Hodgkin lymphoma is a neoplastic transformation of lymphocytes particularly in the lymph node.
Hodgkin disease or Hodgkin’s lymphoma is one of two common types of cancers of the lymphatic system. ( specifically the white blood cells) The other type, non-Hodgkin’s lymphoma, is far more common.
Histologically, the picture is uniquely characterized by 1-2% of neoplastic cells (Reed-Sternberg [RS] cells) in a background of a variety of reactive mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils, and histiocytes.
These cells spread in an orderly, centripetal fashion to contiguous areas of lymph nodes.
Pathophysiology of Hodgkin Disease
The Reed-Sternberg cells represent a clonal proliferation of B-lymphocytes that derive from the germinal centers of lymph nodes.
They consistently express CD15 and CD30 antigens. CD30 is expressed in the majority of nodular sclerosis (NS) and mixed-cellularity subtypes of Hodgkin’s disease.
CD15 is a marker of late granulocytes, monocytes, and activated T cells. It can be induced by viral infections along with the interleukin 2 (IL-2) receptor (CD25).
CD19 and CD20, which are B-lymphocyte antigens, are uncommon in NS HD and mixed-cellularity Hodgkin disease (MCHD).
The up-regulation of bcl2 has been shown to be of prognostic significance, which correlates with EBV expression.
Hodgkin disease is more prevalent in males than in females. This is particularly evident in children, where 85% of the cases are in males.
Age-specific incidence rates have a bimodal distribution in both sexes, peaking in young adults (aged 15-34 y) and older individuals (>55 y).
Clinical presentation of Hodgkin Disease
Most of these patients present with asymptomatic lymphadenopathy may be present (above the diaphragm in 80% of patients).
The hallmark of the disease is enlarged painless, rubbery, nonerythematous, nontender lymph nodes.
Constitutional symptoms that may be associated are;
- Unexplained weight loss of more than 10 kg.
- Drenching night Sweats
- Large mediastinal mass or lung involvement
- Chest pain
- shortness of breath or difficulty in breathing
- Rarely, hemoptysis is observed.
Patients may present with pruritus
Alcohol-induced pain at sites of nodal disease is specific for Hodgkin’s disease.
These patients will present with intermittent fever-. Infrequently, the classic Pel-Ebstein fever (high fever for 1-2 wk followed by an afebrile period of 1-2 wk is observed.
Back or bone pain occurs rarely.
Physical Examination Findings:
- Palpable painless lymphadenopathy which is described as rubbery adenopathy. Cervical, supraclavicular, and axillary lymphadenopathy are the most common initial signs of disease.
- The involvement of the Waldeyer ring or occipital or epitrochlear areas is observed infrequently.
- Patients may have Splenomegaly and hepatomegaly.
- Superior vena cava syndrome resulting from massive mediastinal lymphadenopathy is observed rarely.
- Central nervous system (CNS) symptoms or signs may be due to paraneoplastic syndromes, including cerebellar degeneration, neuropathy, Guillain-Barré syndrome, or multifocal leukoencephalopathy.
Causes of Hodgkin Disease
Idiopathic but Ebstein Bar Virus (EBV) may be involved in the pathogenesis of this condition.
In as many as 50% of HD cases, the tumor cells are EBV-positive; EBV positivity is higher with MCHD (60-70%) versus NS HD (15-30%).
Almost 100% of HIV-associated HD cases are EBV-positive.
Patients with HIV infection have a higher incidence of Hodgkin disease compared to the population without HIV infection. but Hodgkin lymphoma is not an AIDS-defining neoplasm.
1. Full Blood Count for anemia, lymphopenia, neutrophilia, or eosinophilia should be performed.
This will indicate the anemia of chronic disease. However, it may be due to bone marrow involvement or the presence of an autoantibody (positive findings on a warm Coombs test).
Cytopenias are common in advanced disease.
Platelet counts can be increased or decreased.
2. Erythrocyte Sedimentation Rate may be elevated ESR and has been associated with a worse prognosis.
3. Lactate dehydrogenase (LDH) may be increased correlating with the bulk of disease.
4.U/E/C and Liver function tests. Alkaline phosphatase may be elevated which indicates bony metastasis,.
Chest X-Ray for mediastinal involvement should be done.
CT scans of the chest, abdomen, and pelvis.
Possible abnormal findings include enlarged lymph nodes, hepatomegaly and/or splenomegaly with or without focal parenchymal abnormalities, lung nodules or infiltrates, and pleural effusions.
A mediastinal mass, representing mediastinal lymphadenopathy may be noted.
A histological diagnosis always is required.
An excisional lymph node biopsy is recommended as the first step in the diagnosis.
With neck lymphadenopathy that may be due to a head and neck cancer, a fine-needle aspiration usually is advised as the initial diagnostic step, followed by an excisional biopsy if squamous cell histology is excluded.
Includes splenectomy, needle and wedge biopsy of the liver. Currently, this procedure is very rarely indicated.
3-Bilateral bone marrow biopsies
Bone marrow involvement is more common in elderly individuals, in patients with advanced-stage disease, in the presence of systemic symptoms, and in patients with histology indicating a poor prognosis
World Health Organization classification
The first four sub-types are referred to as classic Hodgkin disease.
1. Nodular sclerosis Hodgkin disease – 60-80%
This shows a nodular pattern. The broad bands of fibrosis divide the node into “nodules.” The capsule is thickened.
The characteristic cell is the lacunar-type RS cell.
It is more common in adolescents and young adults.
