T-cell lymphoma is found predominantly in the elderly, although it occasionally occurs in childhood and adolescence. Pathology prefers male patients, occurring in women much less frequently. Most often, T-cell lymphoma affects the lymphatic system and skin cell structures.
What it is?
T-cell lymphomas are usually epidermotropic in origin.
The immediate causes and pathogenic factors in these lymph tumors have not been definitively determined, although most scientists agree that the HTLV-1 virus (or human T-cell leukemia virus type 1) is considered as a fundamental factor in the development of malignant cutaneous T-cell lymphomas.
Classification
There is a certain classification of similar:
- Skin lymphoma.
Often, peripheral lymph tumors, consisting of T-lymphocyte cells, affect internal organs, bone marrow tissues, skin, and peripheral blood. Affected lymph node tissues have diffuse infiltration, completely erasing the normal nodular structure.
- Angioimmunoblastic T-cell lymphoma.
Angioimmunoblastic lymphatic tumors from T-shaped cell structures are a lymph node thickening consisting of immunoblasts and plasma cells. In the future, the structure of such a seal changes, and new pathological blood vessels form.
This lymphoma has a poor prognosis. On average, five-year survival is observed in only a third of patients, and average duration life is about 2.5-3 years.
- T-lymphoblastic lymph formations.
T-lymphoblastic tumors are composed of immature lymphocytic cell structures. They have an irregular nucleus, and their cells rapidly divide and multiply. The tumor is difficult to distinguish from acute lymphoid leukemia, although it is quite rare.
If such a form did not affect the bone marrow structures, then the prognosis is favorable, in the presence of such lesions, the chances of a successful recovery do not exceed 20%.
Causes
Experts find it difficult to name specific reasons T-cell lymphomas, although there are several predisposing factors:
- T-cell leukemia virus type 1;
- HHV-6 virus;
- Epstein-Barr virus;
- Immunopathological processes in epidermal cells;
- hereditary factor;
- Older age, because such patients are more likely to be affected by T-cell lymphoma;
- immune mutations, surgical correction immunological activity, transplantation with forced immune suppression, autoimmune pathologies;
- Prolonged radiation, chemical or ultraviolet effects on the body;
- Immunodeficiency states of hereditary origin.
These factors prove that T-cell lymph formations are multifactorial in nature, arising as a result of pathological lymphocytic activity.
Symptoms
One of the common manifestations of T-cell tumors is fungal mycosis, which accounts for about 7 out of a dozen cases.
The beginning of such an oncological process is indicated by an increase in lymph node structures in the inguinal, axillary or cervical zone.
When prescribing antibiotic therapy, lymph node tumors do not go away, and on palpation they do not cause pain or discomfort.
If speak about skin varieties T-cell lymph formations, they are sometimes accompanied by hyperemic lesions skin, all sorts of rashes like plaques, erythema, nodules or sores. Areas of peeling, swelling, hyperpigmentation, infiltration, etc. may appear on the skin.
The following symptoms also speak about the development of T-cell lymphoncology:
- Hyper sweating at night;
- Causeless apathy and weakness, a tendency to stressful conditions;
- Hyperthermic symptoms, often remaining in the subfebrile range, although sometimes able to reach febrile levels;
- Digestive problems and intense weight loss for no apparent reason.
stages
Experts distinguish four successive stages in the development of T-cell lymph formations.
- At the first stage, only one lymph node structure is involved in the oncological process.
- At the second stage, these processes already spread to two lymph node areas, which are located on one side of the diaphragm.
- At the third stage of development, oncology covers the lymph node zones already on both sides of the diaphragm.
- And at the fourth stage, oncoprocesses extend not only to the departments of the lymphatic system, but also to intraorganic localizations. Metastasis can spread to, renal and hepatic tissues, etc.
Treatment
They are selected in accordance with the state of health of the patient, the type and stage of the lymphatic tumor process.
At times, lymph formations, characterized by slow progression, do not need treatment at all - they are simply monitored. If the patient begins to be disturbed by manifestations like hyperthermia, indicating the progression of the lymphoncological process, then urgency in urgent remedial action.
