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Nuclear Medicine |
1 From the Department of Radiology, Division of Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Box 57, 1515 Holcombe Blvd, Houston, TX 77030. Received June 7, 2004; revision requested August 20; revision received August 31; accepted October 4. Address correspondence to E.M.M. (e-mail: emarom{at}di.mdacc.tmc.edu).
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ABSTRACT |
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MATERIALS AND METHODS: Institutional review board approval was obtained, informed consent was waived, and the study was Health Insurance Portability and Accountability Act–compliant. Whole-body PET/CT scans and medical records of 140 consecutive patients with newly diagnosed NSCLC (80 men, 60 women; mean age, 66 years; range, 39–89 years) were retrospectively reviewed by two experienced PET/CT scan readers. Maximum standardized uptake value (SUV) was calculated for FDG-avid thyroid foci. Corresponding thyroid CT findings were recorded in patients with focal increased FDG thyroid uptake.
RESULTS: PET results showed that six patients (4.3%) had seven foci of increased FDG uptake in the thyroid. Five of the seven foci (in four patients) corresponded to a low-attenuation thyroid lesion on the nonenhanced CT scan. Lesions ranged in diameter from 0.8 to 2.5 cm. Four of the lesions were found to be papillary thyroid cancers at fine-needle aspiration biopsy. The fifth lesion was found to be benign at thyroidectomy. The remaining two patients did not have histologic confirmation of their thyroid lesion because no specific biopsy site was visualized on CT or sonographic images and lesions were considered benign. Maximum SUV of the thyroid cancers ranged from 3.0 to 32.9 (mean, 13.7). Maximum SUV of benign thyroid lesions ranged from 4.6 to 6.2 (mean, 5.4).
CONCLUSION: Focal thyroid FDG uptake found during the initial staging of NSCLC at PET/CT indicates a high likelihood of primary thyroid cancer.
© RSNA, 2005
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INTRODUCTION |
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Twenty-one of 161 patients originally identified as eligible for this study were later excluded because they were found to have undergone imaging for restaging or follow-up of NSCLC (n = 9) or because their presumed NSCLC was diagnosed at follow-up as benign disease (n = 5); small cell lung cancer (n = 2); sarcoidosis (n = 1); or as lung metastases from colon cancer (n = 1), transitional cell bladder cancer (n = 1), esophageal cancer (n = 1), or melanoma (n = 1). Thus, the final study group included 140 patients; these 80 men and 60 women had an average age of 66 years (range, 39–89 years). Histologic evaluation of biopsy-proved lung cancer in these patients showed adenocarcinoma (n = 62), squamous cell carcinoma (n = 41), poorly differentiated NSCLC not otherwise specified (n = 34), large cell carcinoma (n = 2), or carcinoid tumor (n = 1).
Medical Record Review
Two experienced chest radiologists (E.M.M. and J.G.Y., with 7 and 11 years of experience, respectively) retrospectively reviewed the medical records and recorded the age, sex, and type of lung cancer for the initial group of 161 patients. In addition, medical, surgical, and pathologic evaluation information related to the thyroid gland was recorded in those patients who were found to have focal thyroid FDG uptake.
Imaging
All patients underwent imaging after fasting for at least 6 hours. Scanning started 60 minutes after injection of FDG (average dose, 555 MBq [15 mCi]; range, 444–740 MBq [12–20 mCi]). Images were obtained by using an integrated PET/CT scanner (Discovery ST-8; GE Medical Systems, Milwaukee, Wis). PET scans were acquired with the two-dimensional mode for 3 minutes per bed position. PET images were reconstructed by using standard vendor-provided algorithms with ordered subset expectation maximization. Emission data were corrected for scatter, random events, and dead-time losses by using the manufacture's software, and images were reconstructed both with and without attenuation correction. Attenuation correction was performed by using CT. Nonenhanced CT images were acquired with helical mode (speed, 13.5 mm per rotation) performed from the base of the skull to the upper thighs by using a 3.75-mm section thickness, 140 kVp, and 120 mA.
Image Evaluation
The PET and CT images were retrospectively reviewed on a Xeleris workstation (GE Medical Systems) in all standard planes and on maximum intensity projection images and were analyzed visually and quantitatively by two reviewers experienced in reading PET/CT scans (E.M.M., J.G.Y., each with 1 year of experience in PET/CT). Findings were recorded by consensus. A third reviewer (H.A.M., 1.5 years of PET/CT experience) was assigned to resolve differences in interpretation of the scans (n = 1).
