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The term a chronic lymphoid leukosis (a chronic lymphoid leukosis, HLL), integrates diseases of the tumoral nature, heterogeneous on the clinical, morphological and immunological characteristics, of which development monoclonal proliferation of pathological lymphoid elements is the cornerstone.
Among leukoses on structure and annual average indicators of incidence the chronic lymphoid leukosis takes the second place after acute leukoses.
The chronic lymphoid leukosis often occurs among the population of the European countries, Canada, the USA, at the same time it is observed very seldom in the countries of Southeast and East Asia. The disease generally is registered at persons 50 years are more senior. At the age of 30 — 40 with a chronic lymphoid leukosis in 8,5% of cases and extremely seldom occurs at patients at youthful and children's age. Among patients with typical option of an illness men (67,7%) prevail.
Etiology and pathogeny
The majority of cases of this disease — V-cellular forms. Pathological lymphoid elements at this disease come from one cell predecessor, the majority of them contains monoclonal cytoplasmatic immunoglobulin.
At HLL V-lymphocytes are not differentiated before formation of the plasmocytes producing immunoglobulins therefore at patients the infectious diseases which are often a cause of death hard proceed. Along with disturbance of antibodyformation in blood of patients the complement caption, to a lesser extent — 0 lysines is lowered.
The insufficient quantity and functional inferiority of T lymphocytes cause the frequency of some viral diseases, heavy reactions to smallpox vaccination. Disturbance of an immunological homeostasis is the reason of autoimmune hemolitic anemia and thrombocytopenia, revealed at HLL in 13 — 15% of cases. Perhaps, it caused also the high frequency of development of cancer at HLL. At last, functionally inert lymphocytes at typical HLL, having very long life cycle (months, years), collect in parenchymatous bodies and bodies of a hemopoiesis, breaking their function.
Communication of developing of a disease, mainly at persons is more senior than 50 years, cases of family HLL and other limfoproliferativny diseases at relatives of different generations or their identification at several family members — the facts testimonial of existence of genetic factors in development of a disease.
Along with typical HLL allocate its options — pro-lymphocytic, mainly splenomegalichesky, marrowy, hairy cell, tumoral, T-cellular.
Approximate formulation of the diagnosis:
1. The typical chronic lymphoid leukosis proceeding with increase in peripheral, intrathoracic and retroperitoneal lymph nodes, spleens with anemia, a hyperleukocytosis, thrombocytopenia and a hemorrhagic syndrome.
2. Pro-lymphocytic (morphologically atypical) option of a chronic lymphoid leukosis with a splenomegaly, a hyperleukocytosis with insignificant increase in a spleen.
3. Tumoral option of a chronic lymphoid leukosis with the expressed growth of various lymph nodes, a low lymphocytosis in blood, a considerable leukemic infiltration of marrow at relative safety erythro-and a thrombopoiesis.
4. The marrowy option of a chronic lymphoid leukosis proceeding with a deep pancytopenia, a diffusion infiltration of marrow small lymphocytes.
5. A hairy cell leukosis with moderate increase in a spleen, liver and peripheral lymph nodes, anemia, thrombocytopenia, detection of "hairy" cells against a lymphocytosis in blood and marrow.
6. Splenomegalichesky option of a chronic lymphoid leukosis with significant increase in a spleen against a subleukemic lymphocytosis.
Typical option of HLL. The first signs allowing to suspect this disease is increase in number of leukocytes of blood up to 10 — 15*109/l, 60 — 80% of which make small lymphocytes. In the next years the absolute lymphocytosis of blood increases, sometimes it reaches 2*1012/l.
In most cases generalized system increase in peripheral, intrathoracic and retroperitoneal lymph nodes comes to light. A consistence their dense, the sizes vary.
Degree of manifestation of anemia can not depend on prescription of a disease — on the first year of an illness find in 40% of patients various degree anemia. Its character is various. Autoimmune hemolysis is confirmed in most cases by positive direct test of Koombs and the effect caused by use of glucocorticoid hormones. Development of the so-called hidden hemolysis can be suspected on reduction of time of circulation marked radioisotopes of erythrocytes that is more often observed at the anemia which is combined with significant increase in a spleen.
Positive takes of a splenectomy in similar cases show a splenomegaly role in development of anemia. Histologic confirmation of the increased destruction of erythrocytes connected with disturbance of microcirculation of elements of blood in much the increased spleen is the hemosiderosis found in it.
The anemia caused by generally leukemic infiltration of marrow, as a rule, develops on 3 — the 6th year of a disease. It is characterized by lack of signs of hyper hemolysis (low content of bilirubin of serum, urine urobilin, a reticulocytopenia). Effect of antianemic, hormonal therapy insignificant. Anemia is usually combined with a hyperleukocytosis and thrombocytopenia, with the progressing increase in the sizes of a spleen that can indicate existence of disturbances of microcirculation in it. Quite often there is autoimmune thrombocytopenia with the expressed hemorrhagic syndrome, the stopped reception of glucocorticoid hormones. The hyper hemolysis combination to thrombocytopenia of autoimmune genesis is described in literature as Fischer's syndrome — Ivensa. Thrombocytopenia can be also result of a leukemic infiltration of marrow.