Lymphotumor processes, like other oncological formations, are caused by cell division and proliferation, so the applied therapeutic methods based on the destruction of actively dividing cellular structures.
The main method is usually a chemotherapeutic effect, and in rare cases clinical cases resort to removal of the tumor. Often, radiotherapy is used as an additional technique.
In order to permanently and finally rid the patient of cancer, it is necessary to destroy all cancerous cellular structures in his body. If after therapy a small number of tumor cells, then subsequently they will again lead to the formation of lymph formation. Due to these features, therapeutic processes take a lot of time, differing in particular duration.
Chemotherapy involves the use of several drugs at once, which have a destructive effect on oncocellular structures in several directions at once. This approach minimizes the likelihood of cancer cells developing particular resistance to drug exposure.
Chemotherapy drugs can be taken by mouth as a syrup or tablet, or given intravenously. In a number of clinical cases, the introduction of drugs into the spinal canal is indicated.
Radiation treatment involves exposing the tumor to a beam of high-energy rays, but this technique is not usually used in children. In general, the process of treatment of T-cell lymph formations lasts about 2 years.
First, the patient stays in the hospital for a long time, undergoing chemotherapy courses of treatment, then the need for inpatient therapy disappears, and the patient is transferred to an outpatient treatment.
Prognosis of T-cell lymphoma
Prognostic data are determined by the form of the T-cell lymphatic tumor process and the stage of its development.
T-cell lymphogenesis poses the greatest danger to the elderly, although in general timely treatment such a pathology has a favorable prognosis.
Similar variety cancer responds positively to treatment started in the early stages of the disease.
If the therapy was chosen correctly and carried out at the beginning of the development of oncology, then the 5-year survival rate in such clinical cases is about 85-90%. If a five-year period passes from the moment of treatment, during which there are no relapses, then they speak of a complete cure and the absence of further threats from lymphocytic cell structures.
In the absence of relapses after a course of therapy with a diagnosis of T-cell lymphoma, many patients live safely for decades.
If therapeutic measures begin to be carried out after the formation of tumors (at stage 3-4 pathological process), then the prognosis is less favorable for patients. In such clinical cases, the life of the patient can be extended only for a couple of years.
Video about the causes, types, symptoms and methods for diagnosing T-cell lymphoma of the skin:
T-cell large granular lymphocytic leukemia occurs 30-50 times less often than B-cell CLL and develops at the age of 50-55 years, more often in women. Basic morphological trait diseases - the presence of large granular (containing azurophilic granules) lymphocytes in the peripheral blood and bone marrow. The diagnostic criterion is the detection of more than 2 109/l of large granular lymphocytes in the peripheral blood. The most common immunophenotype: CD3+, CD8+, CD4-, TCRab+.
Leukemic cells express markers of apoptosis (Fas or CD95 and Fas ligand) but are resistant to Fas-induced apoptosis.
Splenomegaly is detected in 20% of patients, lymphadenopathy and hepatomegaly are even rarer. In connection with severe neutropenia, recurrent infections often occur. In 30% of patients there is an association with autoimmune diseases(autoimmune hemolytic anemia, rheumatoid arthritis and etc.).
The course of the disease is variable standard treatment not developed.
Adult T-cell leukemia/lymphoma
Adult T-cell leukemia/lymphoma- a rare lymphoproliferative disease, occurring mainly in the Caribbean and Japan. Proven etiological factor is the HTLV-1 retrovirus. In endemic areas, 5% of the population is infected; one out of 50-100 infected people falls ill during a lifetime (in Japan, with about 1 million virus carriers, about 500 cases of the disease are recorded per year). Sporadic cases of adult T-cell leukemia/lymphoma have been reported in Europe and North America.
Tumor cells polymorphic, with polysegmented, petal-like nuclei. Immunophenotype of cells: CD7-, CD2+, CD3+, CD4+, CD5+, CD25+. The most frequent cytogenetic findings are trisomy 12, del 6q.
