eMedicine Specialties > Radiology > Chest

Hodgkin Disease, Thoracic: Imaging

Author: Narainder Gupta, MBBS, MSc, FRCR, MD, Assistant Professor of Cardiothoracic Radiology, Division Director, Division of Cardiothoracic Radiology, Thomas Jefferson University Hospital
Coauthor(s): Jamshed B Bomanji, MBBS, MSc, PhD, Consulting Staff, Institute of Nuclear Medicine, Middlesex Hospital; Nuclear Medicine Consultant, University College Hospital
Contributor Information and Disclosures

Updated: Jan 21, 2009

Radiography

Findings

Hodgkin disease commonly appears as intrathoracic disease. PA and lateral chest radiographs are essential for clinical staging. Mediastinal adenopathy is the most common presentation, and direct extension of the disease can be detected on chest radiographs. Chest images also allow for the evaluation of complications related to chemotherapy and radiation therapy. In follow-up studies for recurrent disease, chest radiography is the primary imaging modality (along with history taking, physical examination, and laboratory investigations).¹⁰

• Of patients with Hodgkin disease, 67-74% have abnormal radiographic findings at presentation.
• Of patients with abnormal radiographic findings on chest images, 90% have bilateral asymmetric nodal disease.
• In Hodgkin disease, disease spreads contiguously along lymph node chains. Prevascular and paratracheal lymph nodes are most commonly affected.
• A single lymph node group is involved in only 15% of patients.
• Rarely, the posterior mediastinal or paracardiac lymph nodes are involved.
• The internal mammary chain of lymph nodes can be enlarged, but not without involvement of other lymph nodes.
• Chest radiographs can demonstrate either a single group with lymph node enlargement or a lobulated appearance resulting from multinodal involvement.
• Calcification is very rarely seen in untreated lymphoma.²⁵
• Direct invasion of the lungs can occur in 15-40% of patients and is nearly always associated with hilar adenopathy.²⁶
• Primary pulmonary involvement without hilar, mediastinal, or extrathoracic involvement is unusual; however, recurrent Hodgkin disease may appear in the absence of adenopathy (especially in nodular sclerosing Hodgkin disease).
• Lung involvement can produce either ill-defined or well-defined nodules, which can be unilateral or bilateral. These nodules may cavitate.
• Lung involvement can also appear as consolidation.
• Other findings in Hodgkin disease that can be detected on radiographs of the chest include pleural effusions and skeletal lesions.¹⁵
• In Hodgkin disease, two thirds of bone lesions are of the mixed lytic and sclerotic variety,  10-15% are sclerotic alone, and a small percentage are lytic alone. Sclerotic lesions tend to be confined to the vertebrae, demonstrating the typical appearance of ivory vertebrae.
• Anterior scalloping of vertebrae can be detected on lateral chest radiographs, especially in the lower thoracic region.
• With chest radiographs, Hodgkin disease can be quantified by calculating the mediastinal mass ratio (the ratio of the maximum width of the mediastinum to the maximum transverse thoracic diameter at the level of the diaphragm), by finding a mediastinal mass larger than one third of the transverse thoracic diameter at the T4-T5 level, or by determining an absolute transverse mediastinal diameter of 10 cm.¹⁷
• In follow-up imaging of mediastinal bulk disease, 60% of chest radiographs demonstrate findings of residual adenopathy after treatment. This residual adenopathy may not contain active disease and may represent only residual scarring, but these can be seen at long-term follow-up.

Degree of Confidence

Most of the time, sufficiently enlarged lymph nodes in the thorax can be detected on chest radiographs, but subtle enlargement can be missed; therefore, further imaging with CT is warranted.

False Positives/Negatives

A confluence of pulmonary veins, especially on the right side, can be mistaken for subcarinal lymphadenopathy. Small pericardiac or diaphragmatic lymph nodes can mimic a fat pad. An enlarged azygos vein can mimic azygous adenopathy. When in doubt, repeat chest radiographs and use the Valsalva maneuver. All of these false-positive findings on chest radiography can be easily identified by performing CT.

Subtle enlargement of intrathoracic lymph nodes can be missed on chest radiographs, and its detection greatly depends on the observer's experience, as well as the type of radiograph performed.

