DOI:10.2214/AJR.06.0552
AJR 2007; 188:1716-1721
© American Roentgen Ray Society
Thymic Extension in the Superior Mediastinum in Patients with Thymic Hyperplasia: Potential Cause of False-Positive Findings on 18F-FDG PET/CT
Clare S. Smith1,
Heiko Schöder and
Henry W. D. Yeung
1 All authors: Department of Radiology/Nuclear Medicine, Memorial
Sloan-Kettering Cancer Center, New York, NY 10021.
Received April 21, 2006;
accepted after revision September 12, 2006.
Address correspondence to C. S. Smith
(smithc{at}mskcc.org).
Abstract
OBJECTIVE. Although 18F-FDG PET/CT is now well
established as an accurate method for the staging and restaging of various
cancers, it is also well recognized that many false-positive results can
occur. One such false-positive is activity within the superior extent of the
thymus in the superior mediastinum.
CONCLUSION. We reviewed all PET/CT examinations performed in
children and young adults under the age of 20 years at our institution over a
2-month period. In 11 (12%) of the 93 examinations, activity was identified in
the superior mediastinum of similar intensity to the thymus, which is
consistent with activity within the superior thymic extension. In light of the
increasing clinical use of FDG PET/CT for cancer imaging, it is important that
nuclear medicine physicians and radiologists be aware of this phenomenon to
avoid misdiagnosis or overstaging of disease.
Keywords: oncologic imaging • PET/CT • thymus
Introduction
It is common to see increased 18F-FDG activity within the thymus
in young children and adolescents. In one series, FDG accumulation in thymic
hyperplasia was noted in 75% of young adults after chemotherapy
[1]. A normal variant in which
the thymus extends superiorly to the left brachiocephalic vein and anteriorly
to the brachiocephalic artery or left common carotid artery can occur. This
has previously been visualized on CT as a soft-tissue nodule that can be
mistaken for superior mediastinal adenopathy
[2].
With the increasing use of combined PET/CT in the workup of cancer
patients, it is important for radiologists and nuclear medicine physicians to
be aware of normal anatomic variants and variants in FDG uptake patterns.
Here, we present three cases in which PET/CT showed increased FDG activity in
the anterior mediastinum consistent with thymic hyperplasia after
chemotherapy. In addition, the fusion images showed increased activity within
the superior mediastinum, corresponding to the normal variant thymic soft
tissue, visualized previously on CT. This prompted us to conduct a
retrospective analysis of FDG PET/CT studies performed over a 2-month period
at our institution to see how often we encountered this phenomenon.
Materials and Methods
We conducted a retrospective review of all FDG PET/CT studies performed at
our institution over a 2-month period. Studies in children and adolescents
under the age of 20 years were analyzed for the presence of thymic tissue on
CT and PET. This review was approved by the institutional review board.
Patients were injected with FDG IV, and images were acquired after an
approximately 45- to 60-minute uptake period. Based on a clinical standard
activity of 15 mCi (555 MBq) of FDG for adults in our clinic and an adult body
surface area of 1.72 m2, we calculated the appropriate activity for
children and adolescents. The patient's body surface area was divided by 1.72
and the results then multiplied by 15. When the patient's body surface area
was equal to or greater than 1.72 m2, an activity of 15 mCi (555
MBq) was injected. Low-dose unenhanced CT and PET images were acquired using a
dedicated PET/CT scanner, either Biograph LSO (Siemens Medical Solutions) or
Discovery LS (GE Healthcare). The field of view extended from at least the
skull base to the inguinal regions, depending on the clinical question.
Parameters for the low-dose CT were 5-mm slice thickness and 120 kVp. The tube
current ranged from 25 to 65 mAs depending on the weight of the patient.
PET, CT, and fusion images were reviewed on an Advantage workstation, which
is integrated in the GE PACS (GE Healthcare). This system allows reformatting
of images with display of transaxial, coronal, or sagittal slices and
calculation of standardized uptake value (SUV) by placing a volumetric region
of interest (ROI) around the structure of interest. The maximum SUV, corrected
for body weight, within a given ROI was recorded.
