Hodgkin Lymphoma

Classic Hodgkin lymphoma - CELL - Atlas of Haematological Cytology

Classical Hodgkin’s lymphoma is one of the most common lymphomas and is generally considered curable cancer with the use of standard first-line radiation therapy and chemotherapy. Although 90% of patients with classical Hodgkin’s lymphoma can now be cured at all stages, it is still unknown why normal B-lymphocytes become malignant biologically active tumor cells. Classical Hodgkin’s lymphoma accounts for almost 10-15% of all lymphomas and is unique cancer with specific clinical signs, features, evolution and therapeutic responses​1​.

In 1832, Thomas Hodgkin first described the classical Hodgkin’s lymphoma as a disease occurring in young adults often presented with weight loss, enlarged cervical lymph nodes, and fever that results in death within a few months​2​.

Classical Hodgkin lymphoma is a cancer of the lymphatic system reporting an incidence of 2-3 cases per 1,00,000 individuals per year in developed countries​3​. Classical Hodgkin’s lymphoma is different from nodular lymphocytic predominant Hodgkin lymphoma, which is a B-lymphocyte antigen CD20-positive lymphoma​4​. Almost 25-40% of Classical Hodgkin’s lymphoma was found to be causally related to Epstein-Barr virus infections. A few cases of classical Hodgkin’s lymphoma were also found to be associated with immune deficiency (including HIV infection) or a history of autoimmune disease and cancer that arise due to the transformation of low-grade B-cell lymphoma (mostly chronic lymphocytic leukaemia).

Since the first diagnosis of classical Hodgkin’s lymphoma, the median age of onset for the lymphoma is 33 years, which has remained unchanged. Classical Hodgkin’s lymphoma is very frequent among adults, while it is rare among children under 12 years. The frequency of lymphoma is also very high among individuals over 80 years. 

The first peak in the incidence pattern of classical Hodgkin’s lymphoma appears at about 20-30 years of age, while the second peak of the disease is more associated with the Epstein-Barr virus, which has a lower curable rate than that observed in the first peak. The second peak of the disease usually appears around the age of 50-70 years​3​.

Classical Hodgkin’s lymphoma is made up of Reed-Sternberg malignant cells within an extensive immune cell, and inflammatory infiltrates. Reed-Sternberg cells derived from germinal centre B-cells actively interact with the microenvironment and form a self-supporting nutrient cell network, paracrine mediators and auto mediators of cellular proliferation, apoptotic inhibition, and cytotoxic killer cell inhibition. Reed-Sternberg cells lose most of their B cell identity, including B cell receptors, and are not subject to programmed cell death​5,6​.

Substantial histological heterogeneity is observed among patients with classical Hodgkin’s lymphoma. Based on that, the classical Hodgkin’s lymphoma are subclassified mostly into two histological subtypes

  •  Nodular sclerosis classical Hodgkin lymphoma: 

Nodular sclerosis classical Hodgkin lymphoma is the most prevalent histological subtype (70% of cases) of classical Hodgkin’s lymphoma. It is most common among younger patients with mediastinal involvement and occasionally bulky disease. Differential diagnosis is with primary mediastinal lymphoma CD20+, CD23+, or CD30+ occurring in young women or in patients with rare grey-zone lymphomas.

  • Mixed cellularity classical Hodgkin lymphoma: 

Mixed cellularity classical Hodgkin lymphoma accounts for 15–30% of all cases. It is more frequent among older patients with associated infra diaphragmatic lymph nodes, Epstein-Barr virus, or bone marrow disease. Differential diagnosis of the disease can be difficult, with some peripheral CD30+ T-cell lymphomas with large cells resembling Reed-Sternberg cells​2​.


  1. 1.
    Brice P, de K, Friedberg J. Classical Hodgkin lymphoma. Lancet. 2021;398(10310):1518-1527. doi:10.1016/S0140-6736(20)32207-8
  2. 2.
    Harris N, Jaffe E, Diebold J, et al. The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Mod Pathol. 2000;13(2):193-207. doi:10.1038/modpathol.3880035
  3. 3.
    Yung L, Linch D. Hodgkin’s lymphoma. Lancet. 2003;361(9361):943-951. doi:10.1016/S0140-6736(03)12777-8
  4. 4.
    Lazarovici J, Dartigues P, Brice P, et al. Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study. Haematologica. 2015;100(12):1579-1586. doi:10.3324/haematol.2015.133025
  5. 5.
    Greaves P, Clear A, Coutinho R, et al. Expression of FOXP3, CD68, and CD20 at diagnosis in the microenvironment of classical Hodgkin lymphoma is predictive of outcome. J Clin Oncol. 2013;31(2):256-262. doi:10.1200/JCO.2011.39.9881
  6. 6.
    Liu Y, Abdul R, Terpstra M, et al. The mutational landscape of Hodgkin lymphoma cell lines determined by whole-exome sequencing. Leukemia. 2014;28(11):2248-2251. doi:10.1038/leu.2014.201