Computed Tomography

Findings

In conjunction with chest radiographs, CT is the modality of choice for initial staging and follow-up monitoring of Hodgkin disease. Contrast-enhanced CT scanning of the thorax, abdomen, and pelvis isperformed in all patients. Any suggestion of lymph node enlargement, as demonstrated on chest radiographs, is usually confirmed with CT scanning.^27,28,19

• Involvement of the lungs and pericardium can be occasionally detected on CT scans; these exclude treatment by radiation therapy.
• CT size criteria for lymph node involvement in the mediastinum are well defined. According to the criteria, subcarinal, paracardiac, and retrocrural lymph nodes are considered enlarged if they are larger than 12, 8, and 6 mm in their short-axis diameter, respectively. The remaining lymph nodes in the body are considered enlarged if they are larger than 10 cm in their short-axis diameter.^17,29,30,31
• On CT, lymph node enlargement can be seen as multiple, rounded soft-tissue masses or bulky soft-tissue masses caused by nodal aggregation. Usually, a homogeneous soft-tissue mass is noted; it may be heterogeneous when it is large, with areas of low attenuation representing necrosis, hemorrhage, or cyst formation.³²
• In rare cases, calcification can be seen in the lymph nodes on pretreatment scans.
• A discrete or infiltrating thymic mass can be seen.
• Associated findings that can be detected on CT scans include mediastinal displacement, compression, and invasion of the vascular structures,  pericardium, heart, pleura, lungs, and chest wall.

Degree of Confidence

CT scans can help differentiate the various causes of mediastinal or hilar enlargement seen on chest radiographs in most patients; however, CT is limited in detecting chest wall invasion (in which case, MRI is the modality of choice). CT is limited in the use of size criteria for lymph node involvement because nodes larger than those defined by the criteria can be reactive without tumor involvement. Also, lymph nodes smaller than those defined by the size criteria can harbor Hodgkin disease. Residual masses can persist during and after treatment without any viable tumor being present.^27,18

False Positives/Negatives

CT scans cannot help in differentiating between fibrosis and viable tumor. MRI, gallium scanning, or PET scanning can be used to identify residual tumor and predict the patient’s response to therapy.^{33,34,35,36,37}

Magnetic Resonance Imaging

Findings

MRI is not the primary modality for evaluating Hodgkin disease, but it can be used in problem solving. Multiplanar capability, high tissue contrast, flow sensitivity, and the use of gadolinium-based contrast agents all make MRI an ideal tool for problem solving. Its soft-tissue contrast and multiplanar capability also make it useful for assessing chest wall invasion, pericardial involvement, pleural involvement, and brachial plexus involvement.⁴

• In thoracic lymphomas, MRI is used to image suggestive spinal cord compression, involvement of the spinal cord and the meninges, involvement of the musculoskeletal system in the chest, cardiac involvement, and involvement of the brachial plexus.
• MRI is also helpful in posttreatment evaluation to differentiate between fibrosis and tumor.²⁴
• On MRI, lymph node involvement is defined by size criteria similar to those of CT.
• MRI is helpful for planning radiation therapy fields because of its multiplanar capabilities.³³
• On T1-weighted images, tumor involvement can be seen as relatively homogeneous masses with low signal intensity (similar to that of muscle).
• On T2-weighted images, high signal intensity equal to or slightly greater than that of fat can result from tumoral edema, inflammation, immature fibrosis, or granulomatous tissue.
• Follow-up T2-weighted images can show signal intensity increased from the baseline. This finding is correlated with disease recurrence.
• Low signal intensity on post-therapeutic T2-weighted images rules out the possibility of relapse in most patients.
• Increased signal intensity on T2-weighted images obtained within 6 months of therapy is nonspecific; however, after 6 months, this finding suggests recurrent disease.³⁷
• Overall, the accuracy of MRI for predicting disease recurrence is similar to that of gallium scintigraphy.³⁵
• An enlarging or new mass may represent recurrent disease, a post-therapeutic thymic cyst, or thymic hyperplasia.⁵
• Dense fibrosis may demonstrate low signal intensity on T2-weighted images.
• MRI also has a role in identifying areas of bone marrow abnormality for targeting bone marrow biopsies; however, MRI is not a replacement for bone marrow biopsy in pathologic staging.³⁸

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. 

