Leukemoid reactions

Leukemoid reactions are changes in blood and hemopoietic organs resembling leukemias and other tumors of the hematopoietic system, but always having a reactive character and not transforming into the tumor to which they are similar. They can be caused by various infections, intoxications, tumors, metastases of tumors in the bone marrow. Pathogenesis. The mechanism of development is not the same for different types of reactions: in some cases, the release of immature cellular elements into the blood, in others, increased production of blood cells or restriction of the cells' exit into tissues, or the presence of several mechanisms simultaneously. Leukemoid reactions may concern changes in blood, bone marrow, lymph nodes, spleen. A special group of reactions are changes in protein blood fractions that mimic tumors of the immunocompetent system - myeloma, Waldenstrom macroglobulinemia.

Leukemoid reactions of the granulocyte type, reminiscent of chronic myelogenous leukemia or subleukemic myelosis, accompany severe infections of intoxication. In the blood there is neutrophilic leukocytosis with a shift of the nuclear formula to the myalocytes. Unlike chronic myelogenous leukemia, reactive leukocytosis always has a severe process, accompanied by an increase in body temperature, the presence of inflammatory foci, sepsis. It is with the massive death of microbial bodies and the ingestion of endotoxin into the blood that a granulocyte reserve of the bone marrow is released into the blood, increased production of granulocytes. At the beginning of chronic myelogenous leukemia and with subleukemic myelosis, with which the inflammatory picture of the blood can be confused, no intoxication is observed, the somatically patient is perfectly preserved. In doubtful cases, dynamic observation will eliminate diagnostic difficulties: either the inflammatory process becomes obvious, or a steady increase in the number of leukocytes will serve as the basis for a special study of the bone marrow (see Chronic myelogenous leukemia). Occasionally neutrophilic leukocytosis without significant rejuvenation of the formula is observed in cancer, but with chronic myelogenous leukemia there is always a "rejuvenation" of the formula to myelocytes and promyelocytes.

Eosinophilic blood reactions are accompanied by allergic diathesis, sensitization of the body with parasites, medications, occasionally tumor growth (eg, lymphogranulomatosis, T-cell lymphosarcoma, cancer, etc.). High eosinophilia of blood requires careful study: first of all, excluding drug sensitization, invasion of parasites (see Helminthiases) In rare cases, high eosinophilia can reflect a reaction to acute T-cell leukemia in the aleyukemic stage (when blast cells have not yet reached the bloodstream) Therefore, unmotivated high eosinophilia requires a comprehensive oncological examination, including bone marrow puncture.The level of leukocytosis with high eosinophilia can reach many tens of thousands in 1 μl.Eosinophilia always combines with a high percentage of eosinophils in the bone marrow.Sometimes there is persistent asymptomatic eosinophilia in Perfectly healthy people - "constitutional eosinophilia" (such a diagnosis can be made only after a qualified special examination of the patient for carriage of parasites, exclusion of other causes mentioned above, and many years of observation.) High eosinophilia may be accompanied by parietal fibroplastic endocarditis ("eosinophilic collagenosis" ); And that, and another is the debut of the development of hematosarcoma.

Reactive erythrocytosis quite often serves as a subject of differentiation with erythremia. The cause of erythrocytosis is most often lung disease with a decrease in blood oxygenation, congenital heart disease, arteriovenous aneurysms. High erythrocytosis, sometimes with slightly increased platelet count, is observed with hypernephroma (which may be accompanied by increased erythropoietin production). A left-sided tumor of the kidney may be mistaken for an enlarged spleen-a characteristic sign of erythremia. In such cases, ultrasound and computer research is necessary. In addition, when puncturing the palpable formation in the punctate, cancer cells are detected, with erythremia-lymphocytes, young granulocyte elements, and erythoacathiocytes. The most important criteria in the differentiation of eootremia with symptomatic erythrocytosis are the picture of bone marrow trepanate and the determination of blood mass. Some role in the differentiation of these processes is the evaluation of ESR, which is sharply slowed by erythremia and is not altered, and sometimes accelerated with erythrocytosis, however this feature is not absolutely reliable.

