Lymphogranulomatosis is a malignant hyperplasia of lymphoid tissue, a characteristic feature of which is the formation of granulomas with Berezovsky-Sternberg cells. For lymphogranulomatosis, an increase in various groups of lymph nodes (more often mandibular, supraclavicular, mediastinal), an increase in the spleen, subfebrility, general weakness, weight loss is specific. In order to verify the diagnosis, lymph node biopsy, diagnostic operations (thoracoscopy, laparoscopy), chest X-ray, ultrasound, CT, bone marrow biopsy are performed. For therapeutic purposes, with lymphogranulomatosis, polychemotherapy, irradiation of affected lymph nodes, splenectomy is performed.
General information
Lymphogranulomatosis (LGM) is a lymphoproliferative disease that occurs with the formation of specific polymorphocellular granulomas in the affected organs (lymph nodes, spleen, etc.). By the name of the author, who first described the signs of the disease and proposed to isolate it into an independent form, lymphogranulomatosis is also called Hodgkin’s disease, or Hodgkin’s lymphoma. The average incidence of lymphogranulomatosis is 2.2 cases per 100 thousand population. Among the cases, young people aged 20-30 years predominate; the second peak of morbidity occurs at the age of over 60 years. In men, Hodgkin’s disease develops 1.5-2 times more often than in women. In the structure of hemoblastoses, lymphogranulomatosis is assigned three times the frequency of occurrence after leukemia.
Causes
The etiology of lymphogranulomatosis has not yet been clarified. To date, viral, hereditary and immune theories of the genesis of Hodgkin’s disease are considered among the main ones, but none of them can be considered exhaustive and generally accepted. In favor of the possible viral origin of lymphogranulomatosis, its frequent correlation with the transferred infectious mononucleosis and the presence of antibodies to the Epstein-Barr virus testifies. At least 20% of the studied Berezovsky-Sternberg cells contain the genetic material of the Epstein-Barr virus, which has immunosuppressive properties. The etiological influence of retroviruses, including HIV, is also not excluded.
The role of hereditary factors is indicated by the occurrence of the familial form of lymphogranulomatosis and the identification of certain genetic markers of this pathology. According to the immunological theory, there is a possibility of transplacental transfer of maternal lymphocytes into the fetus with the subsequent development of an immunopathological reaction. The etiological significance of mutagenic factors – toxic substances, ionizing radiation, drugs and others in provoking lymphogranulomatosis is not excluded.
It is assumed that the development of lymphogranulomatosis becomes possible in conditions of T-cell immunodeficiency, as evidenced by a decrease in all links of cellular immunity, a violation of the ratio of T-helpers and T-suppressors. The main morphological sign of malignant proliferation in lymphogranulomatosis (in contrast to non-Hodgkin’s lymphomas and lymphocytic leukemia) is the presence in the lymphatic tissue of giant multinucleated cells, called Berezovsky-Reed–Sternberg cells and their pre-stages – single-core Hodgkin cells. In addition, the tumor substrate contains polyclonal T-lymphocytes, tissue histiocytes, plasma cells and eosinophils. With lymphogranulomatosis, the tumor develops unicentrically – from one focus, more often in the cervical, supraclavicular, mediastinal lymph nodes. However, the possibility of subsequent metastasis causes the occurrence of characteristic changes in the lungs, gastrointestinal tract, kidneys, and bone marrow.
Classification
In hematology, there is an isolated (local) form of lymphogranulomatosis, in which one group of lymph nodes is affected, and generalized – with malignant proliferation in the spleen, liver, stomach, lungs, and skin. By localization, peripheral, mediastinal, pulmonary, abdominal, gastrointestinal, skin, bone, and nervous forms of Hodgkin’s disease are distinguished.
Depending on the rate of development of the pathological process, lymphogranulomatosis can have an acute course (several months from the initial to the terminal stage) and a chronic course (prolonged, long-term with alternating cycles of exacerbations and remissions).
