Orientation notes for study. After this note you should be able to classify a lymphoma, link each subtype to its translocation, virus and age group, stage a patient, and explain why the biopsy decides everything. Treatment protocols change: check your oncology guideline.
Definition
Lymphomas are clonal neoplasms of lymphoid cells that arise in lymph nodes and other solid lymphoid tissue. A lymphoid cell can transform at any stage of maturation, so the tumour keeps the features of the stage it was frozen at. When the marrow and blood are involved the same disease is called leukaemia; some, such as CLL/SLL, are both.
Hodgkin versus non-Hodgkin lymphoma
| Feature | Hodgkin lymphoma (HL) | Non-Hodgkin lymphoma (NHL) |
|---|---|---|
| Share of lymphomas | About 30% | About 70% |
| Spread | Orderly, node to adjacent node | Irregular, unpredictable |
| Extranodal disease | Uncommon | Common |
| Diagnostic cell | Reed-Sternberg (RS) cell | None |
| Cell of origin | B cell (germinal centre) | 85-90% B cell, 10-15% T/NK cell |
| Typical age | Two peaks: young adults and over 55 | Rises with age; Burkitt in children |
| Curability | Highly curable | Depends on subtype |
Hodgkin lymphoma
- Reed-Sternberg cell: a large cell with bilobed ("owl's eye") nucleus and prominent eosinophilic nucleoli, in a background of reactive cells (lymphocytes, eosinophils, plasma cells, histiocytes). The tumour cells are a small minority; most of the mass is inflammation caused by their cytokines.
- Classical HL markers: CD15+, CD30+, CD45 negative, CD20 usually negative. Nodular lymphocyte-predominant HL differs: CD20+, CD15-, CD30-, with "popcorn" cells.
- Subtypes of classical HL:
- Nodular sclerosis: commonest in young adults, women, mediastinal mass; lacunar cells and collagen bands.
- Mixed cellularity: older patients, HIV-positive patients and developing countries; EBV-associated.
- Lymphocyte-rich: good prognosis.
- Lymphocyte-depleted: rare, older and HIV-positive patients, worst prognosis.
- Features: painless cervical or supraclavicular nodes, often with a mediastinal mass; pruritus; pain in the nodes after alcohol (rare but classic); B symptoms.
Non-Hodgkin lymphoma (WHO classification)
Classification uses cell lineage, stage of differentiation, morphology, immunophenotype, genetics and clinical behaviour.
- B-cell neoplasms (85-90%): diffuse large B-cell (DLBCL, the commonest, about a third), follicular, CLL/SLL, mantle cell, marginal zone/MALT, Burkitt, lymphoplasmacytic, hairy cell leukaemia, plasma cell myeloma.
- T/NK-cell neoplasms (10-15%): peripheral T-cell lymphoma, anaplastic large cell lymphoma (ALCL), mycosis fungoides/Sezary syndrome, adult T-cell leukaemia/lymphoma (HTLV-1), NK/T-cell lymphoma (nasal type, EBV).
- Precursor tumours: B- and T-lymphoblastic leukaemia/lymphoma, in children and adolescents.
Low grade and high grade
| Feature | Low grade (indolent) | High grade (aggressive) |
|---|---|---|
| Examples | Follicular, SLL/CLL, marginal zone | DLBCL, Burkitt, lymphoblastic |
| Course | Slow, often months to years | Fatal in weeks to months untreated |
| Response to chemotherapy | Good but rarely curative | Often curable with intensive treatment |
| Strategy | Watch and wait can be right | Urgent treatment |
Pathogenesis: translocations and viruses
Most NHL arise from translocations that bring an oncogene next to an immunoglobulin gene (chromosomes 14, 2, 22), so the oncogene is overexpressed.
| Lymphoma | Translocation | Overexpressed gene | Effect |
|---|---|---|---|
| Follicular | t(14;18) | BCL2 | Blocks apoptosis |
| Mantle cell | t(11;14) | Cyclin D1 | Drives the cell cycle |
| Burkitt | t(8;14) (also t(2;8), t(8;22)) | MYC | Uncontrolled proliferation |
| ALK-positive ALCL | t(2;5) | ALK | Constitutive kinase signalling |
| Infection | Lymphoma |
|---|---|
| EBV | Burkitt (endemic, jaw, with malaria), classical HL, post-transplant lymphoproliferative disease, CNS lymphoma in AIDS, NK/T-cell lymphoma |
| HIV | DLBCL, Burkitt, primary CNS lymphoma, HL |
| HTLV-1 | Adult T-cell leukaemia/lymphoma |
| HHV-8 | Primary effusion lymphoma, Kaposi sarcoma |
| H. pylori | Gastric MALT lymphoma |
| Hepatitis C | Marginal zone lymphoma |
In Kenya the endemic Burkitt lymphoma of children (jaw and facial tumours, linked to holoendemic malaria and EBV) and HIV-associated lymphomas are the cases examiners expect you to recognise.