In the vast majority of cases T-cell leukemia/lymphoma adults is characterized by an aggressive course, accompanied by anemia, lymphadenopathy, hypercalcemia, early dissemination (damage to bones, skin, central nervous system), severe immunodeficiency (usually CD4+ dysfunction) with the development of severe opportunistic infections. In these cases, the prognosis is poor (median survival does not exceed 6 months). More favorable variants (“smoldering” and chronic) are much less common, which, however, can transform into an aggressive type.
Fungal mycosis- Which doctors should you contact if you have adult T-cell leukemia-lymphoma
What is adult T-cell leukemia-lymphoma
Adult T-cell leukemia-lymphoma is a CD4 lymphocyte tumor caused by human T-lymphotropic virus type 1 (HTLV-I). Characterized by skin lesions and internal organs, resorption bone tissue and hypercalcemia. Atypical lymphocytes are found in the blood.
Diseases are recorded mainly in the south of Japan, less often on the islands of the Caribbean, the coast Pacific Ocean, in South America, Equatorial Africa and in the north of the SSA. Mostly adult blacks and Japanese are sick. Men get sick more often than women. Antibodies to the pathogen are often found in the blood of drug addicts.
What causes adult T-cell leukemia-lymphoma
Human T-lymphotropic virus type 1 belongs to the retrovirus family. Tumor cells are activated CD4 lymphocytes that overexpress the α-chains of the interleukin-2 receptor. The tumor develops in approximately 5% of those infected, the rest are carriers of the provirus in CD4 lymphocytes. Therefore, it is believed that some other factors are involved in the pathogenesis of adult T-cell leukemia-lymphoma. After infection, some of the CD4 lymphocytes acquire the ability to multiply indefinitely; increased mitotic activity, accumulation of genetic defects, and deficiency of cellular immunity. The main role in the development of these disorders is assigned to the viral protein tax.
A genetically determined predisposition to the disease is assumed, however, the possibility of a provocative influence of some factors cannot be excluded. environment.
Symptoms of adult T-cell leukemia-lymphoma
The tumor is manifested by a generalized increase in lymph nodes, hepatosplenomegaly, skin lesions, osteolysis. Characterized by hypercalcemia, increased activity of LDH in serum. Tumor cells are polymorphic and express CD4. Skin lesions are represented by papules, plaques, tumor-like formations, ulcerations. Bone marrow infiltration is insignificant, anemia and thrombocytopenia are uncharacteristic.
The tumor is steadily progressing, treatment is ineffective.
Polychemotherapy allows 50-70% of patients to achieve complete remission, but in half of them remission lasts less than 12 months.
Due to deep immunodeficiency, the frequency of secondary infections is very high, many of which are caused by opportunistic microorganisms.
Also described chronic form diseases - with skin lesions, but without hepatosplenomegaly and enlarged lymph nodes. Moderate lymphocytosis is characteristic, the proportion of tumor cells in the blood is small. The life expectancy of such patients can reach several years - until the disease becomes acute.
There are four forms of adult T-cell leukemia-lymphoma: acute, lymphomatous, chronic, and smoldering. In any form of the disease, the tumor develops due to the monoclonal proliferation of CD4 lymphocytes. In all such cells, the provirus is integrated into the DNA in the same way and a unique rearrangement of the genes encoding the antigen-recognizing receptors of T-lymphocytes is found.
The acute form occurs in 60% of cases; the disease is characterized by a short prodromal period (about 2 weeks from the appearance of the first symptoms to the diagnosis) and a rapid course (life expectancy is 6 months). Clinical manifestations: rapidly progressive skin and lung lesions, hypercalcemia and lymphocytosis. Atypical lymphocytes with lobular nuclei or atypical lymphocytes with cloven hoof nuclei appear. A provirus is embedded in the DNA of tumor cells, and CD4, CD3, and CD25 receptors (low-affinity IL-2 receptors) are expressed on their surface. Serum CD25 level serves tumor marker. Anemia and thrombocytopenia are rare. The skin lesions are sometimes difficult to distinguish from the rash of mycosis fungoides. Often occurring foci of bone lysis usually do not contain tumor cells, but osteoclasts. Osteogenesis in such foci is suppressed. Bone marrow damage in most cases is focal in nature, although with cytological examination blast cells are found.
