cell leukemia - a very rare type of lymphoma that occurs in the elderly. The course of the tumor is slow, not always requiring treatment.
• burkitt's lymphoma - it accounts for about 2% of the NHL. In 90% of cases, the tumor affects young men under 30. Burkitt's lymphoma growth is aggressive; intensive chemotherapy can achieve a cure for half of the patients.
• central lymphoma nervous system - Primary CNS damage may involve the brain or spinal cord. More often associated with HIV infection. The five-year survival rate is 30%.

Non-Hodgkin's lymphomas of T-cell origin are represented by:

• T-lymphoblastic lymphoma or progenitor cell leukemia - meets with a frequency of 2%. They differ in the number of blast cells in the bone marrow:<25% опухолевых клеток патология расценивается как лимфома, при >25% is like leukemia. It is diagnosed mainly in young people, the average age of the sick is 25 years. The worst prognosis has T-lymphoblastic leukemia, the cure rate for which does not exceed 20%.
• peripheral T-cell lymphomasincluding cutaneous lymphoma (Sesary's syndrome, fungal mycosis), angioimmunoblastic lymphoma, extranodal lymphoma from natural killer cells, lymphoma with enteropathy, panniculitis-like lymphoma of the subcutaneous tissue, large cell anaplastic lymphoma. The majority of T-cell lymphomas are rapid and the outcome is poor.

Symptoms

Options clinical manifestations NHL varies greatly depending on the localization of the primary focus, the prevalence of the tumor process, the histological type of tumor, etc. All manifestations of lymphosarcoma fit into three syndromes: lymphadenopathy, fever and intoxication, extranodal lesions. In most cases, the first sign of NHL is an increase in peripheral lymph nodes. At first, they remain elastic and mobile, and later merge into extensive conglomerates. Lymph nodes in one or more areas may be affected at the same time. With the formation of fistulous passages, actinomycosis and tuberculosis must be excluded.

Such nonspecific symptoms of lymphosarcoma as fever for no apparent reason, night sweats, weight loss, asthenia in most cases indicate a generalized nature of the disease. Among extranodal lesions, non-Hodgkin's lymphomas of the Pirogov-Waldeyer ring, gastrointestinal tract, brain dominate, less often the mammary gland, bones, lung parenchyma, and other organs are affected. Nasopharyngeal lymphoma with endoscopic examination has the appearance of a tumor of pale pink color with bumpy contours. The maxillary and ethmoid sinus, orbit often grows, causing difficulty in nasal breathing, rhinophonia, hearing loss, exophthalmos.

Primary testicular lymphosarcoma may have a smooth or bumpy surface, elastic or stony density. In some cases, scrotal edema, ulceration of the skin over the tumor, and enlargement of the inguinal-iliac lymph nodes develop. Testicular lymphomas are prone to early dissemination with damage to the second testicle, central nervous system, etc. Breast lymphoma on palpation is defined as a clear tumor node or diffuse breast lump; retraction of the nipple is uncommon. When the stomach is affected, the clinical picture resembles stomach cancer, accompanied by pain, nausea, loss of appetite, and weight loss. Abdominal lymphosarcomas can manifest themselves as partial or complete intestinal obstruction, peritonitis, malabsorption syndrome, abdominal pain, ascites. Skin lymphoma is manifested by itching, nodules, and reddish-purple induration. Primary CNS damage is more typical for AIDS patients - the course of lymphoma of this localization is accompanied by focal or meningeal symptoms.

Complications

The presence of a significant tumor mass can cause compression of organs with the development of life-threatening conditions. With damage to the mediastinal lymph nodes, compression of the esophagus and trachea develops, the syndrome of compression of the SVC. Enlarged intra-abdominal and retroperitoneal lymph nodes can cause intestinal obstruction, lymphostasis in the lower half of the body, obstructive jaundice, and compression of the ureter. Germination of the walls of the stomach or intestines is dangerous due to the occurrence of bleeding (in case of arrosion of blood vessels) or peritonitis (when the contents enter the abdominal cavity). Immunosuppression makes patients susceptible infectious diseasesthat poses a threat to life. High-grade lymphomas are characterized by early lymphogenous and hematogenous metastasis to the brain and spinal cord, liver, and bones.