Clinical features
- Painless, asymmetric lymphadenopathy that is firm and rubbery and slowly enlarges. Persistence beyond about 4 weeks with no infection needs a biopsy.
- B symptoms: fever above 38 degrees, drenching night sweats, loss of more than 10% of body weight in 6 months.
- Extranodal disease: gut (the commonest extranodal site), Waldeyer's ring, skin, brain, testis, bone marrow.
- Marrow or spleen involvement: anaemia, neutropenia and thrombocytopenia, splenomegaly.
- Complications of mass: superior vena cava obstruction (mediastinal mass), spinal cord compression, obstructive jaundice, ureteric obstruction, pleural effusion.
Differential diagnosis of a lymphomatous node
| Condition | What points to it | What separates it |
|---|---|---|
| Reactive lymphadenopathy (infection) | Tender, recent infection, shrinks with time | Biopsy: reactive follicles, no clonality |
| TB lymphadenitis | Cervical, matted, may discharge, night sweats | Caseating granuloma, AFB, Xpert |
| HIV lymphadenopathy | Generalised, symmetrical | Test; persistent generalised lymphadenopathy is benign |
| Sarcoidosis | Bilateral hilar nodes, erythema nodosum | Non-caseating granulomas |
| Metastatic carcinoma | Hard, fixed, known primary | Biopsy and cytokeratin staining |
| Infectious mononucleosis | Teenager, pharyngitis | Atypical lymphocytes, EBV serology |
Investigations
- Excisional or core (Trucut) node biopsy is the gold standard. A fine-needle aspirate cannot show nodal architecture, which is needed to classify the lymphoma.
- Immunophenotyping (flow cytometry, immunohistochemistry) confirms clonality: light-chain restriction (kappa or lambda only) and the CD markers.
- Cytogenetics or FISH: the translocations in the table above.
- Blood tests: FBC and film, ESR, LDH (tumour burden and prognosis), uric acid, creatinine, LFTs, calcium, HIV test, hepatitis B and C (before rituximab).
- Imaging: chest X-ray and CT of chest, abdomen and pelvis; PET-CT for staging and for response.
- Bone marrow aspirate and trephine in most NHL staging.
Staging: Ann Arbor
| Stage | Meaning |
|---|---|
| I | One node region (or one extranodal site, IE) |
| II | Two or more regions on the same side of the diaphragm |
| III | Regions on both sides of the diaphragm |
| IV | Diffuse extranodal disease (marrow, liver, lung) |
Add A (no B symptoms) or B (B symptoms), E (limited extranodal extension) and X (bulky disease, mediastinum over a third of the chest width).
Treatment principles
- Hodgkin lymphoma: combination chemotherapy (ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine) with or without radiotherapy to bulky disease; cure rates are high, even in advanced disease.
- DLBCL: R-CHOP: rituximab (anti-CD20), cyclophosphamide, doxorubicin, vincristine, prednisolone.
- Follicular and other indolent lymphomas: watch and wait when asymptomatic; rituximab with chemotherapy when treatment is needed.
- Burkitt lymphoma: short, intensive multi-agent chemotherapy; the fastest-growing human tumour, so start treatment urgently and prevent tumour lysis syndrome (hydration, allopurinol or rasburicase, monitoring of potassium, phosphate, calcium and creatinine).
- Gastric MALT lymphoma: **eradicate *H. pylori*** first; many regress without chemotherapy.
- ALCL (CD30+): brentuximab vedotin is an anti-CD30 option.
- Targeted agents: ibrutinib (BTK inhibitor), venetoclax (BCL2 inhibitor), idelalisib (PI3K inhibitor), CAR-T cells in relapse.
- HIV-associated lymphoma: treat the lymphoma and start or optimise antiretroviral therapy together.
Complications
- Tumour lysis syndrome: hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia and acute kidney injury.
- Oncological emergencies: SVC obstruction, spinal cord compression, airway compression.
- Infection and cytopenias from marrow disease and chemotherapy; check for hepatitis B reactivation with rituximab.
- Late effects of treatment: doxorubicin cardiomyopathy, bleomycin pulmonary fibrosis, infertility, second cancers (leukaemia, breast cancer after chest radiotherapy), hypothyroidism after neck radiotherapy.