PET and CT images were first analyzed visually. FDG uptake outside of
normal anatomic structures and of intensity greater than background activity
was considered abnormal. FDG uptake in the anterior superior mediastinum, in
the characteristic inverted V-shape, was considered thymic activity. This was
confirmed on fusion images. The SUV of areas with increased FDG activity
within the superior mediastinum, in the mediastinal blood pool, and in the
thymus was recorded. When available, findings from contrast-enhanced CT or MRI
performed within 2 weeks of the PET/CT were reviewed to evaluate further any
findings noted on PET/CT. All previous imaging was reviewed for those patients
who showed activity in the superior mediastinum on the PET/CT performed during
our 2-month review to see if a staging PET/CT had been performed. Clinical
notes and follow-up imaging of all patients who showed FDG uptake in the
superior mediastinum were also reviewed to assess for stability.
Results
In all, 93 studies were performed in children or young adults (53 males and
40 females) under the age of 20 years for the staging or restaging of various
malignancies. Ten of the studies were performed for staging and 83 were
performed for restaging or follow-up. In 11 (12%) of the 93 studies performed,
increased FDG uptake (SUV mean, 2 ± 0.87 [SD]; range, 1.1–3.8
g/mL) was noted in a nodule in the superior mediastinum. On PET/CT fusion
images, this was consistent with superior thymic extension. This group of 11
patients included six boys and five girls with a mean age of 9 years (range,
3–16 years). Three patients had a diagnosis of Hodgkin's lymphoma, two
had a diagnosis of non-Hodgkin's lymphoma, one had been treated for
hepatoblastoma, and five had a diagnosis of rhabdomyosarcoma.
At the time of this PET/CT study, all patients had been treated with
chemotherapy; the median time interval from completion of chemotherapy to
PET/CT was 12 months (range, 2–24 months). In addition to superior
thymic extension, all of these 11 patients had associated thymic hyperplasia
with increased FDG uptake (SUV mean, 2.8 ± 1.38; range, 1.5–6.6
g/mL) on PET images. The SUV of nodules in the superior mediastinum was
similar to or slightly lower in intensity than the SUV in the thymus itself
(mean, 0.82 ± 0.69; range, 0.22–2.8 g/mL.
All patients underwent concurrent contrast-enhanced CT (n = 7) or
MRI (n =2); two patients underwent both CT and MRI. These studies
confirmed that the findings on PET/CT did indeed represent superior
mediastinal extension of the thymus.
Six of the 11 patients had undergone a PET/CT before the initiation of
chemotherapy, and three of these six patients showed mild FDG uptake within a
nodule in the superior mediastinum and mild uptake in the thymus. The other
three patients had a nodule in the superior mediastinum that was revealed on
CT, but there was no FDG activity in either the nodule or the thymus at the
time of the initial study.
Five patients had their first PET/CT examination after commencement of
chemotherapy (time on chemotherapy: range, 3–8 months; mean, 4.5
months). Four of these five patients had no FDG uptake in the superior
mediastinum, but a nodule was identified on CT. The fifth patient, who had
been on chemotherapy for 6 months, showed some mild FDG uptake within a
superior mediastinal nodule, consistent with superior mediastinal extension of
the thymus.
Ten of the 11 patients with increased FDG uptake in a superior mediastinal
nodule at the time of our review had follow-up imaging between 6 and 12 months
afterward. In eight patients, follow-up PET/CT revealed stable or decreased
tracer uptake in the upper mediastinal nodule. In two other patients,
stability of the superior mediastinal nodule was confirmed on CT and MRI,
respectively. All 11 patients with increased FDG uptake in the superior
mediastinal nodule were disease-free at 1-year follow-up.
Case 1
The patient was a 3.5-year-old boy with stage IV Burkitt's lymphoma treated
with chemotherapy. A pretreatment FDG PET/CT showed a 2-mm nodule anterior to
the left brachiocephalic vein, which had no FDG activity. The posttreatment
PET/CT performed 5 months after completion of treatment showed enlargement of
the thymus with increased FDG activity (SUV, 2.0; 56 H) and increased activity
in the superior mediastinum, corresponding to an enlarged soft-tissue nodule,
which now measured 7 mm on the CT component (SUV, 2.0; 51 H) Follow-up PET/CT
6 months later showed no significant change in activity or in the size of the
nodule and no evidence of disease recurrence (Fig.
1A,
1B,
1C,
1D,
1E).
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Fig. 1A —3.5-year-old boy with abdominal Burkitt's lymphoma. Axial CT
image from 18F-FDG PET/CT study performed before chemotherapy shows
small 2-mm nodule (arrow), which is not FDG avid, anteromedial to
left brachiocephalic vein.
