Mediastinal Germ Cell Tumor Imaging
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Germ cell tumors occur most frequently in the gonad, but in rare cases, they occur in extragonadal locations, usually in or near the midline. A variety of extragonadal germ cell tumors are known. The mediastinum is the most common extragonadal location. In adults, approximately 10-15% of mediastinal tumors are germ cell tumors; in children, 25% of mediastinal tumors are germ cell tumors. Germ cell tumors derive from germ cell rest remnants in the mediastinum. Images of mediastinal masses are depicted below.
Germ cell tumors may be benign or malignant. Benign varieties include benign teratoma and teratodermoids. Malignant tumors include seminomas and nonseminomatous tumors (malignant teratomas). Nonseminomatous tumors are further classified as teratocarcinomas, choriocarcinomas, embryonal carcinomas, and endodermal sinus or yolk-sac tumors. About 80% of mediastinal germ cell tumors are benign; these occur with equal frequency in males and females. Malignant tumors are predominant in men; the male-to-female ratio is 9:1. Benign germ cell tumors are termed teratomas or dermoids if they are primarily solid. Some tumors are predominantly cystic; these are referred to as epidermoid or dermoid cysts. Most patients are men 20-40 years of age.
About one third of patients are asymptomatic. Symptoms, when present, are related to the size of the lesion. Human chorionic gonadotropin (HCG) levels are elevated in 7-18% of patients, but alpha-fetoprotein (AFP) levels are usually normal. Metastatic spread involves the regional lymph nodes, lungs, and bone. The neoplasm is highly chemosensitive and radiosensitive, and 5-year survival rates greater than 75% are not uncommon.
Malignant germ cell tumors are subdivided into seminomas and malignant teratomas (nonseminomatous tumors). Seminoma is the second most common mediastinal germ cell tumor. The imaging features of seminomas are usually those of a large, well-marginated, homogeneous, anterior mediastinal mass with soft-tissue opacity or attenuation that shows minimal contrast enhancement. Calcification is exceptional. Embryonal carcinoma, endodermal sinus tumor, choriocarcinoma, and combinations of these histologic types constitute nonseminomatous germ cell tumors. These lesions occur almost exclusively in men.
A combination of radiotherapy and chemotherapy is the treatment of choice; 5-year survival is about 50%. These patients are at risk for concurrent hematologic malignancy that is unrelated to chemotherapy. Imaging features include a large, anterior mediastinal mass that may contain large areas of hemorrhage and necrosis. The surrounding fat planes are typically obliterated. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
Computed tomography (CT) scanning is the imaging modality of choice in the evaluation of mediastinal lesions. CT scanning is an excellent modality for determining the exact location of the mediastinal tumor, as well as its relationship to adjacent structures. It also is useful in differentiating masses that originate in the mediastinum from those that encroach upon the mediastinum from the lung or other structures. CT scans may help in differentiating various tissue attenuations, and they are highly accurate in differentiating fluid, fat, calcification, and cysts from solid tumors. CT may be used to assess the degree of vascularity of mediastinal tumors. [11, 12, 13, 14]
Conventional radiographs still have a major role in the initial diagnosis of a mediastinal mass.
Ultrasonography is advancing, particularly in the pediatric age group, and it is highly sensitive in differentiating cystic from solid mediastinal masses. [15]
Echocardiography is an invaluable tool for differentiating tumors arising from the pericardium and/or myocardium from other tumors.
Radionuclide imaging may provide a near–tissue-specific diagnosis for functioning endocrine tumors, such as mediastinal carcinoid, aberrant thyroid and/or parathyroid tissue, and pheochromocytomas.
Angiography is occasionally needed to evaluate anterior mediastinal vascular malformations and/or aneurysms and to differentiate these from other mediastinal tumors. [16, 17, 18, 11]
CT scanning can be invasive, and sedation or general anesthesia may be required in young patients. In addition, CT delivers a radiation dose to the patient. Patients may be allergic to iodinated contrast medium, which should be used with caution in patients with renal failure.
