Lymphogranulomatosis is a pathological granulomatous-tumor lesion of the lymphatic system, which is also called Hodgkin's lymphoma. Lymphogranulomatosis was first described in 1832 by the doctor Thomas Hodgkin, who explained several moments of the course of the disease. At first, lymph nodes usually grow and spleen, then there is a fever and cachexia, subsequently leading the patients to death. And already in 1875 Kutarev conducted the first histological examination of the lymph node, which was removed during the life of the patient.
In 1890 the Russian scientist Berezovsky described the histological picture of lymphogranulomatosis. He was diagnosed pathognomonic giant cells, characteristic for this disease. And already Viennese pathologists in 1897-1898 described polymorphic cell granuloma, which has giant multinucleated cells, which later became known as Berezovsky-Reed-Sternberg cells.
The need for studying lymphogranulomatosis is explained by the defeat of patients, beginning with a young age (mainly from 15 to 40 years). Also, this disease is characterized by the waviness of its course. The first is at the age of twenty, and the second - after 60 years.
Lymphogranulomatosis ranks the tenth place among oncological pathologies, in which the greatest percentage of lesions falls on men, rather than on women.
Until recently, lymphogranulomatosis was considered as a disease of an infectious origin. It was believed that his pathogen could be a tuberculosis bacillus. Less often this role was prescribed streptococcus, Escherichia coli, pale spirochaete and diphtheria bacillus. There were also suggestions of a viral etiology of lymphogranulomatosis, but this was also not confirmed.
At the moment, it has been established that a tumor neoplasm (hematosarcoma and leukemia) is considered a certain pathology of the hematopoietic system, and Berezovsky's malignant-Sternberg cells are the cause of the development of lymphogranulomatosis.
Also, certain factors of life that can contribute to the onset of the disease are not fully understood. These include lifestyle, bad habits, eating habits and occupational hazards. Some studies provide data on the possible risk of developing lymphogranulomatosis in individuals who have had infectious mononucleosis or skin diseases, working in the sewing or woodworking industry, in agriculture, as well as among chemists and doctors.
Cases of lymphogranulomatosis among several members in one family or in one group have been reported. This suggests that there is a role for the weakly virulent infection of the viral etiology and the genetic predisposition of the organism, however, there is as yet no definitive evidence for this. Thus, definite and precise causes of the onset of lymphogranulomatosis have not yet been found.
The clinical picture of lymphogranulomatosis is characterized by two types: natural and chronic.
In the natural course of lymphogranulomatosis, there is an alternation of the processes of exacerbation and remission, but sometimes the disease acquires a violent, acute onset with high temperature rises, torrential sweating, and the spread of the tumor to various internal organs. Without medical care, such patients may die within a few weeks of the onset of the pathological process or in the coming months.
But basically in 90%, the lymphogranulomatosis is chronic, with periodic exacerbations, as a result of which the pathological process passes to new lymph nodes, tissues and organs.
The course of lymphogranulomatosis is adversely affected by several factors, such as solar radiation, pregnancy and physiotherapy.
For clinical symptoms of the disease, local and general symptoms are characteristic. During the diagnosis of pathology, general manifestations can be of great importance. Among them, there is an increase in various groups of lymph nodes and the appearance of pathological lesions in tissues and internal organs. First of all, peripheral lymph nodes are affected, which is characterized by an increase in size without special reasons, or it may coincide with catarrhal diseases. Such lymph nodes on palpation have an unequal round or oval shape with an elastic consistency. As a rule, they are not connected with each other and with neighboring tissues, mobile and painless. The skin does not have any changes and it can easily be gathered into a crease, fistulas do not appear.
In 80% of the lymphogranulomatosis affects the lymph nodes located in the neck. Its circumference increases, the contours acquire irregularities, and sometimes the protrusions of the lymph nodes are visually noticeable if they are affected in plural quantity. At the time of the doctor's visit, almost 25% of patients are simultaneously palpable with cervical lymph nodes and significantly enlarged supraclavicular.