Diagnostics

Diagnostics of non-Hodgkin's lymphomas are in the competence of oncohematologists. Clinical criteria lymphosarcomas are an increase in one or several groups of lymph nodes, intoxication phenomena, extranodal lesions. To confirm the proposed diagnosis, it is necessary to carry out morphological verification of the tumor and instrumental diagnostics:

• Study of the tumor cell substrate... Diagnostic operations are performed: puncture or excisional biopsy of lymph nodes, laparoscopy, thoracoscopy, aspiration puncture of the bone marrow with subsequent immunohistochemical, cytological, cytogenetic and other studies of the diagnostic material. In addition to diagnostics, establishing the structure of NHL is important for choosing treatment tactics and determining prognosis.
• Imaging techniques... An increase in the mediastinal and intra-abdominal lymph nodes is detected by ultrasound of the mediastinum, X-ray and CT of the chest, abdominal cavity. According to the indications, the examination algorithm includes ultrasound of lymph nodes, liver, spleen, mammary glands, thyroid gland, scrotum organs, gastroscopy. For the purpose of staging the tumor, MRI of the internal organs is performed; lymphoscintigraphy and bone scintigraphy are informative in detecting metastases.
• Laboratory diagnostics ... Aimed at assessing risk factors and function of internal organs in lymphomas of various localizations. In the risk group, the HIV antigen, anti-HCV is determined. A change in peripheral blood (lymphocytosis) is characteristic of leukemization. In all cases, a biochemical complex is studied, including liver enzymes, LDH, uric acid, creatinine, and other indicators. B2-microglobulin can serve as a kind of NHL tumor marker.
• Chemotherapy... Most often, treatment of lymphomas begins with a course of chemotherapy. This method can stand alone or be combined with radiation therapy. Combined chemoradiation therapy can achieve longer remissions. The treatment continues until complete remission is achieved, after which it is necessary to carry out another 2-3 consolidating courses. It is possible to include hormone therapy in treatment cycles.
• Surgical interventions... It is usually used for isolated damage to an organ, more often the gastrointestinal tract. Whenever possible, operations are radical in nature - extended and combined resections are performed. In advanced cases, with the threat of perforation of hollow organs, bleeding, bowel obstruction, cytoreductive interventions can be performed. Surgical treatment is necessarily complemented by chemotherapy.
• Radiation therapy... As a monotherapy, lymphomas are used only for localized forms and a low degree of malignancy of the tumor. In addition, radiation can also be used as a palliative method if other treatment options are impossible.
• Additional treatment regimens. Of the alternative methods, immunochemotherapy with the use of interferon and monoclonal antibodies has proven itself well. In order to consolidate remission, autologous or allogeneic bone marrow transplantation and the introduction of peripheral stem cells are used.

Forecast and prevention

The prognosis for non-Hodgkin's lymphomas is different, depending mainly on the histological type of tumor and the stage of detection. With locally advanced forms, long-term survival is on average 50-60%, with generalized forms - only 10-15%. Adverse prognostic factors are age over 60 years, stages III-IV of the oncological process, involvement of the bone marrow, the presence of several extranodal foci. At the same time, modern PCT protocols in many cases allow achieving long-term remission. The prevention of lymphomas correlates with known causes: it is recommended to avoid infection with cytopathogenic viruses, toxic effects, excessive sun exposure. If you have risk factors, you should undergo regular examination.

Lymphomas are regional neoplastic diseases. There can be B- and T-cell passage. Often, lymphomas are the terminal stage of lecosis, and they themselves can transform into it. These include:

1. Lymphosarcoma: lymphocytic, prolymphocytic, lymphoblastic, immunoblastic, lymphoplasmacytic, African lymphoma (Burkit's tumor)

2. Mushroom mycosis

3. Cesari's disease

4. Reticulosarcoma

5. Lymphagranulomatosis (b. Hodgkin's)

Hodgkin's lymphoma: macro- and microscopic picture, forms, complications. The causes of death.

Hodgkin's lymphoma is a chronic recurrent disease in which the growth of the tumor occurs mainly in the lymph nodes. Morphologically distinguish between isolated (one group of lymph nodes is damaged, more often cervical, mediastinal and retroperitoneal, they increase in size and fuse together) and generalized lymphogranelematosis (they detect not only the focus of primary localization, but also far beyond it, the spleen increases, its tissue on section has a variegated appearance).