The appearances of an anterior mediastinal mass on chest radiographs are nonspecific, and the differential diagnosis is wide. Differentiation between benign lesions and malignant lesions may not be possible. Subtle calcification and bone erosions may be missed on radiographs. Underlying masses with pleural and pericardial effusions may not be detected. Fat may be obscured by tumoral hemorrhage or rupture, and a false diagnosis of a malignant lesion may be made.
The vascularity of mediastinal tumors cannot be assessed on conventional radiographs. A standard posteroanterior (PA) chest radiograph may be difficult to obtain in ill patients, and in young children, anterior mediastinal masses may be obscured on anteroposterior (AP) radiographs with mediastinal magnification.
Ultrasonography is operator dependent, and access to the anterior mediastinum may be difficult because of the thoracic bony cage and lungs.
Angiography is invasive and poses a minor morbidity risk.
Although radionuclide scanning is more tissue specific than other imaging modalities, false-positive results are possible, and uptake may occur in a variety of normal, inflammatory, and neoplastic tissues.
Standard chest radiography is usually the first imaging procedure performed in an individual with symptoms referable to the thorax (see the images below).
Most asymptomatic anterior mediastinal masses, particularly benign masses, are discovered incidentally on PA and lateral chest radiographs. The radiographs are often obtained for reasons unrelated to the germ cell tumor. The lateral chest radiograph is valuable in localizing the mass to the appropriate mediastinal compartment; it provides a clue as to what may be the pathology, and it limits the number of disorders in the differential diagnosis. This information, combined with the patient’s age, sex, and associated clinical findings, aids the radiologist in the appropriate choice of further diagnostic techniques.
On chest radiographs, benign tumors appear as well-circumscribed, anterior mediastinal masses. Calcification can be seen in up to 26% of cases. Malignant lesions are less well defined than benign ones; they have fuzzy margins, and they may obliterate fat planes between the great vessels and the pericardium. The sternum may be eroded, and associated lung and bone lesions and mediastinal lymphadenopathy may be depicted. Calcification occurs in less than 1% of malignant anterior mediastinal masses.
Despite major advances in cross-sectional imaging, the conventional chest radiograph retains a major role in the initial diagnosis of mediastinal masses. It guides the clinician in what to ask next in the investigation of the patient with a mediastinal mass. The radiograph may be reassuring when a well-defined, asymptomatic anterior mediastinal mass with calcification is detected.
Standard chest radiography is universally available, noninvasive, and inexpensive; it also imparts a low dose of radiation, and the images are easy to interpret.
As with any other anatomic imaging study, the appearances of an anterior mediastinal mass are nonspecific, with a wide differential diagnosis (see the images below). Differentiation between benign and malignant lesions may not be possible. CT is superior at depicting calcification and obliteration of fat planes, mediastinal lymphadenopathy, and bone erosions. Most patients with anterior mediastinal masses are further evaluated with cross-sectional imaging.
Benign anterior mediastinal masses are typically depicted on CT scans as well-marginated, lobulated, encapsulated, mixed solid and cystic masses. The lesions typically extend to 1 side of the midline. In 13% of patients with an anterior mediastinal mass, the tumor extends into the middle and posterior mediastinal compartments. Cystic areas that are often multilocular and thinly septate are found in up to 88% of cases (see the images below).
Tumors are predominantly cystic in 80% of cases. About 50-73% of benign tumors have fat content, and 25-50% tumors are calcified. A fat-fluid layer may be found in up to 11% of patients, pleural effusion may be found in up to 17% of cases, and pericardial effusion may be found in 5%.
CT may useful in differentiating ruptured from unruptured mediastinal teratomas. Severe symptoms (chest pain or hemoptysis) are more common in patients with ruptured tumors (71%) than in patients with unruptured tumors. With ruptured mediastinal teratomas, the internal components are generally inhomogeneous, whereas with unruptured tumors, each internal compartment of the mass shows homogeneous attenuation. Other CT findings in ruptured tumors include fat-containing masses in adjacent lung parenchyma, consolidation or atelectasis in the adjacent lung, pericardial effusion, and pleural effusions.