Axillary and inguinal lymph nodes are very rarely diagnosed in primary lymphogranulomatosis. Much more common is the simultaneous damage of these lymph nodes with cervical lymph nodes or mediastinal. Sometimes the disease can begin with inflammation of the occipital, submandibular and parotid lymph nodes.
In 20% of patients, lymph node granulomas mediate lymph nodes of the mediastinum. Diagnosis of this period of the disease is possible with a random radiographic examination of the lungs. But the clinical picture for a long period does not show any symptoms, but when the lymph nodes increase in size, the patients complain of difficulty breathing, shortness of breath, chest pain and cough.
At percussion it is impossible to define small sizes of lymph nodes. But enlarged conglomerates blunt percussion sound, and breathing weakens in large and small areas of the chest. In the later stages of the disease, after lymph node compression of the thoracic duct or when second infection is added, pleurisy is formed. Sometimes patients develop a mediastinal syndrome of compression type or atelectasis of the lung.
In rare cases, it is possible to encounter retroperitoneal lymph nodes or iliac in the primary form of lymphogranulomatosis. Such a lesion occurs without any particular visible clinical symptoms. Only during multiple lesions there are pains of a permanent or recurrent nature in the lumbar region, abdomen, lower limbs; bloating and upset of the stool.
With a significant increase in lymph nodes in the iliac region, there is a violation of the outflow of lymph from the extremities, which is a consequence of the swelling of the distal parts of the foot and lower leg.
Lymphogranulomatosis affects the internal organs. The second place after the lymph nodes in the lesion is occupied by the spleen. However, this does not appear in clinical symptoms. With palpation, the spleen is almost normal and does not reach a large size, so it is difficult to feel and it can be done only with multiple and large lesions of the organ.
Much less common is the lymphogranulomatosis of other organs with primary manifestations of the disease. And basically this pathological process passes in a combination with defeat of lymphonoduses and is shown in the form of pains, and the symptoms connected with infringements of functions of these organs.
When the lymphogranulomatosis affects the bones, patients complain of pain of varying intensity and swelling from the affected hearth.
Sometimes the disease spreads to the skin. In this case, small rounded infiltrates and ulcers appear, acquiring a dark red color or changes in the form of rashes, urticaria, eczema associated with impaired immunity of patients.
Almost 50% of patients have symptoms of intoxication, which increase body temperature, sweating at night, skin pruritus and a sharp decrease in weight. Many patients complain of a state of general weakness, aches in joints, muscles and bones, as well as a headache.
There are three main clinical symptoms that worsen the prediction of lymphogranulomatosis. First, it is the loss of body weight without certain reasons for half a year to ten percent. Secondly, this is a profuse night sweating. And, thirdly, an inexplicable rise in body temperature above 39 ° C for three days.
The manifestation of generalized skin itching also refers to symptoms of intoxication.
Lymphogranulomatosis affects the bone marrow without specific features and it is diagnosed in 5%, and at autopsy in 30% of cases.
Stages of lymphogranulomatosis
Lymphogranulomatosis usually affects the lymph nodes, much less often the pathological process extends to the spleen, liver, lungs and other organs. Therefore, the manifestations of lymphogranulomatosis are classified as lymphatic and extralymphatic.
When "lymphatic" lymph nodes, spleen, thymus gland, lymphoid pharyngeal ring, vermiform appendix and Peyer's plaques are affected. All other lesions are extralymphatic manifestations of the disease.
Today the classification of lymphogranulomatosis, which was proposed in 1966 by Lukasem, was most widely spread. It distinguishes four histological types of lymphogranulomatosis: lymphohistiocytic, nodular-sclerotic, mixed-cell and reticular.
It is believed that lymphogranulomatosis develops unicentrically. First of all, one site of lymphoid tissue in the lymph node is affected, and then malignant cells spread through the lymphatic system to new foci, and there new lymph nodes are affected. Therefore, it is this lymphogranulomatosis that differs from other pathological formations, since it can affect lymphoid tissue in remote areas from the main malignant focus. At one time, this made it difficult to develop a division of lymphogranulomatosis at a stage that was finally adopted by the international classification in 1971. She considers the four stages of the disease.
