Lymphoma — Symptoms, Causes & Treatment | MyMedicPlus

Lymphoma is a malignancy of the lymphatic system arising from abnormal clonal proliferation of lymphocytes — the white blood cells responsible for immune defence. It is broadly classified into two major categories: Hodgkin lymphoma (HL), characterised by the presence of Reed-Sternberg cells (large binucleate B-cells) within a reactive inflammatory background, and Non-Hodgkin lymphoma (NHL), a heterogeneous group of over 60 distinct subtypes of varying aggressiveness and prognosis. Hodgkin lymphoma primarily affects young adults (bimodal peak at ages 20-30 and over 55) and is one of the most curable cancers, with overall cure rates exceeding 85%. NHL is far more common and diverse — the most prevalent subtypes include diffuse large B-cell lymphoma (DLBCL, 25-30% of NHL, aggressive), follicular lymphoma (20%, indolent), mantle cell lymphoma, and T-cell lymphomas. Together, lymphomas account for approximately 570,000 new diagnoses annually worldwide, making NHL the sixth most common cancer globally. Lymphoma staging uses the Lugano classification (stages I-IV based on anatomical extent), with PET-CT being the gold standard for staging and treatment response assessment.

Lymphoma aetiology is multifactorial with infectious, immunological, and genetic contributions. Epstein-Barr virus (EBV) is detected in 30-40% of classical Hodgkin lymphoma cases and in EBV-positive DLBCL — EBV transforms B cells through latent membrane proteins. HIV infection dramatically increases NHL risk (40-100x), particularly DLBCL, Burkitt lymphoma, and primary CNS lymphoma; antiretroviral therapy has significantly reduced but not eliminated this risk. HTLV-1 (human T-lymphotropic virus type 1) causes adult T-cell leukaemia/lymphoma, endemic in Japan, the Caribbean, and parts of Africa. Helicobacter pylori infection drives gastric MALT (mucosa-associated lymphoid tissue) lymphoma — H. pylori eradication alone achieves complete remission in 70-80% of early-stage gastric MALT lymphoma. Autoimmune diseases (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus) increase NHL risk 2-5x through chronic immune stimulation. Organ transplantation with sustained immunosuppression causes post-transplant lymphoproliferative disorder (PTLD), predominantly EBV-driven B-cell lymphomas. Prior chemotherapy (alkylating agents) and radiotherapy increase secondary NHL risk 5-10 years after treatment. Family history of lymphoma confers a 2-4x increased risk.

The hallmark presentation is painless, progressive lymphadenopathy — firm, rubbery, non-tender enlarged lymph nodes most commonly in the cervical (neck), axillary (armpit), or inguinal (groin) regions. Nodes may be matted together and are characteristically painless, distinguishing them from reactive (infectious) lymphadenopathy which is typically tender. B symptoms — defined as unexplained fever above 38°C, drenching night sweats requiring change of clothes or bedding, and unexplained weight loss exceeding 10% of body weight within 6 months — are present in 30-40% of lymphoma patients and indicate more aggressive disease and worse prognosis. Splenomegaly (enlarged spleen) causes left-sided abdominal fullness, early satiety, and occasionally left shoulder-tip pain (Kehr's sign). Mediastinal lymphadenopathy in HL causes cough, chest tightness, dyspnoea, or superior vena cava syndrome (facial swelling, arm oedema, distended neck veins) from bulky mediastinal disease. Generalised pruritus (itching without rash) is characteristic of classical Hodgkin lymphoma and may precede other symptoms by months. Hepatomegaly, bone marrow infiltration (causing pancytopenia — anaemia, thrombocytopenia, neutropenia), and extranodal disease (skin, CNS, GI) occur in aggressive NHL subtypes.

Tissue biopsy with histopathological, immunohistochemical, and molecular analysis is mandatory for definitive lymphoma diagnosis and subtype classification — a core or excisional lymph node biopsy is strongly preferred over fine-needle aspiration (FNA), which is insufficient for architectural assessment. Immunohistochemistry (IHC) panels identify cell lineage: CD20 (B-cell), CD3 (T-cell), CD15/CD30 (Reed-Sternberg cells in HL). Flow cytometry on peripheral blood, bone marrow, or fresh tissue identifies surface markers for NHL subtype classification and clonality. Cytogenetics and FISH detect specific chromosomal translocations: t(14;18) BCL2 translocation in follicular lymphoma; t(8;14) MYC translocation in Burkitt lymphoma; t(11;14) in mantle cell lymphoma; MYC/BCL2/BCL6 double-hit or triple-hit in high-grade B-cell lymphoma. DLBCL requires cell-of-origin testing (germinal centre B-cell [GCB] vs activated B-cell [ABC] by gene expression profiling or Hans algorithm IHC) to guide treatment selection. PET-CT with 18F-FDG is the gold standard for staging (Lugano classification I-IV), interim response assessment (Deauville 5-point scale), and end-of-treatment evaluation. Bone marrow trephine biopsy is performed in NHL staging. LDH (elevated in aggressive NHL), beta-2 microglobulin, and serum albumin inform the International Prognostic Index (IPI) — the key prognostic tool in DLBCL.

