|Classical Hodgkin lymphoma|
|Diagnosis in short|
HL mixed cellularity - cytology.
|LM||Reed-Sternberg cell (large binucleated cell (>= 45 micrometres), +/-multinucleated, +/-horseshoe-like shape, macronucleolus - approximately the size of a RBC (~8 micrometers)), well-defined cell border, abundant cytoplasm.|
|Subtypes||nodular sclerosis CHL, mixed cellularity CHL, lymphocyte-rich CHL, lymphocyte-depleted CHL|
|IHC||CD30 Reed-Sternberg cells (RSCs) +ve ~98%, CD15 Reed-Sternberg cells +ve ~80% (also stains neutrophils), CD45 often negative in RSCs, CD20 -ve/+ve, PAX5 +ve|
|Site||usu. lymph node - classically in the neck|
|Clinical history||young adults, older adults (bimodal distribution)|
|Signs||lymphadenopathy - usu. neck, +/-B symptoms (fever, night sweats, weight loss)|
|Prognosis||usu. good, dependent on stage|
Hodgkin lymphoma, abbreviated HL, is a haematological malignancy. If not otherwise specified, Hodgkin lymphoma generally refers to classical Hodgkin lymphoma (CHL) rather than nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The latter accounts for only about 5% of the loose label of Hodgkin lymphoma and shows a sufficiently different biology and immunophenotype that is essentially a different disease (see main article on NLPHL). The common feature is large atypical cells: Hodgkin/Reed-Sternberg cells in the case of classical Hodgkin lymphoma and "popcorn"/lymphohistiocytic/L&H cells in NLPHL. However, at least in typical cases, there are morphological and immunophenotypic differences.
Classical Hodgkin lymphoma has a bi-modal distribution, afflicting young adults and with a further peak in incidence in middle-age. Fortunately, it usually has a good prognosis.
Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells (or Popcorn cells); if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.
- "B symptoms" - all required: weight loss, night sweats and fever.
- Infections due to immune dysfunction.
- HL cannot be diagnosed with standard flow cytometry (FC) - but has been diagnosed with specialized FC.
- Usually good.
- Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.
- Clinically classified into early favourable, early unfavourable and late/advanced disease.
Classic HL sub-types
Subtypes of classic HL
There are four CHL subtypes:
- Nodular sclerosis CHL - ~70% of CHL.
- Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
- Nodular sclerosing fibrosis - thick strands fibrosis.
- Mixed cellularity CHL - ~20-25% of CHL.
- Lymphocyte-rich CHL - rare.
- T lymphocytes only (no mix of cells).
- Lymphocyte-depleted CHL - rare.
- May be associated with HIV infection.
- The subtypes prevalence is in reverse alphabetical order.
- Almost always arises from a lymph node - classically in the neck, but may be in the axilla and mediastinum
- Spleen may be involved
- Bone marrow involvement is unusual (~5% of cases, higher in HIV-associated cases), so bone marrow assessment is usually not performed
- Extranodal Hodgkin lymphoma is (case report) rare.
Defined by Reed-Sternberg cells (RSCs). Morphologically similar mononuclear cells are known as Hodgkin cells. RSCs are:
- Large binucleated cell (>= 45 micrometres).
- May be multinucleated.
- May have a horseshoe-like shape.
- Macronucleolus - approximately the size of a RBC (~8 micrometers).
- Well-defined cell border.
- Abundant cytoplasm.
RSC may show peri-cellular clearing, making the cells appear within a space. These are called lacunar cells (as they are in a "lake"). Apoptotic RSC may show pyknotic nuclei and scant eosinophilic cytoplasm and are sometimes known as "mummified" cells.
Images (classic HL)
DDx both CHL & NLPHL
- Diffuse large B cell lymphoma (DLBCL), esp. T-cell/histiocytic-rich LBCL.
- Anaplastic large cell lymphoma (ALCL).
- B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. (typically in cases of numerous large atypical cells where the morphology and immunophenotype do not neatly fit into either DLBCL or CHL).
- CD30 Reed-Sternberg cells (RSCs) +ve ~98% (beware of mis-interpreting CD30+ activated lymphoid cells)
- CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
- Both CD30 and CD15 are classically positive in a membranous and Golgi pattern
- MUM1 +ve
- CD45 often negative in RSCs.
- CD20 may stain RSCs (usually negative, but can be weak).
- PAX5 +ve, though said to be weaker than background normal B-cells
Additional - for completeness:
- CD3 (T lymphocytes) - negative in RSCs
- OCT2/BOB1 negative (co-transcription factors for immunoglobulin production, one or the other is usually negative)
- 40% are EBV positive.
NLPHL IHC differs from the classical HL:
- LCA +ve.
- CD20 +ve.
- CD10 +ve.
- Bcl-6 +ve.
- EMA +ve (40-50%)
- CD30 -ve
- CD15 -ve.
|CD30||-ve||+ve (most sensitive).|
|CD21||networks present||no networks|
|CD23||networks present||no networks|
|PAX5||+ve||+ve (proves B cell linage)|
|CD3||usu. < benign B cell||usu. > benign B cell component|
|CD57||rosettes around malign. cells||-|
Lymph Node, Right Neck, FNA: - Large binucleated and multinucleated cells with macronucleoli in a background of abundant lymphocytes, histiocytes, rare eosinophils. Comment: A cell block is not available for further work-up. The findings raise the possibility of Hodgkin's lymphoma. A further biopsy is required for the diagnosis.
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