Medicine chapters
Hodgkin and non-Hodgkin lymphoma
Hodgkin lymphoma (Reed-Sternberg cells, young adults, contiguous spread, ABVD) and non-Hodgkin lymphoma (B or T cell, older adults, extranodal, R-CHOP), with Ann Arbor staging and B symptoms.
- Hodgkin lymphoma: young adults (and a second peak in older age), painless rubbery cervical nodes, Reed-Sternberg cells (CD15, CD30), orderly contiguous spread; staged by Ann Arbor; treated with ABVD ± radiotherapy and often curable.
- B symptoms = fever above 38 °C, drenching night sweats, weight loss over 10% in 6 months; they carry a worse outlook and add "B" to the stage.
- Non-Hodgkin lymphoma: mostly B cell, older adults, non-contiguous and often extranodal; diagnose by excision biopsy; DLBCL is commonest and treated with R-CHOP.
On this page
Overview
Lymphomas are cancers of lymphocytes that form masses, usually in lymph nodes but also in other tissues. They are split into:
- Hodgkin lymphoma (HL): defined by Reed-Sternberg cells in a background of reactive cells.
- Non-Hodgkin lymphoma (NHL): all other lymphomas, a large group of B-cell (about 80%) and T-cell (about 20%) tumours.
The commonest presentation of both is painless lymph node enlargement. Diagnosis always needs tissue.
Hodgkin lymphoma
Epidemiology and aetiology
- Peak in young adults (third decade); slight male excess overall. A second smaller peak occurs in older age.
- Linked to Epstein-Barr virus (previous infectious mononucleosis; EBV found in some tumours) and to HIV.
Pathology
- The malignant cell is the Reed-Sternberg cell: a large B cell with a bilobed or multilobed nucleus and big nucleoli ("owl's eye"). It is CD15+ and CD30+.
- These cells are few; most of the mass is reactive lymphocytes, eosinophils, plasma cells, histiocytes and fibrosis, attracted by cytokines from the Reed-Sternberg cells.
| Type | Key points |
|---|---|
| Classical HL (90-95%) | |
| Nodular sclerosis | Commonest (about 70%); young adults, often women; mediastinal mass; bands of fibrosis; lacunar cells |
| Mixed cellularity | About 20%; many eosinophils; associated with EBV and HIV |
| Lymphocyte-rich | About 5%; best prognosis |
| Lymphocyte-depleted | Rare; worst prognosis; elderly, HIV |
| Nodular lymphocyte-predominant HL | About 5%; "popcorn" cells, which are CD20+ (not CD15/CD30) |
Clinical presentation
- Painless, rubbery cervical lymphadenopathy is the commonest presentation.
- Mediastinal mass: cough, breathlessness, sometimes superior vena cava obstruction (often young women, nodular sclerosis).
- Spread is orderly, to the next (contiguous) node group; extranodal disease is uncommon.
- Hepatosplenomegaly in more widespread disease.
- B symptoms (see below).
- Less common but classic: generalised pruritus, pain in the nodes after drinking alcohol, and a cyclical fever (Pel-Ebstein fever).
- Lab: anaemia, eosinophilia, lymphopenia, high ESR and LDH; anergy (impaired cell-mediated immunity).
Alcohol-induced pain in the enlarged nodes and itching are classic (though uncommon) clues to Hodgkin lymphoma.
B symptoms
| B symptom | Definition |
|---|---|
| Fever | Temperature above 38 °C |
| Night sweats | Drenching sweats |
| Weight loss | More than 10% of body weight in the previous 6 months, unexplained |
Patients with any of these are labelled B; those without are A. B symptoms suggest a heavier disease burden and a worse prognosis.
Pruritus and alcohol pain are not B symptoms, even though they are typical of Hodgkin lymphoma.
Staging (Ann Arbor, Cotswolds modification)
| Stage | Extent |
|---|---|
| I | A single node region, or a single lymphoid organ such as the spleen, thymus or Waldeyer's ring, or a single extralymphatic site |
| II | At least two node regions, all above or all below the diaphragm |
| III | Nodes above and below the diaphragm (S = spleen involved) |
| IV | Diffuse involvement of one or more extranodal organs (e.g. liver, bone marrow, lung) |
Suffixes: A (no B symptoms), B (B symptoms), X (bulky disease: mediastinal mass wider than one-third of the chest, or a node mass over 10 cm), E (a single extranodal site next to involved nodes).
