Hodgkin’s disease, also known as lymphoreticular sarcoma, is a chronic, progressive, painless tumor of lymphoid tissue with an eccentric distribution of primary tumors originating in one or a group of lymph nodes, more commonly in the cervical lymph nodes, gradually spreading to adjacent lymph nodes and then invading the spleen, liver, bone marrow and lung. The clinical manifestations are varied due to the different sites of onset, and the incidence is rare before the age of 5 years and gradually increases after 5 years, with a significant increase in the incidence during adolescence and a peak between 15 and 34 years. The incidence is more frequent in males than in females.
There is overexpression of human cellular antigenic components among affected siblings, and in many reports it has been found that the same family may be affected by 2 or more members with close timing of onset. There is good evidence that genetics is associated with Hodgkin’s lymphoma, and its incidence can be increased 5-7 times in siblings of patients, and patients with this disease may have chromosomal abnormalities.
The current study is more about infectious factors, because most patients have enlarged lymph nodes in the neck as the first episode, followed by mediastinal lymph nodes; enlarged lymph nodes in other areas are rare as the first episode, and there is a relationship between Hodgkin’s lymphoma and infectious factors (viruses) that consider the respiratory tract as the portal of invasion.
Clinical presentation
The earliest manifestations are mostly painless progressive enlargement of superficial lymph nodes, often lacking systemic symptoms and progressing slowly. About 60% of the cases originate in the cervical lymph nodes, and less frequently in the supraclavicular, subclavicular and inguinal lymph nodes. At the beginning, the lymph nodes are soft, not adherent to each other, and not painful to touch. In later stages, they increase rapidly and may adhere to form a large mass. It is characterized by the absence of inflammation in the adjacent tissues and cannot be used to explain the cause of the enlarged lymph nodes. Enlarged lymph nodes can cause local compression symptoms, such as enlarged mediastinal lymph nodes compressing the tracheobronchial tubes and causing a dry cough. Unexplained abdominal pain can be due to enlarged posterior peritoneal lymph nodes. Systemic symptoms may be hypothermia, or a characteristic regressive fever pattern, in which a high fever for several days is followed by a fever-free period of several days or weeks. There is often loss of appetite, nausea, night sweats and weight loss, which are often absent when the lesion is confined. Pruritus, a common symptom in adults, is rarely seen in pediatric patients, even when there is widespread systemic organ involvement. About 1/4 of children have metastases to tissues other than lymph nodes at the time of diagnosis, most often to the spleen, liver, lungs, or bone and bone marrow. Radiographic changes of pulmonary infiltrates are mostly villi-like exudative changes, which are not easily distinguishable from fungal infections, and there is mostly accelerated respiration and fever, and even respiratory failure. Liver involvement may present with symptoms of intrahepatic bile duct obstruction, moderate liver enlargement, scleral yellowing, and increased serum direct and indirect bilirubin and alkaline phosphatase. Bone marrow infiltration is associated with neutropenia, thrombocytopenia and anemia. Mucosal ulceration and gastrointestinal bleeding may occur with digestive tract involvement. Lymphomas occurring in the epidural space of the spinal cord may cause symptoms of compression. In addition, various immune dysfunctions such as immune hemolysis, thrombocytopenia or nephrotic syndrome may occur.
Hodgkin’s disease itself or chemotherapy can lead to cellular immune deficiency, and children with this disease are susceptible to secondary infections, including herpes zoster in about 1/3 of cases, which can spread to the lung. Mycobacterial infections such as Cryptococcus, Histoplasma and Candida albicans are also common complications, and the lesions are more widespread.
Examination
Blood picture changes are nonspecific and vary greatly between types and stages. When the lesions are limited, the blood picture may be completely normal; in extensive lesions leukocytes and neutrophils are increased and there is anemia. In advanced stages there is often a decrease in both leukocytes and lymphocytes. S-rays cells are occasionally seen in the peripheral blood. Bone marrow aspiration can be of special value for diagnosis if SRCs are found, but they are not easily found. Bone marrow biopsy can be done in stage III or IV of the disease and has a higher positive rate of finding SRCs than a puncture smear.
Blood sedimentation and blood copper quantification are done when the lesion is in remission, and if increased, it is an indication of relapse. Normal serum copper levels are 73-114 μg/ml in school-aged children, which are increased in all cases of this disease, and then fall to normal after treatment remission.
Pulmonary hilar lymph node enlargement and pulmonary infiltrates may be found.