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Fig. 1B —3.5-year-old boy with abdominal Burkitt's lymphoma. Axial CT
image from FDG PET/CT study performed 5 months after treatment shows
enlargement of nodule (arrow). Nodule now measures 7 mm.
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Fig. 1C —3.5-year-old boy with abdominal Burkitt's lymphoma. Axial
fusion FDG PET/CT image obtained 5 months after treatment shows that FDG
activity corresponds to enlarged nodule anteromedial to left brachiocephalic
vein (arrow).
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Fig. 1D —3.5-year-old boy with abdominal Burkitt's lymphoma. Axial
fusion FDG PET/CT image performed 5 months after treatment shows increased
activity in enlarged thymus (arrow) (standardized uptake value, 2.0)
of similar intensity to activity in superior mediastinum.
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Fig. 1E —3.5-year-old boy with abdominal Burkitt's lymphoma. Coronal
FDG PET scan obtained 12 months after completion of treatment shows persistent
activity in thymus and in superior thymic extension (arrow). Note
physiologic activity within right neck in sternocleidomastoid muscle.
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Case 2
The patient was a 3-year-old girl with hepatoblastoma treated with surgery
and chemotherapy. An FDG PET/CT performed 2 months after completion of therapy
showed FDG accumulation in the thymus and superior mediastinum, which was
persistent but stable 12 months after treatment (Fig.
2A,
2B).
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Fig. 2B —3-year-old girl with hepatoblastoma. Axial PET image from
18F-FDG PET/CT study shows increased FDG activity in superior
mediastinum (arrow) (standardized uptake value [SUV], 3.2). SUV of
activity in thymus was 3.6.
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Case 3
The patient was a 14-year-old boy with B-cell lymphoma treated with
chemotherapy. Pretreatment FDG PET/CT showed increased FDG uptake in the right
elbow, indicating the known site of his disease. There was some mild
physiologic activity in the thymus and no abnormal activity in the anterior
superior mediastinum. Posttreatment PET/CT performed 8 months after
chemotherapy showed resolution of activity in the right elbow but increased
activity in the thymus and new activity in the superior mediastinum. This was
consistent with FDG uptake in the superior extension of the thymus. A
follow-up study at 12 months showed unchanged activity in the superior
mediastinum (Fig. 3A,
3B,
3C,
3D).
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Fig. 3A —14-year-old boy with B-cell lymphoma of right elbow. Coronal
18F-FDG PET image at time of diagnosis shows physiologic FDG
activity in thymus (black arrow) and increased activity at right
elbow (white arrow) consistent with patient's known disease.
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Fig. 3B —14-year-old boy with B-cell lymphoma of right elbow. Axial CT
image from FDG PET/CT study obtained 8 months after completion of therapy
shows nodule in superior mediastinum (arrow). This nodule is somewhat
obscured by beam-hardening artifact.
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Fig. 3C —14-year-old boy with B-cell lymphoma of right elbow. Coronal
PET image from FDG PET/CT study performed 8 months after completion of
chemotherapy shows increased FDG activity in thymus and superior extension in
superior mediastinum (arrow).
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Fig. 3D —14-year-old boy with B-cell lymphoma of right elbow. Sagittal
PET image from PET/CT study performed 8 months after completion of
chemotherapy shows increased FDG activity in thymus and superior extension in
mediastinum (arrows).
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Biopsy of the superior mediastinal nodule was not performed in any of the
11 patients because the findings on FDG PET/CT were pathognomic of FDG
activity within the superior mediastinal thymic extension. The findings were
corroborated with other cross-sectional imaging, and all of the patients
showed stability or a decrease in activity or size of nodule on follow-up
imaging, confirming that this activity was due to superior mediastinal thymic
extension..
Discussion
The thymus develops from the ventral wing of the third pharyngeal pouch on
each side. During the eighth week of fetal life, the bilateral thymic
primordia fuse in the midline and start to migrate down behind the sternum to
their final location in the anterior mediastinum
[3]. Occasionally, thymic
tissue can persist anywhere along the path of its migration
(Fig. 4). It has been
estimated that residual thymic tissue in the neck is found in 1.8–21% of
individuals [4]. It usually
presents as an asymptomatic neck mass and is one of the differential diagnoses
of neck masses in children
[5].
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Fig. 4 —Drawing of anterior view of thyroid gland, thymus, and
parathyroid glands illustrates various congenital anomalies that may occur.
