Hodgkin's disease must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer especially Non-Hodgkin's lymphoma. Definitive diagnosis is by lymph node biopsy (removal of a lymph node for pathological examination). The pathological diagnosis of Hodgkin's lymphoma depends on the presence of Reed-Sternberg cells and their variants in the biopsy material.
Because the lymph node architecture is important for histological classification, an excisional lymph node biopsy is recommended.
Fine needle aspiration
When a patient presents with neck lymphadenopathy that may be due to a head and neck cancer, a fine-needle aspiration is usually advised as the initial diagnostic step, followed by excisional biopsy if squamous cell histology is excluded. A concern exists that an incisional or a needle-core biopsy will result in regional spread of a head and neck squamous cell carcinoma.
The World Health Organization classification system combines nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted subtypes of HD under the subheading "classic HD". Immunohistochemistry may be required in the diagnosis of some cases.
Classical Hodgkin's Lymphoma (CD15+, CD30+, CD20-, CD45-)
- H-RS cells frequently express CD30 and CD15 (80% of cases)
- expression of CD20 on a minor sub-population of H-RS cells in up to 2/3 of cases
- vast majority of cases show expression of a 55kD actin-bundling protein termed FASCIN in the H-RS cells.
- evidence of Epstein-Barr virus either by LMP1 immunohistochemistry or by EBER in situ hybridisation in up to 30% of cases in UK
- lymphoid population shows a predominance of CD4+ peripheral T-cells adjacent to the H-RS cells, around which they may form rosettes.
Nodular Lymphocyte Predominant Hodgkin's Lymphoma (CD20+, CD45+, CD15-, CD30-)
- nodules are composed of mantle zone B-cells expressing IgM and IgD, with admixed follicular dendritic cells
- L&H cells have a B-cell phenotype expressing CD20 and CD79a, and show evidence of immunoglobulin-synthetic capacity with expression of cytoplasmic J-chain
- epithelial membrane antigen is frequently expressed by the L&H cells
- numerous T-cells are also present with a CD4 predominance, some co-expressing the germinal centre-associated T-cell marker CD57. T-cells form rosettes around the L&H cells.
CytogeneticsThe cytogenetics of both Classical HL and the rare cases of Nodular Lymphocyte Predominant HL which have been karyotyped show complex numerical and structural abnormalities affecting all chromosomes, with as yet no identifiable non-random cytogenetic abnormality.
- molecular genetic analysis of micro-dissected single H-RS cells from cases of classical HL demonstrate clonal hypermutated immunoglobulin heavy chain genes with 'crippling' mutations.
- similar analysis of L&H cells from cases of Nodular Lymphocyte Predominant HL show somatically hypermutated immunoglobulin heavy chain genes without crippling mutations and ongoing antigen-driven hypermutation in an identical fashion to the follicle centre lymphomas.
Non-Hodgkin's lymphoma is the most important item in the differential diagnosis of Hodgkin's lymphoma. A biopsy usually settles the confusion. However, there is occasional difficulty differentiating HD from T-cell rich B-cell NHL, anaplastic large cell lymphoma or peripheral T-cell lymphoma, because of overlapping clinical and pathologic characteristics.
1. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835-49.
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