Hodgkins Lymphoma

Overview

Hodgkin lymphoma (HL) arises from germinal center or post-germinal center B cells. HL has a unique cellular composition, containing a minority of neoplastic cells (Reed-Sternberg cells and their variants) in an inflammatory background.

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Epidemiology

• Lymphoma is divided into Hodgkins and Non-Hodgkins
• Hodgkins lymphoma accounts for 10% of all lymphomas
• It has a bimodal age distribution curve – most adolescent

Classification

Classical HL – (90-95% of cases). The tumor cells in this group are derived from germinal center B cells, but typically fail to express many of the genes and gene products that define normal germinal center B cells. Classical HL is further divided into the following subtypes:

• Nodular sclerosis classical HL (NSHL) – (most common)
• Mixed cellularity classical HL (MCHL)
• Lymphocyte rich classical HL (LRHL)
• Lymphocyte depleted classical HL (LDHL)

Nodular lymphocyte predominant HL – The tumor cells in this subtype retain the immunophenotypic features of germinal center B cells.

Risk Factors

• History of EBV infection
• Family history
• Young adults from higher socio-economic status
• Immunosuppression
• Autoimmune disorders

Clinical Manifestations

• Painless lymphadenopathy – most commonly cervical and supraclavicular lymph nodes.
• B symptoms:
  • Unexplained fever >38°C.
  • Drenching night sweats.
  • Unintentional weight loss >10% in 6 months.
• Pruritus
• Fatigue and malaise
• Mediastinal mass – cough, chest pain, dyspnea, SVC obstruction
• Hepatosplenomegaly – abdominal fullness or discomfort.
• Advanced disease: bone marrow involvement causing anemia, leukopenia or thrombocytopenia.
• Contiguous lymph node spread – spreads from one lymph node group to adjacent groups.

Investigations

Diagnosis and staging

• Excisional lymph node biopsy (diagnostic for HL and its variants)

Classic Hodgkins Lymphoma is characterised by the presence of diagnostic Reed-Sternberg cells in an inflammatory back ground.

Ann Arbor staging system

1. Single lymph node group
2. Multiple lymph node groups on same side of diaphragm
3. Multiple lymph node groups on both sides of diaphragm
4. Multiple extranodal sites

Pathology

Classical HL is characterised by the the presence of Reed-Sternberg cells in an inflammatory background containing other immune and non-immune cells.

• lymphocytes
• eosinophils
• neutrophils
• macrophages
• plasma cells
• fibroblasts.

Reed Sternberg cells are large cells with abundant, slightly basophilic cytoplasm, bilobed, double, or multiple nuclei, and two or more prominent, eosinophilic, inclusion-like nucleoli.

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Pathophysioloy

HL is a B-cell malignancy

1. B-cells arise from the bone marrow and matures in Germinal Centres within lymph nodes
2. B-cells do not undergo proper gene re-arrangments and somatic hypermutation resulting in an abnormal B-cell
3. Abnormal B-cells are able to escape apoptosis and can replicate in an uncontrolled manner.
4. The abnormal B-cells survive by mimicking cellular receptors that are essential for B-cell growth and survival.

Treatment

Most patients with HL

Chemotherapy (ABVD – doxorubicin, bleomycin, vinblastine, dacarbazine) +/- Radiotherapy

Refractory and relapsing

Chemotherapy +/- radiotherapy + autologous stem cell transplantation is preferred

Complications & Prognosis

Complications

• Radiotherapy related thyroid abnormalities
• Chemotherapy side effects including increase risk of secondary malignancies.

Prognosis

Patients with early stage (stage I-II) HL have a high likelihood of achieving long-term complete remission. A variety of prognostic factors allow for the discrimination of patients with “favourable prognosis” early stage HL and those with “unfavorable prognosis” early stage HL.

• Stage I-II (favourable) 85-90% with chemotherapy followed by low dose radiotherapy.
• Stage I-II (unfavourable) 80-90% with chemotherapy followed by low dose radiotherapy.

Among patients with advanced stage (stage III/IV) HL, prognosis is largely determined by the International Prognostic Score

• Stage III-IV 60-80% with chemotherapy.

References

1. National Cancer Institute. Hodgkin Lymphoma Treatment (PDQ®) – Health Professional Version. National Cancer Institute.
2. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36:1720–1748. doi:10.1038/s41375-022-01620-2.
3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–3068. doi:10.1200/JCO.2013.54.8800.