Introduction
A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
A CT scan showing bulk disease.
A CT scan showing lung parenchyma involvement with Hodgkin disease.
Background
Hodgkin disease is a cancer of the lymph system (a lymphoma) that is characterized by the presence of large, abnormal Reed-Sternberg cells in a background of lymphocytes, macrophages, fibroblasts, and granulocytes. Dr Thomas Hodgkin first described Hodgkin disease in 1832.1,2,3,4
The lymphatic system is composed of lymph nodes, lymphatic channels, the spleen, bone marrow, and the thymus. Because the lymphatic system is located throughout the body, Hodgkin disease can start almost anywhere; however, in this article, only thoracic involvement is addressed.
In the thorax, Hodgkin disease most commonly involves the mediastinum. The nodular sclerosing histologic subtype of Hodgkin disease is the most common form found in the thorax, and it has a predilection for the anterior mediastinum (especially the thymus). The diagnosis of Hodgkin disease must be based on tissue biopsy results, because treatment strategies are based on the histologic type, the stage of disease, and the age and performance status of the patient. Imaging is essential for tumor staging, for assessing the response to treatment, for diagnosing relapses, and for evaluating treatment-related disorders.2,5,6,7,8,9,10
Related eMedicine topics:
Hodgkin Disease (Hematology)
Hodgkin Disease (Pediatrics)
Lymphomas, Endocrine, Mesenchymal, and Other Rare Tumors of the Mediastinum
Pathophysiology
The etiology of Hodgkin disease remains unknown. A strong association with the Epstein-Barr virus (EBV) exists; however, the presence of EBV is not specific for Hodgkin disease, and it can be found in other malignancies.11
Measures to prevent Hodgkin disease have not been established because no definite cause has been identified.
Frequency
United States
According to the American Cancer Society, an estimated 8220 new cases of Hodgkin disease will be diagnosed in the United States in 2008.12
Patients with Hodgkin disease usually have an increased incidence of Hodgkin disease in their family history; however, the genetic nature of Hodgkin disease has not been established, and an increased family history may be caused by exposure of family members to identical environmental hazards. The incidence is increased in patients who are immunocompromised (eg, patients with AIDS and organ - transplant recipients).
Mortality/Morbidity
The aim of treatment is to cure Hodgkin disease. More than 75% of newly diagnosed cases of Hodgkin disease can be cured with chemotherapy and/or radiation therapy. The prognosis depends on various factors, including the presence of systemic symptoms, the stage of the disease at presentation, the presence of large masses, and the treatment administered. Effective treatment has led to high survival rates (ie, 1-year survival rate, 92%; 5-year survival rate, 85%; 10-year survival rate, 80%; and 15-year survival rate, 74%).12,13,14
Sex
The male-to-female ratio is 1:1.5. In nodular sclerosing Hodgkin disease, females are affected twice as often as men; however, in patients with nodular sclerosing Hodgkin disease, thymic involvement is more common in men.6
Age
Hodgkin disease has a bimodal incidence, with peaks seen in adults aged 15-40 years and in adults older than 55 years.4
Anatomy
Knowledge of lymph node distribution and lymphatics in the thorax is important because mediastinal involvement of the lymph nodes is the most common manifestation of thoracic Hodgkin disease. A clear understanding of normal radiographic findings in chest radiography is pivotal to recognizing subtle enlargement of the lymph nodes.2,10
(Click Image to enlarge.) A schematic diagram showing the location of the mediastinal lymph nodes.
On chest radiographs of the left side, the normal aortopulmonary window is slightly concave, straight, or invisible. Any departure should be viewed with suspicion, and further investigations are needed. In the prevascular area, adenopathy is the most common cause for convexity of the aortopulmonary bay toward the left lung.
On chest radiographs of the right side, the azygos node lies variably in relation to the azygos vein as the vein passes forward above the right bronchus to enter the superior vena cava (SVC). This node is the lowest member of the group of right paratracheal lymph nodes. Any convexity in this region that has a greater part of its curvature above the right main bronchus probably should be regarded as abnormal. Low right prevascular nodal enlargement also can distort this region.
Subcarinal lymph nodes are difficult to recognize until they are large. They can cause displacement of the azygoesophageal pleural reflection. Paravertebral adenopathy can be diagnosed by distortion of the paravertebral pleural reflections, which produces convexity toward the lungs.
Pericardiac and diaphragmatic lymph nodes can fill the cardiophrenic angle on posteroanterior (PA) chest radiographs. On lateral views, these may lie retrosternally or at the level of the inferior vena cava or phrenic nerve. Smaller lymph nodes in these areas may simulate a pericardiac fat pad.
On PA chest radiographs, internal mammary lymph nodes can produce ill-defined increased opacity lateral to the sternum when sufficiently enlarged. On lateral views, these can appear as anterior extrapleural masses against the chest wall.
Presentation
- Patients most commonly present with enlarged, painless lymph nodes. Cervical lymph nodes are the most common.15
- Hodgkin disease can appear as an incidental finding on routine chest radiographs.
- An important feature of Hodgkin disease is its tendency to arise within lymph node areas and spread in an orderly fashion to contiguous lymph nodes.
