Hodgkin Lymphoma
Lymphomas are broadly classified into 1) Hodgkin lymphoma and 2) non-Hodgkin lymphoma:
- Hodgkin lymphoma is a distinct lymphoid malignancy (on its own) defined by the presence of Reed-Sternberg cells
- Non-Hodgkin lymphoma represents a heterogeneous group of lymphoid malignancies characterised by the absence of Reed-Sternberg cells
Definition
Lymphomas are malignancies arising from lymphoid tissue, most commonly derived from B cells, but also T cells or NK cells
Main lymphoid tissues affected in Hodgkin and non-Hodgkin lymphoma:
| Hodgkin lymphoma | Non-Hodgkin lymphoma |
|---|---|
Primarily affects and presents as nodal disease:
Extra-nodal involvement is uncommon |
Can affect and present as BOTH:
|
Lymphoma may be confused with chronic lymphocytic leukaemia (CLL) because both arise from mature lymphocytes.
However, the distinction is based on the predominant site of disease:
- Lymphoma is a disease that originates and predominantly presents as a solid tumour in lymphoid tissue
- CLL is a disease that originates in and predominantly involves the bone marrow with spillover into the peripheral blood
Epidemiology
Hodgkin lymphoma demonstrates a bimodal age distribution: [Ref]
- First peak in young adults (20-30 y/o)
- Second peak in older adults (50-70 y/o)
Median age of onset is 33 y/o (it is the most frequent lymphoma in adolescents and young adults) [Ref]
Non-Hodgkin lymphoma is more common than Hodgkin lymphoma and in contrast: [Ref]
- Typically affects older adults
- Incidence rate increases steadily with age and peaks in >65 y/o
Aetiology
Key risk factors:
- EBV infection – the most important association (related to 25-40% of cases)
- Immunodeficiency (e.g. HIV infection, post-transplant immunosuppression)
- Autoimmune diseases (e.g. RA, SLE, Sjogren’s syndrome, sarcoidosis)
HIV infection increases the risk of both Hodgkin and non-Hodgkin lymphoma.
However, the association is strongest with high-grade non-Hodgkin lymphomas (esp. Burkitt lymphoma, diffuse large B-cell lymphoma and primary CNS lymphoma). It is also worth noting that high-grade non-Hodgkin lymphomas are AIDS-defining malignancies.
Classification and Subtypes
The WHO histological classification, with relevant high-yield information: [Ref]
| Classification | Subtype | Prevalence and prognosis | Pathology |
|---|---|---|---|
| Classical Hodgkin lymphoma (95%) | Nodular-sclerosing | Most common subtype
Good prognosis |
Presence of Reed-Sternberg cells |
| Mixed-cellularity | Good prognosis | ||
| Lymphocyte-rich | Best prognosis | ||
| Lymphocyte-depleted | Worse prognosis | ||
| Non-classical Hodgkin lymphoma (5%) | Nodular lymphocyte-predominant | Good prognosis | Presence of lymphocyte-predominant (LP) cells |
Reed-Sternberg cells vs LP (“popcorn”) cells:
| Feature | Reed-Sternberg cells | Lymphocyte-predominant cells |
|---|---|---|
| Nuclear morphology | Owl’s eye appearance (binuclear / multinucleate) | Popcorn appearance (multilobulated, folded nucleus) |
| Immunophenotype | CD30 +ve (100% cases), and CD15 +ve | CD 20 and 45 +ve |
| Background infiltrate | Mixed inflammatory background (eosinophils, plasma cells, histiocytes) | Predominantly small reactive lymphocytes |
Clinical Features
The clinical features of Hodgkin lymphoma are broadly similar across subtypes: [Ref]
| Nodal disease | Painless lymphadenopathy – classic feature
|
| Splenomegaly (typically only seen in advanced disease) | |
| Systemic B symptoms | B symptoms:
|
| Characteristic but rare features |
|
Extra-nodal involvement is uncommon in Hodgkin lymphoma, its presence is indicative of poor prognosis.
It is important to differentiate features suggestive of malignant lymphadenopathy (as seen in Hodgkin lymphoma) from reactive lymphadenopathy.
| Feature | Malignant lymphadenopathy | Reactive lymphadenopathy |
|---|---|---|
| Mobility | Immobile / fixed to surrounding tissue | Mobile |
| Consistency | Hard / firm / rubbery | Soft / rubbery |
| Tenderness | Non-tender | Tender |
In contrast, non-Hodgkin lymphoma has the following characteristic features:
- Symmetrical / generalised lymphadenopathy
- Non-contiguous spread
- Extra-nodal disease is common
This is at least true for exams (text-book), but less clean-cut in real practice.