Mature teratomas of the mediastinum typically appear on CT as heterogeneous anterior mediastinal masses containing areas of soft-tissue, fluid, fat, or calcium attenuation, or any combination of these. Fluid-containing cystic areas, fat, and calcification occur frequently. Cystic lesions without fat or calcium are seen in 15% of tumors. Fat-fluid levels, considered highly specific for the diagnosis of mediastinal mature teratoma, are uncommon. CT is the imaging technique of choice in the evaluation of these lesions.
Malignant lesions are ill defined and have irregular borders, which infiltrate the mediastinal fat. [19, 20]
CT is the imaging modality of choice in the evaluation of mediastinal lesions. CT is an excellent modality for determining the exact location of the mediastinal tumor, as well as its relationship to adjacent structures. It also is useful in differentiating masses that originate in the mediastinum from those that encroach upon the mediastinum from the lung or other structures. CT scans may help in differentiating various tissue attenuations, and they are highly accurate in differentiating fluid, fat, calcification, and cysts from solid tumors. CT may be used to assess the degree of vascularity of mediastinal tumors.
CT scanning is better than other cross-sectional imaging studies in revealing evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases.
Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. Most reviews have concentrated on clinical manifestations. Li and associates described 9 cases of pathologically proven neuroendocrine tumors of the thymus retrospectively analyzed by CT. All patients underwent nonenhanced and contrast-enhanced CT. Multiple CT features were scrutinized, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. A number of distinct CT characteristics were described, including the heterogeneous density of the tumors associated with tumor necrosis or cystic degeneration and moderate-to-intense contrast enhancement following a bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis of neuroendocrine tumors and provide critical information for surgical planning. [12]
Although CT is highly sensitive in the diagnosis of anterior mediastinal masses, its specificity is low with regard to differentiating benign from malignant lesions and in classifying malignant lesions of various histologic types (see the images below).
Continuing developments in MRI have resulted in improved image quality and decreased acquisition times. MRI is largely used as an adjunct to CT scanning in the evaluation of mediastinal tumors. In this setting, MRI provides additional information about the nature, location, and extent of disease.
MRI reveals masses of heterogeneous signal intensity, and it is more sensitive than CT in depicting infiltration of the adjacent structures by fat plane obliteration. It is performed as an ancillary study.
CT is more accurate than MRI in detecting mediastinal tumors, but MRI appears to be better than CT for evaluating spread through the capsule of the tumor, as well as infiltration of adjacent areas of mediastinal fat.
MRI is an accurate, noninvasive technique in the evaluation of superior vena cava syndrome and/or mediastinal and thoracic-inlet venous obstruction caused by mediastinal tumors. [21, 22]
The fact that MRI does not require ionizing radiation, as well as its multiplanar capability, makes MRI an excellent modality for the initial diagnosis of a mediastinal mass and for follow-up evaluation after treatment. The vascular images provided are superior to CT scans and can better delineate the relationship of an identified mediastinal mass to adjacent intrathoracic vascular structures. MRI may be used to differentiate between a suspected mediastinal mass and a vascular abnormality, such as an aortic aneurysm.
MRI contrast agents may be used when iodinated contrast material is contraindicated. MRI provides increased detail of the subcarinal and aortopulmonary window areas, as well as of the inferior aspects of the mediastinum at the level of the diaphragm. MRI is preferred to CT scanning in the evaluation of invasion or extension of tumors, especially tumors closely associated with the heart. In addition, MRI is superior to CT for defining masses impinging upon the thoracic inlet or occurring at the thoracoabdominal level.
As with other cross-sectional imaging modalitites, MRI is nonspecific with regard to tissue diagnosis of anterior mediastinal masses. The differential diagnosis of anterior mediastinal masses is wide, and false-positive diagnoses are possible.
Ultrasonography has traditionally been used to differentiate solid from cystic masses in places other than the mediastinum. However, its role has been extended, and it is now used to differentiate such masses in the anterior mediastinum (see the images below). Ultrasonograms may assist in determining a connection between a mass and adjacent structures. These studies are more useful in the evaluation of masses associated with the heart, as well as in vascular abnormalities. [15]
In general, given the accuracy and detail provided by CT scanning, MRI, and selected radionuclide scans, ultrasonographic techniques are generally not used as primary tools in the evaluation of mediastinal tumors and cysts. [23]
In addition to determining the size and topographic characteristics of mediastinal masses, ultrasonography precisely depicts the internal structure of the tumor; ultrasonographic findings may suggest a specific diagnosis when considered in light of the clinical presentation and the location of the tumor.