At the first or local stage of lymphogranulomatosis one zone of lymph nodes or one extralymphatic tissue is affected, and maybe an organ.
In the second or regional stage of lymphogranulomatosis, two zones of lymph nodes are affected, and sometimes more, localized on one side of the diaphragm. But different zones of the lymph nodes can be involved in the pathological process simultaneously with the lesions of one extralymphatic tissue, the organs located on the same side of the diaphragm.
In the third or generalized stage of lymphogranulomatosis, zones of lymph nodes in the singular or plural on both sides of the diaphragm are affected. This process can include the affected spleen, one extralymphatic tissue or organ.
In the fourth or disseminated stage of lymphogranulomatosis, one or more extralymphatic tissues or organs are diffusely affected with simultaneous lesions or without it, lymph nodes.
In addition, with symptoms of intoxication present in patients, the index is added to the stage - "B" and in the absence of "A". It is also known that the prognosis of lymphogranulomatosis worsens when these symptoms join the stages of the pathological process.
Lymphogranulomatosis in children
This malignant pathology is found among children in a ratio of 1: 100,000. And this is much lower than among adults. Lymphogranulomatosis also does not affect children until the first year of life. The main peak of the disease is at preschool age. In addition, up to ten years, this age group among boys in the incidence prevails over girls. And already with 15-16 years the parity between sexes is leveled.
Children's lymphogranulomatosis is characterized by malignant changes in the lymphoid tissue and the spread of lymphogranules into the lymph nodes and somatic organs. As a rule, lymphogranulomatosis passes from one affected area to another.
Children mainly diagnosed with cervical lymphadenopathy, which is characterized by various inflammatory processes in the nasal and pharyngeal. As a rule, these lesions are associated with lesions of the upper and submaxillary lymph nodes. And here already at defeat supraclavicular and nizhneysheinyh there is a suspicion in occasion of a lymphogranulomatosis. Sometimes (in 20% of cases) the axillary lymph nodes are involved in the pathological process, and in less than 5% - inguinal.
If the lymph nodes of the mediastinum are involved in a large number, then the tissue of the lung, and the pleura, and the pericardium, and the chest with possible development of compression syndrome are affected. At this time, the child's face becomes puffy with signs of cyanosis , develops a cough of torment and shortness of breath with minor physical exertion, as well as tachycardia.
With a rare lesion of the sub-diaphragmatic lymph nodes, children do not make any special complaints. Then the pathological process joins the spleen, and in rare cases - the liver. The child has a high body temperature, weakness, night sweats, decreases appetite, he becomes constantly drowsy and apathetic. In the analysis of blood, an increase in ESR is possible. At the fourth stage (disseminated) lymphogranulomatosis, the reduction of erythrocytes and platelets in the blood is determined. Therefore, with these manifestations, a biopsy is mandatory.
Still mark certain signs of activity of pathological process. These include: elevated levels of haptoglobin, the presence of increased amounts of ceruloplasmin, fibrinogen, and lactate dehydrogenase.
When lesions with lymphogranulomatosis of the intrathoracic lymph nodes, the child develops a cough that begins with a cough and changes into seizures. The child constantly complains of pains in the chest or in the heart, worse with the next bout of coughing.
In children with lymphogranulomatosis there is a lesion of para-aortic lymph nodes, which are located near the vessels, in the region of the gates of the liver, kidneys and spleen. With lesions of retroperitoneal lymph nodes in combination with spleen, children complain of the occurrence of periodic pain in the abdomen of varying intensity.
Lymphogranulomatosis practically alters all tissues and organs in the body of sick children. To extranodal lesions include lung tissue, bones, pleura and liver. Much less often, the lymphogranulomatosis changes the bone marrow.