Hypercalcemia in adult T-cell leukemia-lymphoma is caused by several causes. Tumor cells produce osteoclast activating factors (TNF-alpha, TNF-beta, IL-1), and are also capable of producing PTH-like peptides. The disease is accompanied by immunodeficiency, against which opportunistic infections occur, similar to those found in AIDS. The pathogenesis of immunodeficiency has not been established. X-ray changes chest in half of the cases are due to leukemic infiltration of the lungs, and the rest is due to pneumonia caused by opportunistic pathogens (Pneumocystis carinii and other fungi). Gastrointestinal disorders almost always associated with opportunistic infection. Serum levels of LDH and alkaline phosphatase are often elevated. Approximately 10% of patients have symptoms of leptomeningitis: weakness, mental disorders, paresthesia and headache. Unlike other lymphomas that affect the CNS, CSF protein content may remain normal in adult T-cell leukemia-lymphoma. The diagnosis is confirmed by the presence of tumor cells in the CSF.
The lymphomatous form develops in 20% of patients. By clinical picture and the course of this form resembles an acute one, but differs in a small number of atypical lymphocytes in the blood and a pronounced increase in lymph nodes. The histological picture is diverse: the tumor is characterized by pronounced cellular and nuclear polymorphism. However, the course of the disease does not depend on histological structure tumors. The birth of a patient in an endemic area, a characteristic skin lesion and hypercalcemia are signs that allow you to put provisional diagnosis, which is confirmed by the detection of antibodies to human T-lymphotropic virus type 1 in the serum.
In the chronic form, the central nervous system, bones, and gastrointestinal tract are usually not affected, and serum calcium and LDH activity remain normal. Typically, the life expectancy of patients is 2 years. Sometimes the chronic form becomes acute.
The smoldering form occurs in no more than 5% of patients. The DNA of monoclonal tumor cells contains an embedded provirus; the proportion of atypical lymphocytes in the blood is less than 5%; hypercalcemia, lymphadenopathy and hepatosplenomegaly, as well as changes in the central nervous system, bones and gastrointestinal tract are absent, but the lungs and skin may be affected. Typically, the life expectancy of patients is 5 years or more.
Course and forecast
In chronic and smoldering forms of adult T-cell leukemia-lymphoma, the only symptoms of the disease may be skin infiltration and slight lymphocytosis in the blood and bone marrow. Acute and lymphomatous forms are characterized by a rapid course, severe damage to the skin, lungs and bones. At normal level calcium in the blood, the average life expectancy is 50 weeks from the time of diagnosis, and with hypercalcemia - 12.5 weeks (from 2 weeks to 1 year). Causes of death: opportunistic infections, DIC.
Diagnosis of adult T-cell leukemia-lymphoma
Clinical picture and detection of antibodies to human T-lymphotropic virus type 1. The diagnosis is confirmed by molecular genetic testing (provirus DNA is embedded in the DNA of the affected CD4 lymphocytes).
Additional Research
General blood analysis
The number of leukocytes is from normal to 500,000. In a blood smear - atypical lymphocytes with lobular nuclei, similar to Cesari cells.
Skin pathology
In the upper and middle layers of the dermis, perivascular or diffuse infiltrates from large atypical lymphocytes are detected; the epidermis is usually not affected. Sometimes infiltrates in the dermis are dense, and in the epidermis there are Potrier microabscesses, consisting of a large number of large atypical lymphocytes, among which giant cells come across.
Blood chemistry Hypercalcemia: at the beginning of the disease - in 25% of patients, later - in more than half.
Serological tests Antibodies to human T-lymphotropic virus type 1 are detected by enzyme immunoassay and immunoblotting. Among injection drug users infected with HIV, about 30% are simultaneously infected with human T-lymphotropic virus type 1.
Treatment of adult T-cell leukemia-lymphoma
Use various combinations anticancer drugs. Remissions are short, achieved in less than 30% of cases. Acute and lymphomatous forms of the disease are not sensitive to standard chemotherapy regimens. Recent encouraging results have been obtained with combined treatment zidovudine (orally) and interferon a (s / c).
