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Clinical Observations |
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
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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
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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.
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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.
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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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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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