Based on the morphological study of the tumor and the quantitative ratio of various cellular elements, 4 histological forms of lymphogranulomatosis are distinguished:
- lymphohistiocytic, or lymphoid predominance
- nodular-sclerotic, or nodular sclerosis
- mixed-cell
- lymphoid depletion
The clinical classification of lymphogranulomatosis is based on the criterion of the prevalence of the tumor process; according to it, the development of Hodgkin’s disease goes through 4 stages:
- Stage I (local) – one group of lymph nodes (I) or one extralymphatic organ (IE) is affected.
- Stage II (regional) – two or more groups of lymph nodes located on one side of the diaphragm (II) or one extralymphatic organ and its regional lymph nodes (IIE) are affected.
- Stage III (generalized) – the affected lymph nodes are located on both sides of the diaphragm (III). Additionally, one extralymphatic organ (IIIE), spleen (IIIS) or they are together (IIIE + IIIS) may be affected.
- Stage IV (disseminated) – the lesion affects one or more extralymphatic organs (lungs, pleura, bone marrow, liver, kidneys, gastrointestinal tract, etc.) with or without simultaneous lymph node damage.
To indicate the presence or absence of common symptoms of lymphogranulomatosis over the past 6 months (fever, night sweats, weight loss), the letters A or B are added to the number indicating the stage of the disease, respectively.
Symptoms
Symptoms characteristic of lymphogranulomatosis include intoxication, enlargement of lymph nodes and the occurrence of extranodal foci. Often the disease begins with nonspecific symptoms – periodic fever with temperature peaks up to 39 ° C, night sweats, weakness, weight loss, itching.
Often, the first “messenger” of lymphogranulomatosis is an increase in the lymph nodes available for palpation, which patients discover on their own. More often these are cervical, supraclavicular lymph nodes; less often – axillary, femoral, inguinal. Peripheral lymph nodes are dense, painless, mobile, not soldered together, with the skin and surrounding tissues; they usually stretch in the form of a chain.
In 15-20% of patients, lymphogranulomatosis debuts with an increase in mediastinal lymph nodes. When mediastinal lymph nodes are affected, dysphagia, dry cough, shortness of breath, ERW syndrome can serve as the first clinical signs of Hodgkin’s disease. If the tumor process affects retroperitoneal and mesenteric lymph nodes, abdominal pain and swelling of the lower extremities occur.
Among extranodal localizations in lymphogranulomatosis, lung damage is most common (in 25% of cases). Lymphogranulomatosis of the lungs proceeds according to the type of pneumonia (sometimes with the formation of cavities in the lung tissue), and when the pleura is involved, it is accompanied by the development of exudative pleurisy.
With the bony form of lymphogranulomatosis, the spine, ribs, sternum, pelvic bones are more often affected; skull bones and tubular bones are much less common. In these cases, vertebralgia and ossalgia are noted, destruction of vertebral bodies may occur; radiological changes usually develop after a few months. Tumor infiltration of the bone marrow leads to the development of anemia, leukocytopenia and thrombocytopenia.
Lymphogranulomatosis of the gastrointestinal tract occurs with invasion of the muscular layer of the intestine, ulceration of the mucosa, intestinal bleeding. Complications in the form of perforation of the intestinal wall and peritonitis are possible. Signs of liver damage in Hodgkin’s disease are hepatomegaly, increased activity of alkaline phosphatase. If the spinal cord is affected, transverse paralysis may develop within a few days or weeks. In the terminal stage of lymphogranulomatosis, generalized lesion can affect the skin, eyes, tonsils, thyroid gland, mammary glands, heart, testicles, ovaries, uterus, etc. organs.
Diagnostics
An increase in peripheral lymph nodes, liver and spleen along with clinical symptoms (febrile fever, sweating, weight loss) always causes oncological concerns. In the case of Hodgkin’s disease, instrumental imaging techniques play an auxiliary role.