In order to diagnose this malignant lesion in children, in the USA in 1971, certain types of examination were taken, which are necessary for the correct determination of the stage of lymphogranulomatosis and the choice of its treatment. First of all, when the child's anamnesis is collected, special attention is focused on all the symptoms. Then, if necessary, do a biopsy and examine the affected areas. After this, laboratory tests are scheduled to determine biochemical parameters. A compulsory study is the radiography of chest organs in different projections, both direct and lateral, as well as computer tomography. In those cases where there are suspicions of pathological changes in the bone marrow, trepanobiopsy is prescribed, and for damage to the bones, kidneys and liver, scanning is performed.
The main methods of treatment of the pathological process in the lymph system are the medicinal method, radiotherapy and their combination.
However, in the past few decades, one of the ways to treat lymphogranulomatosis has been surgical excision of affected lymph nodes. But already in the nineteenth century it was found that surgical interventions lead to the spread of the pathological process. Therefore, the treatment of lymphogranulomatosis was limited by restorative means.
The first irradiation of lymph nodes was done in 1901 in two patients with lymphogranulomatosis. And in 1906 this method of treatment appeared in Russia. But only in the 1940s, chemotherapy was added to radiotherapy. The first chemotherapeutic drug was Mustargen, which is part of the group chloroethylaminosis. Since 1947, Larionov uses his analogue - embichin. However, until the sixties of the last century, chemotherapy drugs for the treatment of lymphogranulomatosis were applied irregularly. This, as a rule, looked palliative and had a research character. At the heart of the treatment of the disease remained irradiation, but from the beginning of 1960 the newest course of drug therapy was proposed - the MORP.
For a radical irradiation treatment as an independent therapy, the total dose to affected lesions is 40 Gy for four or six weeks, and for preventive zones - 30-50 Gy for three or four weeks. This method of treatment is prescribed to patients in I-II A pathological stages of lymphogranulomatosis with favorable prognosis.
Combined therapy programs have become more common in recent times. Patients diagnosed with a favorable prognosis for lymphogranulomatosis undergo a therapy according to a certain program: two courses of polychemotherapy in any scheme from the first line, irradiation to the affected areas at a dose of 36 Gy, two cycles of drug therapy according to the chosen scheme, which was prescribed before irradiation.
Combination therapy refers to a method considered the choice of patients I, II (I E-II E) stages of lymphogranulomatosis with unfavorable prognosis. Therapy in this case begins with polychemotherapy. By volume, such treatment is always much more than with a favorable prognosis. Here, the program is applied in three courses of polychemotherapy from any scheme related to the first line, radiation therapy of the affected areas (36 Gy), and three consolidation courses of chemotherapy.
To treat the third stage (A) of lymphogranulomatosis, chemoradiation combined therapy is mainly used. Such patients with a favorable prognosis are prescribed four courses of first-line polychemotherapy, then radiation irradiation for the affected zones (30-40 Gy). And for patients with an unfavorable prognosis, 6-8 cycles of chemotherapy from first-line regimens, irradiation at 30 Gy (with absolute remission) and 40 Gy (with residual tumor processes). Patients of the third (B) - fourth stage with generalization of the process apply cyclic chemotherapy.
The schemes of the first line are: MOPP, MVPP, CVPP, COPP, LVPP, ABVD.
The MOPP scheme includes the administration of intravenous drugs such as Embihina and Onkovina; Inside - Procarbazine and Prednisolone with interruptions in two weeks.
The MVPP scheme, similar to MORP, only Onkovin was replaced with Vinblastine with a break between cycles in four weeks.
CVPP Scheme: Orally administered Procarbazine and Prednisolone for two weeks; in the 1st and 8th days intravenously: Vinblastine and Cyclophosphamide with interruptions in two weeks.
The CORP scheme, identical to CVPP, only Vinblastine is replaced with Vincristine, with a break between courses in two weeks.
A LVPP scheme similar to CVPP but replacing Cyclophosphane with Chlorbutin from the first to the fourteenth day for ingestion and a break between cycles of three or four weeks.