Hodgkin lymphoma treatment achieves cure in over 85% of patients. Early-stage classical HL (stages I-II non-bulky): 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-site radiotherapy (ISRT). Early-stage bulky or advanced HL (stages III-IV): 6 cycles of ABVD or BV-AVD (brentuximab vedotin replacing bleomycin — ECHELON-1 trial showed superior PFS over ABVD for advanced HL); PET-CT-adapted therapy refines treatment based on interim response. Relapsed/refractory HL: brentuximab vedotin (anti-CD30 antibody-drug conjugate), nivolumab or pembrolizumab (PD-1 inhibitors achieving 70-80% ORR in relapsed HL), followed by autologous SCT consolidation. DLBCL first-line: R-CHOP (rituximab 375mg/m² + cyclophosphamide + doxorubicin + vincristine + prednisolone) — 6 cycles; polatuzumab vedotin added to R-CHP (pola-R-CHP, POLARIX trial) improves PFS in high-risk DLBCL. Relapsed/refractory DLBCL: CAR-T cell therapies (axicabtagene ciloleucel [axi-cel], tisagenlecleucel) achieve 40-55% long-term remission in heavily pre-treated patients — transforming outcomes in this historically difficult setting. Follicular lymphoma (indolent): active surveillance ('watch and wait') for asymptomatic low-burden disease; rituximab monotherapy or R-bendamustine for symptomatic disease; obinutuzumab-based regimens for high-burden or relapsed disease. Marginal zone lymphoma: H. pylori eradication for gastric MALT.

Febrile neutropenia from chemotherapy-induced myelosuppression requires immediate broad-spectrum intravenous antibiotics (piperacillin-tazobactam or ceftazidime) and hospitalisation — mortality without prompt treatment exceeds 10% in high-risk patients. Bleomycin-related pulmonary toxicity (pulmonary fibrosis) occurs in 5-10% of HL patients treated with ABVD, particularly those with prior thoracic radiotherapy, baseline lung disease, renal impairment, or supplemental oxygen exposure — manifesting as progressive dyspnoea, dry cough, and bilateral CT infiltrates; bleomycin must be stopped immediately. Anthracycline (doxorubicin)-related cardiotoxicity causes dilated cardiomyopathy — cumulative dose-dependent, detected by echocardiography surveillance; left ventricular dysfunction occurs in 5-10% at standard doses. Alkylating agents (cyclophosphamide, procarbazine from BEACOPP) and topoisomerase inhibitors cause secondary haematological malignancies (AML, MDS) in 1-2% within 10 years. Thoracic radiotherapy increases late risks of secondary breast cancer (particularly in female patients treated before age 30), lung cancer, coronary artery disease, and valvular heart disease — requiring long-term cardiovascular surveillance. Tumour lysis syndrome from rapid tumour cell lysis at treatment initiation causes hyperkalaemia, hyperuricaemia, hyperphosphataemia, and acute kidney injury — prophylaxis with allopurinol and IV hydration is standard in high-risk cases.

No specific prevention exists for most lymphomas as the majority arise without an identifiable or modifiable cause. Effective HIV antiretroviral therapy (ART) reduces HIV-associated lymphoma risk substantially — all HIV-positive individuals should be on ART regardless of CD4 count. Helicobacter pylori eradication with triple or quadruple antibiotic therapy achieves complete remission in 70-80% of early-stage (Stage IE-IIE) gastric MALT lymphoma, avoiding cytotoxic chemotherapy entirely. Hepatitis C virus treatment with direct-acting antivirals induces regression of HCV-associated splenic marginal zone lymphoma. Minimise unnecessary long-term immunosuppression in transplant recipients — reducing CNI doses or switching immunosuppressive regimens can cause PTLD regression in some EBV-driven cases. Long-term lymphoma survivors require structured surveillance for late treatment toxicities: annual breast screening from age 25-30 for females who received thoracic radiotherapy before age 30; regular echocardiography for anthracycline or radiotherapy recipients; skin surveillance for secondary cutaneous malignancies; and thyroid function testing for those who received neck irradiation. Psychological support, fertility counselling (prior to gonadotoxic chemotherapy), and rehabilitation are essential components of comprehensive survivorship care.

See your GP promptly for: a persistently enlarged lymph node that is painless, firm, and not resolving after 2-4 weeks (particularly in the neck, axilla, or groin), unexplained weight loss of more than 10% over 6 months, drenching night sweats (soaking bedclothes), persistent unexplained fever, severe fatigue, or an itchy skin rash without explanation. These are the classic 'B symptoms' of lymphoma and warrant urgent referral for assessment and imaging. Do not assume a neck lump is 'just a gland' — see a doctor within 2 weeks. Seek emergency care for superior vena cava obstruction (facial swelling, headache, arm swelling — from mediastinal mass) or spinal cord compression from lymphomatous deposits. See your haematologist/oncologist urgently if on lymphoma treatment and develop fever above 38°C — this may indicate neutropenic sepsis requiring immediate assessment.