Lymphoma

Risk Factors

• Exposure: Radiation, smoking, benzene or other solvents

• Infectious: EBV (especially in Hodgkin and Burkitt’s lymphoma), HIV, HTLV-1

• Autoimmune Disorders: SLE, RA, Sjögren’s syndrome

• Immunosuppression: Post-transplant, long-term corticosteroid use

• Family History: Familial clustering noted in some subtypes

Pathophysiology

• Malignant proliferation of lymphocytes (B, T, or NK cells)

• In Hodgkin Lymphoma (HL), EBV can drive B-cell dysregulation with Reed-Sternberg cells

• Non-Hodgkin Lymphoma (NHL) often involves more diverse genetic/epigenetic mutations leading to abnormal lymphocyte proliferation

Presentation

• Lymphadenopathy

  • HL: Often painless, contiguous spread, commonly cervical or mediastinal nodes

  • NHL: Widespread nodal involvement, can be peripheral or central, often non-contiguous spread

• B Symptoms (fever >38°C, night sweats, weight loss >10% in 6 months)

  • More common in classical HL but can occur in high-grade NHL

  • Important for Ann Arbor staging classification

• Extranodal Disease

  • NHL commonly affects GI tract (e.g. MALT lymphoma), skin, bone marrow, CNS

• Mediastinal Mass

  • May cause cough, chest discomfort, SVC syndrome (facial swelling, venous engorgement)

• Other Signs

  • Fatigue, pruritus, recurrent infections (immune dysfunction), or organ-specific symptoms if infiltration (e.g. hepatic, splenic)

HODGKIN LYMPHOMA (HL)

Features

• Often affects younger adults (bimodal peaks: 30s and 50s)

• Characterised by Reed-Sternberg cells (large, binucleate B cells) on excisional biopsy

• Typically spreads contiguously from one lymph node region to adjacent areas

• Generally higher cure rates compared to most NHL subtypes

Investigations

• Excisional Lymph Node Biopsy: To identify Reed-Sternberg cells and classify HL subtype (e.g. nodular sclerosis, mixed cellularity)

• Baseline Staging

  • PET/CT scan for both staging and assessment of metabolic activity

  • FBC, ESR, LDH, albumin, LFTs, renal function, HIV status

  • Bone marrow biopsy if indicated by PET findings or advanced disease

Treatment

• Early Stage (I–II)

  • Often combined modality: ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) for 2–4 cycles plus involved-site radiotherapy (especially bulky disease)

  • Stage IIA disease might receive fewer chemo cycles plus radiation

• Advanced Stage (IIB–IV)

  • ABVD for more cycles or escalated BEACOPP in high-risk disease

  • Radiotherapy to bulky sites if needed

• Prognosis

  • Generally excellent long-term survival in early stage

  • Late toxicity includes secondary malignancies (breast, lung), cardiac or pulmonary complications

NON-HODGKIN LYMPHOMA (NHL)

Features

• Diverse group with various histologies: Indolent (follicular, MALT) vs Aggressive (diffuse large B-cell lymphoma [DLBCL], Burkitt’s)

• More common than HL, typically non-contiguous spread

• B symptoms less consistent but present in aggressive subtypes

• Extranodal involvement (GI tract, skin, CNS, Waldeyer’s ring, bone marrow)

Subtypes

• MALT Lymphoma

  • Often gastric, associated with H. pylori infection

  • Early stage may resolve with H. pylori eradication

• Burkitt’s Lymphoma

  • Highly aggressive, c-myc translocation

  • Associated with EBV in endemic (African) form

• Diffuse Large B-Cell Lymphoma (DLBCL)

  • Most common aggressive NHL in adults

  • Presents with rapidly enlarging mass, can involve extranodal sites

Investigations

• Excisional Biopsy (preferred) or core biopsy for histological diagnosis

• PET/CT for staging and treatment response

• Bone Marrow Biopsy if suspicion of marrow involvement

• Lab Tests: FBC, LDH (prognostic marker), LFTs, renal function, HIV, hepatitis B/C screening

Treatment

• Early Stage (I–II)

  • Involved-field or involved-site radiotherapy ± short-course chemo (e.g. R-CHOP for DLBCL)

  • Indolent lymphoma (e.g. follicular) can be treated with radiotherapy alone in localised disease

• Advanced Stage (≥IIB)

  • R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) mainstay for B-cell lymphomas

  • Intensive regimens (e.g. Hyper-CVAD, CODOX-M/IVAC) for high-grade subtypes (Burkitt’s)

  • Consider autologous stem cell transplant in refractory or relapsed disease

• H. pylori-Positive MALT

  • Eradication therapy (PPI + clarithromycin + amoxicillin/metronidazole) may induce remission in early gastric MALT

Complications

• Tumour Lysis Syndrome

  • High cell turnover (especially Burkitt’s, DLBCL)

  • Prophylaxis with IV fluids, allopurinol or rasburicase

• SVC Syndrome

  • Mediastinal mass compresses the superior vena cava → facial swelling, distended neck veins

  • Urgent treatment with steroids or radiotherapy to relieve obstruction

• Infections

  • Immunosuppression from disease or therapy (e.g. neutropenia, hypogammaglobulinaemia)

  • Prophylactic antimicrobials or IVIG in select cases

• Bone Marrow Failure

  • Anaemia, neutropenia, thrombocytopenia

  • May require transfusions, growth factors, or dose adjustments

• CNS Involvement

  • More common in aggressive subtypes (DLBCL, Burkitt’s)

  • Prophylactic intrathecal chemo if high risk (testicular involvement, high IPI score)

Follow-Up and Survivorship

• Response Evaluation

  • Repeat PET/CT after therapy to assess remission or persistent disease

  • Physical exams and blood tests at regular intervals (every 3–6 months initially)

• Long-Term Monitoring

  • Look out for late relapses, secondary malignancies, cardiac/pulmonary toxicity (anthracyclines, bleomycin)

  • Encourage vaccination (influenza yearly, pneumococcal, avoid live vaccines if immunosuppressed)

  • Lifestyle advice (no smoking, manage CV risk factors)

• Fertility

  • Consider fertility preservation prior to chemo (sperm/egg freezing)

• Palliative Care

  • For refractory or relapsed disease, symptom control and quality of life remain priorities

Notes:

• Suspect lymphoma in patients with unexplained lymphadenopathy (especially >2 cm, persistent >4 weeks), B symptoms, or mediastinal masses

• Excisional lymph node biopsy is crucial for histological classification (FNA not sufficient)

• Prompt referral to haematology/oncology for staging and management if suspicion is high

• Monitor for acute complications (TLS, SVC syndrome) and coordinate supportive care

• Emphasise adherence to follow-up: cure rates can be high in some subtypes (HL, DLBCL) but vigilant post-treatment surveillance is essential