"One, same side, both sides, beyond nodes": stages I to IV.
Investigations
- Excision lymph node biopsy for histology and immunohistochemistry (core biopsy if the mass is deep). Fine needle aspiration is not enough.
- Blood count, ESR, LDH, liver and renal function, uric acid; HIV, hepatitis B and C.
- Chest X-ray (mediastinal widening).
- PET-CT for staging and to assess response (interim PET after two cycles).
- Bone marrow biopsy only if PET cannot assess the marrow.
- Before treatment: echocardiogram (doxorubicin), lung function (bleomycin), fertility preservation.
Treatment
- Early stage: 2-4 cycles of ABVD (Adriamycin/doxorubicin, Bleomycin, Vinblastine, Dacarbazine) followed by involved-field radiotherapy. Most achieve lasting remission.
- Advanced stage: ABVD cycles guided by interim PET; bleomycin can be dropped if PET shows complete response; escalate to BEACOPP if disease remains.
- Relapsed or resistant: salvage chemotherapy then high-dose chemotherapy with autologous stem cell transplant; brentuximab vedotin (anti-CD30) and checkpoint inhibitors (nivolumab, pembrolizumab).
- Nodular lymphocyte-predominant HL: rituximab-based treatment (it is CD20+); early disease may need radiotherapy alone.
Prognosis is good; most patients are cured. Advanced-stage outlook uses the Hasenclever score (low albumin, low Hb, male sex, age over 45, stage IV, high white count, low lymphocyte count).
Late effects of treatment
- Second cancers (breast, lung, thyroid, leukaemia), especially after radiotherapy.
- Bleomycin lung fibrosis; doxorubicin cardiomyopathy.
- Hypothyroidism after neck radiotherapy; infertility (less with ABVD).
Non-Hodgkin lymphoma
Aetiology and risk factors
- Immunodeficiency: HIV, organ transplant drugs, inherited syndromes (ataxia-telangiectasia, Wiskott-Aldrich).
- Infections: EBV (Burkitt, post-transplant lymphoma, primary CNS lymphoma in HIV), HTLV-1 (adult T-cell leukaemia/lymphoma), H. pylori (gastric MALT lymphoma), HHV-8 (primary effusion lymphoma), hepatitis C.
- Autoimmune disease: Sjögren's syndrome (salivary MALT), Hashimoto's thyroiditis (thyroid lymphoma), coeliac disease (enteropathy-associated T-cell lymphoma).
Main types
| Type | Grade | Key facts |
|---|---|---|
| Diffuse large B-cell (DLBCL) | High (aggressive) | Commonest NHL; older adults; fast-growing node or extranodal mass; can arise from a low-grade lymphoma |
| Follicular | Low (indolent) | Second commonest; middle/old age; widespread painless nodes; t(14;18), BCL2 overexpression (blocks apoptosis); can transform to DLBCL |
| Burkitt | Very high | t(8;14), MYC; "starry sky" appearance; endemic (African) form in the jaw, linked to EBV and malaria; sporadic form in the abdomen (ileocaecal); very high risk of tumour lysis |
| Mantle cell | Aggressive | t(11;14), cyclin D1; CD5+, CD23- |
| Marginal zone / MALT | Low | Chronic inflammation: H. pylori (stomach), Sjögren's, Hashimoto's; gastric MALT may regress with H. pylori eradication |
| Mycosis fungoides / Sézary syndrome | T cell | Skin plaques; Sézary cells with cerebriform nuclei in blood |
| Adult T-cell leukaemia/lymphoma | T cell | HTLV-1; skin rash, lytic bone lesions, hypercalcaemia |
| Anaplastic large cell | T cell | t(2;5), ALK; CD30+ |
The stomach is the commonest site of gastrointestinal lymphoma; most gastric lymphomas are linked to H. pylori.
Clinical presentation
- Painless lymphadenopathy (often several sites, may be non-contiguous).
- Extranodal disease is common: stomach and gut (pain, bleeding, obstruction), skin, brain, testis, bone marrow (cytopenias), Waldeyer's ring.
- B symptoms, hepatosplenomegaly.
- Low-grade types may be slow and wax and wane; high-grade types grow over weeks.
- Emergencies: superior vena cava obstruction, spinal cord compression, tumour lysis syndrome, bowel obstruction.
