After reading this note you will be able to describe what lymphomas are, list the local risk factors, explain how they develop, recognise the key clinical features and outline the step‑wise investigations and immediate management. Always verify drug choices, doses and local protocols against the Kenya Ministry of Health guidelines and your hospital formulary.
Definition
Lymphomas are malignant proliferations of lymphoid cells that arise in the lymphoid system (lymph nodes, spleen, thymus, Waldeyer’s ring, gastrointestinal tract, bone marrow and extranodal sites). They are broadly classified into Hodgkin lymphoma (HL) and non‑Hodgkin lymphoma (NHL) based on histopathology and immunophenotype.
Anatomy and physiology you need
| Structure | Relevance to lymphoma |
|---|---|
| Lymph node | Site of organised B‑cell germinal centres and T‑cell zones; common primary site |
| Spleen | Filters blood, houses marginal zone B cells; frequent involvement in NHL |
| Thymus | Site of T‑cell maturation; primary site for T‑cell lymphomas |
| MALT (mucosa‑associated lymphoid tissue) | Extranodal origin for many gastric and intestinal NHL |
| Bone marrow | Produces lymphoid precursors; site of disease spread and staging |
| Lymphatic vessels | Conduit for tumour spread to contiguous nodes and distant sites |
Understanding the normal flow of lymph (afferent → node → efferent → thoracic duct) helps explain patterns of nodal spread and why certain nodal groups are commonly involved first.
Causes and risk factors
| Factor | Why it matters in Kenya |
|---|---|
| HIV infection | Immunosuppression reduces tumour surveillance; high incidence of aggressive NHL (especially Burkitt and diffuse large B‑cell) |
| Endemic EBV exposure | EBV drives B‑cell proliferation; linked to endemic Burkitt lymphoma and some HL |
| Chronic malaria | Repeated immune activation may facilitate EBV‑driven B‑cell transformation |
| Tuberculosis (especially disseminated) | Chronic antigenic stimulation; co‑infection with HIV amplifies risk |
| Sickle cell disease | Functional asplenia and chronic inflammation increase lymphoma risk |
| Autoimmune rheumatic diseases (e.g., SLE, rheumatoid arthritis) | Persistent immune activation and immunosuppressive therapy raise NHL risk |
| Occupational pesticide exposure (agricultural workers) | Possible genotoxic effect on lymphoid cells |
| Family history of lymphoid malignancy | Genetic susceptibility (e.g., polymorphisms in DNA repair genes) |
| Age and gender | HL peaks in young adults; NHL incidence rises after 50, slight male predominance |
Pathophysiology
- Chronic antigenic stimulation (e.g., EBV, malaria, TB, autoimmune disease) →
- Clonal expansion of B‑ or T‑lymphocytes →
- Acquisition of genetic lesions (translocations, MYC activation, BCL2/BCL6 dysregulation) →
- Escape from apoptosis (p53 pathway alteration) →
- Uncontrolled proliferation →
- Formation of a malignant lymphoid mass →
- Spread via lymphatic channels and bloodstream → Clinical disease
In HIV‑positive patients, loss of CD4‑mediated immune surveillance accelerates steps 2–5, leading to high‑grade NHL. In endemic Burkitt lymphoma, the classic t(8;14) MYC‑IGH translocation is driven by EBV‑induced activation‑induced cytidine deaminase (AID) during intense germinal‑centre reactions stimulated by malaria.