Pro-lymphocytic (morphologically atypical) option meets seldom. Along with the cases which are characterized by a preferential splenomegaly and a hyperleukocytosis options with a considerable hyperplasia of lymph nodes are less often observed. In blood, marrow, lymph nodes reveal to 50 — 60% of the cells having big, than a lymphocyte, at HLL typiform the sizes, wider cytoplasm and the kernel with quite rough chromatin containing a nukleola. These cells have no characteristic cytochemical features. At immunological researches of morphologically atypical cells the high density of surface immunoglobulins is noted, the M - or D-type is more often. Besides, the percent of the lymphocytes forming sockets with mouse erythrocytes is less, than at typical option of a chronic lymphoid leukosis. Thus, the pathological pool of lymphoid elements consists of immunological more mature lymphoid elements, than at typical V-option of a chronic lymphoid leukosis.
The expressed growth of lymph nodes of various localization is characteristic of tumoral option (including mediastinums) at rather low lymphocytosis of blood (10 — 20*109). The relatively young age of patients attracts attention. Despite the expressed marrow infiltration, relative safety of a myelopoiesis is noted. In prints of lymph nodes find bigger, than at a typiform, quantity of blast forms, and also lymphoid elements with a cytoplasm basophilia.
The Splenomegalichesky option which is found less than in 5% of cases is characterized by a preferential splenomegaly, absence of a hyperplasia or a moderate hyperadenosis, a subleykemi-chesky lymphocytosis. The diffusion type of a lymphatic infiltration of marrow distinguishes this option from a spleen lymphocytoma.
Marrowy option. There is no hyperadenosis, a liver, a spleen. The deep pancytopenia caused by a diffusion infiltration of marrow small lymphocytes with dense chromatin of a kernel is observed. Anemia is hardly stopped by transfusions of eritrotsitny weight.
Hairy cell leukosis. Most of researchers carry it to rare option of HLL. On superficial membranes of cells the immunological determinants indicating their V-cellular origin though isolated cases of the T-cellular nature of a hairy cell leukosis are described come to light. Frequency of a hairy cell leukosis makes 1 — 3% among all leukoses. The age of patients fluctuates from 19 to 90 years, men are ill more often. In most cases increase in a spleen is found and is slightly more rare than a liver. Peripheral lymph nodes, as a rule, small sizes. In blood the cytopenia is noted. Subleukemic and especially leukemic options of a disease meet seldom. In a gemogramma the quantity of lymphocytes is increased, "hairy" cells often are found, the quantity of granulocytes and monocytes is reduced; anemia and thrombocytopenia are characteristic.
"Hairy" cells have quite large sizes (10 — 18 microns), excentricly located kernel of a polymorphic configuration with more gentle, than at a lymphocyte, chromatin. Sometimes small kernels are found. Cytoplasm often plentiful, pale gray-blue color. The thin shoots of cytoplasm giving to cells a characteristic look are typical. Bright diffusion reaction to acid phosphatase is typical for "hairy" cells that it is an important diagnostic character. Histologic research reveals in marrow a leukemic infiltration and the phenomena of fibrosis, in a spleen against an infiltration "hairy" cells formation of the pseudo-sine filled with blood and covered by "hairy" cells.
T-cellular option of HLL. It is diagnosed in 1,5 — 5% of cases. Proceeds with more often isolated спленомегалие& and the damage of skin, quantity of leukocytes of blood which is not exceeding 15" 109/l. In aspirates and bioptata of marrow find a lymphocytic infiltration. Gemogramma is characterized one - two - or a trekhrostkovy cytopenia. Quite often the polyclonal gammapathy comes to light (unlike typical V-cellular option).
Pathological T lymphocytes morphologically there is not enough otlichima from V-lymphocytes; they have a little big zone of cytoplasm containing azurophilic granules. An obligatory cytochemical sign of these cells — high activity of acid phosphatase with localization in lizosomalny granules; accurately positive reactions to 0 glucuronidase and 0-glyukozaminaza. Immunological lymphocytes can be T-helperami, T-suppressors or that and others.
The T-cellular option of a chronic lymphoid leukosis should be differentiated from the chronic T-cellular lymphocytosis representing a high-quality limfoproliferation or with a redistribution lymphocytosis.
Tumoral progression at a chronic lymphoid leukosis. The so-called syndrome of Richter which is clinically characterized by fast increase in the sizes of one or several lymph nodes and spleens against rather quiet or, on the contrary, the progressing course of a chronic lymphoid leukosis is more often observed; lymph nodes get a dense consistence, quite often causing a prelum of bodies that to unusually typical option of a disease. Tumoral educations appear outside the hemopoietic fabric (bones, a pleura, TsNS, skin, etc.).
As a rule, during malignant transformation of a chronic lymphoid leukosis fever, symptoms of intoxication (loss of body weight, lack of appetite, the increased perspiration) are observed. Quite often the quantity of leukocytes and small lymphocytes in a gemogramma decreases. Against a tumoral progression the clinical and morphological features inherent in a chronic lymphoid leukosis can disappear.
In a histologic picture of tumoral educations blasts lymphoid (more rare not lymphoid) type, histiocytes and other cells in one or several centers whereas in others the structure drawing typical for a chronic lymphoid leukosis remains prevail. "Prolimfotsitarny" transformation, development of lymphoblastoid crisis in an end-stage of progressing of a chronic lymphoid leukosis are described as casuistic cases. At primary diagnosing of a subleukemic phase of a chronic lymphoid leukosis the biopsy of a lymph node, marrow allows to establish this or that option of a lymphosarcoma at early stages of a disease.