What is the Pathological Anatomy of the Lesion of the Membranes?
Clinically, a metastasis such as neuroleukemia appears only when the cells significantly infiltrate the nervous tissue, which was first detected by Pierce and Johnson in 1973. These authors studied the histology of the nervous tissue in 126 cases of neuroleukemia in children with acute lymphoblastic leukemia, only 70 patients she is represented clinically. As a result of their observations, they came to the conclusion that neuroleukemia is a pathology primarily of the arachnoid membrane and the space of the tissue between the pia mater and the superficial mesothelium of the arachnoid. Where leukemic infiltration affected the superficial parts of the arachnoid membrane, which include connective tissue, blood vessels, and cerebrospinal fluid lined with mesothelium, which form the intraarachnoid space, in 90% of cases there were no clinical signs of neuroleukemia. In addition, according to the observations of Pierce and Johnson, if the integrity of the trabeculae is not disturbed by the leukemic process, then the leukemic cells do not enter the spinal canal, and its puncture does not allow to diagnose lesions. They also revealed that “leukemic infiltrates reached the brain substance only when deep parts of the arachnoid, deep vascular structures of the hemispheres were involved in the process” (quote from Pierce, Johnson).
The defeat of the substance of the brain with neuroleukemia is associated with the destruction of the pia mater, or the so-called piaglial membrane directly covering the brain. Pierce and Johnson showed that with infiltration of the deep sections of the arachnoid membrane and with damage to the brain substance, neuroleukemia has always manifested itself clinically.
Thus, in many cases, neuroleukemia is diagnosed only by spinal puncture, and at the same time, even such a diagnostic method is not absolutely reliable. Still, the main criterion for the diagnosis of neuroleukemia remains spinal puncture, it must be done at an earlier time from the onset of acute leukemia.
Diagnosis of the Pathological Anatomy of Shell Lesions
The diagnosis of neuroleukemia is established on the basis of a study of cerebrospinal fluid: by detecting cytosis in it above 10 in 1 μl and necessarily blast cells; the absence of neurological symptoms does not contradict the diagnosis of neuroleukemia.
Treatment of Pathological Anatomy of the Lesions of the Membranes
A day after the first diagnostic puncture revealing neuroleukemia, repeated puncture with endolumbal administration of methotrexate is performed. With each subsequent puncture, the dose of cytosar increases with good tolerance. The interval between punctures is 2-3 days.
Both methotrexate and cytosine-arabinoside, when introduced into the spinal canal, are diluted with isotonic sodium chloride solution. It is advisable to discharge from the spinal canal an amount of fluid approximately equal to the amount of the injected solution of the cytostatic preparation.
The introduction of drugs into the spinal canal is stopped:
1) with a normal composition of cerebrospinal fluid with 3 sequentially performed punctures;
2) with a clear increase in signs of irritation of the meninges against the background of the introduction of drugs.
In some cases, with the ineffective treatment of neuroleukemia with methotrexate and cytosar, radiation therapy can be used.
With a combination of neuroleukemia with a developed picture of leukemia (lack of bone marrow improvement), treatment of neuroleukemia is carried out together with general cytostatic treatment without intravenous administration of methotrexate, without prescribing it inside, and the blood condition is monitored at least 2-3 times a week.
Intravenous administration of large doses of methotrexate began to be used to treat intracerebral tumors. The drug is administered within 24 hours (the first third of the dose – within 2 hours). Since reliable methods of treating intracerebral leukemic tumors are still unknown, in some cases, intravenous administration of large doses of methotrexate may be required.
After radiological prophylaxis of neuroleukemia, medical irradiation of the brain, the administration of large doses of methotrexate requires special care, since the manifestation of its toxic effect in such cases is more likely.
In the case of leukemic spinal cord infiltration, both local radiation therapy and the endolumbal administration of methotrexate and cytosar in doses used to damage the membranes of the brain are effective.
