Lucan · Conditions

Lymphoma (Hodgkin and non-Hodgkin)

Australian guidance: Cancer Council Australia Lymphoma Guidelines + Lymphoma Australia

1. Definition and epidemiology

Lymphoma is a malignancy of lymphocytes arising in lymph nodes or extranodal lymphoid tissue, broadly divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). NHL represents a heterogeneous group of B-cell and T-cell neoplasms; low-grade (indolent) NHL subtypes include follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). In Australia, lymphoma is among the most common haematological malignancies; FL accounts for 20 to 30 per cent of all NHL, MZL for approximately 8 per cent, and MCL is a rarer subtype that can behave aggressively despite its indolent classification. HL typically affects younger adults with a bimodal age distribution, while indolent NHL incidence rises with advancing age.

2. Pathophysiology

Hodgkin lymphoma is characterised by the Reed-Sternberg cell, a binucleated or multinucleated giant cell derived from germinal centre B lymphocytes that has lost normal B-cell surface markers and aberrantly expresses CD15 and CD30. Reed-Sternberg cells secrete cytokines that recruit a reactive inflammatory background of lymphocytes, eosinophils, plasma cells, and macrophages, driving the characteristic histological subtypes (nodular sclerosing, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) described in Robbins Ch 13.

Non-Hodgkin lymphomas arise from clonal expansion of B or T lymphocytes arrested at specific stages of differentiation. Follicular lymphoma characteristically carries the t(14;18) translocation, placing BCL2 under immunoglobulin heavy chain promoter control, blocking apoptosis of germinal centre B cells and allowing progressive clonal accumulation. Mantle cell lymphoma carries t(11;14), overexpressing cyclin D1 and driving aberrant cell cycle progression through the G1 to S checkpoint. Marginal zone lymphomas frequently arise at extranodal sites in the context of chronic antigen stimulation: gastric mucosa-associated lymphoid tissue (MALT) lymphoma is driven by Helicobacter pylori gastritis in approximately 90 per cent of cases, and splenic MZL is associated with hepatitis C infection. High-grade transformation to diffuse large B-cell lymphoma can occur in approximately 10 per cent of FL patients during their disease course.

3. Clinical presentation and diagnostic criteria

Low-grade NHL frequently presents insidiously over weeks to months and may be detected incidentally on imaging or blood tests. Key features that warrant investigation include painless lymphadenopathy persisting beyond two weeks, splenomegaly, and unexplained cytopenias or persistent lymphocytosis. B symptoms, specifically unintentional weight loss greater than 10 per cent of body weight, drenching night sweats, and fevers above 38 degrees Celsius, indicate systemic disease burden and prompt urgent specialist referral within 72 hours. Hodgkin lymphoma classically presents in young adults with mediastinal lymphadenopathy, B symptoms, and the pathognomonic sensation of alcohol-induced nodal pain. Markedly elevated lactate dehydrogenase (LDH) and organ dysfunction are red flags across all subtypes. Diagnosis requires tissue biopsy; excisional lymph node biopsy is the preferred method to preserve nodal architecture. Fine-needle aspiration is generally inadequate for lymphoma diagnosis. Staging follows the 2014 Lugano classification (stage I to IV based on number of nodal regions and extranodal involvement) and should be completed within four weeks of referral.

4. Investigations and AU-specific cutoffs

Initial general practitioner investigations include full blood count, urea, electrolytes, creatinine, liver function tests, LDH, and beta-2 microglobulin (B2M); no blood test alone can exclude lymphoma. Imaging begins with chest X-ray and computed tomography (CT) of the affected area; ultrasound can characterise superficial lymphadenopathy. Specialist workup adds immunoglobulins, serum protein electrophoresis, and autoimmune screens (particularly relevant in MZL where haemolytic anaemia occurs). PET-CT is the staging modality of choice for FL and MCL due to superior sensitivity for nodal and extranodal disease; some MZL subtypes are PET-CT negative and CT alone may be preferred. Bone marrow aspirate and trephine completes staging for most low-grade lymphomas when it will alter management. TP53 mutation testing is performed for MCL. Testing for occult infection (HIV, hepatitis B and C, tuberculosis) is mandatory before immunosuppressive therapy, as hepatitis B reactivation is a recognised complication of anti-CD20 monoclonal antibody treatment. Site-specific tests for MZL include endoscopic ultrasound for gastric MALT and MRI for orbital or ocular adnexal disease. Referral to specialist should occur within 72 hours when lymphoma is confirmed or strongly suspected on biopsy, or within four weeks when no indicators of concern are present.

5. Management

All newly diagnosed patients must be discussed at a multidisciplinary meeting (MDM) before treatment is initiated. Treatment intent is established as curative, life-prolonging, or palliative according to subtype, stage, and performance status.

Hodgkin lymphoma: Standard treatment for classical HL is doxorubicin-containing combination chemotherapy (ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine) for limited stage disease, with PET-CT-adapted escalation or de-escalation. Involved-site radiotherapy consolidates early-stage disease with favourable characteristics.

