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Original Report |
1 Department of Radiology, Massachusetts General Hospital and Harvard
University, 55 Fruit St., Boston, MA 02114.
2 Department of Pathology, Massachusetts General Hospital and Harvard
University, Boston, MA 02114.
3 Department of Radiology, Thoracic Imaging, New York University, 560 1st Ave.,
New York, NY 10016.
Received June 14, 2002;
accepted after revision July 30, 2002.
Address correspondence to C. Wittram.
Abstract
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CONCLUSION. In three adults, we found a physiologic uptake of FDG by the thymus with standardized uptake values in the range of thymic neoplasia.
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A LightSpeed CT scanner (General Electric Medical Systems, Milwaukee, WI) was used to acquire the images from the lung apices to the kidneys with a 5-mm slice thickness, 15-mm table feed, and 0.8 sec/rotation. These scans were obtained during the IV injection of 100 mL of ioxilan 300 mg I/mL at the rate of 2 mL/sec using a power injector (MCT Plus; Medrad, Pittsburgh, PA). The scanning parameters were 140 kVp and 250 mA in two patients and 220 mA in one patient. Images were reviewed on lung window settings (window width, 1500 H; window level, -600 H) and mediastinal windows settings (window width, 350 H; window level, 40 H) on a PACS (picture archiving and communication system) monitor (IMPAX version 4.1; Agfa, Teterboro, NJ).
FDG PET images were obtained 5-21 days (average, 10 days) after the CT scans. The FDG PET studies were performed with a CT/i HR PET camera (Siemens Systems, Knoxville, TN) 45 min after IV injection of 15.5-17.5 mCi (573.5-647.5 MBq; average, 16.4 mCi [606.8 MBq]) of FDG. Attenuation correction was performed from transmission images acquired using a pin source containing germanium-68.
From 1 to 5 weeks after the FDG PET studies were performed (average, 3 weeks), two patients underwent mediastinotomy and thymus resection. One patient had a mediastinoscopy and biopsy of the right lobe of the thymus. Pathologic specimens were available in all patients and were reviewed by an experienced lung pathologist.
CT and FDG PET images were assessed retrospectively by two chest radiologists and a nuclear medicine physician. Decisions concerning the findings were reached by consensus. The CT analysis included the location, size, shape, margins, and internal characteristics of the bilobed structures. The longest and shortest perpendicular CT measurements were recorded. Thymic thickness was measured perpendicular to the length of the lobe [6, 7]. The standardized uptake value (SUV) was calculated in each case using a region of interest that included the highest activity area of the thymus but not covering the entire thymus. The SUV was determined as the concentration of FDG in the thymus divided by the injected radioactivity per gram of body weight.
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All FDG PET scans depicted increased uptake of FDG in the anterior mediastinum corresponding to the anterior mediastinal soft-tissue opacity seen on CT. The SUVs ranged from 1.1 to 2.2 (average, 1.8 ± 0.55).
Histologic examination in all three patients revealed normal-appearing cortex, medulla, and Hassall's corpuscles, with no evidence of malignancy.
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In this series, the histology of all three thymic specimens was normal. However, in each patient, the thickness of the thymus exceeded 13 mm [6, 7]. Therefore, these patients showed thymic enlargement. Interestingly, findings in all the patients revealed slight convexity of the thymus, particularly affecting the left lobe of the thymus seen on CT. Figure 1A,1B,1C,1D displays an anatomic variant of the thymus, with thymic tissue revealed in the superior mediastinum among the left brachiocephalic vein, right brachiocephalic artery, and left common carotid arteries.
Embryologically, the thymus originates from the third branchial pouch. This endothelial tissue migrates from the pharynx to the anterior mediastinum during embryogenesis; therefore, thymic tissue can remain at any point along this path. In a surgical—anatomic study of 50 consecutive patients, the variant seen in a 29-year-old woman in our study was identified in one patient [8].
The cause of thymic enlargement in a 32-year-old woman in our study was likely related to thymic regrowth in response to chemotherapy. In a CT evaluation by Choyke et al. [9] of thymic atrophy and regrowth in response to chemotherapy, three patients with thymic enlargement, like the patients in our study, had normal findings at histology. The cause of thymic enlargement seen on CT in our study in 29- and 44-year-old patients is unknown.
In a study by Nakahara et al. [5], increased FDG uptake was found in 32 of 94 adult patients (range, 18-29 years; mean age, 25.4 years) who had normal-appearing thymuses on CT. These patients had no symptoms suggestive of thymus-related disease or mediastinal tumor. These subjects had normal clinical follow-up periods ranging from 6 to 69 months; however, there was no histologic correlation. Nakahara et al. suggested that the upper age limit of normal FDG uptake in the thymus is 29 years. However, two of our patients were 32 and 44 years old, indicating normal thymic FDG uptake can occur in older patients. To our knowledge, there is only one previous case report of an adult patient with uptake of FDG in the thymus and biopsy-proven normal thymic tissue: a 54-year-old woman with a history of recurrent thyroid follicular cancer treated with a high dose of iodine-131 therapy [10]. The case report by Alibazoglu et al. [10] supports our observations of physiologic uptake of FDG in the thymus in adults. To the best of our knowledge, ours is the only series of patients in whom an increase in uptake of FDG in the thymus has been correlated with CT and pathologic examination.
In a study by Sasaki et al. [11], 31 patients with histologically proven thymic tumors were evaluated with FDG PET. In their study, the SUVs for 14 patients with thymic cancer (mean ± SD, 7.2 ± 2.9) were higher than those of nine patients with invasive thymoma (3.8 ± 1.3), five patients with noninvasive thymoma (3.0 ± 1.0), and three patients with thymic cysts (0.9). In our study, the mean SUV of normal thymic tissue was 1.8 ± 0.55, which overlaps with the values obtained for thymomas in the article by Sasaki et al. The SUV is subject to many sources of variability, including body composition and habitus, the period of FDG uptake, plasma glucose value, recovery coefficient, and partial volume effects. These factors can cause potential errors of 50% or more [12]. Therefore, one must consider these numbers as a guide and not as an absolute.
In summary, enlargement of the thymus, as seen on CT, is also manifest with convex lateral borders. An increase in FDG uptake in adults can be seen in normal thymic tissue, and the degree of FDG uptake by the thymus overlaps the values of thymic neoplasia.
Acknowledgments
We thank Anne-Marie Reardon for preparation of this manuscript.
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