Microscopically, the proliferation of atypical cells is detected: 1) small Hodgkin cells (similar to lymphoblasts); 2) Large Hodgkin cells; 3) multinucleated cells of Reed-Berezovsky-Sternberg

There are 4 variants of the disease: 1) with a predominance of lymphoid tissue (lymphohistiocytic) is characteristic of the early phase of the disease stage 1-2, only the proliferation of mature lymphocytes is detected.

2) nodular (nodular) sclerosis, often has a benign course, with predominant localization in the mediastinum. Microscopically, the proliferation of fibrous tissue is detected around the bowels with atypical cells.

3) the mixed cell variant corresponds to the 2-3 stage of the disease. Microscopically, the proliferation of lymphoid elements of various degrees of maturity, atypical cells, basophils, eostnophils, neutrophils, plasma cells are detected.

4) the variant with the suppression of lymphoid tissue occurs with an unfavorable course of the disease. Diffuse proliferation is noted connective tissue, among the fibers of which there are atypical cells, or lymphoid tissue can be displaced by atypical cells.

Non-Hodgkin's lymphomas: typing, classification, pathological anatomy, causes of death.

1. Lymphosarcoma malignant tumorarising from cells of the lymphocytic series. It affects the lymph nodes, often mediastinal and retroperitoneal. The lymph nodes increase, solder, forming packets that squeeze the surrounding tissues. There are the following histocytological variants of lymphomas: lymphocytic, prolymphocytic, lymphoblastic, immunoblastic, lymphoplasmacytic, African lymphoma (Burkit's tumor). Tumors consisting of mature lymphocytes are called lymphocytomas, from lymphoblasts and immunoblasts - lymphosarcomas.

Burkit's tumor is an endemic disease that occurs among the population of equatorial Africa. Usually children 4-8 years old are ill. Localized in the upper or lower jaw, as well as in the ovaries. The tumor consists of small lymphocyte-like cells, among which are scattered large macrophages with a light cytoplasm (picture of the "starry sky"). The development of African lymphoma is associated with the herpes-like virus.

2. Fungal mycosis - a relatively benign T-cell lymphoma of the skin, refers to skin lymphomatosis. Multiple tumor nodes in the skin are composed of proliferating large cells with a large number mitoses. The nodes are of a soft consistency, protrude above the surface of the skin, sometimes resemble the shape of a fungus, have a bluish color, and are easily manifested. Also, the nodes can be in CO, muscles, internal organs.

3. Sesari's disease - T-lymphocytic lymphoma of the skin with leukemization, refers to skin lymphomatosis. Tumor nodes are more often formed on the face, back, legs. They are composed of atypical mononuclear Cesari cells.

4. Reticulosarcoma is a malignant tumor from reticular cells and histiocytes. Tumor cells produce reticular fibers that entwine reticulosarcoma cells.

Multiple myeloma.

The disease is based on the proliferation of myeloma tumor cells, both in the BM and outside it. Depending on the nature of myeloma cells, they are distinguished: plasmacytic, plasmablastic, polymornocellular and small cell myeloma.

Myeloma cells secrete paraproteins, which are found in the urine and blood of patients (for example, Bens-Jones protein in the urine, it freely passes through the glomerular filter, since it has a low molecular weight).

Morphologically, depending on the nature of the infiltrate, which is usually located in the BM and bones, there are:

Diffuse formwhen BM infiltration is combined with osteoporosis

Diffuse-nodular form, when tumor nodes appear

Multiple nodular form, when diffuse myeloma infiltration is absent.

The proliferation of myeloma cells is most often observed in flat bones (ribs, bones of the skull) and the spine, less often in tubular bones, this leads to destruction bone tissue... Bone substance liquefies in it osteoclasts appear, this leads to osteolysis and osteoporosis. Bones become brittle, fractures are frequent. Hyperkalemia is also observed, with which the development of calcareous metastases is associated.

A number of changes in organs are associated with the secretion of paraprotein by myeloma cells, these include: 1) Amyloidosis;

2) deposition in tissues of amyloid and crystalline substances;

3) the development of paraproteinemic edema, or paraproteinosis of organs, which leads to their functional failure;

4) paraproteinemic nephrosis (is the cause of death of 1/3 of patients), there is a "clogging" of the kidneys with Bens-Jones paraprotein, leading to sclerosis of the brain, and then the cortex and wrinkling of the kidneys;

5) Syndrome of increased viscosity and paraproteinemic coma, associated with the accumulation of paraproteins in the blood, protein stasis.