Hodgkin's lymphoma (Hodgkin's disease)

Hodgkin's lymphoma (Hodgkin's disease) is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, affecting primarily the tissue of the lymph nodes, spleen, liver and bone marrow.

Symptoms of the disease include painless lymphadenopathy, sometimes with fever, night sweats, progressive weight loss, pruritus, splenomegaly and hepatomegaly. The diagnosis is based on lymph node biopsy. Treatment in 75% of cases leads to recovery and consists of chemotherapy and / or radiation therapy.

In the US, about 75,000 new cases of Hodgkin's lymphoma are diagnosed each year. The ratio of men and women is 1.4: 1. Hodgkin's lymphoma is rare until 10 years and most often between 15 and 40 years.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]

Causes and pathophysiology of Hodgkin's lymphoma

Hodgkin's lymphoma is the result of clonal transformation of B-cells, which leads to the formation of binuclear Reed-Sternberg cells. The causes of the disease are unknown, but there is a relationship with heredity and external factors (for example, a profession such as wood processing, phenytoin treatment, radiation therapy or chemotherapy, infection with the Epstein-Barr virus , Mycobacterium tuberculosis, type 6, HIV). The risk of the disease is increased in persons with a certain type of immune suppression (for example, patients who undergone transplantation receiving immunosuppressants), in patients with congenital immunodeficient conditions (eg, ataxia-telangiectasia syndromes Kleinfelter, Chediak-Higashi, Viscott-Aldrich), in patients with certain autoimmune diseases (rheumatoid arthritis, non-tropical sprue, Sjogren's syndrome, SLE).

In the majority of patients, there is a slowly progressive impairment of cellular immunity (T-cell function), which promotes the development of bacterial, atypical fungal, viral and protozoal infections. Humoral immunity (production of antibodies) is also impaired in patients with progression of the disease. The cause of death is often sepsis.

[12], [13], [14], [15], [16], [17], [18], [19]

Symptoms of Hodgkin's Disease

Most patients go to the doctor with painless enlarged cervical lymph nodes. However, pain in the area of affected areas can occur after drinking alcohol, which is one of the earliest signs of the disease, although the mechanism of the occurrence of pain is unclear. Another manifestation of the disease develops when the tumor spreads through the reticuloendothelial system into adjacent tissues. It is characterized by the early appearance of intense itching. Common symptoms include fever, night sweats, spontaneous weight loss (> 10% body weight in 6 months), signs of involvement of internal lymph nodes (mediastinapic or retroperitoneal), visceral organs (liver), or bone marrow may be present. Often there is splenomegaly, hepatomegaly can develop. Sometimes there is Pel-Ebstein fever (alternation of elevated and normal body temperature, the appearance of high body temperature for several days, then a change to normal or lower temperature in the next few days or weeks). With the progression of the disease, cachexia occurs.

Bone involvement often occurs asymptomatically, but vertebral osteoblastic lesions (elephant vertebrae) and less pain can occur due to osteolytic lesions and compression fractures. Intracranial lesions, as well as lesions of the stomach and skin are rare and suggest the presence of HIV-associated Hodgkin's lymphoma.

Local compressions of tumor masses often cause symptoms, such as jaundice caused by intrahepatic or extrahepatic biliary obstruction; Foot swelling due to obstruction of the lymphatic ducts in the inguinal region or pelvis; shortness of breath and wheezing, with tracheobronchial compression; pulmonary abscesses or cavities due to infiltration of the pulmonary parenchyma, which can simulate fractional consolidation or bronchopneumonia. Epidural invasion can lead to compression of the spinal cord and cause paraplegia. Horner's syndrome and laryngeal paralysis can be caused by compression by enlarged lymph nodes of the sympathetic cervical and recurrent laryngeal nerves. Neuralgia may be a consequence of compression of the nerve root.

