What is Adult T-Cell Leukemia Lymphoma?
Adult T-cell leukemia lymphoma is a tumor from CD4 lymphocytes caused by human T-lymphotropic virus type 1 (HTLV-I). Lesions of the skin and internal organs, bone resorption and hypercalcemia are characteristic. 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 Pacific coast, in South America, Equatorial Africa and the northern United States. 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.
Causes of Adult T-Cell Leukemia
Type 1 human T-lymphotropic virus belongs to the family of retroviruses. Tumor cells are activated CD4 lymphocytes, which in excess express interleukin-2 receptor a-chains. A tumor develops in approximately 5% of those infected, while the rest show carriage of 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, part of the CD4 lymphocytes becomes capable of unlimited reproduction; increased mitotic activity, accumulation of genetic defects and deficiency of cellular immunity are also noted. The main role in the development of these disorders is assigned to the viral tax protein.
A genetically determined predisposition to the disease is assumed, but the possibility of a provoking effect of some environmental factors cannot be ruled out.
Symptoms of adult T-Cell Leukemia Lymphoma
The tumor is manifested by a generalized enlargement of the lymph nodes, hepatosplenomegaly, skin lesions, osteolysis. Hypercalcemia, increased activity of LDH in serum are characteristic. Tumor cells are polymorphic and express CD4. Skin lesions are represented by papules, plaques, tumor formations, ulcerations. Bone marrow infiltration is negligible, anemia and thrombocytopenia are uncharacteristic.
The tumor is progressing steadily, treatment is ineffective.
Polychemotherapy allows 50-70% of patients to achieve complete remission, however, 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.
A chronic form of the disease is also described – 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.
Four forms of adult T-cell leukemia lymphoma are distinguished: 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 genes encoding antigen-recognizing T-lymphocyte receptors is detected.
The acute form occurs in 60% of cases; the disease is characterized by a short prodromal period (from the onset of the first symptoms to the diagnosis takes about 2 weeks) and a rapid course (life expectancy of 6 months). Clinical manifestations: rapidly progressive skin and lung lesions, hypercalcemia and lymphocytosis. Atypical lymphocytes with lobed nuclei or atypical lymphocytes with nuclei in the form of a cloven hoof appear. A provirus is built into 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 as a tumor marker. Anemia and thrombocytopenia are rare. Skin lesions are sometimes difficult to distinguish from a rash with fungal mycosis. Frequently occurring foci of lysis of bone tissue usually do not contain tumor cells, but osteoclasts. Osteogenesis in such foci is suppressed. The lesion of the bone marrow in most cases is focal in nature, although blast cells are detected during cytological examination.
Hypercalcemia in adult T-cell leukemia lymphoma is caused by several causes. Tumor cells produce activation factors of osteoclasts (TNF-alpha, TNF-beta, IL-1), and are also able to produce 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. Changes in the chest x-ray in half of the cases are due to leukemic pulmonary infiltration, and the rest is due to pneumonia caused by opportunistic pathogens (Pneumocystis carinii and other fungi). Gastrointestinal disturbances are almost always associated with opportunistic infection. In serum, LDH and alkaline phosphatase activity are often increased. Approximately 10% of patients have symptoms of leptomeningitis: weakness, mental disorders, paresthesia and headache. Unlike other lymphomas affecting the central nervous system, with adult T-cell leukemia lymphoma, the protein content in CSF may remain normal. The diagnosis confirms the presence of tumor cells in the CSF.
Lymphomatous form develops in 20% of patients. According to the clinical picture and course, this form resembles acute, but differs in a small number of atypical lymphocytes in the blood and a pronounced increase in lymph nodes. The histological picture is diverse: pronounced cellular and nuclear polymorphism is characteristic of tumors. However, the course of the disease does not depend on the histological structure of the tumor. The birth of a patient in an endemic region, characteristic skin lesions and hypercalcemia are signs that make it possible to make a preliminary diagnosis, which is confirmed when antibodies to human T-lymphotropic virus type 1 are detected in serum.
In the chronic form of the central nervous system, bones and gastrointestinal tract are usually not affected, and the concentration of calcium and serum LDH activity remain normal. Usually patients have a life expectancy of 2 years. Sometimes the chronic form becomes acute.
The smoldering form is found in no more than 5% of patients. Monoclonal tumor cell DNA contains an integrated 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 can be affected. Usually, patients have a life expectancy of 5 years or more.
The course and forecast
In chronic and smoldering forms of adult T-cell leukemia, 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. With a normal level of calcium in the blood, the average life expectancy is 50 weeks from the moment 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
The clinical picture and detection of antibodies to human T-lymphotropic virus type 1. The diagnosis is confirmed by molecular genetic studies (provirus DNA is embedded in the DNA of affected CD4 lymphocytes).
General blood analysis
The number of leukocytes from normal to 500,000. In a blood smear – atypical lymphocytes with lobed nuclei, similar to Cesari’s cells.
Pathomorphology of the skin
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 are found.
Hypercalcemia: at the beginning of the disease – in 25% of patients, in the future – more than half.
Serological reactions Antibodies to human T-lymphotropic virus type 1 are detected by enzyme-linked immunosorbent assay and immunoblotting. Among injecting drug users infected with HIV, about 30% are simultaneously infected with type 1 human T-lymphotropic virus.
Treatment of Adult T-Cell Leukemia Lymphoma
Various combinations of anticancer agents are used. Remissions are short-lived, achieved in less than 30% of cases. Acute and lymphomatous forms of the disease are not sensitive to standard chemotherapy regimens. Promising results have recently been obtained with the combined treatment of zidovudine (by mouth) and interferon a (s / c).
Prevention of Adult T-Cell Leukemia Lymphoma
To prevent the further spread of infection, all family members and sexual partners of the patient are examined. Seropositive carriers should not become donors.