Investigation and Diagnosis
Diagnostic Test
Definitive diagnosis of lymphoma requires a lymph node biopsy [Ref]
- Preferred: peripheral lymph node excisional biopsy
- Alternative: CT-guided biopsy on internal nodes (e.g. mediastinal nodes)
Be aware that fine needle aspiration is inadequate to diagnose lymphoma, as the lymph node architecture is lost and immunophenotyping may be incomplete.
If excisional tissue biopsy is not feasible, core biopsy is an alternative (but inferior to excisional biopsy).
Interpretation: [Ref]
- The presence of characteristic Reed-Sternberg cells, or lymphocyte-predominant (LP) cells is diagnostic
- Immunophenotyping supports classification rather than being the primary diagnostic tool
| Feature | Reed-Sternberg cells | Lymphocyte-predominant cells |
|---|---|---|
| Nuclear morphology | Owl’s eye appearance (binuclear / multinucleate) | Popcorn appearance (multilobulated, folded nucleus) |
| Immunophenotype | CD30 +ve (100% cases), and CD15 +ve | CD 20 and 45 +ve |
| Background infiltrate | Mixed inflammatory background (eosinophils, plasma cells, histiocytes) | Predominantly small reactive lymphocytes |
Remember, 95% cases of Hodgkin lymphoma are classical, that is, defined by the presence of Reed-Sternberg cells.
The remaining 5% of nodular lymphocyte predominant Hodgkin lymphoma (non-classical), is defined by the presence of lymphocyte-predominant cells.
Laboratory Tests
- FBC is typically normal in early stages
- Anaemia is common in advanced cases (typically anaemia of chronic disease)
- ↑ CRP and ESR
- ↑ LDH
In lymphoma, FBC is often normal apart from possible anaemia.
In contrast, CLL is characterised by a markedly elevated white cell count due to lymphocytosis.
Staging
Gold standard for staging: PET-CT (of the neck, chest and abdomen) [Ref]
Due to the high sensitivity of PET-CT for showing bone marrow involvement, bone marrow biopsy is NO longer indicated.
Anatomical staging (Ann Arbor / Lugano Classification): [Ref]
| Stage | Definition |
|---|---|
| I |
|
| II |
|
| III |
|
| IV |
|
As mentioned above, lymph node chains and the spleen are considered a nodal organ. Every other organ affected is classified as extranodal. [Ref]
The numerical stage is accompanied by specific letters and definitions: [Ref]
- A: absence of B symptoms
- B: presence of B symptoms
- E: extranodal contiguous extension (when the disease has spread directly from a lymph node into adjacent tissue)
- Bulky disease: single nodal mass of at least 10 cm, or mediastinal mass that exceeds 1/3 of the trans-thoracic diameter
Prognosis
Poor prognostic factors: [Ref]
| Disease subtype | Lymphocyte-depleted classical Hodgkin lymphoma (worse prognosis compared to all other subtypes) |
| Demographics | Older age (specifically >50 y/o) |
| Presence of significant comorbidities | |
| Symptoms | Presence of B symptoms (fever, night sweats, weight loss) |
| Laboratory markers | ↑ ESR or ↑ CRP |
| Anaemia | |
| Disease extent | Stage III / IV disease (involvement of both sides of the diaphragm or extranodal disease) |
| 3 or more nodal involvement | |
| Bulky disease (>10 cm) |
Management
Mainstay of treatment is chemotherapy [Ref]
- Gold standard regimen: ABVD (doxorubicin [adriamycin], bleomycin, vinblastine, dacarbazine)
- BEACOPP is an alternative intensive chemotherapy regimen for advanced stage disease
Site-specific radiotherapy maybe helpful, depending on the stage of disease and response to chemotherapy: [Ref]
- Typically used if there is +ve PET scan (evidence of disease) following initial chemotherapy
- If a patient has a -ve PET scan after initial chemotherapy, radiation may be omitted entirely to reduce long-term risks
- Radiotherapy is NOT very useful in advanced stage (III-IV)
The management of Hodgkin lymphoma is a major success of modern oncology, with cure rates now reaching 90%. [Ref]