Staging of Hodgkin's disease

After the diagnosis is established, the choice of therapy is determined by the stage of the disease. Usually, the staging system adopted in Ann Arbor is used and is based on the following data: external medical examination; results of instrumental studies, including CT of chest, abdominal, pelvic organs; bone marrow biopsy. Laparotomy is not a prerequisite. Other examinations to determine the stage of the disease may be PET scan, functional cardiological and pulmonological tests.

Cotswold-modification of the NN RBOR system for the staging of Hodgkin's lymphoma and non-Hodgkin's lymphomas

Stage	Criteria
I	The defeat of one lymphoid zone
II	Defeat of 2 or more lymphoid zones on one side of the diaphragm
III	Lesion of lymph nodes, spleen or both on both sides of the diaphragm
IV	Extranodal lesions (bone marrow, lungs, liver)

Subcategory E indicates the involvement of extranodal zones adjacent to the affected lymph nodes (for example, lesion of mediastinal lymph nodes, lung roots with infiltration of adjacent zones of lung tissue is classified as NOT a stage). A category classified as "A" indicates a lack of systemic symptoms, "B" indicates the presence of systemic symptoms (weight loss, fever, or night sweats). Systemic symptoms usually occur in stages III or IV (20-30% of patients); "X" is used to indicate the size of the lesion that is greater than 10 cm in the maximum dimension or greater than 1/3chest diameter on the roentgenogram.

The letter A at any stage indicates the absence of the patient's systemic clinical manifestations. The letter B indicates that the patient has an anamnesis with at least one systemic symptom. The presence of systemic symptoms correlates with the response to treatment.

Diagnosis of Hodgkin's Lymphoma

Hodgkin's lymphoma is suspected in patients with painless lymphadenopathy or mediastinal adenopathy, found on a routine X-ray examination. Such lymphadenopathy can result from infectious mononucleosis, toxoplasmosis, cytomegalovirus infection, non-Hodgkin's lymphoma or leukemia. X-ray picture of chest organs is similar to lung cancer, sarcoidosis or tuberculosis.

Chest radiography is usually followed by a biopsy of the lymph node, if the data are confirmed on CT or PET. With an increase in only the mediastinal lymph nodes, a mediastinoscopy or Chamberlain procedure is performed (limited left upper thoracotomy allowing mediastinoscope biopsy of the mediastinal lymph node). To diagnose lymphoma, biopsy can also be recommended under CT control.

It is necessary to perform a general blood test, ESR, alkaline phosphatase, liver and kidney functional tests. The performance of other examinations depends on the indications (for example, MRI with symptoms of spinal cord injury, bone scanning with ossalgies).

Biopsy reveals Reed-Sternberg cells (large binocular cells) in a characteristic heterogeneous cellular infiltrate consisting of histiocytes, lymphocytes, monocytes, plasma cells and eosinophils. Classical Hodgkin's lymphoma has 4 histological subtypes; there is also a type of lymphocyte prevalence. Certain antigens on Reed-Sternberg cells can help in differentiating Hodgkin's lymphoma from NHL and classical Hodgkin's lymphoma with a type of lymphocytic predominance.

There may be deviations in the results of other methods of research, but they do not have a great diagnostic value. In a general blood test, there may be a small polymorphonuclear leukocytosis. Sometimes at an early stage, lymphocytopenia develops, which, with the development of the disease, becomes deeper. Eighty percent of patients may have eosinophilia and thrombocytosis. Anemia, often microcytic, usually develops with the progression of the disease. Anemia is characterized by a violation of iron reutilization and a low serum iron level, low iron binding capacity and an elevated iron content in the bone marrow. With bone marrow infiltration, which is typical for the type of lymphoid depletion, pancytopenia develops. Hyperplenism may occur in patients with severe splenomegaly. An increase in the serum alkaline phosphatase level may be observed, but this does not always indicate a lesion of the liver or bone marrow. An increase in the level of leukocyte alkaline phosphatase, serum haptoglobin, ESR and other acute phase parameters usually reflects the activity of the disease.