Mielemia - the presence of bone marrow cells in my blood - myelocytes, promyelocytes, erythrocaryocytes, less often megakaocyte nuclei. This picture to some extent may resemble acute erythromyelosis, from which it is distinguished by the absence of blast cells, in a large number of those present in this leukemia in the blood (in the early stages they may not be there) and in the bone marrow. Mielemia occurs with miliary cancer metastases in the bone with an acute hemolytic crisis. In cancerous myelemia, bone marrow punctate usually contains very few bone marrow cells, and with careful examination of the smear it is possible to detect accumulations of cancer cells (in hemolysis punctate is very rich in cellular elements, erythrocaryocytes predominate).

Leukemoid lymphatic reactions are most often the result of a viral infection. The most common reactive lymphocytosis is a low-symptom infectious lymphocytosis. According to the picture of blood, it can easily be taken for chronic lymphocytic leukemia, but it occurs almost exclusively in children, and they do not have chronic lymphocytic leukemia. Infectious lymphocytosis usually lasts several days, accompanied by mild catarrhal phenomena. To differentiate the process with chronic lymphocytic leukemia, there is no need for bone marrow puncture - you just need to wait a few days with the final judgment about the diagnosis. Reactive lymphocytosis can occur after splenectomy.

Leukemoid reactions of monoritic type are found in tuberculosis, sarcoidosis, Walden-stroma macroglobulinemia, chronic inflammatory processes. Reactive monocytosis differs from chronic monocytic leukemia by the presence of signs of any disease, while chronic monocytic leukemia during the first years of the disease is practically asymptomatic. In doubtful cases with prolonged monocytosis, bone marrow biopsy is shown, which in chronic monocytic leukemia reveals pronounced cellular hyperplasia with almost complete fat displacement. With reactive monocytosis, the bone marrow is normal. Waldenstrom's macroglobulinemia is characterized by lymphatic hyperplasia in the bone marrow (by punctate), monoclonal increase of IgM in serum.

In rare cases, infectious mononucleotide is taken for acute leukemia. This is possible only when analyzing poorly prepared blood smears: in children, mononuclears of infectious mononucleosis often contain nucleols. But in a properly prepared smear with mononucleosis, there are never any blast cells required for acute leukemia. In doubtful cases, any attempt to treat a suspected leukemia with prednisolone or cytotoxic drugs is unacceptable! The correct diagnosis is established with repeated blood tests, in which, with infectious mononucleosis, there is a regular morphological evolution: the broad-plasma cells become narrow-plasma, the chromatin of the nuclei acquires a less homogeneous structure. With acute leukemia, the blastozes appear rapidly in the blood. In all such cases, the preservation of smears before the final diagnosis is mandatory.

Broad-clotting cells (as in infectious mononucleosis) cells can occur with drug dermatitis. The absence of the blast structure of the nucleus (the blast cell has a non-structural chromatin network with uniform color and calyora of strands, in the thick smear blast cells acquire the features of a mature lymphocyte) distinguishes this reaction from acute leukemia.

Some forms and stages of agranulocytosis, and especially the stages of "exit" from it, are referred to as leukemoid bone marrow reactions. The picture of the bone marrow in these cases imitates acute leukemia. There is almost complete absence of mature granulocytes in the blood. As a rule, there is an infection associated with agranulocytosis. Blastnye cells in the blood with agranulocytosis never appear. The duration of the release from agranulocytosis, when there may be a lot of promyelocytes in the bone marrow or somewhat earlier - a large number of progenitor cells that resemble large lymphocytes outward but have a homogeneous structure of nuclear chromatin, is 2 to 3 days. In doubtful cases, it is necessary to wait several days for the final judgment of the diagnosis: when the agranulocytosis leaves the blood, the blood composition is normalized and there is no need for repeated bone marrow puncture, with granulocytopenia remaining in acute leukemia, and to repeat the bone marrow puncture to clarify its nature.