Clinical features
| History element | Why it matters |
|---|---|
| Duration of symptoms | Distinguishes indolent (months‑years) from aggressive (weeks) disease. |
| B‑symptoms (fever > 38 °C, drenching night sweats, unexplained weight loss > 10 % in 6 mo) | Classic systemic response to cytokine release; indicate higher tumour burden and poorer prognosis. |
| Site of lymphadenopathy (cervical, supraclavicular, axillary, inguinal, mediastinal) | Certain subtypes favour specific regions (e.g., Hodgkin’s often cervical/supraclavicular; Burkitt’s may present with abdominal mass). |
| Pain or tenderness | Tender nodes suggest infection or inflammatory cause; painless nodes are typical of lymphoma. |
| Rapid growth of a mass | Suggests aggressive histology (e.g., diffuse large B‑cell, Burkitt’s). |
| Pruritus | Common in Hodgkin’s disease; reflects cytokine‑mediated skin irritation. |
| History of HIV infection | Immunosuppression predisposes to high‑grade B‑cell lymphomas and primary CNS lymphoma. |
| Previous TB or chronic malaria exposure | Chronic antigenic stimulation may contribute to certain endemic lymphomas (e.g., EBV‑associated). |
| Autoimmune disease (SLE, rheumatoid arthritis) | Long‑standing immune activation raises risk of lymphoma, especially diffuse large B‑cell. |
| Family history of haematological malignancy | May indicate inherited susceptibility (e.g., familial CLL). |
| Exposure to pesticides or herbicides | Occupational risk factor for non‑Hodgkin lymphoma in agricultural regions. |
| Symptoms of organ compression (dyspnoea, dysphagia, superior vena cava syndrome) | Large mediastinal masses can impinge on airway or vessels. |
| Neurological deficits (cranial nerve palsies, seizures) | May indicate CNS involvement or paraneoplastic phenomena. |
| Bleeding tendency or easy bruising | Suggests marrow infiltration or thrombocytopenia. |
| Nighttime cough or hemoptysis | Mediastinal or pulmonary involvement. |
| Abdominal fullness, early satiety, palpable mass | Intra‑abdominal lymphadenopathy or organomegaly (e.g., splenic, hepatic). |
Examination findings and rationale
| Finding | Pathophysiological explanation |
|---|---|
| Painless, firm, rubbery lymph nodes | Neoplastic proliferation replaces normal nodal architecture, producing a non‑tender, solid mass. |
| Supraclavicular (Virchow’s) node | Drainage from thoracic and abdominal cavities; enlargement often signals advanced disease. |
| Mediastinal widening on inspection | Large anterior mediastinal mass (common in Hodgkin’s and primary mediastinal B‑cell lymphoma). |
| Splenomegaly | Lymphoid infiltration of the spleen; common in CLL, follicular lymphoma, and some aggressive subtypes. |
| Hepatomegaly | Hepatic involvement by lymphoma cells or secondary infiltration. |
| Palpable abdominal mass | Enlarged mesenteric or retroperitoneal nodes (e.g., Burkitt’s, mantle‑cell). |
| Skin lesions (pruritic rash, nodules) | Paraneoplastic pruritus or cutaneous lymphoma involvement. |
| Neurological signs (cranial nerve palsy, focal deficits) | Direct CNS infiltration or compression by lymphomatous mass. |
| Anemia, thrombocytopenia, leukopenia on bedside CBC | Marrow replacement reduces normal haematopoiesis. |
| Elevated lactate dehydrogenase (LDH) on bedside test | High tumour turnover releases LDH; correlates with aggressive disease. |
| Bilateral cervical node enlargement with “B‑symptoms” | Classic presentation of Hodgkin’s disease. |
| Peripheral lymphadenopathy with “B‑cell” pattern (e.g., diffuse, non‑tender) | Suggests non‑Hodgkin lymphoma. |
Differential diagnosis
