Classic Hodgkin lymphoma (ORPHA:391)
Classical Hodgkin lymphoma (CHL) is a B-cell lymphoma characterized histologically by the presence of large mononuclear Hodgkin cells and multinucleated Reed-Sternberg (HRS) cells.
Epidemiology
The annual incidence of CHL in developed countries is approximately 1/40,000. It accounts for 95% of HL cases.
Clinical description
Onset most commonly occurs in young adults aged 15-30, followed by adults over the age of 55. In the early stages of the disease many patients are asymptomatic. The most common sign of CHL is the painless enlargement or swelling of upper body lymph nodes (most frequently in the neck, axillae or mediastinum). Itchy skin, fatigue and decreased appetite can also be presenting symptoms. Cellular immune deficiency seen in CHL patients increases susceptibility to bacterial, fungal and viral infections. When lymph nodes inside the chest are affected patients can have trouble breathing or a cough. A group of symptoms known as B-symptoms are sometimes present and include: fever, drenching night sweats and unexplained weight loss. Other organs can be affected such as the liver, lung, spleen, bones or bone marrow.
Etiology
The exact cause of CHL is unknown. Epstein-Barr virus (EBV) may have a role in the pathogenesis of CHL as EBV-encoded RNA is present in HRS cells in 40% of cases. A genetic predisposition could also be involved in CHL pathogenesis as polymorphisms seen in the human leukocyte antigen (HLA) genes are often associated with cases of sporadic and familial CHL. They are potentially responsible for an impaired immune response which is usually found in CHL patients. HIV patients have a 5 to 15 fold increased risk of developing CHL, further suggesting the link between immune deficiency and CHL.
Diagnostic methods
A biopsy (usually of a lymph node) is performed in order to diagnose CHL and determine one of the 4 histological subtypes of CHL: nodular sclerosis (most common subtype), mixed cellularity, lymphocyte-rich and lymphocyte-depleted. Staging based on the Cotswold staging system is performed in order to determine the severity and spread of CHL and decide on the best course of therapy. Postero-anterior and lateral radiograph and computed tomography (CT) of the chest, neck, abdomen and pelvis are taken. Bone marrow biopsy should be performed unless peripheral blood counts are normal and B symptoms absent. Positron emission tomography (PET) scans can identify sites of disease more accurately than other imaging techniques. Predominant prognostic factors are age and stage.
Differential diagnosis
Influenza, infectious mononucleosis, other lymphomas (non-Hodgkin lymphoma), systemic lupus erythematosus (see these terms) and HIV infections should be dismissed.
Management and treatment
Radiotherapy and combination chemotherapy are the methods used to treat CHL. Involved field radiotherapy (IFRT) is much preferred over extended-field radiation therapy (EFRT) which has long-term side effects but is sometimes needed in advanced cases. Two cycles of combination chemotherapy followed by IFRT (20Gy) or chemotherapy alone are acceptable standard treatments for adults with limited stage CHL. Care is taken to minimize the gonadotoxic effects of alkylating agents on male children. When standard treatment does not work (or if CHL recurs) high-dose chemotherapy and hematopoietic stem cell transplant may be a final option. Surgery is not recommended. A new targeted agent, the antibody-drug conjugate brentuximab vedotin, has shown substantial effectiveness against recurrent CHL and is being tested in combination with standard agents.
Prognosis
The prognosis of those with HL has greatly improved, with a 5 year survival rate of 80%-85%. The elderly usually have a poorer prognosis as they have a reduced tolerance for chemotherapy and treatment-related deaths can occur. The cure rates are 90% for early-stage CHL and 70% for advanced stage CHL.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Joseph CONNORS