Ultrasonography remains operator dependent, and the anterior mediastinum may not be accessible because of the thoracic bony cage. As with other cross-sectional imaging modalities, tissue diagnosis may not be possible, because the differential diagnosis of solid, cystic, and complex mediastinal masses is extensive.
Radioiodine scans are particularly useful in identifying anterior mediastinal masses at the level of the thoracic inlet, such as the substernal extension of cervical thyroid goiter. Because germ cell tumors and thyroid abnormalities may both appear as anterior mediastinal masses, radioiodine scans may help to confirm or eliminate the involvement of thyroid tissue.
Indium-111 octreotide and pentetreotide scans may help in differentiating germ cell tumors from mediastinal carcinoids. Like other neuroendocrine tumors, carcinoids have somatostatin receptors and can therefore be imaged with somatostatin analogues (octreotide, pentetreotide) tagged to an appropriate radioisotope. Single-photon emission CT (SPECT) and subtraction techniques improve detection.
Sarcoid anterior mediastinal lymphadenopathy may be differentiated from germ cell tumors by use of radionuclide scanning. Gallium-67–avid sarcoid disease has been reported in more than 90% of cases of pulmonary involvement.
Through advances in physiologic imaging of mediastinal lymph nodes with fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning, this modality now provides better diagnostic accuracy than that obtained with anatomic CT scanning or MRI.
At present, an imaging strategy that uses both FDG-PET and CT scanning appears to be the most accurate, noninvasive, and cost-effective means of assessing nodal status in patients with non–small cell lung cancer. The use of FDG-PET in the imaging and staging of germ cell tumors has not yet been investigated. [24, 13, 14]
The uptake of technetium-99m pertechnetate and radioiodine is not specific for thyroid tissue, and uptake may occur in ectopic gastric mucosa in duplication cysts and Barrett’s esophagus. Gallium-67 uptake may occur in neoplastic, inflammatory, and infective foci. The results of FDG-PET are also nonspecific, and findings must be correlated with clinical presentation and other imaging findings.
Conventional angiography has been used to differentiate mediastinal masses from vascular abnormalities and to demonstrate the relationship between known masses and adjacent vascular structures. MRI and MR arteriography appear to satisfactorily define masses in this area.
Angiography is invasive, but it is still regarded as the criterion standard in imaging the heart and major blood vessels. MR arteriography and CT angiography are increasingly being used in these roles.
False-negative results may occur in cases involving aneurysms that are associated with laminar intraluminal thrombus. The sensitivity and specificity of angiography in the diagnosis of aortic aneurysms are 85% and 95%, respectively.
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Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK
Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England
Disclosure: Nothing to disclose.
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR Chief Medical Officer, Silk Road Medical
Sumaira Macdonald, MBChB, PhD, FRCP, FRCR, EBIR is a member of the following medical societies: British Medical Association, Cardiovascular and Interventional Radiological Society of Europe, British Society of Interventional Radiology, International Society for Vascular Surgery, Royal College of Physicians, Royal College of Radiologists, British Society of Endovascular Therapy, Scottish Radiological Society, Vascular Society of Great Britain and Ireland
Disclosure: Received salary from Silk Road Medical for employment.
Klaus L Irion, MD, PhD Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK
Klaus L Irion, MD, PhD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
W Richard Webb, MD Professor, Department of Radiology, University of California, San Francisco, School of Medicine
Disclosure: Nothing to disclose.
Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging
Disclosure: Nothing to disclose.
Kitt Shaffer, MD, PhD
Kitt Shaffer, MD, PhD is a member of the following medical societies: American Roentgen Ray Society
Disclosure: Nothing to disclose.
Nigel Thomas, MBBS Vice-Chair, Manchester (North) Research Ethics Committee; Honorary Lecturer, Visiting Professor, University of Salford, UK
Disclosure: Nothing to disclose.
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