# The Hodgkin microenvironment: when the cancer cell is the minority

Source: https://onco.cc/terms/lymphoma-bio-hodgkin-microenvironment/  
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## TL;DR

In Hodgkin lymphoma most of the swollen lymph node is not cancer. The cancer cells are scattered giants that make up a small fraction of the tissue; everything else is immune cells the tumour has recruited and put to work.

## Summary

A classical Hodgkin lymph node under the microscope is mostly lymphocytes, eosinophils, plasma cells, macrophages and fibrous tissue, with occasional very large cells scattered through it. Those giants, the Hodgkin and Reed-Sternberg cells, are the cancer, and for most of the twentieth century it was not clear what they even were: they had lost almost every marker of a B cell.

The question was settled by picking single cells off a histological section with a micromanipulator and amplifying their immunoglobulin genes. Each of three cases gave a single clonal heavy-chain rearrangement, proving the scattered giants were one clone; somatic mutation patterns placed their origin in the germinal centre in one case and earlier in B-cell development in another (Kuppers 1994).

The minority status is not a curiosity. It shapes the diagnosis, because a small needle sample can easily miss the diagnostic cells and a Hodgkin diagnosis often needs an excisional biopsy. It shapes the research, because sequencing a whole Hodgkin biopsy mostly measures the infiltrate, which is why the 9p24.1 amplification work needed laser capture and in situ hybridisation rather than bulk sequencing. And the infiltrate itself carries information: in an independent cohort of 166 patients, more CD68-positive macrophages meant shorter progression-free survival, more relapse after autologous transplant and shorter disease-specific survival, outperforming the International Prognostic Score (Steidl 2010).

None of that is yet a test that changes treatment. What the Hodgkin plan is adapted to is the interim PET scan, not the infiltrate.

## Fields

- Kind: Term
- Last checked: 2026-09-30
- Also known as: Reed-Sternberg cell; Hodgkin and Reed-Sternberg cells; Hodgkin tumour microenvironment; HRS cells

## Sources

- Kuppers et al., PNAS 1994: micromanipulated Hodgkin and Reed-Sternberg cells carry clonal immunoglobulin rearrangements: https://doi.org/10.1073/pnas.91.23.10962
- Steidl et al., N Engl J Med 2010: tumour-associated macrophages and survival in classical Hodgkin lymphoma: https://doi.org/10.1056/NEJMoa0905680
- Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma: https://doi.org/10.1038/nrc2542

## Connected records

- cancers: [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [PET-adapted (response-adapted) therapy](https://onco.cc/technologies/pet-adapted-therapy/)
- targets: [CD30](https://onco.cc/targets/cd30/), [JAK2](https://onco.cc/targets/jak2/), [PD-L1](https://onco.cc/targets/pdl1/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Deauville score and PET-adapted therapy](https://onco.cc/terms/deauville/), [Epstein-Barr virus latency programmes, and why they decide which lymphoma](https://onco.cc/terms/lymphoma-bio-ebv-latency/)
- biomarkers: [9p24.1 alteration of the PD-1 ligand loci](https://onco.cc/biomarkers/pd-ligand-9p24-alteration/), [CD30 expression (CD30-positive)](https://onco.cc/biomarkers/cd30-expression/)

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