Hodgkin lymphoma (HL) is a malignant lymphoid neoplasm characterized by the presence of Reed–Sternberg cells or mononuclear Hodgkin cells within an inflammatory cellular background in lymph node tissue.

Hodgkin lymphoma accounts for approximately 30% of all lymphomas and is distinguished from non-Hodgkin lymphomas by its unique histopathological features and high sensitivity to chemotherapy and radiotherapy.

Hodgkin lymphoma is classified into two main groups:

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)

Characterized by lymphocyte-predominant cells with different immunophenotypic features from classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (CHL)

Classical Hodgkin lymphoma is subdivided into:

• Nodular sclerosis classical Hodgkin lymphoma (NSCHL)

• Mixed cellularity classical Hodgkin lymphoma (MCCHL)

• Lymphocyte-rich classical Hodgkin lymphoma (LRCHL)

• Lymphocyte-depleted classical Hodgkin lymphoma (LDCHL)

Epidemiology

Hodgkin lymphoma has a bimodal age distribution, commonly affecting:

• Young adults

• Older adults

Epidemiological characteristics include:

• Represents a significant proportion of lymphoid malignancies

• Slight male predominance

• More common in developed countries but occurs worldwide

• Classical Hodgkin lymphoma is the most common subtype

• Nodular sclerosis subtype is common among young adults

Risk factors

Epstein–Barr virus infection

EBV infection is associated with several classical Hodgkin lymphoma subtypes, particularly mixed cellularity and lymphocyte-depleted forms.

Immunodeficiency

Risk is increased in:

• HIV infection

• Post-transplant immunosuppression

• Congenital immunodeficiency disorders

Family history

A positive family history of Hodgkin lymphoma increases risk.

Age

Risk varies according to age groups, with increased incidence among adolescents, young adults, and older individuals.

Pathophysiology

Hodgkin lymphoma develops from malignant transformation of B lymphocytes, usually originating from germinal-centre B cells.

The disease is characterized by:

1. Abnormal proliferation of Hodgkin and Reed–Sternberg cells

2. Recruitment of inflammatory cells including:

   • Lymphocytes

   • Eosinophils

   • Plasma cells

   • Macrophages

3. Cytokine release causing systemic symptoms

4. Progressive lymphatic spread

The disease usually spreads in an orderly manner from one lymph node region to adjacent lymph node groups.

Common sites include:

• Cervical lymph nodes

• Mediastinal lymph nodes

• Axillary lymph nodes

• Para-aortic lymph nodes

Advanced disease may involve:

• Spleen

• Liver

• Bone marrow

• Extranodal tissues

Clinical presentation

Hodgkin lymphoma commonly presents with painless lymphadenopathy and may be associated with constitutional symptoms.

Clinical features depend on:

• Disease stage

• Site of lymph node involvement

• Presence of extranodal disease

Symptoms

Lymph node symptoms

• Painless progressive lymph node enlargement

• Commonly involving cervical lymph nodes

B symptoms

• Unexplained fever

• Drenching night sweats

• Unintentional weight loss (>10% body weight over 6 months)

Other symptoms

• General fatigue

• Pruritus

• Reduced appetite

• Alcohol-induced lymph node pain

Respiratory symptoms

Due to mediastinal involvement:

• Cough

• Chest discomfort

• Difficulty breathing

• Superior vena cava obstruction symptoms

Clinical signs

Lymph node examination

Findings may include:

• Enlarged painless lymph nodes

• Firm consistency

• Non-tender nodes

• Matted nodes in advanced disease

• Cervical lymphadenopathy

Assessment should include:

• Site

• Number

• Size

• Consistency

• Mobility

• Matting

General examination

• Fever

• Weight loss

• Cachexia

• Pruritus-related skin changes

Respiratory system

May reveal:

• Mediastinal mass features

• Signs of superior vena cava obstruction

Abdominal examination

May demonstrate:

• Hepatomegaly

• Splenomegaly

• Abdominal masses

Skeletal examination

• Bone tenderness in advanced disease

Differential diagnosis

• Non-Hodgkin lymphoma

• Tuberculous lymphadenitis

• Metastatic carcinoma

• Infectious mononucleosis

• Sarcoidosis

• Chronic lymphocytic leukemia

• Reactive lymphadenopathy

• HIV-associated lymphadenopathy

Diagnostic criteria

Diagnosis of Hodgkin lymphoma requires:

• Persistent painless lymphadenopathy

• Presence of B symptoms or systemic symptoms where applicable

• Histological confirmation demonstrating:

  • Reed–Sternberg cells or Hodgkin cells

  • Appropriate inflammatory background

Definitive diagnosis requires lymph node biopsy.

Investigations

Laboratory investigations

Full blood count (FBC)

To assess:

• Anaemia

• Leukocytosis

• Cytopenias

Liver function tests (LFT)

To assess hepatic involvement and treatment baseline.

Renal function tests (RFT)

To assess renal function before chemotherapy.

Erythrocyte sedimentation rate (ESR)

May be elevated and has prognostic significance.

Lactate dehydrogenase (LDH)

Marker of tumour burden.

HIV testing

Recommended for all patients.