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

As with the criteria used in CT, a lymph node larger than 10 cm can be reactive without tumor involvement. Lymph nodes smaller than those that fall within the size criteria can also harbor disease.¹⁷

MRI is more sensitive for detecting bone marrow involvement associated with lymphoma.³⁸

False Positives/Negatives

False-positive findings can result from residual lymph node masses that may not harbor any disease. To evaluate this possibility further, gallium scanning and PET scanning can help.

Radiation-induced inflammatory changes can result in increased signal intensity on T2-weighted images. These changes can mimic active disease.

Ultrasonography

Findings

Ultrasonography can help in performing mediastinal biopsies, but it is primarily used for the evaluation and biopsy of lesions involving the chest wall. Rubens et al used prebiopsy CT to identify the window for real-time ultrasonographic biopsy. Echocardiography is useful for the detection of clinically undetectable pericardial disease.^{39,20,40,41,4}

Degree of Confidence

Ultrasonography cannot help in differentiating the causes of pericardial effusion (eg, malignant, radiation-induced, drug-induced, or idiopathic effusion).

Nuclear Imaging

Findings

Gallium-67 citrate scintigraphy (gallium scanning)

Gallium-67 citrate scintigraphy (GS) has been shown to provide important diagnostic and prognostic information in patients with lymphoma. In Hodgkin disease, GS provides additional information in conjunction with CT for planning radiation therapy. GS is helpful for distinguishing residual disease from posttreatment fibrosis in bulky mediastinal Hodgkin disease.^35,42,43,44

Posttreatment⁶⁷ Ga uptake is a poor prognostic factor in Hodgkin disease and non–Hodgkin lymphoma, and it is an accurate predictor of both the patient’s response to therapy and the overall outcome. In patients with aggressive lesions, advanced - stage tumors, or difficult-to-treat cases, sequential gallium scintigraphy can be performed before, during, or after therapy. These studies help in understanding the gallium avidity of the tumor, the response of tumor to therapy, and the timing of the therapeutic response.^{35,36,42,43,44,45}

Gallium uptake in tumor cells is mediated by transferrin receptors, and binding to cell-surface transferrin receptors allows this complex to be taken by actively growing tumor cells. Radiation therapy results in transient or permanent loss of⁶⁷ Ga uptake, although recurrent Hodgkin disease is invariably associated with the return of increased uptake.^43,44,45,46

In Hodgkin disease, the sensitivity of GS is 85-97% and the specificity is 90-100%. Use of high-dose GS and single-photon emission computed tomography (SPECT) techniques has increased the sensitivity of GS, especially for evaluating the mediastinum and abdomen.^45,47

FDG PET evaluation

Uptake of FDG is increased in malignant cells compared with normal tissues because of a patient’s altered metabolism during malignancy (in which glycolysis becomes the major metabolic pathway). Several studies have suggested that FDG scintigraphy is as good as CT for staging lymphomas. Moog et al showed that FDG PET is superior to CT in staging nodal lymphoma.⁴⁸ Bangerter et al found that for detecting hilar and mediastinal sites of disease before treatment, the sensitivity of FDG PET is 98% and the specificity is 90%, while the positive predictive value is 92% and the negative predictive value is 97%.^{22,34,36,49,50,51}

FDG PET studies may cause upstaging of the disease because of bone marrow involvement. These studies can be used to guide targeted MRI scans and bone marrow biopsies. FDG PET can also help in characterizing residual masses after therapy, when morphologic imaging modalities are of limited value. PET can be used in the detection of relapse, and Bangerter et al found a sensitivity of 86% and a specificity of 96% for the detection of recurrent disease in mediastinal and hilar nodes in patients with lymphoma.^{22,34,36,48,49,50,51}

Degree of Confidence

For GS, a posttreatment FDG PET scan with negative findings has a negative predictive value of 100%, but positive scans have a positive predictive value of only 61%.

False Positives/Negatives

Gallium uptake is nonspecific, and uptake can be seen in various tumors, inflammation, and infection; however, in a known setting of Hodgkin disease, any abnormal uptake should be viewed as active disease, residual disease, or recurrence.

Angiography

Findings

Angiography does not have much of a role in the diagnosis and management of Hodgkin disease, but superior venacavography is performed in patients believed to have SVC syndrome.

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