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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
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-,
- 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
- 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.
The 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.
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- 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
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.