The former may reveal enlarged lymph nodes adjacent to the aorta above the second lumbar vertebrae, and the latter may show whether the ureter is displaced, in addition to the location of the kidney when doing abdominal radiotherapy.
If elevated, it suggests the possibility of bone and liver metastases.
A B-mode ultrasound scan can be very helpful in detecting abdominal lesions. If there is a high suspicion of abdominal lymph node pathology, a dissection can be performed, along with splenectomy and pathological biopsy of the abdominal and retroperitoneal lymph nodes and liver tissue.
Diagnosis
The disease should be suspected in older children with persistent unexplained cervical lymph node enlargement, as cervical lymph node enlargement due to inflammation of the upper respiratory tract is less common in this age group. Chronic lymph node enlargement in other areas without a cause should also be considered. The final diagnosis depends on the pathological examination of the lymph nodes, which should be done on the entire larger lymph nodes.
Treatment
Hodgkin’s disease is currently treated with good results and can be cured in milder cases, even in patients with progressive disease. Treatment depends on correct pathological staging and clinical staging. Radiation therapy can be used for localized simple lymph node enlargement. Chemotherapy can be added for patients in the progressive stage. Properly grasp the principles of treatment for each patient to develop a reasonable treatment plan.
Surgery is not necessary for the treatment of Hodgkin’s lymphoma, and complete resection is not possible. The main task is to provide sufficient diagnostic tissue specimens to aid in pathological staging, to obtain sufficient material for a better definitive diagnosis by imaging, and to adopt appropriate surgical approaches for masses where the extent of the lesion is already clear.
The specific surgical approach is determined based on the site and extent of the tumor revealed by imaging. There are generally the following: mediastinoscopic mediastinotomy, suprasternal partial sternotomy, median sternotomy, and postero-lateral standard open thoracotomy. Invasive surgery such as mediastinotomy can be performed for occupying lesions that are not diagnosed by repeated punctures. Regardless of the method, rapid pathology should be performed after obtaining the specimen to clarify the diagnosis. Based on the opinion of the pathologist, the decision to obtain a satisfactory specimen is made, and if a definitive diagnosis can be obtained, repeat biopsies are not needed to minimize complications and resulting delays in treatment. In addition to performing a biopsy, it is possible to understand the mediastinal involvement and to biopsy suspicious areas in the surgical field. Therefore, it is of great value in selecting the best treatment and helping to determine the extent of radiotherapy. Since resection of part of the tumor does not increase complications, it can be extended when necessary, but care should be taken that the examination and biopsy have the potential to cause intra-thoracic (lung, pericardium, chest wall, intramammary lymph nodes, diaphragm) dissemination.
There are 3 types of irradiation methods: local irradiation, incomplete lymph node irradiation and total lymph node irradiation. Incomplete lymph node irradiation includes the affected lymph nodes and tumor tissues as well as the nearby lymph node areas that may be invaded. If the lesion is on the diaphragm, the “cloak” irradiation will include the lymph nodes from the mastoid end to the upper and lower clavicle, axilla, hilum, mediastinum and diaphragm, but the humeral head, larynx and lungs should be protected from irradiation. The dose is 35-40 Gy, and the course of treatment is 3-4 weeks. For Hodgkin’s disease stages IA, IB, IIA, IIB, and IIIA, radiotherapy is the first and most appropriate treatment. stage IA patients with primary lesions on the diaphragm can be irradiated with only the “cape” field; stage IB, IIA, IIB, and IIIA patients must be irradiated with the whole lymph node area.
The most commonly used regimen of MOPP [nitrogen mustard, vincristine, procarbazine (methylbenzylhydrazine), prednisone (prednisone)] has greatly improved the prognosis of advanced Hodgkin’s disease. The rate of complete remission in primary care patients has increased from 65% to 85%. MOPP is administered for at least 6 courses, or until complete remission, with an additional 2 courses given. Hodgkin’s disease is resistant to MOPP, plus the nitrogen mustard in the MOPP regimen can cause severe phlebitis and vomiting, so the literature recommends different treatment regimens, among which the ABVD [adriamycin, bleomycin, permethrin sulfate (permethrin), and dacarbazine (methacholine)] regimen is more established, which has a remission rate of 62% and is as effective as MOPP for the tuberous sclerotic type. Another advantage is the absence of alkylating agents in the regimen. The addition of bleomycin and adriamycin on top of MOPP has also been used. The use of the above combination chemotherapy regimen in stage IIIB and IV patients is best followed by the addition of localized 25-30 Gy radiation therapy to the primary site of the original apparent tumor.