Non-Hodgkin lymphoma (NHL) is a cancer of mature B, T and NK cells. The population it affects, the exposures that predispose to it and its distribution across the world differ from one subtype to another, and the comparison with Hodgkin lymphoma (HL) is the natural starting point.
Incidence and prognosis
NHL is about 10 times more common than HL overall. HL is cured in about 85% of patients, whereas for NHL the cure rate depends on the exact subtype, and most subtypes have a worse prognosis than HL.
Three demographic patterns recur in NHL:
- it is more common in men than in women
- it is more common in White than in Black populations
- its incidence rises with age
Infections and immune stimulation
Several infections raise the risk of particular NHL subtypes. The link runs through two mechanisms: chronic antigenic stimulation keeps B cells dividing, and some viruses carry oncogenes or drive B-cell proliferation directly, a risk that is greatest when immune control is weak. Each infection favours a characteristic subtype:
- Helicobacter pylori — gastric MALToma (mucosa-associated lymphoid tissue lymphoma)
- Epstein-Barr virus (EBV) — endemic Burkitt lymphoma, most primary central nervous system (CNS) lymphomas, and extranodal nasal T/NK-cell lymphoma
- HIV — diffuse large B-cell lymphoma (DLBCL), through the immunosuppression HIV causes and through the abnormally high IL-6 (interleukin-6, a signalling protein) production that drives clonal proliferation of B cells
- Hepatitis C virus (HCV) — marginal zone lymphoma (MZL)
- Chlamydia psittaci — ocular MALToma
- Borrelia species — skin MALToma
- Campylobacter jejuni — small-intestine MALToma
Immune suppression
The same point about weak immune control applies to drug-induced immune suppression, which is central to NHL pathogenesis. The drugs that prevent rejection after a solid organ transplant also remove the immune surveillance that normally holds EBV-infected B cells in check. The risk of NHL after solid organ transplant is therefore several times that of the general population — reported estimates range from about 3-fold to more than 100-fold, with the highest figures in children.
Geographic patterns
Besides infection and immune suppression, where a person lives is also associated with the subtype they are likely to develop, and a few subtypes cluster in particular regions:
- HTLV-1 (human T-cell lymphotropic virus type 1)-related lymphoma — mostly Japan and the Caribbean
- T-cell lymphoma — mostly Asian regions
- Follicular lymphoma (FL) — mostly Western countries
What each of these subtypes carries at the molecular level is the next question.