- Transformation: follicular lymphoma can transform into DLBCL.
High-yield exam points
- Biopsy, not FNA, makes the diagnosis; LDH is a prognostic marker.
- RS cell with CD15+ CD30+ is classical Hodgkin lymphoma; nodular sclerosis is the commonest type overall; mixed cellularity is the EBV and HIV-linked one.
- Follicular lymphoma = t(14;18) = BCL2; mantle cell = t(11;14) = cyclin D1; Burkitt = t(8;14) = MYC, with the "starry sky" histology; ALCL = t(2;5) = ALK.
- Burkitt in a Kenyan child with a jaw mass: EBV and malaria.
- H. pylori and gastric MALT: antibiotics first.
- Spread: Hodgkin is contiguous and rarely extranodal; NHL is non-contiguous and often extranodal.
- Staging: Ann Arbor with A/B; stage IV is marrow or liver involvement.
- Before rituximab: screen for hepatitis B.
Clinical case
A 9-year-old boy from Kisumu presents with a rapidly enlarging, painless swelling of the right jaw over three weeks, loosening teeth and fever. Examination shows facial distortion and hepatosplenomegaly is absent. LDH is very high and the uric acid is raised.
- What is the most likely diagnosis? Endemic Burkitt lymphoma, a high-grade B-cell NHL associated with EBV and holoendemic malaria.
- How is it confirmed? Biopsy of the mass: "starry sky" pattern (tingible-body macrophages among sheets of monomorphic cells), CD20+, t(8;14) MYC, Ki-67 near 100%.
- What must be done before and during chemotherapy? Aggressive hydration and tumour lysis prophylaxis (allopurinol or rasburicase) with monitoring of potassium, phosphate, calcium and creatinine; test for HIV and hepatitis B; stage with imaging and CSF examination.
Practice questions
Question 1
A 24-year-old woman has painless left supraclavicular nodes, itching and drenching night sweats. A node biopsy shows large cells with bilobed nuclei and prominent nucleoli, positive for CD15 and CD30. What is the most likely subtype overall in this age group?
A. Mixed cellularity B. Nodular sclerosis C. Lymphocyte-depleted D. Nodular lymphocyte-predominant
Answer: B. Nodular sclerosis Explanation: Nodular sclerosis is the commonest classical Hodgkin type in young adults, often with a mediastinal mass and lacunar cells.
Question 2
A node biopsy from a 55-year-old man shows follicular architecture; the cells overexpress BCL2. Which translocation is expected?
A. t(8;14) B. t(11;14) C. t(14;18) D. t(2;5)
Answer: C. t(14;18) Explanation: Follicular lymphoma carries t(14;18), which places BCL2 under the immunoglobulin heavy-chain promoter and blocks apoptosis.
Question 3
A child has a rapidly growing jaw mass. The biopsy shows a "starry sky" pattern. Before starting chemotherapy, which measure is most important to prevent a life-threatening complication?
A. Prophylactic antibiotics only B. Hydration with allopurinol or rasburicase C. Splenectomy D. Radiotherapy to the jaw first
Answer: B. Hydration with allopurinol or rasburicase Explanation: Burkitt lymphoma has a very high turnover, so treatment causes tumour lysis syndrome with hyperkalaemia and renal failure.
Question 4
A 60-year-old man has a gastric ulcer. Biopsy shows a low-grade marginal zone (MALT) lymphoma and H. pylori is present. What is the first-line management?
A. R-CHOP B. Total gastrectomy C. H. pylori eradication therapy D. Radiotherapy to the whole abdomen
Answer: C. H. pylori eradication therapy Explanation: Early gastric MALT lymphoma is driven by chronic antigenic stimulation from H. pylori; eradication can induce remission.
Question 5
Why is fine-needle aspiration insufficient for the primary diagnosis of a suspected lymphoma?
A. It cannot be done on deep nodes B. It does not show nodal architecture needed for classification C. It always causes tumour seeding D. It cannot detect B cells
Answer: B. It does not show nodal architecture needed for classification Explanation: Classification depends on architecture (for example follicular versus diffuse), so an excisional or core biopsy is needed.
Question 6
Which investigation or finding is the best marker of tumour burden and prognosis in lymphoma?
A. ESR B. Serum calcium C. Serum LDH D. Alkaline phosphatase
Answer: C. Serum LDH Explanation: LDH rises with rapid cell turnover and is part of the prognostic scores for aggressive NHL.
Written for study from standard haematopathology and oncology references. Check details against your lecture notes and the current guideline.