Follicular lymphoma: Asymptomatic stage III to IV FL is appropriately managed with watchful waiting; the decision to initiate systemic therapy is guided by Groupe d'Etude des Lymphomes Folliculaires/British National Lymphoma Investigation (GELF/BCNI) criteria including organ dysfunction, cytopenias, or rapid progression. Early-stage (I and II contiguous) FL is potentially curable with radiation therapy. Symptomatic advanced disease is treated with chemoimmunotherapy followed by rituximab maintenance for two years. Systemic therapy should begin within four weeks of meeting GELF/BCNI criteria.

Marginal zone lymphoma: Gastric MALT is treated with Helicobacter pylori eradication regardless of stage; response assessment is deferred for 12 months as regression may be delayed. Residual disease is managed with radiation therapy or chemoimmunotherapy. Early-stage extranodal MZL at other sites (conjunctival, orbital, cutaneous) is managed with radiation therapy. Splenic MZL first-line options are rituximab monotherapy or splenectomy after appropriate vaccinations. Nodal MZL receives chemoimmunotherapy plus anti-CD20 monoclonal antibody.

Mantle cell lymphoma: Symptomatic MCL is treated with intensive chemoimmunotherapy incorporating high-dose cytarabine in younger, fitter patients, followed by consolidation with autologous stem cell transplantation (ASCT); rituximab maintenance after ASCT improves overall survival. Older or frail patients receive less intensive chemoimmunotherapy regimens. Most symptomatic MCL patients should begin treatment within two weeks of completing staging.

Relapsed or refractory disease is managed with re-biopsy to confirm histology, re-staging, and MDM review. Options include alternative chemoimmunotherapy, novel targeted agents, and clinical trial enrolment.

6. Pharmacology and AU PBS notes

Rituximab (Mabthera, biosimilars Riximyo and Ritemvia) is a chimeric anti-CD20 monoclonal antibody central to most NHL regimens. PBS streamlined authority is available for follicular lymphoma and other CD20-positive NHL subtypes in combination with chemotherapy and as maintenance therapy.

Common regimens: - R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone. Used in symptomatic FL, MZL, and aggressive NHL transformation. - R-Bendamustine (R-Benda): rituximab plus bendamustine. PBS authority applies for indolent NHL including FL and MZL in patients unsuitable for anthracycline-based therapy. - ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine. Standard for classical HL; PBS-listed. - Ibrutinib (Imbruvica): Bruton tyrosine kinase (BTK) inhibitor PBS-listed for relapsed or refractory MCL and chronic lymphocytic leukaemia. Oral daily dosing. - Acalabrutinib (Calquence): second-generation BTK inhibitor available via PBS for relapsed MCL.

Rituximab maintenance following induction in FL is continued for two years; ongoing therapy prolongs progression-free survival but has not been shown to extend overall survival, and carries additional infectious toxicity risk requiring counselling. Antimicrobial prophylaxis and immunoglobulin supplementation are recommended for hypogammaglobulinaemic patients per national prescribing criteria. Annual influenza vaccination and five-yearly pneumococcal vaccination are recommended in accordance with the Australian National Immunisation Schedule.

7. Complications and monitoring

Treatment-related complications: - Infusion reactions to rituximab: premedication with paracetamol and antihistamine reduces risk; severe reactions require cessation and resuscitation. - Hepatitis B reactivation: screen all patients before anti-CD20 therapy; those with hepatitis B core antibody require a documented antiviral prophylaxis plan and ongoing monitoring. - Bleomycin pulmonary toxicity: cumulative dose-dependent risk; monitor with pulmonary function tests and chest imaging. - Anthracycline-induced cardiomyopathy: follow-up echocardiography two to five years after therapy in patients with prior anthracycline exposure. - Secondary malignancies: increased risk following cytotoxic therapy and radiation; ongoing surveillance required.

Disease-related complications: - Histologic transformation: FL transforming to diffuse large B-cell lymphoma presents with rapid nodal enlargement, markedly elevated LDH, and B symptoms. Re-biopsy is mandatory. - Tumour lysis syndrome: rare in indolent NHL but relevant with bulky disease or rapid response to initial therapy. - Cytopenias from bone marrow infiltration: transfusion support may be required.

Surveillance schedule: - After radiation therapy with curative intent: history and examination every six months for two years, then annually. - After continuous systemic treatment: history and examination every three to six months for two years, then every six to twelve months. - After chemoimmunotherapy: history, examination, and blood tests every three months for at least two years, then clinician-directed intervals indefinitely. - Thyroid function: annually in patients who received radiation to the neck. - Bone mineral density: periodic evaluation given risk of endocrinopathy following systemic therapy.

Psycho-oncology referral is recommended for patients on watchful waiting given the significant anxiety associated with active surveillance of untreated disease.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.