| Condition | Points toward it | Key discriminators |
|---|---|---|
| Reactive lymphadenitis | Recent infection, tender nodes, fever | Tenderness, rapid resolution, normal labs |
| Tuberculous lymphadenitis | TB exposure, constitutional symptoms, caseating necrosis on FNAC | Positive TB PCR/IGRA, necrotic nodes, response to anti‑TB |
| HIV‑related lymphadenopathy | Known HIV, generalized nodes | CD4 count, viral load, absence of clonal cells |
| Metastatic carcinoma | Known primary tumour, hard fixed nodes | Cytology showing epithelial cells, imaging of primary |
| Castleman disease | Unilateral massive node, systemic symptoms | Hyaline‑vascular vs plasma‑cell histology, normal LDH |
| Autoimmune lymphoproliferative syndrome | SLE/RA, serology positive, mild lymphadenopathy | Autoantibodies, response to immunosuppression |
| Primary CNS lymphoma | HIV+, focal neuro deficits, brain mass | MRI ring‑enhancing lesion, EBV DNA in CSF |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Full blood count with peripheral smear | Marrow involvement, cell line abnormalities | Cytopenias suggest infiltration; atypical lymphocytes point to CLL/lymphoma |
| ESR / CRP | Inflammatory activity | Elevated in aggressive disease, but non‑specific |
| LDH | Tumour burden & cell turnover | High level = high‑grade lymphoma, worse prognosis |
| HIV test | Immunosuppression status | Positive → higher risk of high‑grade NHL |
| EBV PCR (blood or CSF) | EBV‑driven lymphoma (e.g., endemic Burkitt’s, CNS) | Detectable viral DNA supports EBV‑associated lymphoma |
| Chest X‑ray / CT thorax | Mediastinal mass, pulmonary involvement | Widened mediastinum or nodal clusters |
| Abdominal ultrasound / CT abdomen | Intra‑abdominal nodes, organomegaly | Enlarged mesenteric nodes, splenomegaly |
| PET‑CT (FDG) | Metabolic activity, staging | High uptake = active disease; guides stage |
| Excisional lymph node biopsy (histology + immunophenotyping) | Definitive diagnosis, subtype | CD20+, CD3‑ for B‑cell NHL; CD15+, CD30+ for Hodgkin |
| Bone‑marrow aspirate/biopsy | Marrow infiltration, staging | Involvement upstages disease |
| Flow cytometry on biopsy | Clonality, cell surface markers | Light‑chain restriction, specific antigen profile |
| Cytogenetics / FISH (e.g., MYC, BCL2, BCL6) | Genetic abnormalities, prognosis | MYC rearrangement → aggressive Burkitt‑type |
Diagnosis and severity
- Establish histological subtype – Excisional biopsy with immunohistochemistry is mandatory. Distinguish Hodgkin (classical vs nodular‑lymphocyte‑predominant) from non‑Hodgkin (B‑cell vs T‑cell, grade).
- Stage the disease – Use Ann Arbor system (I–IV) based on number of nodal regions, extranodal sites, and presence of systemic symptoms (A/B). PET‑CT is preferred for accurate staging; CT and bone‑marrow biopsy complement when PET unavailable.
- Risk stratify –
- International Prognostic Index (IPI) for aggressive NHL: age, LDH, performance status, stage, extranodal sites.
- International Prognostic Score (IPS) for advanced Hodgkin disease: albumin, hemoglobin, male sex, age > 45, stage IV, leukocytosis, lymphocytopenia.
- Assign treatment intent – Curative (early‑stage, favourable‑risk) vs palliative (relapsed, refractory, poor performance).
- Document response criteria – Use Lugano classification: complete metabolic response (PET negative), partial response (≥50 % reduction), stable disease, progressive disease.
Severity is therefore a composite of histology, stage, IPI/IPS score, and patient performance status. This guides choice of chemotherapy regimen, need for radiotherapy, and intensity of supportive care.