(Reprinted with permission from Moore KL, Persaud TVN. The developing
human, 6th ed. Philadelphia, PA: W. B. Saunders, 1998:230
[8])
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FDG PET has become a widespread tool in the staging and restaging of
cancers. FDG uptake in the thymus can be seen normally in children and young
adults [6]. FDG has also been
shown to accumulate in the thymus in adults after chemotherapy
[1]. Cory et al.
[2] previously described the CT
findings of extension of the thymus above the left brachiocephalic vein, a
normal variant that can occur in children and adolescents and can sometimes be
confused with superior mediastinal adenopathy. They identified this nodule on
the basis of several CT findings: equal density of the superior mediastinal
nodule and the thymic lobes, no displacement or narrowing of the adjacent
structures, absence of a fat plane between the nodule and the thymic lobes,
and parallel reduction in the size of the nodule and the rest of the thymus.
This reduction in size is due to involution of normal thymic tissue.
In this case series, we present the corresponding findings on FDG PET/CT.
In 11 (12%) of 93 children or adolescents whose studies were reviewed, the
PET/CT fusion images showed FDG uptake in a soft-tissue nodule anterior to the
left brachiocephalic vein. In all 11 cases, there was also increased activity
in the anterior mediastinum, corresponding to hyperplastic thymus. Of note,
the SUV in the thymus and the superior thymus extension were quite similar.
Concurrent cross-sectional imaging studies confirmed that this activity did
indeed represent activity within superior extension of the thymus. The nodule
in the superior mediastinum had similar Hounsfield units as the thymus on CT.
Both the thymus and the superior mediastinal nodule showed similar signal
characteristics on MRI. On T1-weighted images, the thymus has homogeneous
relatively low signal intensity slightly greater than that of muscle. On
T2-weighted images, the signal intensity of the thymus approaches that of fat
[7]. When follow-up studies
were available, we noted either resolution of FDG uptake in the thymus and its
superior extension or stability of findings without further treatment. In
addition, all patients were clinically disease-free at 1-year follow-up. This
confirms that the superior mediastinal nodule represented thymus extension
rather than lymphadenopathy.
We had one case in which the pretreatment PET/CT showed a 2-mm soft-tissue
nodule in the superior mediastinum without FDG activity. After completion of
chemotherapy, the nodule had increased in size to 7 mm and now exhibited FDG
activity of similar intensity as the thymus. This example shows that both the
normal thymus and its superior mediastinal extension can undergo hyperplasia
after chemotherapy and that FDG activity in both sites can then be quite
marked.
We also noted, however, that increased FDG activity in the superior thymic
extension is sometimes present even before or during chemotherapy. Three of
six patients who had a baseline FDG PET/CT examination showed this phenomenon,
and one of five patients whose first PET/CT was performed while the patient
was undergoing chemotherapy also had activity in the superior thymic
extension. However, in all cases, the FDG activity was higher after the end of
chemotherapy than before or during treatment.
FDG uptake in a superior mediastinal thymic extension can lead to
misdiagnosis if physicians interpreting a PET/CT study are not aware of this
entity. The differential diagnosis for masses in this region includes
lymphoma, metastasis, thyroid malignancy, or even a teratoma or dermoid
tumor.
In case 3, in which there was increased FDG activity in the superior
mediastinum, CT streak artifacts in the sternal notch obscured visualization
of structures in this region. The FDG activity in the superior mediastinum was
of similar intensity to that in the thymus and was in a typical location for a
superior thymic extension of the thymus. Therefore, if reporting physicians
are aware of this normal variant on PET, misdiagnosis can be avoided even if
there are artifacts on the accompanying CT of the combined PET/CT study.
In conclusion, increased FDG activity within a soft-tissue nodule
anteromedial in relation to the left brachiocephalic vein can often be seen in
children and young adults on PET/CT, particularly after chemotherapy when
there is thymic hyperplasia. This finding represents a normal variant of
superior extension of the thymus and should not be mistaken for a mediastinal
mass or lymphadenopathy. In our series, all patients with FDG uptake in the
superior thymic extension also had thymic hyperplasia and their SUVs were
similar. In light of the increasing clinical use of FDG PET/CT, it is
important that nuclear medicine physicians and radiologists be aware of this
phenomenon to avoid misdiagnosis or overstaging of disease and unnecessary
biopsy, especially when there are artifacts on the CT component of the
combined PET/CT study. SUV measurement may also be helpful. If the activity in
the superior mediastinal nodule is clearly higher than that of the thymus,
this would not be consistent with thymic extension and malignancy should be
considered instead.
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Abstract
Introduction