Changes in protein fractions of blood resembling myeloma or Waldenstrom's disease can occur in chronic hepatitis, chronic nephritis, hypernemia, parasitic invasions and some other conditions. Changes in serum proteins are often accompanied by an increased percentage of plasma cells in the bone marrow. From myeloma, these reactive changes are characterized by the following symptoms: a) the absence of monoclonality of gamma globulin (even if an M gradient is determined, there is usually no monoclonality of the protein determined by immunoelectrophoresis); B) the percentage of plasma cells in the bone marrow is less than 10-12 (for evidence of myeloma, their percentage should be significantly higher). In rare cases of chronic hepatitis, chronic nephritis, autoimmune hemolytic anemia, generalized vasculitis, the true monoclonality of an immunoglobulin can also occur. If we are talking about monoclonality of IgM, we can suspect Waldenstrom's macroglobulinemia, with the monoclonality of other proteins, myeloma. The latter should in all cases be confirmed by the presence in the bone marrow of a high percentage of plasma cells. Valdenstrom's disease is confirmed by a high percentage of lymphocytes (less often - plasma cells or both) in the bone marrow. And with that, and with another type of leukemia, the level of normal immunoglobulins in the blood serum usually decreases.

Serious suspicions of the existence of paraproteinemic gemobastosis can be caused by the so-called disease of immune complexes: generalized vasculitis, manifested primarily by either the Shenlein-Genoch syndrome, or a picture of nephritis, or by a combination of multiple hemorrhages in the lung tissue and jade (Goodpasture's syndrome), or by widespread vasculitis capillarotoxicosis) All organs and systems, including the brain. This process is based on the appearance of a complex of antigen and immunoglobulin or two immunoglobulins, to which complement is added (its level in the blood in this connection drops sharply); Large immune complexes precipitate in the cooled serum (cryoglobulinemia); Their circulation in the blood leads to damage to the endothelium and the development of organ pathology. In the immune complex of two immunoglobulins, one of the immunoglobins is an antigen (more often G), the other is an antibody (more often M). In this case, there can be a true monoclonal IgM.

The "culprit" of complexation is usually an antibody capable of combining not only with its own, but also with the donor's corresponding immunoglobulin. The source of monoclonal IgM can be Waldenstrom's disease, lymphosarcoma, the lymphocytic cell lymphocytic tumor, lymphocytic leukemia, and this product may not be associated with a lymphocytic tumor but triggered by an autoaggressive process (in particular autoimmune hemolysis), a cancer tumor, parasitic infestation. In addition, the cause of the appearance of immune complexes may remain unexplained (idiopathic form). Occasionally, cryoglobulinemia is a short-lived episode during acute infections, in particular hepatitis, severe pneumonia, etc. Therefore, the phenomenon of cryoglobulinemia, especially when one of the immunoglobulins is monoclinic, requires a specialized examination of the patient to exclude all listed diseases that may be her Cause.

Lymphadenitis is an immunoblastic-reactive growth of the lymph nodes (sometimes spleen), caused by an increase in the number and size of follicles due to hyperplasia of their reproductive centers, the cells of which are represented by young large luminous nuclei with lymphocytes-immunoblasts. It should be noted that until recently, these pathogistologists were called reticular cells. Now it is strictly proven that they have nothing to do with stromal, reticular cells, that they are lymphocytes, which, under the influence of antigenic stimulation, increase in size, sometimes become binuclear. Immunoblastic lymphadenitis develops with medicinal dermatitis, is a pathogistological substrate of infectious mononucleosis, occurs in response to intoxication (eg, tuberculosis), the introduction of vaccines, serums; It can be the first symptom of systemic lupus erythematosus and take place with other collagenoses. Immunoblastic lymphadenitis resembles the modular form of lymphosarcoma, lymphogranulomatosis.