Management
1. Immediate stabilisation
| Situation | Action | Rationale |
|---|---|---|
| Airway/respiratory compromise from mediastinal mass | Give supplemental O₂, position upright, arrange urgent radiology and possible steroids (e.g., dexamethasone) to reduce mass effect | Prevent airway collapse; steroids shrink lymphoid tissue rapidly |
| Hyper‑uricaemic tumour lysis risk (large tumour burden, high LDH) | Start aggressive IV hydration, allopurinol or rasburicase, monitor electrolytes | Prevent acute kidney injury and cardiac arrhythmias |
| Severe anaemia or thrombocytopenia causing bleeding | Transfuse packed red cells or platelets as indicated | Maintain tissue oxygenation and haemostasis |
2. Definitive treatment – chosen according to histology, stage and patient factors
| Lymphoma type | First‑line regimen (class) | When to add radiotherapy | Special considerations in Kenya |
|---|---|---|---|
| Diffuse large B‑cell (DLBCL) | Anthracycline‑based chemo (e.g., CHOP) + anti‑CD20 monoclonal antibody | Bulky disease >10 cm or residual mass after chemo | Ensure availability of rituximab; monitor cardiac function |
| Hodgkin lymphoma (classical) | ABVD‑type regimen (adriamycin, bleomycin, vinblastine, dacarbazine) | Early stage favourable disease may use combined chemo‑radiotherapy | Bleomycin pulmonary toxicity – avoid in pre‑existing lung disease |
| Burkitt lymphoma (endemic) | Intensive short‑course chemo (e.g., cyclophosphamide‑based) + CNS prophylaxis | Not routine; consider radiotherapy for residual CNS disease | High prevalence of EBV; screen for HIV, treat concurrently |
| T‑cell lymphomas | CHOP‑like or newer agents (e.g., pralatrexate) | Rarely; consider radiotherapy for localized disease | Limited drug access – may need referral to tertiary centre |
3. Monitoring & follow‑up
- During chemo: CBC, renal & liver panels twice weekly; LDH weekly; cardiac echo before anthracyclines; pulmonary function if bleomycin used.
- After completion: Clinical exam and PET/CT at 6 months; then CT or ultrasound every 6–12 months for 2 years, then annually.
- Late effects: Monitor for secondary malignancies, cardiomyopathy, infertility, endocrine dysfunction; vaccinate against encapsulated organisms if splenectomy performed.
4. Contra‑indications & safety
- Anthracyclines contraindicated in severe left‑ventricular dysfunction.
- Bleomycin avoided in patients with baseline pulmonary fibrosis or oxygen dependence.
- Anti‑CD20 therapy deferred in active severe infections (e.g., uncontrolled TB, disseminated fungal disease).
- All patients should receive prophylaxis for opportunistic infections when on high‑dose steroids or rituximab (e.g., TMP‑SMX for PCP).
Complications and prognosis
| Complication | Typical timing | Clinical clue | Management |
|---|---|---|---|
| Tumour lysis syndrome | Early cycles | Rising uric acid, hyper‑K, falling Ca | Aggressive hydration, uric acid‑lowering agents, electrolyte correction |
| Infections (bacterial, fungal, viral) | Throughout therapy | Fever, neutropenia, mucositis | Empiric broad‑spectrum antibiotics; antifungal if persistent; consider antiviral for HSV/CMV |
| Secondary malignancies (AML, MDS) | Years after therapy | Cytopenias, new blasts | Bone‑marrow evaluation; refer to oncology for salvage |
| Cardiotoxicity (anthracyclines) | Cumulative dose‑related | Dyspnoea, reduced EF | Cardiac monitoring; switch to non‑anthracycline regimen if needed |
| Pulmonary toxicity (bleomycin) | After several cycles | Dry cough, hypoxia | Stop bleomycin, give steroids, oxygen support |
| Relapse / refractory disease | Variable | New lymphadenopathy, B symptoms | Re‑staging, consider salvage chemo, autologous stem‑cell transplant if eligible |
Prognosis depends on histology, stage, LDH, performance status and HIV status. In Kenya, early‑stage Hodgkin lymphoma has >80 % cure rates; DLBCL 5‑year survival ~60 % with full therapy; HIV‑associated lymphomas have poorer outcomes but improve markedly with combined antiretroviral therapy and chemo.
High‑yield exam points
- Look‑alike conditions: Tuberculous lymphadenitis (cold abscess, caseation on FNAC), sarcoidosis (non‑caseating granulomas), metastatic carcinoma (epithelial markers).
- Common wrong first step: Starting steroids before tissue diagnosis – can mask histology and worsen infection.
