classical Hodgkin lymphoma

classical Hodgkin lymphoma. It is a B-cell lymphoma characterized by the presence of distinctive malignant cells known as Reed–Sternberg cells within a reactive inflammatory background. This malignancy is one of the two principal categories of Hodgkin lymphoma, the other being nodular lymphocyte-predominant Hodgkin lymphoma. Diagnosis typically involves excisional biopsy of an affected lymph node and is further classified into four histological subtypes. Treatment has evolved significantly, with modern regimens offering high cure rates.

Epidemiology

The incidence of this disease demonstrates a bimodal age distribution, with peaks in early adulthood and again after age 55. It is more common in developed nations such as the United States and Western Europe. Risk factors include a history of Epstein–Barr virus infection, with the virus detectable in a significant proportion of cases. Other associations include HIV infection and a family history of the disease, particularly among identical twins. The International Agency for Research on Cancer classifies it as a virus-associated cancer. Incidence rates vary globally, with lower frequencies reported in parts of Asia and Africa.

Signs and symptoms

The most common presenting feature is painless enlargement of lymph nodes, often in the neck, mediastinum, or axilla. Systemic "B symptoms" as defined by the Ann Arbor staging system include unexplained fever, drenching night sweats, and significant weight loss. Patients may experience generalized pruritus or pain in affected nodes following alcohol consumption, a phenomenon historically noted by clinicians like Thomas Hodgkin. Other possible manifestations include fatigue, cough, or shortness of breath due to mediastinal involvement, and splenomegaly may be detected on physical examination.

Pathophysiology

The malignant Reed–Sternberg cells are derived from germinal center B-cells that have undergone crippling mutations but escape apoptosis. These cells constitute only a small fraction of the tumor mass, which is predominantly composed of non-neoplastic inflammatory cells including T-cells, eosinophils, and fibroblasts. The survival and proliferation of the malignant cells are driven by constitutive activation of signaling pathways such as NF-κB and aberrant production of cytokines like interleukin-13 and TARC. The frequent association with Epstein–Barr virus suggests viral proteins like LMP1 may contribute to oncogenesis by mimicking CD40 signaling.

Diagnosis

Definitive diagnosis requires an excisional biopsy of an involved lymph node for histopathological examination. The identification of classic Reed–Sternberg cells within an appropriate cellular background is essential. Immunohistochemistry is critical, with the malignant cells typically positive for CD30 and CD15, and usually negative for CD45 and CD20. The World Health Organization classifies the disease into four subtypes: nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. Staging involves the Cotswolds modification of the Ann Arbor staging system and utilizes imaging such as PET-CT and bone marrow biopsy.

Treatment

Treatment strategy is determined by the disease stage and prognostic factors. For early-stage favorable disease, combined modality therapy with abbreviated chemotherapy like ABVD followed by involved-site radiotherapy is standard. Advanced disease is treated with full-course chemotherapy, with ABVD, BEACOPP, or Stanford V being common regimens. The monoclonal antibody brentuximab vedotin, which targets CD30, is used in relapsed or refractory settings. High-dose chemotherapy followed by autologous stem cell transplantation is the standard salvage therapy for chemosensitive relapse. Research from institutions like the German Hodgkin Study Group continues to refine protocols.

Prognosis

The prognosis is generally excellent, especially for early-stage disease, with cure rates exceeding 90% for many patients. The International Prognostic Score helps stratify risk in advanced stages. Long-term survival is common, leading to increased focus on managing late effects of therapy, which can include secondary malignancies like breast cancer or acute myeloid leukemia, and cardiovascular disease. Follow-up care often involves surveillance imaging and monitoring for complications such as hypothyroidism or pulmonary fibrosis. Outcomes have improved dramatically since the introduction of modern chemotherapy and radiotherapy techniques.