Mediastinal Germ Cell Tumor Imaging

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.

Smooth, well-defined anterior mediastinal tumor wiSmooth, well-defined anterior mediastinal

tumor with heterogeneous attenuation associated with calcific intratumoral nodules suggests a
mediastinal teratodermoid. Note also the curvilinear calcification.

Contrast-enhanced axial CT scan shows an ill-definContrast-enhanced axial CT scan shows an

ill-defined anterior mediastinal mass with irregular borders that is infiltrating the mediastinal fat.
CT-guided needle biopsy revealed a mediastinal seminoma.

Patient with asymmetrically placed anterior mediasPatient with asymmetrically placed anterior
mediastinal mass. Lateral linear tomogram (not shown here) revealed a well-defined, uniformly
attenuating mass; sonogram shows a mass with smooth, uniform echotexture. The patient had not
undergone surgery, and findings on follow-up over several years showed little change.
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]

Preferred examination
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.
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.
Echocardiography is an invaluable tool for differentiating tumors arising from the pericardium
and/or myocardium from other tumors.
Radionuclide imaging may provide a neartissue-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.[11, 12, 13, 14, 15, 16, 17, 18, 19, 20]
Limitations of techniques
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, falsepositive results are possible, and uptake may occur in a variety of normal, inflammatory, and
neoplastic tissues.

Radiography
Standard chest radiography is usually the first imaging procedure performed in an individual
with symptoms referable to the thorax (see the images below).\

Smooth, well-defined anterior mediastinal tumor wiSmooth, well-defined anterior mediastinal

tumor with heterogeneous attenuation associated with calcific intratumoral nodules suggests a
mediastinal teratodermoid. Note also the curvilinear calcification.

Coned view of the superior mediastinum shows a welConed view of the superior mediastinum
shows a well-defined anterior mediastinal tumor with calcific intratumoral nodules suggestive of
a mediastinal teratodermoid. Note also the curvilinear calcification

Smooth, well-defined anterior mediastinal tumor wiSmooth, well-defined anterior mediastinal

tumor with uniform attenuation. At surgery, a mediastinal dermoid was diagnosed. Note the
hilum-overlay sign, suggestive of an anterior or posterior mediastinal mass.

Lateral conventional tomogram shows a smooth, wellLateral conventional tomogram shows a

smooth, well-defined, uniformly attenuating anterior mediastinal mass with no calcification.

Lobulated but smooth and well-defined superior medLobulated but smooth and well-defined
superior mediastinal mass with uniform attenuation.

A patient with a biopsy-proven anterior mediastinaA patient with a biopsy-proven anterior

mediastinal dermoid extending across both sides of the midline.

Posteroanterior (left) and lateral (right) chest rPosteroanterior (left) and lateral (right) chest
radiographs show a biopsy-proved posterior mediastinal dermoid.
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.

Degree of confidence
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.
False positives/negatives
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.

Differential diagnosis. Mediastinal widening in a Differential diagnosis. Mediastinal widening in

a child with acute lymphatic leukemia caused by mediastinal lymphadenopathy.

Differential diagnosis. Chest radiograph shows extDifferential diagnosis. Chest radiograph

shows extensive mediastinal lymphadenopathy due to non-Hodgkin lymphoma.

Differential diagnosis. Posteroanterior chest radiDifferential diagnosis. Posteroanterior chest

radiograph shows a mass in continuation with the aortic knuckle. Findings on contrast-enhanced
CT confirmed that the mass was an aortic aneurysm (not shown).

Differential diagnosis. Posteroanterior (top left)Differential diagnosis. Posteroanterior (top left)

and lateral (top right) chest radiographs and CT scans in mediastinal (bottom left and middle)
and bone window (bottom right) show an Askin tumour with bone destruction.

Computed Tomography
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).

Contrast-enhanced axial CT scan shows an ill-definContrast-enhanced axial CT scan shows an

ill-defined anterior mediastinal mass with irregular borders that is infiltrating the mediastinal fat.
CT-guided needle biopsy revealed a mediastinal seminoma.

Contrast-enhanced CT scan obtained through the medContrast-enhanced CT scan obtained

through the mediastinum in 56-year-old man shows an infiltrative enhancing tumor. Note the
pleural effusion. Biopsy confirmed a sarcomatous-type germ cell tumor.

Posteroanterior chest radiograph and nonenhanced CPosteroanterior chest radiograph and

nonenhanced CT scans obtained through the mediastinum in 18-year-old man shows a large
tumor involving the anterior, middle, and posterior mediastinum. Note the left pleural effusion.
Biopsy confirmed a malignant teratoma.

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.
[21, 22]

Degree of confidence
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.
False positives/negatives
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).

Differential diagnosis. Contrast-enhanced CT throuDifferential diagnosis. Contrast-enhanced CT

through the anterior mediastinum shows a minimally enhancing anterior mediastinal mass. At
surgery, a malignant thymoma was diagnosed.

Contrast-enhanced CT through the anterior mediastiContrast-enhanced CT through the anterior

mediastinum shows a minimally enhancing anterior mediastinal mass. At surgery, a malignant
thymoma was diagnosed.

Magnetic Resonance Imaging

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.[23, 24]

Degree of confidence
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.
False positives/negatives
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
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.

Mediastinal sonogram obtained through the right paMediastinal sonogram obtained through the
right parasternal area of an anterior intercostal space shows a mass of uniform echogenicity with
posterior acoustic enhancement.

Mediastinal sonogram obtained through the suprasteMediastinal sonogram obtained through the
suprasternal notch shows an ill-defined tumor with a heterogeneous echo pattern. At surgery, a
teratodermoid was diagnosed. The mass contained small foci of calcification.

Patient with asymmetrically placed anterior mediasPatient with asymmetrically placed anterior
mediastinal mass. Lateral linear tomogram (not shown here) revealed a well-defined, uniformly
attenuating mass; sonogram shows a mass with smooth, uniform echotexture. The patient had not
undergone surgery, and findings on follow-up over several years showed little change.
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.[25]
Degree of confidence
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.
False positives/negatives
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.

Nuclear Imaging
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-67avid 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.[26, 27]
False positives/negatives
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.

Angiography
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.

Degree of confidence
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 positives/negatives
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.