Table of Contents
Definition of Hodgkin’s Disease
What is Hodgkin’s disease?
The Hodgkin’s lymphoma is named after its describer Thomas Hodgkin (first description in 1832) and is a malignant disease of the lymphatic system. The malignant neoplasms of the lymphatic system are divided into Hodgkin’s lymphoma with histologically detectable Hodgkin and Reed-Sternberg cells and the non-Hodgkin’s lymphomas.
It is about a monoclonal B-cell lymphoma with formation in the lymph nodes. In advanced stages it results in a haematological scattering from the lymph nodes with resettlement in the bone marrow and extra lymphatic tissues such as the liver.
Epidemiology of Hodgkin’s Disease
Spread of the Hodgkin’s disease
Hodgkin’s lymphomas account for about 30 % of all lymphomas. The incidence is about 2 – 4/100,000. The age of manifestation is bimodal, with a peak incidence around the 30th and at the 60th year of age. The ratio of male to female patients is 3:2. In the industrialized nations, a slight decline in incidence rate is observed.
Even children can fall sick with Hodgkin’s disease. The peak age is around 12 years of age. The gender distribution corresponds to it in adulthood.
Etiology of Hodgkin’s Disease
Causes of Hodgkin’s disease
Till date, the etiology of Hodgkin’s disease is not fully clarified. It stands to reason that oncogenic viruses such as the Epstein-Barr virus are the triggers, since EBV DNA in the Hodgkin and Reed-Sternberg cells is found in about half of the patients. In developing countries, EBV DNA can even be detected in 90 % of the Hodgkin’s lymphomas.
The risk of suffering from a Hodgkin’s lymphoma is increased by 3 times after an undergone infectious mononucleosis (glandular fever). In addition, even mutations in oncogenes and tumour suppressor genes, which inhibit apoptosis, can be detected. Patients with impaired immune defences have an increased risk, for example, under immunosuppressive therapy after transplantation, but also in HIV infection.
Signs and Symptoms of Hodgkin’s Disease
Signs of Hodgkin’s disease
Clinically the disease manifests itself mostly with lymph node swelling. 60 % of these lymphadenopathy are unilaterally cervical. Other localisations include the axilla, the inguinal area, the mediastinum and the abdomen, whereby the lymph node involvement progresses centripetally. The swollen lymph nodes are usually indolent and of solid, rubbery consistency. In 60 % of the cases, the mediastinal nodes are already initially affected.
Symptoms of Hodgkin’s disease
- Very often, the patients also exhibit B symptoms, i.e. fever, night sweats and weight loss of more than 10 % of the body weight in 6 months.
- Typical but not very often is the so-called Pel-Ebstein fever. It is characterized by an undulant fever pattern with a period of a few days to weeks and a subsequent fever break.
- The alcohol pain is also rather rare. Thereby, it is about the pain in the affected lymph nodes immediately after alcohol consumption, which is pathognomonic for the Hodgkin’s lymphoma.
- Even agonizing itching occurs as a paraneoplastic symptom. Other paraneoplastic syndromes are ichthyosis and pemphigus.
- The Ophelia syndrome is indeed rare, but particularly impressive due to the combination of hippocampal sclerosis and dementia.
- In disseminated systemic disease, a hepatosplenomegaly is often found and other non-lymphoid organs, such as the lungs, skin and gastrointestinal tract that are infected, can cause corresponding symptoms.
Diagnosis of Hodgkin’s Disease
Histological investigation in Hodgkin’s disease
The confirmation of diagnosis is carried out by the histological lymph nodes investigation. It is always important to extirpate an entire lymph node, since a lymph node puncture does not provide enough material.
The histologic evidence of mononuclear Hodgkin and polynuclear Sternberg Reed cells is groundbreaking. The Sternberg Reed cells (also Hodgkin Reed-Sternberg cells) are giant cells with a diameter greater than 20 μm and prominent eosinophilic nucleoli and vesicular chromatin structure. They express in their classical form CD25 (IL-2 receptor), CD30 and CD20. However, they account for only about 1 % of lymphoma. They are surrounded by a reactive inflammatory infiltrate of lymphocytes, monocytes, eosinophilic granulocytes and fibroblasts.
Staging in Hodgkin’s disease
The computed tomographic investigation of the neck, thorax, abdomen and pelvis is done for staging. Nowadays, the PET-CT is also used often.
A bone marrow puncture to rule out bone infiltration is also obligatory.
The classification into a clinical stage is based on the Ann Arbor staging, in which the number and the localization of the affected lymph nodes stations, the presence of extranodal foci, the diffuse involvement of extra-lymphatic organs and the presence of B-symptoms are undertaken.
|Stage I||Infestation of a single lymph node region of a single localized extranodal foci|
|Stage II||Infestation of two or more lymph node regions on one side of the diaphragm or localized extranodal foci and infestation of one or more lymph node regions on one side of the diaphragm|
|Stage III||Infestation of two or more lymph node regions on both sides of the diaphragm or localized extranodal foci on both sides of the diaphragm|
|Stage IV||Widespread (disseminated) infection of one or more extralymphatic organs or without lymph node involvement|
In children and adolescents, the infection of the bone with the destruction of the substance or an infestation of the bone marrow is always considered as stage IV, regardless of the affected lymph node stations.
A: without B symptoms
B: with B symptoms
E: extranodal involvement
S: splenic infestation
X-larger tumour mass (bulk or bulky disease: tumour >10 cm maximum diameter)
[Reference: Hodgkin’s Lymphoma via Wikipedia]
Other typical examination findings are a relative lymphopenia and eosinophilia in differential blood count. In case of bone marrow involvement with resulting bone marrow failure, a peripheral pancytopenia can be present. The CRP and LDH are often increased. An increase in transaminases also points to a liver involvement. The erythrocyte sedimentation rate is an activity sign of the process and is increased by the increase in the a2-globulins as well as by the increase of gamma globulins.