The ABVD scheme includes intravenous administration on the first and fourteenth days of such drugs: DTIK at 375 mg / m2, Bleomycin at 10 mg / m2, Vinblastine at 6 mg / m2 and Adriamycin at 25 mg / m2 with intermittent cycles of two weeks.
When cyclic chemotherapy is used for patients at any stage of lymphogranulomatosis, treatment is performed until the remission is fully achieved. Then you need to make two more control courses. Absolute cure in patients with generalized stages of lymphogranulomatosis, before the fourth course of polychemotherapy can not be achieved. Therefore, it is necessary to conduct a minimum course of the entire program in six cycles.
For the treatment of late relapses of pathological processes that occurred after two years of complete recovery, the same methods are used in treatment as with the first diagnosis of the disease.
Early relapses (up to two years) that did not achieve complete remission cause great difficulties in treatment. Patients of the first and second stage of lymphogranulomatosis with a favorable prognosis for marginal relapses, which appeared five months after irradiation, undergo radiation therapy at a dose of 40 Gy. All other patients are being changed chemotherapy.
In the treatment of early generalized relapse after chemoradiotherapy, second-line regimens or high-dose chemotherapy (third-line regimen) are prescribed for primary-resistant patients and patients with recurring relapses.
The schemes of the second line are:
B-CAVe, which includes such drugs that are administered intravenously on the first day - Vinblastine at 6 mg / m2 and Doxorubicin at 60 mg / m2, and Bleomycin also intravenously at 5 mg / m2 on the first, twenty-eighth and thirty-fifth days and Lomustine at 100 mg / m2 orally. The course is repeated on the forty-second day.
CEP: intravenous drip is administered from the first to the fifth days of etoposide at 100 mg / m2; inside - on the first day of CCNU at 80 mg / m2 and prednisolone at 60 mg / m2 from the first to the fifth days. With the repetition of the course on the 28th day.
Reuss: all preparations are taken internally - on the first day of CCNU at 100 mg / m2, Etoposide at 200 mg / m2 from the first to the third days, Leukeron 20 mg / m2 from the first to the fifth and Prednisolone 40 mg / m2 from the first to the seventh days. Break - three weeks.
ABVD: prescribe drugs only intravenously. This is the 1st and the 14th days of Bleomycin at 10 mg / m2 and Doxorubicin at 25 mg / m2; from the first to the fifth days - Imidazole-Carboxamide 175 mg / m2. Break - four, six weeks.
MOPP / ABV: intravenously administered on day 1 - Onkovin and Mustargen, and on the 8th day - Vinblastine, Adriamycin and Bleomycin; Inside - Natulan and Prednisolone. With a break between the cycles in three weeks.
High-dose chemotherapy is a BEAM scheme that includes intravenous administration of drugs such as Carmustine, Etoposide, Cytosar, Melphalan on the sixth day, and stem cell transplantation on the seventh day.
Patients with the third stage of lymphogranulomatosis are assigned splenectomy with expressed symptoms of splenomegaly and with poor blood formation, which interferes with cytostatic treatment, after ineffectiveness of chemoradiotherapy.
After the chosen and conducted treatment, the patient's condition undergoes a certain evaluation. There are some criteria for assessing the results of treatment of patients with lymphogranulomatosis. It is carried out by physical examination, X-ray and ultrasonography after the third and sixth courses of therapy.
The main criteria include complete and partial remission, stabilization or progression. With complete remission, all clinical symptoms of lymphogranulomatosis disappear completely, including laboratory indications of the tumor process with a period of four weeks. Partial remission is characterized by a decrease in pathological neoplasm by almost 50%. Stabilization indicates a decrease in the tumor also by half, in the absence and appearance of new malignant lesions by 25%. With progression, new foci of lesions appear and tumors increase in size.
The overall five-year and no-relapse survival of patients with localized form of lymphogranulomatosis with super-diaphragmatic tumor localization and complex treatment is 90%. For the third stage of type A disease, 80% of survival rate, for the same stage of type B - 60%, and for the fourth stage - about 45%.