Reliable verification, correct staging and adequate choice of the method of treatment of lymphogranulomatosis are possible only after morphological diagnosis. In order to collect diagnostic material, a biopsy of peripheral lymph nodes, diagnostic thoracoscopy, laparoscopy, laparotomy with splenectomy is indicated. The criterion for confirming lymphogranulomatosis is the detection of giant Berezovsky-Sternberg cells in the biopsy under study. The detection of Hodgkin cells only allows us to assume an appropriate diagnosis, but cannot serve as a basis for prescribing special treatment.
In the system of laboratory diagnostics of lymphogranulomatosis, a general blood test, biochemical blood parameters that allow assessing liver function (alkaline phosphate, transaminases) are necessarily examined. If bone marrow involvement is suspected, a sternal puncture or trepanobiopsy is performed. In various clinical forms, as well as to determine the stage of lymphogranulomatosis, chest and abdominal x-ray, CT, ultrasound of the abdominal cavity and retroperitoneal tissue, mediastinal CT, lymphoscintigraphy, skeletal scintigraphy, etc. are required.
In differential diagnostic terms, differentiation of lymphogranulomatosis and lymphadenitis of various etiologies is required (in tuberculosis, toxoplasmosis, actinomycosis, brucellosis, infectious mononucleosis, sore throat, flu, rubella, sepsis, AIDS). In addition, sarcoidosis, non-Hodgkin’s lymphomas, cancer metastases are excluded.
Treatment
Modern approaches to the treatment of lymphogranulomatosis are based on the possibility of a complete cure of this disease. At the same time, treatment should be phased, comprehensive and taking into account the stage of the disease. In Hodgkin’s disease, schemes of radiation therapy, cyclic polychemotherapy, a combination of radiation therapy and chemotherapy are used.
As an independent method, radiation therapy is used in stage I-IIA (lesions of single lymph nodes or one organ). In these cases, radiation may be preceded by removal of lymph nodes and splenectomy. With lymphogranulomatosis, subtotal or total irradiation of lymph nodes (cervical, axillary, supra- and subclavian, intra-thoracic, mesenteric, retroperitoneal, inguinal) is carried out, capturing both groups of affected and unchanged lymph nodes (the latter for preventive purposes).
Patients with stages IIB and III are prescribed combined chemoradiotherapy: first, introductory polychemotherapy with irradiation of only enlarged lymph nodes (according to the minimum program), then irradiation of all other lymph nodes (according to the maximum program) and supportive polychemotherapy for the next 2-3 years.
In disseminated stages III and IV of lymphogranulomatosis, cyclic polychemotherapy is used to induce remission, and at the stage of maintaining remission, cycles of drug therapy or radical irradiation are used. Polychemotherapy for lymphogranulomatosis is performed according to specially developed schemes in oncology (MORR, SORR, SURR, CVPP, DORR, etc.).
The results of the therapy can be:
- complete remission (disappearance and absence of subjective and objective signs of lymphogranulomatosis within 1 month)
- partial remission (relief of subjective signs and reduction of the size of lymph nodes or extranodal foci by more than 50% within 1 month)
- clinical improvement (relief of subjective signs and reduction of the size of lymph nodes or extranodal foci by less than 50% within 1 month)
- lack of dynamics (preservation or progression of signs of lymphogranulomatosis).
Forecast
For stages I and II of lymphogranulomatosis, the relapse-free 5-year survival after treatment is 90%; at stage IIIA – 80%, at stage III – 60%, and at IV – less than 45%. Unfavorable prognostic signs are acute development of lymphogranulomatosis; massive conglomerates of lymph nodes more than 5 cm in diameter; expansion of the mediastinal shadow by more than 30% of the chest volume; simultaneous lesion of 3 or more groups of lymph nodes, spleen; histological variant of lymphoid depletion, etc.
Relapses of lymphogranulomatosis can occur when the maintenance therapy regime is violated, provoked by physical exertion, pregnancy. Patients with Hodgkin’s disease should be monitored by a hematologist or oncologist. Preclinical stages of lymphogranulomatosis in some cases can be detected during preventive fluorography.