Blast infiltration of the liver is noted in any form of acute leukemia. The liver thus increases, the edge becomes dense; usually the liver is painless. Since the change in the size of the liver, like the spleen, is an important and not duplicated indicator, indicating the effectiveness of the cytostatic treatment in this regard, the doctor determines the size of these organs.
In a puncture examination of the liver, the need rarely arises, since an isolated lesion of its parenchyma is unlikely, and cellular control for complete improvement is carried out using bone marrow examination.
The histological picture of a specific liver lesion according to the autopsy materials is characterized by diffuse infiltration of the liver tissue, but the infiltrates can be more or less clearly delimited and can be found only in the region of the portal tracts or inside the lobules and in the portal area. In acute lymphoblastic leukemia, for example, the infiltration is clearly delimited, located around the lobules, in the area of the portal tracts and connective tissue septa. In acute myeloid leukemia, infiltrates from blast cells of a linear type are found both inside the lobules and in the portal area.
However, impaired liver function in acute leukemia is often associated with the toxic effect of cytostatic drugs. Less commonly, there is obstructive jaundice caused by compression of the intrahepatic bile ducts by proliferation of leukemia cells. However, it is sometimes difficult to differentiate these conditions. The whole complex of biochemical studies comes to the rescue, establishing the sequence and connectedness of liver damage either with the use of cytostatic drugs, or with exacerbation of leukemia.
Skin leukemids in acute leukemia, especially in myeloid, are often found in the late stages of the disease; as a rule, they are multiple. Dense or soft, they often rise above the surface. Their color is either pink or light brown, although there are dense skin leukemids without changing its color. A puncture study of leukemid reveals blast cells. Histological examination shows infiltration of the dermis by young cells. Leukemic infiltration can also capture subcutaneous tissue, forming dense, soldered nodes to the skin.
Testicular damage occurs in all acute leukemia, but mainly in lymphoblastic. The patient suddenly, often against the background of improvement, becomes dense and one testicle increases. The density of the testis and the one-sidedness of the lesion suggest a tumor of the gonads. Diagnosis of testicular leukemia with a puncture study is simple. The appearance of a dense testicular tumor, its rapid increase in a patient with acute leukemia is a fairly reliable sign of metastasis of leukemic cells in the testicle. If specific treatment for the infiltration of one testicle is not carried out, then almost inevitably another metastasis is affected. This pattern of metastasis is quite common for all paired organs and is predetermined by the appearance of a specific clone that can be implanted into the tissue of this organ.
Leukemic gum infiltration is most often observed in acute monoblastic leukemia. At the same time, the gums are hyperemic, have red patches resembling hemorrhages, and hang over the teeth; decay in the field of leukemic infiltrates is often noted.
In the kidneys there can be both separate foci of tumor growth, and diffuse infiltration, sometimes leading to renal failure up to the absence of urine. The process is usually bilateral, enlarged kidneys can be felt. Since local irradiation of the kidneys eliminates leukemic infiltration, it is in doubtful cases also used for diagnostic purposes. Macroscopically, the foci of leukemic infiltration look like tubercles of different sizes under the capsule of the kidney or on its incision.
The development of leukemic myocardial infiltration is indicated by the appearance of heart failure in patients, which is preceded by deafness of heart sounds, decreased ECG voltage and negative T. .
Leukemic pneumonitis is characterized by the appearance of a dry cough; often fever, shortness of breath; during a physical examination, increased expiration is determined over the lesions, less often bronchial breathing, meager localized dry rales, wet rales are rarely heard.
On the radiograph, as a rule, the following are detected: local strengthening of the pulmonary pattern, sometimes small or large focal shadows. Less common is specific pleural infiltration with effusion in the pleural cavity. Histologically, the picture of pulmonary lesion is characterized by blast cell infiltration of the alveolar septa or the formation of peribronchiolar couplings; in cases of high leukocytosis there are leukostasis phenomena.
Diagnosis of leukemic pneumonitis is also complicated by the fact that in the terminal stage deep granulocytopenia is often noted, against which ordinary pneumonia occurs atypically due to the absence of cellular infiltration in the focus of inflammation; physical and radiological data are scarce.