A crucial role in the diagnosis of this condition belongs to the pathologist examining the biopsy material. But to avoid an irreparable mistake (when diagnosed with sarcomas, a powerful cytostatic therapy begins that will destroy all traces of lymphadenitis and it will be impossible to audit the diagnosis, and this therapy is extremely unsafe, in particular, it increases the risk of getting leukemia hundreds or sometimes thousands of times ) The pathologist should receive the most accurate information about the patient. A dubious picture should always be interpreted against a tumor. Sometimes to clarify the diagnosis you have to do repeated biopsies.

A great help in diagnosis is the imprint and smear from the surface of the biopsy lymph node (this must be done with all biopsies). With lymphosarcoma, the vast majority of cells (at least 30%) are monotonous blast cells. When immunoblastic lymphadenitis of blast cells is usually less than 10%, they are diverse in the degree of maturity of the nucleus, basophilia of the cytoplasm, many plasma cells are detected. Pathohistological conclusion on the study of the lymph node should be very detailed, excluding uncertain diagnostics. A pathohistologist can not always diagnose a tumor according to the picture, and this should be accurately reflected in the conclusion. For example, to diagnose the initial forms of benign lymphomas (lymphocytes), it is sometimes necessary to observe the patient and examine the lymph nodes repeatedly. To diagnose the initial forms of myeloma, suspected of detecting a monoclonal immunoglobulin, many years of follow-up and repeated bone marrow puncture are sometimes required. Until the diagnosis is clarified, antitumor therapy is contraindicated. Mononukleosis infectious (glandular fever, monocytic angina, Filatov-Pfeiffer's disease) is a viral infectious disease characterized by blasttransformation of lymphocytes, the appearance of these peculiar cells in the peripheral blood, reactive lymphadenitis, enlarged lymph nodes, spleen. The causative agent is the Epstein virus-Barr. At the heart of the disease is the blast-transformation of lymphocytes caused by a specific viral infection.

The clinical picture is diverse. In mild cases, impaired well-being due to rhinitis. Typical symptoms: angina ("glowing pharynx"), difficulty in nasal breathing in the early days of the disease due to edema of the mucous membrane, increase and soreness of the posterodermal lymph nodes (often lymph nodes and other groups), enlarged spleen. Blood picture: leukocytosis to 15-20 € 10 (ninth degree) / l (less often leukopenia), moderate (sometimes sharp) neutropenia, an increase in the percentage of lymphocytes, monocytes, eosinophils.

Necessary and sufficient for the diagnosis of the disease is the presence in the blood of specific mononuclear cells (more than 10-20%) - cells that have the nucleus of a large lymphocyte and a wide basophilic cytoplasm with a violet hue with pronounced perinuclear clearance (however, a similar picture can be given by iersinioz). The duration of the disease is several weeks, but in some cases the normalization of the blood picture is delayed for months. Relapses are also observed-with a lighter course, sometimes at intervals of several years after the first acute period. Complications: rupture of the spleen due to its rapid increase, acute hepatitis, agranulocytosis, autoimmune hemolysis, encephalitis.

Treatment. Usually, patients do not need special drug therapy, because for several days the main symptoms disappear, the blood picture is normalized. With prolonged flow, the patient's severe condition is used pathogenetic treatment: prednisolone in a dose of 20-30 mg per day or other glucocorticoids.

The forecast is usually favorable. Contagiosity is low, so isolation of the patient is not necessary. Danger of rupture of the spleen. Recovery of work capacity is determined by the appearance of undoubted signs of a decrease in the size of the body, as well as normalization of body temperature, disappearance of angina. If infectious mononucleosis manifests itself as hepatitis, hospitalization of the patient is necessary.