Prevention of adult T-cell leukemia-lymphoma
To prevent further spread of infection, all family members and sexual partners of the patient are examined. Seropositive carriers should not donate.
Most often, a disease such as T-cell lymphoma occurs in the elderly, less often it is diagnosed in children and adolescents.
The disease, as a rule, affects men, cases of morbidity in women are recorded less often.
It is known that T-cell lymphoma has an epidermotropic nature (affects skin cells and lymph nodes).
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Classification of T-cell lymphomas
In clinical oncology, it is customary to distinguish between the following types:
- T-lymphoblastic lymphoma(is a tumor of immature T-lymphocytes, the nucleus, as a rule, has an irregular shape, there is a high level of cell division and reproduction);
- T-cell angioimmunoblastic lymphoma(during a histological examination, the lymph node becomes denser with plasma cells and immunoblasts, followed by the erasure of its structure and the pathological formation of new blood vessels);
- peripheral lymphoma(includes all types of lymphoma of T- and NK-cell etiology, with the exception of T-lymphoblastic leukemia and lymphoma from immature T-lymphocytes);
- cutaneous lymphoma(this type of lymphoma is a consequence of the mutation of T or B lymphocytes, further leading to their uncontrolled division and movement into the epidermis).
Causes
The causes of the disease have not been fully studied, to date, T-cell leukemia type 1 (HTLV-1) I is one of the causes of this disease, but the following strains are also considered as an option: Epstein-Barr virus and HHV-6.
In people with T-cell lymphoma, the focus of the virus can be found in the epidermis, in blood plasma and Langerhans cells. An important role in the development of oncology is occupied by the immunopathological process in the cells of the epidermis, the key of which is the uncontrolled reproduction of clonal lymphocytes.
Considering the causes of T-cell lymphoma, it should be mentioned hereditary factor, which plays an important role in the formation of this disease.
Considering in detail the hereditary factor, a pattern was found in the detection of histocompatibility antigens, namely: HLA A-10 - for slow-flowing lymphomas, HLA B-5 and HLA B-35 - for high-level cutaneous lymphomas and HLA B-8 - for erythrodermic form fungal mycosis.
These factors prove the existence of a direct hereditary relationship in the formation of the disease. Based on this, T-cell lymphoma can be attributed to multifactorial pathologies that originate from the activation of lymphocytes.
Symptoms
One of the most widespread diseases in the group of cutaneous T-cell lymphomas is mycosis fungoides, it is recorded in 70% of cases. This disease is divided into three forms: classical lymphoma, erythrodermic and decapitated.
The first signs of T-cell lymphoma are an increase in lymph nodes in the neck area armpits or in the groin.
A characteristic feature of these manifestations is the painlessness of these formations and the absence of a response to antibiotics.
Less common symptoms of T-cell lymphoma include:
- general weakness and fatigue;
- febrile temperature;
- sudden weight loss;
- disruption of the gastrointestinal tract.
Diagnostic methods
In order to correctly diagnose T-cell lymphoma, a number of studies should be performed, namely:
- full examination by a specialist;
- pass necessary tests blood;
- biopsy of the affected tissue.
The key test for diagnosing T-cell lymphoma is a biopsy ( prompt removal lymph node with subsequent study). This fabric subjected to morphological analysis, which is carried out by a specialist pathologist. The purpose of the study is to detect tumor lymphoma cells, then, if their presence is confirmed, the type of lymphoma should be determined.
There are a number diagnostic studies one of which is radiodiagnosis. Radiation diagnostics includes x-ray, magnetic resonance and computer research.
Peculiarity this method consists in identifying neoplasms in those parts of the body that are not subject to examination by a specialist. This technique is well suited for determining the stage of the disease.
Additional diagnostic methods:
- cytogenetic studies;
- molecular genetic research;
- immunophenotyping method.
Treatment
Treatment is based on the type of lymphoma and general condition patient, for example, slowly flowing lymphomas are not always treated, sometimes it is enough to be constantly monitored by a specialist oncologist or hematologist. In cases where the disease begins to progress (lymph nodes increase, body temperature rises, etc.), it is necessary to start therapeutic treatment as soon as possible.