With the appearance of shortness of breath, cyanosis, dry cough, intoxication, even if it is not possible to reliably localize the pneumatic focus, antibiotics of a wide spectrum of action are prescribed. Due to the fact that leukemic pneumonitis, as a rule, develops against the background of an exacerbation of the tumor, the ineffectiveness of antibiotic treatment proves blast infiltration of the lung tissue and the need to change the cytostatic drug. Often, leukemic pneumonitis is observed in combination with bacterial pneumonia.
In recent years, active cytostatic treatment, γ-irradiation of local leukemia tumors, the use of broad-spectrum antibiotics, the use of platelet mass, fresh frozen plasma for the treatment and prevention of hemorrhage, the inclusion of heparin in the treatment of thrombotic complications significantly changed the clinical picture of leukemia. Vast necrosis in the oral cavity and nose practically disappeared, which developed on the basis of the breakdown of leukemic proliferates, became noticeably less pronounced hemorrhages.
The classification of the stages of acute leukemia pursues purely practical goals: the choice of treatment method and prognosis.
Currently, due to the success of treatment with cytotoxic drugs of leukemia, clear boundaries of the stages of the process determine all therapeutic measures. In some cases, it is necessary to use powerful complexes of cytostatic agents aimed at eradicating (eradicating) leukemia, in others it is necessary to prevent exacerbations by means of a long but weak cytostatic effect, and in the third, to eliminate local exacerbation. But very often, the struggle to eradicate tumor growth becomes impossible, and the doctor is forced to confine himself to retaining the achieved partial effect.
These differences in treatment methods formed the basis for the classification of stages, which is as follows: the first acute period (advanced stage of the disease), complete improvement, recovery, incomplete improvement, exacerbation, indicating whether it is first or repeated, its localization, terminal stage.
The extended period of the disease is characterized by marked inhibition of normal blood formation, high bone marrow blastosis, with the exception of low-percentage leukemia.
Complete improvement includes conditions in which no more than 5% of blast cells or a total number of lymphoid cells of less than 10% are found in bone marrow puncture, of which less than 5% of blast cells. Recovery from acute leukemia is considered complete remission for 5 years or more.
Incomplete remission is a rather heterogeneous group of conditions characterized by a distinct hematological improvement (a significant decrease in the percentage of blast cells in the bone marrow with an increase in the percentage of normal cells, combined with an improvement in blood composition). Incomplete improvement is also understood as the disappearance of blast cells from the blood while maintaining bone marrow blastosis, or a decrease in the number of blast cells in the cerebrospinal fluid during the elimination of the clinical symptoms of neuroleukemia, or some suppression of other foci of leukemic proliferation outside the bone marrow.
Exacerbation of acute leukemia can be bone marrow (the appearance of more than 5% of blast cells in punctate) or local – extramedullary with any localization of leukemic infiltration.
Regardless of the cause of the improvement, the hematological and clinical picture of the disease has a natural dynamics. If the patient had a leukemic phase of the disease, then with effective treatment, tumor cells in the blood often lose the characteristic structure of nuclear chromatin and turn into lymphocyte-like cells, the so-called “treated” cells.
The term “clinical improvement” is used. By it is meant an improvement in the general condition of the patient, the disappearance of septic complications, hemorrhages. However, the hematological picture of the disease changes little.
A terminal exacerbation of leukemia is often preceded by a partial improvement.
The terminal stage of acute leukemia at first glance does not have certain features, however, in the development of leukemia there comes a time when all cytotoxic drugs not only turn out to be ineffective, but the process progresses against their background: granulocytopenia, thrombocytopenia, necrosis on the mucous membranes and spontaneous hemorrhages increase.
Also, the occurrence of foci of sarcoma growth in the skin, in the myocardium, and kidneys also refers to the manifestations of the terminal stage. However, the decisive role in the development of the terminal stage belongs to the complete suppression of the normal sprouts of blood formation, and not to organ lesions.