Classification of Hodgkin’s Disease
The Hodgkin’s lymphomas can be divided into 2 main groups according to morphological, cytochemical and immunological criteria defined by the WHO classification.
Classic Hodgkin lymphoma
The classic Hodgkin’s lymphoma accounts for 95 %. It is divided into 4 subtypes:
- Lymphocytes rich classic Hodgkin’s lymphoma 4 %: Lymphohistiocytic (B lymphocytes) image with involvement of cervical or axillary lymph nodes. Clustered in male patients at the age of 30.
- Nodular sclerosing form 60 – 80 %: nodular infiltrates and collagen scar. In addition, the typical binucleate so called lacunar cells, which are a subspecies of the HRS cells. This form especially affects young female patients with mediastinal and supraclavicular infestation.
- Mixed type 15 – 30 %: This form is common in patients in the second peak incidence. Men are affected more often than women in this form. The infestation is typically cervical or abdominal.
- Lymphocyte-poor type 1 – 2 %: Anaplastic large cell with mitosis and few lymphocytes. This rare form for patients at an advanced age with manifestation of lymphoma in the abdomen is typical
Nodular lymphocyte-predominant Hodgkin lymphoma
In 5 % it is about the nodular lymphocyte predominant Hodgkin lymphoma (nodular paragranuloma), which is CD30 and C15-negative in contrast to the classical Hodgkin lymphoma, but CD20-positive (B-cell markers). The popcorn cells are a speciality, a variation of the Reed-Sternberg cells.
Treatments of Hodgkin’s Disease
Three prognostic and therapeutic groups in Hodgkin’s disease patients
The patients are divided into three prognostic and therapeutic groups prior to the treatment using the following criteria, namely early, intermediate and advanced stage:
- Large mediastinal tumour, so-called bulk (> 1/3 of the thorax diameter)
- Extranodal involvement
- Erythrocyte sedimentation speed value highly increased
- Three or more lymph nodes stations infested
Chemotherapy in Hodgkin’s disease
Early and intermediate stages receive a combined radiochemotherapy. Advanced stages are treated with intensified chemotherapy without radiotherapy.
In Europe, the combination of bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisolone and supportive G-CSF (BEACOPP) or the ABVD protocol from adriamycin, bleomycin, vinblastine and dacarbazine is preferable for chemotherapy. The duration of treatment comprises of 4-8 months.
Since 2012, an antibody-drug conjugate with the substance brentuximab vedotin is available for the treatment of CD30 + Hodgkin’s lymphoma. It is intended for the treatment of patients after autologous stem cell transplantation, or after two previous therapies without remission or with relapse.
Prognosis of Hodgkin’s Disease
Hodgkin’s disease has a good chance of recovery
In all three stages a complete remission can be reached in about 90 % and over 80 % of the patients can be cured in the long term. Negative prognostic factors are over 60 years of age, relapse disease within three months after completion of the initial treatment, B symptoms, incomplete remission and progress under ongoing therapy.
Follow-up and Aftercare
Essential measures to ensure the reproductive ability of the patient must be taken prior to therapy e.g. cryopreservation of the sperm, since the cytotoxic drugs, particularly the used procarbazine, have a toxic effect on the sperm formation.
Restaging in Hodgkin’s disease
In order to check the success of the therapy, a new diagnosis called restaging takes place at regular intervals. During restaging, the same investigation procedure as in the staging is used as part of the initial diagnosis. Classically, the restaging takes place after two, four or six chemotherapy cycles and before and after radiotherapy.
After the end of treatment, the follow-up takes place in the first year every 3 months, from the second year onwards, in 6-month intervals and yearly from the fifth year onwards. The follow-up thereby consists essentially of the sonography of the formerly infested area and blood count checks. Radiographs of the thorax and CT examinations are carried out to minimize the radiation exposure at larger distances.
Hypothyroidism can develop after the thoracic irradiation. Moreover, there is the risk of heart damage. Therefore, regular checks of thyroid values and echocardiography should be performed.
Depending on the radiation field, the risk of a second malignancy for example of breast carcinoma, thyroid cancer or AML, also exists. The incidence rate of second neoplasms lies at 15 – 20 % in 20 years. In order to minimize this risk, it is important to reduce the exposure to what is absolutely necessary, especially in young patients, whilst the size of the radiation field is reduced.
The solutions are located below the sources.
1. Which cells are not typically be found in Hodgkin’s lymphoma?
- Sternberg-Reed cells
- Eosinophilic granulocytes
- Owl‘s eye cells
- Hodgkin cells
2. Which subtype is the most common of the classical Hodgkin’s lymphoma?
- Lymphocyte rich form
- Nodular sclerosing form
- Mixed type
- Low lymphocytes type
- Nodular Paragranuloma
3. A 36-year-old, clearly obese man presents himself with a swelling in area of the right neck, in your general medicinal practice. He cannot say, since when the swelling exists, since it was first noticed by his sister, whom he had seen again a week ago after a long time. He indicates to have sweated heavily in the recent weeks, even at night, which he had however pushed on his weight. You arrange to have a lymphonodectomy with histological and immunohistochemical diagnosis, where the Hodgkin’s lymphoma diagnosis is made. What further diagnostic measure is not a part of the standard of the staging or the diagnosis confirmation in case of Hodgkin’s disease?
- CT abdomen
- Bone marrow puncture
- CT thorax
- MRI skull
- Large blood count