Diagnosis
- Excision biopsy of a node (or core biopsy of a deep mass) for histology, immunohistochemistry (e.g. CD20 for B cells), flow cytometry and genetics. FNA is inadequate.
- Staging as for Hodgkin: PET-CT, blood count, LDH (prognosis), renal and liver function, urate, HIV/hepatitis serology; marrow biopsy where needed.
- Lumbar puncture if there is a high risk of CNS spread.
- Prognosis in DLBCL: International Prognostic Index (age over 60, stage III/IV, high LDH, more than one extranodal site, poor performance status).
Management
- DLBCL: R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin/doxorubicin, Oncovin/vincristine, Prednisolone), usually 6 cycles for advanced disease; radiotherapy for bulky sites; CNS prophylaxis (methotrexate) in high-risk cases. Aim is cure.
- Follicular (low grade): watch and wait if well; radiotherapy for early localised disease; rituximab- or obinutuzumab-based chemo-immunotherapy when treatment is needed; rituximab maintenance. Generally not curable but long survival.
- Burkitt: intensive chemotherapy with CNS-directed treatment; prevent tumour lysis (fluids, rasburicase).
- Gastric MALT: H. pylori eradication first.
- Relapse: salvage chemotherapy and autologous stem cell transplant; CAR-T cell therapy in some.
Rituximab is an anti-CD20 antibody used in B-cell lymphomas; it does not work for T-cell lymphomas or classical Hodgkin (CD20-negative Reed-Sternberg cells).
Hodgkin versus non-Hodgkin
| Feature | Hodgkin | Non-Hodgkin |
|---|---|---|
| Malignant cell | Reed-Sternberg (CD15, CD30) | Lymphoid cells (mostly B) |
| Age | Young adults (bimodal) | Older adults (except Burkitt) |
| Spread | Contiguous | Non-contiguous, often widespread |
| Extranodal disease | Rare | Common |
| Leukaemic phase | No | Can occur |
| B symptoms | More common | Less common |
| Staging importance | Guides therapy strongly | Less important than grade/type |
| Standard chemotherapy | ABVD | R-CHOP (B-cell) |
| Prognosis | Usually curable | Varies by type |
Expect: a young adult with painless rubbery neck nodes, itching or alcohol pain; Reed-Sternberg cells and CD15/CD30; nodular sclerosis as the commonest type and lymphocyte-rich as the best prognosis; the definition of B symptoms; Ann Arbor stages (both sides of the diaphragm = III, extranodal organ = IV); ABVD and its toxicities (bleomycin lung, doxorubicin heart); excision biopsy as the diagnostic test; DLBCL as the commonest NHL treated with R-CHOP; translocations t(14;18), t(8;14), t(11;14); EBV and Burkitt; H. pylori and gastric MALT lymphoma; stomach as the commonest GI site.
Quick revision
- HL: Reed-Sternberg (owl-eye, CD15+ CD30+) in reactive background; contiguous spread.
- Nodular sclerosis commonest; lymphocyte-rich best; lymphocyte-depleted worst.
- Classic clues: rubbery cervical nodes, mediastinal mass, pruritus, alcohol pain, Pel-Ebstein fever.
- B symptoms: fever above 38 °C, drenching night sweats, over 10% weight loss in 6 months.
- Ann Arbor: I one region; II same side; III both sides; IV extranodal organ.
- HL: ABVD ± radiotherapy; relapse: autologous transplant, brentuximab.
- NHL: mostly B cell; DLBCL commonest → R-CHOP.
- Follicular t(14;18) BCL2; Burkitt t(8;14) MYC; mantle t(11;14) cyclin D1.
- Diagnosis: excision biopsy, not FNA; staging PET-CT.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Pathoma: Fundamentals of Pathology).
FAQ
What are B symptoms?
Unexplained fever above 38 °C, drenching night sweats and loss of more than 10% of body weight in the previous 6 months; they indicate more active disease.
Which is the most common type of Hodgkin lymphoma?
Nodular sclerosis, typically in young adults (often women) with a mediastinal mass.
Why is fine needle aspiration not enough to diagnose lymphoma?
Lymphoma typing needs the node architecture, immunohistochemistry and genetic tests, which require an excision or core biopsy.
What does stage III lymphoma mean?
Nodes are involved both above and below the diaphragm, with or without spleen involvement.
What is the treatment of diffuse large B-cell lymphoma?
R-CHOP chemo-immunotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), with radiotherapy for bulky disease; many patients are cured.