Introduction
Lymphomas are the third most common childhood cancers of which 40% are Hodgkin's disease. It is lymphocytic cancer originating from B or T lymphocytes. It is characterized by pleomorphic lymphocytic infiltrate with malignant multinucleated giant cells Reed-Sternberg cells).
Presentation
Hodgkin's disease has a bimodal peak with an early peak in the late 20s and the second peak in late adulthood. In developing countries, the early peak occurs before adolescence. Hodgkin's disease is rare before 5 years of age. In children <10 years, the incidence is more in boys. In developing countries, it has been associated with the presence of Ebstein Barr virus in the Reed-Sternberg.
Clinically, the patients present with painless enlargement of the lymph nodes, commonly in the supraclavicular and cervical region. The enlarged nodes are firm and rubbery. Sometimes the nodes may fluctuate in size. Almost 60% of the patients may have the mediastinal disease at diagnosis. Patients may also have systemic symptoms such as fever, night sweats, and weight loss most probably due to the release of lymphokines by the Hodgkin's cells. The disease spreads contiguously via the lymphatics from one node to another; in later stages, it may disseminate to organs.
Hodgkin's Lymphoma - Diagnosis
Any peripheral lymph node >1 cm in size that does not regress after 6 weeks of observation should be biopsied. (Care should be taken not to biopsy the edge of the lymph node as it as it may appear as "reactive" on histopathology, but central nodes should be biopsied.) Once, the diagnosis is confirmed, it is necessary to determine the stage of the disease for prognosis and treatment evaluation. Staging is based on a combination of history, physical examination, and x-rays (including CT Scan of chest, abdomen, and pelvis), gallium scan, bone marrow biopsy, and laboratory biochemical profile. In patients with mediastinal mass, if pleural effusion is present, a thoracocentesis should be done as the cytological diagnosis is possible. Mediastinoscopy, anterior mediastinotomy, and thoracoscopy are procedures of choice when other methods fail to establish the diagnosis.
Pathologic staging requires laparotomy with splenectomy, retroperitoneal lymph node biopsy, and liver biopsy. However, in children, chemotherapy alone has been used increasingly for treatment. Hence, staging laparotomy is rarely required.
Staging of Hodgkin's Disease
Hodgkin's disease is staged by the Ann Arbor staging system. It is divided into 4 stages and sub-classified into A & B categories with a special subcategory E.
A: Patients are asymptomatic
B: Patients with following symptoms:
- Unexplained loss of weight >10% in last 6 months
- Unexplained fever with temperature >38 degree Celsius for more than 3 days
- Drenching night sweats
E: Minimal extralymphatic disease from direct extension. It denotes limited involvement of a single extranodal site
Stage I
: Involvement of a single lymph node region (I) or single extralymphatic site (IE).
Stage II
: Involvement of 2 or more lymph node regions on the same side of the diaphragm (II) or extension from these lymph nodes to the extra lymphatic adjacent organ (IIE).
Stage III
: Involvement of lymph nodes on both sides of the diaphragm (III); with extension to an adjacent extra lymphatic organ (IIIE) or involvement of the spleen (IIIS+) or both (IIIE+S).
Stage IV
: Disseminated disease with or without associated lymph node disease. (Occurs due to spread through the bloodstream as opposed by lymphatics).
Hodgkin's disease is histologically classified as:
- Lymphocytic predominance
- Nodular sclerosis
- Mixed cellularity
- Lymphocyte depletion
- Unclassified
Patients with lymphocyte predominance, generally have localized disease, are usually asymptomatic and can be cured with less intensive therapy as compared with other subtypes. They are also at a higher risk of secondary malignancy.
However, determining the histologic subtype is not as important as in Non - Hodgkin's lymphoma, as with effective multiagent chemotherapy, histologic subtype does not influence the outcome.
Treatment
More than 90% of all children with newly diagnosed Hodgkin's disease are curable with modern therapy. Multiagent chemotherapy alone or with relatively low dose field radiation is used to treat children in all stages. Historically, radiation alone was used to cure stage I, II, III disease. However, with the potential for secondary malignancies (solid tumors, breast cancer), irradiated field growth retardation, and benign and malignant changes in the thyroid, radiation therapy alone has been discarded. However, patients with the massive mediastinal disease (>1/3rd the maximal thoracic diameter, or tumor involving the pericardium or chest wall), should be treated with chemotherapy and radiotherapy, even if they have stage I or II diseases.
Adolescent patients who have achieved maximum growth and have localized childhood Hodgkin's disease (pathologically staged I and II) may be treated as adults with standard-dose radiation alone.
The various chemotherapy protocols used are:
MOPP - Mechlorethamine, vincristine, prednisolone, and procarbazine.
ABVD - Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine.
VEEP - Vincristine, Etoposide, Epirubicin, and Prednisolone.
Stage I and II a - Treatment includes combination chemotherapy with or without low dose radiation to involved fields.
Stage II B - Treatment is controversial. Combined modality therapy is preferred.
Stage III A - Combined modality therapy.
Stage III B & IV - Chemotherapy + full dose involved-field radiotherapy.
Hodgkin's Lymphoma - Relapse
Most of the relapses occur within the first 3 years. Patients whose disease recurred after radiation alone may be considered for chemotherapy: e.g. with MOPP, ABVD, or other combinations. Those treated with one chemotherapy regimen may be considered for alternative chemotherapy and radiation.
Autologous bone marrow may be most useful in patients in the second remission with chemotherapy.