- The constitutional signs and symptoms include the following:
- Fever
- Fatigue
- Decreased appetite
- Coughing and breathlessness
- Drenching night sweats
- Itching
- Weight loss
- Bone pain
- Pressure symptoms resulting from enlarged lymph nodes
- SVC syndrome
- Dysphagia
- Paraneoplastic syndromes
- Dermatologic manifestations
- Renal and metabolic manifestations
- Neurologic manifestations
Currently, Hodgkin disease is classified according to the World Health Organization/Revised European-American Lymphoma classification system. According to a number of characteristics, such as the appearance of cells, their genetic characteristics, chemistry, and clinical behavior, Hodgkin disease is classified into 2 types as follows:
- Classic Hodgkin lymphoma (95% of cases of Hodgkin disease), which is further subdivided into 3 subtypes:
- Nodular sclerosis Hodgkin lymphoma
- Mixed-cellularity Hodgkin lymphoma
- Lymphocyte-depletion Hodgkin lymphoma
- Nodular lymphocyte-predominant Hodgkin lymphoma (5% of cases of Hodgkin disease)
Hodgkin disease is staged according to the guidelines set out by the Ann Arbor, Michigan, conference of 1971. Some modifications were made to this classification at the Cotswolds, United Kingdom, meeting.16 Staging of Hodgkin disease is important for planning effective treatment, for follow-up monitoring, and for comparing trial treatment plans available in various centers.
Staging is as follows:
- Stage I - Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ (IE)
- Stage II - Involvement of 2 or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single extralymphatic organ or site and its regional lymph node or nodes, with or without involvement of the other lymph node region on the same side of the diaphragm (IIE)
- Stage III - Involvement of lymph node regions on both sides of the diaphragm (III) with or without localized involvement of an associated extralymphatic organ or site (IIIE), with or without involvement of the spleen (IIIS), or with or without involvement of both (IIIE+S)
- Stage IV - Disseminated/multifocal involvement of 1 or more extralymphatic organs, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distal nodal involvement
Bulk disease or massive mediastinal disease is defined as the ratio of the maximum transverse diameter of a mass to the internal transverse thoracic diameter being 0.33 or greater, as measured on chest radiographs at the T5-T6 vertebral disk level. Other authors have defined bulk disease as a lymph node mass measuring 10 cm or more in its greatest dimension.17
The presence of other symptoms (eg, fever, weight loss >10%, drenching night sweats) and bulk disease is associated with a worse prognosis for patients with clinical stage I or stage II Hodgkin disease.
Preferred Examination
A complete patient history should be elicited and a physical examination performed.
Procedures and laboratory studies
A lymph node biopsy is performed for pathologic analysis and classification.
Laboratory investigations are performed to assess the full blood count with erythrocyte sedimentation rate, liver function, biochemistry, and renal function biochemistry.
Radiologic examinations
Chest radiographs are obtained at presentation, during therapy, and for follow-up monitoring. Mediastinal lymph node enlargement can be detected in 60-75% of patients.
Computed tomography (CT) of the thorax, abdomen, and pelvis is performed for initial staging purposes. Compared with other methods, CT is more sensitive for detecting lymphadenopathy and extralymphatic involvement. CT scanning may be most useful for evaluating patients with lymphoma because it can depict the lymph nodes in the chest, abdomen, and pelvis.18,19
Magnetic resonance imaging (MRI) is performed in patients with suggested chest wall involvement because it offers better tissue contrast.
Ultrasonography and echocardiography are useful for detecting pericardial effusion and for directing lymph node biopsies and pleural interventions.20
Bone scanning is useful for evaluating bone involvement in Hodgkin disease. Gallium-67 scans obtained at baseline, during therapy, and in the posttreatment period can help in differentiating active Hodgkin disease from nonactive Hodgkin disease.15
Positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) is most useful for detecting disease relapse.21,22
Bilateral bone marrow aspirations and biopsies are performed to assess stage III or IV disease with associated symptoms (eg, fever, weight loss >10%, drenching night sweats).23
Other investigations are directed to a particular clinical problem. For example, a superior venacavogram is obtained if the patient has clinical findings of SVC syndrome. Immunoscintigraphy is used on an experimental basis only.
Limitations of Techniques
Radiography is available everywhere and is inexpensive; however, it is limited for evaluating soft - tissue involvement of the chest wall. Chest radiographs cannot be used to differentiate the various causes of lymph node enlargement.
CT scanning is limited in its availability, especially in developing countries. CT scans cannot be used to differentiate the various causes of lymph node enlargement or to determine whether tumor residue is active or inactive.24
MRI is limited in its availability because of its high cost. Also, some patients are claustrophobic and cannot tolerate the MRI examination.
Ultrasonography is limited in the thorax because air contained in the lungs is not a suitable window through which the ultrasound waves can travel.
Nuclear medicine is limited because of its availability in expert centers only. At present, PET imaging is limited in availability and the studies are expensive.
Differential Diagnoses
Other Problems to Be Considered
Leukemia
Pneumoconiosis
Histiocytosis X
Castleman disease
Agammaglobulinemia
Parasitic disorders
Connective tissue disorder
More on Hodgkin Disease, Thoracic |
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Further Reading
Keywords
Hodgkins disease, Hodgkin's disease, Hodgkin disease, Hodgkins, Hodgkin's, lymphoma, Hodgkin lymphoma, Hodgkin's lymphoma, Epstein-Barr virus