Usually involves the mediastinum and other supra-diaphragmatic sites.
2. Mixed-cellularity Hodgkin disease – 15-30%
RS cells are of the classic type (large, with bilobate, double or multiple nuclei, and a large eosinophilic inclusion like nucleolus).
It commonly affects the abdominal lymph nodes and spleen.
Patients with this histology typically have an advanced-stage disease with systemic symptoms and immunodeficiency.
3. Lymphocyte-depleted Hodgkin disease – Less than 1%
Diffuse and often appears hypocellular.
Large numbers of RS cells and bizarre sarcomatous variants are present.
It is associated with older age and HIV positivity. Patients usually present with advanced-stage disease. EBV proteins are expressed in many of these tumors.
Many cases of LDHD diagnosed in the past actually were non-Hodgkin lymphomas, often of the anaplastic large-cell type.
4. Lymphocyte-rich classic Hodgkin disease – 5%
In this type of HD, RS cells of the classic or lacunar type are observed, with a background infiltrate of lymphocytes.
It requires an immunohistochemical diagnosis. Some cases may have a nodular pattern. Clinically, the presentation and survival patterns are similar to those for MCHD.
5. Nodular lymphocyte-predominant Hodgkin disease- 5%
In contrast subtypes, the typical RS cells are rare.
Instead, a variant of RS cells, the lymphocytic and histiocytic cells (L&H), or popcorn cells (their nuclei resemble an exploded kernel of corn), are seen within a background of inflammatory cells, predominantly benign lymphocytes.
The L&H cells are positive for B-cell antigens, such as CD19 and CD20.
Has a distinct natural history characterized by a generally indolent clinical course, late relapses, and the subsequent development of aggressive non-Hodgkin lymphomas.
Patients are usually young males who present with the localized disease to the peripheral lymph nodes.
With localized disease may be treated with involved-field radiotherapy alone.
The above features, reminiscent of low-grade non-Hodgkin lymphoma, have led to the separate classification of this entity
The Ann Arbor classification (1971) is used most commonly.
Clinical staging involves the assessment of disease extent by clinical examination and imaging techniques.
When staging laparotomies are used as part of staging, the disease extent is designated pathologic staging.
Stage I denotes a single lymph node area or single extranodal site.
Stage II denotes 2 or more lymph node areas on the same side of the diaphragm. (above or below)
Stage III denotes lymph node areas on both sides of the diaphragm or involvement of any extra lymphatic organ contiguous to the primary nodal site
Stage IV denotes disseminated or multiple involvements of extranodal organs such as bone marrow or liver
For staging classifications, the spleen is considered a lymph node area.
Each stage can be designated as stage A or B.
A or B designations denote the presence or absence of B symptoms.
B designation includes the presence of 1 or more of the following:
(1) fever (temperature >38°C)
(2) drenching night sweats
(3) unexplained loss of more than 10% of body weight within the preceding 6 months.
A designation is the absence of the above
Treatment of Hodgkin Disease
Hodgkin’s lymphoma or disease treatments depend on the type and stage of the disease, the patient’s overall health, and preferences.
Treatment is entirely based on the stage of the disease. Stage IA and IIA are managed predominantly with radiation. In the early stages (IA, IIA), adjunct chemotherapy may be used with radiation. Patients with “B” symptoms as well as stage III or stage IV disease are managed with chemotherapy.
Several combinations of chemotherapy drugs are used to treat Hodgkin’s lymphoma.
ABVD is the most common regimen used over others because ABVD has fewer adverse effects such as permanent sterility, secondary cancer formation, leukemia, aplastic anemia, and peripheral neuropathy
- Adriamycin® (doxorubicin)
- Dacarbazine (DTIC)
Other common regimens include:
- Etoposide (VP-16)
- Adriamycin (doxorubicin)
- Cyclophosphamide (Cytoxan®)
- Oncovin® (vincristine)
- Doxorubicin (Adriamycin)
- Mechlorethamine (nitrogen mustard)
Radiation is given after chemo in the Stanford V regimen. It’s sometimes given after the ABVD or BEACOPP regimens, too.
Chemo is given in cycles that include a period of treatment followed by a rest period to give the body time to recover. Each cycle lasts for several weeks.
For classical Hodgkin’s lymphoma, radiation therapy is often used after chemotherapy. patients with early-stage nodular lymphocyte-predominant Hodgkin’s lymphoma may undergo radiation therapy alone.
For classical Hodgkin lymphoma, radiation is often given after chemotherapy, especially when there’s a large or bulky tumor mass.
Radiation therapy can also be used by itself to treat some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NHLPL).
Involved-site radiation therapy (ISRT). Here the radiation is aimed only at the lymph nodes that originally contained lymphoma, as well as any nearby areas cancer extended into.
Involved field radiation therapy (IFRT). Only the lymph node regions that have HL are treated, but this includes larger treatment areas than ISRT does.
Extended field radiation
Total body irradiation
Bone marrow transplant
Bone marrow transplant, also known as stem cell transplant, is a treatment to replace diseased bone marrow with healthy stem cells that help grow new bone marrow. A bone marrow transplant may be an option if Hodgkin’s lymphoma returns despite treatment.
During a bone marrow transplant, blood stem cells are removed, frozen and stored for later use. Next, the patient receives high-dose chemotherapy and radiation therapy to destroy cancerous cells. Finally, the stem cells are thawed and injected into the body through your veins. The stem cells help build healthy bone marrow.
Spread in HD takes place via the lymphatics, hematogenous routes, and direct extension.