Histological subtypes of Hodgkin's lymphoma (WHO classification)

Histological type	Morphological features	Immuno-phenotype	Appearance
Classical
Nodular sclerosis	Dense fibrous tissue around the nodules of Hodgkin's tissue	CD15, CD30	67%
Mixed cell	Moderate number of Reed-Sternberg cells with mixed infiltrate	CD30	25%
Lymphoid prevalence	Few Reed-Sternberg cells, many B cells, mesh sclerosis	CD30
Lymphoid depletion	Numerous Reed-Sternberg cells and intensive fibrosis	CD30	Rarely
Nodular type of lymphoid prevalence
	Few neoplastic cells (L & H cells), many small B cells, nodular signs	CD30-EMA

[20], [21], [22], [23], [24]

Treatment of Hodgkin's lymphoma

Treatment of patients with IA, IIA, IB or IIB stages of the disease is usually performed using chemotherapy in combination with radiation therapy. Such therapy leads to the recovery of 80% of patients. In patients with the presence of the main tumor mass in the mediastinum, the timing of chemotherapy may be longer and before the start of radiotherapy, various chemotherapy regimens are used.

In the IIIA stage, combined chemotherapy is usually used in combination with radiotherapy to or without the main lesion zone. Recovery is achieved in 75-80% of cases.

At the IIIB stage, polychemotherapy is required, sometimes in combination with radiation therapy. The use of radiotherapy alone does not lead to a cure. Recovery is achieved in 70-80% of cases.

In IVA or IVB stages, polychemotherapy is used according to the ABVD scheme [doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine], resulting in a complete remission of 70-80% of patients, with 10-15-year survival without symptoms in 50% of patients. The MOPP scheme [mechlorethamine, vincristine (onkovin), procarbazine, prednisolone] is no longer used due to side effects, including secondary anemia. Effective are also the following drugs: nitrosourea, ifosfamide, cisplatin or carboplatin, etoposide. Promising is a combination of drugs Stanford V, representing a 12-week regimen of chemotherapy. Patients who do not achieve complete remission or who have relapsed within 12 months have a poor prognosis. In patients with relapse or refractory disease in the presence of a response to chemotherapy, autologous stem cell transplantation can be effective.

Complications of Hodgkin's Disease Therapy

Chemotherapy with regimens like MEPP increases the risk of secondary leukemia, which usually develops after 3 years. Chemotherapy and radiation therapy increase the risk of malignant solid tumors (for example, breast, GI, lung, soft tissue sarcoma). Irradiation of the mediastinum increases the risk of developing coronary atherosclerosis. The risk of breast cancer increases in women 7 years after the completion of radiotherapy for nearby lymph nodes.

Lymphoma of Hodgkin. Follow-up after treatment

Evaluation	Program
Medical examination, general blood test, platelets, ESR, biochemical blood test	The first 2 years - in 3-4 months, 3-5 years - in 6 months,> 5 years - in 12 months
Radiography of chest organs at each visit, if chest CT was not performed	The first 2 years - in 3 months, 3-5 years - in 6 months,> 5 years - in 12 months
CT of thoracic organs	The first 2 years - in 6-8 months, 3-5 years - in 12 months,> 5 years if there are violations on radiography
KG of abdominal cavity of small pelvis	Stages I and II: the first 5 years annually, At other stages: the first 2 years every 6 months, from 3 to 5 years - annually
The level of thyroid hormones	Every 6 months after neck irradiation
Annual mammography after 7 years after treatment	When irradiated above the diaphragm in patients under 30 years of age
Annual mammography since the age of 37	When irradiated above the diaphragm in patients older than 30 years

[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35]

Prognosis for Hodgkin's lymphoma

With Hodgkin's lymphoma, the absence of recurrence of the disease for 5 years is considered a recovery; the occurrence of relapse after 5 years is an extremely rare case. Chemotherapy with radiation therapy or without it allows to achieve recovery in more than 75% of newly diagnosed patients. The choice of treatment is rather complicated and depends on the stage of the disease.