Imaging investigations

Chest X-ray

Used to assess:

• Mediastinal widening

• Thoracic involvement

CT scan of neck, chest, abdomen and pelvis

Used for:

• Disease staging

• Assessment of nodal involvement

PET/CT

Recommended for:

• Initial staging

• Treatment response assessment

• Detection of residual disease

Histological investigations

Lymph node biopsy

Required for diagnosis.

Preferred method:

• Excisional lymph node biopsy

Allows assessment of:

• Reed–Sternberg cells

• Hodgkin cell morphology

• Histological subtype

Bone marrow assessment

Bone marrow aspirate and biopsy

Not routinely required in:

• Stage I disease

• Stage II A disease

May be required in advanced disease or abnormal blood findings.

Cardiac assessment

MUGA scan or echocardiography

Performed before anthracycline-containing chemotherapy to assess cardiac function.

Staging

Hodgkin lymphoma is staged using the Ann Arbor staging system.

Stage I

Single lymph node region involved.

Stage II

Two or more lymph node regions involved on the same side of the diaphragm.

Stage III

Lymph node involvement on both sides of the diaphragm.

Stage IV

Diffuse involvement of extranodal organs such as:

• Liver

• Bone marrow

• Lung

Management

Hodgkin lymphoma is highly sensitive to chemotherapy and radiotherapy.

Management depends on:

• Disease stage

• Prognostic factors

• Performance status

• Bulky disease

• Presence of B symptoms

Treatment objectives:

• Achieve complete remission

• Prevent relapse

• Minimize treatment toxicity

Management includes:

1. Initial assessment and staging

2. Combination chemotherapy

3. Radiotherapy in selected patients

4. Salvage treatment for relapse

Non-pharmacological treatment

Radiotherapy

Radiotherapy may be used as:

• Consolidation after chemotherapy

• Treatment of localized disease

• Palliation of symptomatic disease

Radiotherapy techniques include:

• Involved field radiotherapy (IFRT)

• Mantle field radiotherapy

• Inverted Y field radiotherapy

Recommended dose:

• 1.8–2 Gy per fraction

• Total dose 30–40 Gy

Supportive care

Includes:

• Infection prevention

• Nutritional support

• Management of chemotherapy complications

• Fertility counselling where appropriate

Pharmacological treatment

First-line chemotherapy

Chemotherapy aims for cure at all stages and is indicated mainly in:

• Stage II–IV disease

The recommended first-line regimen is ABVD.

ABVD regimen

Doxorubicin

Doxorubicin – 25 mg/m² – intravenous infusion over 30 minutes – day 1 and day 15

AND

Bleomycin – 10 IU/m² – intravenous administration over 10 minutes – day 1 and day 15

AND

Vinblastine – 6 mg/m² – intravenous administration over 10 minutes – day 1 and day 15

AND

Dacarbazine – 375 mg/m² – intravenous infusion over 30 minutes – day 1 and day 15

Frequency:

• Every 28 days

Duration:

• 4–8 cycles

Salvage chemotherapy regimens

Used in relapsed or refractory disease.

Recommended regimens include:

• DHAP

• DHAC

• ICE

• IGEC

• MINE-ESHAP

These regimens are used according to specialist oncology protocols.

Management according to disease stage

Early-stage disease

Includes:

• Limited chemotherapy

• Involved field radiotherapy where indicated

Advanced-stage disease

Management includes:

• Combination chemotherapy with ABVD

• PET-based response assessment

• Consolidative radiotherapy in selected cases

Relapsed or refractory disease

Management includes:

• Salvage chemotherapy

• Consideration of autologous stem cell transplantation

• Specialist oncology management

Referral

All patients with suspected or confirmed Hodgkin lymphoma should be referred to specialized hematology or oncology centres.

Urgent referral indications

• Rapidly enlarging lymph nodes

• Airway compromise

• Superior vena cava obstruction

• Severe systemic symptoms

• Bone marrow involvement

• Spinal cord compression

Complications

Disease-related complications

• Superior vena cava obstruction

• Bone marrow failure

• Organ infiltration

• Recurrent infections

• Advanced-stage disease complications

Treatment-related complications

Chemotherapy complications

• Neutropenia

• Febrile neutropenia

• Infection

• Infertility

• Cardiomyopathy from doxorubicin

• Pulmonary toxicity from bleomycin

Radiotherapy complications

• Skin toxicity

• Secondary malignancies

• Cardiovascular complications

• Pulmonary fibrosis

Prognosis

Hodgkin lymphoma has one of the highest cure rates among adult malignancies.

Prognosis depends on:

• Disease stage

• Age

• Performance status

• ESR level

• Bulky disease

• Response to treatment

Most patients achieve long-term remission with appropriate therapy.

Prevention

Primary prevention

• HIV prevention and treatment

• Avoidance of unnecessary immunosuppression

• Early management of chronic viral infections

Secondary prevention

• Early evaluation of persistent lymphadenopathy

• Prompt lymph node biopsy

• Early specialist referral

Tertiary prevention

• Long-term follow-up after treatment

• Monitoring for relapse

• Screening for late treatment effects including:

  • Cardiac disease

  • Secondary malignancies

  • Pulmonary complications