Radiotherapy is used to treat locally advanced stages of lymphoma. In generalized stages of the disease effective methodology is chemotherapy.
Used to treat slow-moving lymphomas
- "Chlorbutin" and other medicines.
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Such a type of lymphoma as "indolent" is poorly curable, in this case, therapy is aimed at increasing life expectancy and improving the general condition of the patient. An aggressive course requires immediate initiation of therapy (CHOP chemotherapy, in combination with the use of the monoclonal antibody Rituximab).
Extremely aggressive types of lymphomas are treated according to the program of therapy for lymphoblastic leukemia. The ultimate goal of this method is complete cure and remission, however, this outcome is not always possible, it all depends on the degree of damage to the body and how timely the diagnosis was made. Most effective view treatment is high-dose chemotherapy followed by hematopoietic stem cell transplantation.
The choice of treatment method is one of the key stages on the path to recovery, here it is necessary to take into account the stage and classification of the disease, individual characteristics patient and so on. To confirm the treatment, it is necessary to consult with the patient and his close relatives, so that the therapy technique can be the most effective and practical in each case.
Video: Details about T-cell lymphomas
Prognosis for T-cell lymphoma
The prognosis of T-cell lymphoma directly depends on the degree of the disease, and of course, on how early the treatment was started. If the disease is started to be treated at the first or second stage, there is a high probability of obtaining a favorable result, long remission and as a result, longer life. In that case, the probability lethal outcome can only be due to complications or the appearance of other concomitant diseases.
If treatment begins after the formation of tumors, the prognosis is less encouraging, on average, life expectancy can be extended by 1-2 years.
adult T-cell leukemia
The adult T-cell leukemia virus is endemic, that is, it is distributed among people only in certain regions of the world. Most of it is in Japan and the Caribbean islands. High level infection was found in the natives of Papua New Guinea, Australia and the Solomon Islands. Another focus of this virus has formed around the Caspian Sea. In Russia, the virus is surprisingly found only among the Nivkhs in the village of Nogliki, located in the central part of Sakhalin Island. The virus is transmitted from person to person by breastfeeding, during sexual intercourse and during the transfusion of infected blood (or when using a common syringe by drug addicts).
In endemic areas, many are infected with the virus, but, as a rule, infected individuals become asymptomatic virus carriers for life. Only in 2–3% of carriers, after a long latent period lasting a decade, the virus breaks the “vow of silence”. In this case, a malignant disease develops, in which the number of immature lymphocytes increases sharply, the liver and spleen increase, bone tissue is destroyed, and a skin rash often develops.
The target for the T-cell leukemia virus is T-lymphocytes. After infection, the virus inserts its genetic material into the host's chromosome. Although the virus does not have its own oncogene, viral proteins activate a large number of cellular genes, including cellular oncogenes. Thus, infected cells, in which the virus has suddenly become active, become malignant and begin to multiply uncontrollably. In addition, they enhance the work of genes that direct the synthesis of interleukins - small proteins, with the help of which cells immune system communicate with each other. Sharp rise the amount of interleukins, provoked by the T-cell leukemia virus, creates an information noise that disorganizes the immune system. In particular, the number of T-killers decreases. The immune system is deprived essential tool lesions of tumor cells and are no longer able to cope with their expansion. Therefore, the prognosis for this disease is poor: life expectancy usually does not exceed six months after diagnosis.
The adult T-cell leukemia virus is one of the most ancient satellites of man. It is believed that it originated about 20 thousand years ago. It was found among the Indians South America and among the African pygmies, that is, among the representatives of the tribes, for a long time isolated from outside world. The study of the genetic diversity of this virus allows us to trace the migration paths ancient man. In particular, the comparison of Asian and American isolates of the T-cell leukemia virus served as further evidence for the hypothesis that the ancestors of the American Indians were Mongoloids of Asian origin. Probably 10-40 thousand years ago they penetrated into America along the isthmus, which then connected Asia and North America.
America in the place of the current Bering Strait, and settled throughout the American continent.
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