Lymphoma

Introduction

Lymphoma is a malignancy of lymphocytes, typically arising within lymph nodes but capable of involving almost any organ. The fundamental division is between Hodgkin lymphoma, a single, biologically distinct entity defined by the presence of Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL), an umbrella term covering a large and diverse group of B-cell and T-cell malignancies with very different behaviours and treatments.¹

Hodgkin lymphoma

Hodgkin lymphoma has a characteristic bimodal age distribution, with peaks in young adults (20s) and again in the elderly. It is strongly associated with prior Epstein-Barr virus (EBV) infection.

Pathology

Defined by the presence of Reed-Sternberg cells - large, binucleate ("owl's eye") malignant B cells - within a background of reactive inflammatory cells that make up the bulk of the tumour mass. Nodular sclerosing is the commonest histological subtype in the UK.

Clinical features

• Painless, firm, rubbery lymphadenopathy, most often cervical or supraclavicular, which can wax and wane in size
• Alcohol-induced lymph node pain - a classic, if uncommon, and highly specific feature
• B symptoms - fever, drenching night sweats, unintentional weight loss - present in a minority but important for staging and prognosis
• Pruritus, sometimes generalised and severe
• Mediastinal mass - may be found incidentally on a chest X-ray, or cause cough/breathlessness, or rarely superior vena cava obstruction
• Spread is characteristically contiguous, moving predictably from one nodal group to the adjacent one, unlike the more unpredictable spread of NHL

Management

ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) is the standard regimen, with radiotherapy added for localised or bulky disease. Outcomes are excellent, particularly in early-stage disease.²

Non-Hodgkin lymphoma

A large, heterogeneous group, roughly 85% B-cell and 15% T-cell in origin, ranging from indolent disease that may never need treatment to highly aggressive tumours that are fatal within weeks if untreated but curable with prompt chemotherapy.

Key subtypes

Clinical features

• Lymphadenopathy, but less predictably contiguous in spread than Hodgkin lymphoma, and more often with extranodal involvement (GI tract, skin, CNS, bone marrow)
• B symptoms are common in aggressive subtypes
• Symptoms from the specific site involved - e.g. dyspepsia in gastric MALT lymphoma, abdominal mass in Burkitt lymphoma, skin plaques in cutaneous T-cell lymphoma
• Bone marrow involvement causing cytopenias is more frequent than in Hodgkin lymphoma

Management

• Aggressive B-cell NHL (e.g. DLBCL): R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) with curative intent
• Follicular and other indolent lymphomas: "watch and wait" if asymptomatic and low burden - treatment does not improve survival in this setting and adds toxicity without benefit; rituximab-based therapy when treatment is indicated
• Burkitt lymphoma: intensive, short-cycle chemotherapy with aggressive tumour lysis syndrome prophylaxis, given the extremely high proliferation rate
• Gastric MALT lymphoma: H. pylori eradication therapy alone for early, localised disease
• CAR-T cell therapy and other novel immunotherapies for relapsed/refractory aggressive lymphoma

Investigations common to lymphoma

• Excision or core lymph node biopsy is required for diagnosis - fine needle aspiration alone is inadequate, since architecture, immunohistochemistry and (where relevant) molecular/cytogenetic testing are needed to reliably subtype lymphoma
• FBC, blood film, LDH and urate - LDH is a marker of tumour bulk/proliferation and part of prognostic scoring; urate anticipates tumour lysis risk
• PET-CT for staging in most subtypes, and to assess treatment response (particularly useful given lymphoma's characteristic FDG avidity)
• Bone marrow biopsy in selected cases to assess marrow involvement
• HIV testing - lymphoma risk is significantly increased in HIV, and this changes management

Ann Arbor staging

Each stage is suffixed A (no B symptoms) or B (B symptoms present), which affects prognosis and treatment intensity.

Complications

• Superior vena cava obstruction from a mediastinal mass
• Spinal cord compression from vertebral or epidural disease
• Tumour lysis syndrome, especially with rapidly proliferating subtypes (Burkitt lymphoma) or high tumour burden at treatment initiation
• Treatment-related toxicity - anthracycline cardiotoxicity, bleomycin pulmonary toxicity, infertility, and an increased long-term risk of secondary malignancy, particularly after combined chemoradiotherapy
• Immunosuppression from both the disease and its treatment, increasing infection risk
• Richter-type transformation of indolent lymphoma into a more aggressive subtype over time

Red flags

Prognosis

Hodgkin lymphoma has one of the best prognoses in oncology, with over 80-90% cure rates for early-stage disease and good outcomes even in advanced disease with modern combination chemotherapy.²

Prognosis in non-Hodgkin lymphoma varies enormously by subtype: DLBCL is potentially curable with R-CHOP in a majority of patients, Burkitt lymphoma has high cure rates with intensive short-course chemotherapy despite its aggressive behaviour, while follicular lymphoma typically follows an indolent, relapsing-remitting course over many years - not usually curable, but compatible with long survival and good quality of life for long periods.