Hodgkin lymphoma

Definition

Hodgkin lymphoma (Hodgkin disease, lymphogranulomatosis) is a malignant lymphoma arising from clonally transformed cells of the B-cell lineage. It is characterized by large, binucleated Reed-Sternberg cells in a mixed reactive infiltrate. Lymph nodes, spleen, liver, and bone marrow are mainly involved. Orderly spread to contiguous lymph node regions is typical.

Classification

Classic Hodgkin lymphoma (tumor cells CD15+, CD30+, CD20−) with four histologic subtypes:

• Nodular sclerosis: dense fibrous bands surround nodules of Hodgkin tissue
• Mixed cellularity: a moderate number of Reed-Sternberg cells in a mixed background infiltrate
• Lymphocyte-rich: few Reed-Sternberg cells, many B cells
• Lymphocyte-depleted: numerous Reed-Sternberg cells and extensive fibrosis

Nodular lymphocyte-predominant Hodgkin lymphoma (CD15−, CD30−, CD20+) is now listed as a B-cell lymphoma by the International Consensus Classification.

Stages (Lugano): I one lymph node region or a single extranodal site; II ≥ 2 regions on the same side of the diaphragm; III lymph nodes and/or spleen on both sides of the diaphragm; IV disseminated extranodal involvement (e.g., bone marrow, lung, liver). Suffix A/B for absent or present B symptoms; "bulky" denotes a single mass ≥ 10 cm.

Occurrence & epidemiology

In Germany, about 1,050 women and 1,400 men were diagnosed in 2022. Hodgkin lymphoma is rare but relatively often occurs in young adulthood: between ages 15 and 35, it is among the five most common cancer diagnoses. The age distribution is bimodal, with one peak between 15 and 40 years and a second beyond 60 years; it is rare before age 10.

Aetiopathogenesis

The cause is only partly understood. Discussed factors include:

• Epstein-Barr virus (for some cases) and HIV infection
• congenital immunodeficiencies (e.g., ataxia-telangiectasia, Wiskott-Aldrich syndrome) and immunosuppression, for example in organ transplant recipients
• certain autoimmune disorders (rheumatoid arthritis, celiac disease, Sjögren syndrome, systemic lupus erythematosus)
• familial clustering: children and siblings of affected persons have a slightly increased risk

Many patients develop a slowly progressive defect in cell-mediated immunity.

Clinical features

• Painless lymphadenopathy, mostly cervical; mediastinal lymphadenopathy often an incidental finding on chest x-ray.
• Rarely, pain in involved areas immediately after drinking alcohol.
• B symptoms: fever, night sweats, and unintentional weight loss of more than 10 % of body weight in 6 months; rarely Pel-Ebstein fever (cyclic alternation of febrile and afebrile periods).
• Intense pruritus, often early.
• Splenomegaly common, hepatomegaly unusual.
• Signs of compression: dyspnea and stridor with a mediastinal mass, superior vena cava syndrome, jaundice, lymphedema, Horner syndrome, recurrent laryngeal nerve palsy, spinal cord compression.
• Bone involvement sometimes with osteoblastic vertebral lesions (ivory vertebrae).

Diagnosis

• Lymph node biopsy (preferably excisional biopsy or core needle biopsy; fine-needle aspiration is often inadequate): Reed-Sternberg cells in an infiltrate of histiocytes, lymphocytes, monocytes, plasma cells, and eosinophils; immunohistochemistry (CD15, CD30, CD20).
• Laboratory: complete blood count with differential (slight leukocytosis, lymphocytopenia, eosinophilia, thrombocytosis; anemia in advanced disease), ESR, LDH, alkaline phosphatase, kidney and liver tests.
• FDG-PET/CT of chest, abdomen, and pelvis for staging; alternatively contrast-enhanced CT.
• Bone marrow biopsy only if no PET/CT is available.
• MRI in patients with neurologic symptoms.
• Echocardiography and pulmonary function tests as baseline findings.

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Further reading (open access)

1. MSD Manual Professional: Hodgkin Lymphoma
2. RKI, Zentrum für Krebsregisterdaten: Morbus Hodgkin
3. MSD Manual Professional: Overview of Lymphomas
4. Onkopedia-Leitlinie Hodgkin-Lymphom (DGHO)

Cross-references