- Bedside examiner questions:
- “What B‑symptoms would make you suspect lymphoma?”
- “How does a mediastinal mass cause superior vena cava syndrome?”
- “Explain why you would obtain a PET‑CT before deciding on radiotherapy.”
- “What infection prophylaxis is indicated when giving rituximab?”
Clinical case
Case: 28‑year‑old male, HIV‑positive (CD4 180 cells/µL), presents with 3 weeks of painless cervical swelling, night sweats, weight loss of 5 kg, and intermittent dyspnoea. Examination shows multiple firm, non‑tender cervical nodes, a bulky mediastinal shadow on chest X‑ray, and mild hepatomegaly. CBC shows mild anaemia, normal platelets, LDH markedly raised.
Questions
- What is the most appropriate next diagnostic step?
Answer: Perform an excisional lymph node biopsy for histopathology and immunophenotyping before initiating therapy.
- Which immediate management is required before chemotherapy?
Answer: Start aggressive IV hydration and allopurinol to prevent tumour lysis syndrome, and give prophylactic TMP‑SMX for PCP because of impending immunosuppression.
- If the biopsy confirms diffuse large B‑cell lymphoma, what is the first‑line regimen in this patient?
Answer: Anthracycline‑based combination chemotherapy (CHOP) plus anti‑CD20 monoclonal antibody, with concurrent antiretroviral therapy optimisation.
Practice questions
Question 1
A 45‑year‑old woman presents with a rapidly enlarging axillary mass, fever, and LDH twice the upper limit. She is afebrile now, with a platelet count of 90 ×10⁹/L. What is the most appropriate next step?
A. Start high‑dose steroids immediately
B. Begin empiric broad‑spectrum antibiotics
C. Obtain an excisional biopsy of the node
D. Give platelet transfusion and discharge
Answer: C. obtain an excisional biopsy of the node
Explanation: Tissue diagnosis is essential before therapy; steroids can obscure pathology, and antibiotics are not indicated without infection.
Question 2
A 60‑year‑old man with known DLBCL is on his third cycle of CHOP. He develops dyspnoea, non‑productive cough, and an O₂ saturation of 88 % on room air. Which drug is most likely responsible?
A. Cyclophosphamide
B. Doxorubicin
C. Vincristine
D. Bleomycin
Answer: D. bleomycin
Explanation: Bleomycin is associated with pulmonary toxicity presenting as cough and hypoxia, especially after cumulative dosing.
Question 3
A child from a malaria‑endemic area presents with jaw swelling, abdominal mass, and a starry‑sky appearance on peripheral smear. Which co‑factor is most strongly linked to this lymphoma type?
A. HIV infection
B. EBV infection
C. Chronic hepatitis B
D. Sickle cell disease
Answer: B. EBV infection
Explanation: Endemic Burkitt lymphoma is tightly associated with Epstein‑Barr virus, often in malaria‑exposed children.
Question 4
During treatment of Hodgkin lymphoma, a patient develops a fever, neutropenia (ANC 0.4 ×10⁹/L) and a new rash. Which of the following is the safest immediate action?
A. Start high‑dose steroids for presumed drug reaction
B. Discontinue all chemotherapy and observe
C. Initiate empiric broad‑spectrum antibiotics and hold chemotherapy
D. Give a single dose of filgrastim and continue chemo
Answer: C. initiate empiric broad‑spectrum antibiotics and hold chemotherapy
Explanation: Neutropenic fever mandates prompt antibiotics; steroids may worsen infection, and chemotherapy must be paused.
Question 5
A patient with relapsed T‑cell lymphoma is being considered for autologous stem‑cell transplant. Which pre‑transplant assessment is mandatory?
A. Serum ferritin level
B. Cardiac ejection fraction measurement
C. Hepatitis C viral load only
D. Bone‑density scan
Answer: B. cardiac ejection fraction measurement
Explanation: High‑dose conditioning regimens are cardiotoxic; adequate cardiac function is required before transplant.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.