Focal uptake was defined as FDG uptake in fewer than one lobe of the thyroid gland. This definition was used in an attempt to separate patients with thyroiditis, which usually manifests with diffuse FDG thyroid uptake (14), from those with malignancy, which usually manifests with focal FDG thyroid uptake (15). Uptake in fewer than one lobe was chosen to differentiate between diffuse and focal uptake in patients who may have undergone a partial thyroidectomy. FDG uptake was considered abnormal at visual analysis when activity was substantially greater than that in the mediastinal blood on attenuation-corrected images. In addition, a pixel region of interest was outlined within the regions of increased FDG uptake, and the maximum standardized uptake value (SUV) was semiquantitatively analyzed according to the following equation: SUV = A/(ID/BW), where A is the decay-corrected activity in tissue (in millicuries per milliliter), ID is the injected dose of FDG (in millicuries), and BW is the patient's body weight (in grams).
When focal FDG activity was seen in the thyroid region, the fused images and the CT images were evaluated to ensure that uptake was from within the thyroid gland. Among the patients who were found to have focal FDG-avid thyroid lesions, CT findings were recorded. These included any thyroid focal lesions and their size, presence of thyroid enlargement, thyroid heterogeneity, thyroid calcifications, and neck adenopathy.
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RESULTS |
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Maximum SUV of the thyroid cancers ranged from 3.0 to 32.9 (mean, 13.7; standard deviation, 13.2). Maximum SUV of the benign thyroid lesions ranged from 4.6 to 6.2 (mean, 5.4; standard deviation, 0.8).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Several authors have reported that FDG accumulation may vary in the normal thyroid gland, increasing the potential for erroneous interpretation of FDG PET images (5,6,17,18). Some authors believe that diffuse or focal moderate to intense FDG activity in the thyroid gland may be normal (5,6). To automatically assume such FDG thyroid uptake is normal could have clinical consequences when determining disease stage in patients who may have an occult thyroid metastasis from early cancer elsewhere in the body. Similarly, in a patient with a known malignancy, regarding a thyroid lesion as a metastatic focus until proved otherwise, as suggested (12,13), may have grave consequences by preventing curative treatment of early disease. With PET/CT, we are encountering patients who have focal FDG uptake in the thyroid that corresponds to small thyroid lesions. Because of the discrepancy between the rates at which thyroid metastases are found at autopsy and on images, we decided to evaluate FDG-avid thyroid lesions in patients undergoing dual-modality PET/CT staging of newly diagnosed NSCLC.
Accurate assessment of the presence or absence of metastatic disease in the thyroid gland would require thyroidectomy and histologic proof in all of the 140 patients in our study. Within the clinical realm, our results support the idea that metastatic disease to the thyroid gland is very rare—none of the FDG-avid thyroid lesions in our patients were proved to be a metastasis. However, we found a higher rate of foci of increased FDG thyroid uptake (4.3%) than that previously reported (2.3%) (8,10). The prior results were based on PET scans alone and relied on the original PET interpretation. As mentioned, thyroid uptake of FDG is often considered normal, which may have accounted for the difference in the reported rates of abnormal FDG uptake. Another possibility is that dual-modality PET/CT depicts increased FDG better than does single-modality PET.
The major advantage of dual-modality PET/CT over PET alone is an improvement in the certainty of lesion location and characterization (1,2,19,20). On PET/CT images, thyroid FDG uptake is not likely to be misinterpreted as adjacent nodal uptake, and there is less tendency to disregard increased FDG activity as representing normal variation when it clearly corresponds with a morphologic abnormality. In addition, the SUV measured on PET/CT images is up to 15% higher than that measured on PET images (21); detection of a higher SUV may have increased our detection rate, specifically in those thyroid lesions with moderate FDG uptake. Although we found a higher percentage of primary thyroid malignancies (2.9%) than that reported in other series (0.1%–0.3%) (8,10), it is possible that this increase was due to the higher biopsy rate in our study.
It is important to note that uptake of FDG by the thyroid in patients with NSCLC does not necessarily signal the presence of metastatic disease in the thyroid. The thyroid lesion should be investigated separately so that appropriate therapy for both it and the NSCLC can be initiated. Although it has been suggested that SUV measurements can help successfully discriminate between benign and malignant tumors (10,22), it is not uncommon to see overlap in the values, with malignant thyroid lesions sometimes showing moderate FDG uptake and benign lesions showing high uptake (4,8). Thus, in our opinion, diagnosis should not rely heavily on any specific measured SUV.
Thyroid cancer is generally considered to have a good prognosis, but because it is the most common endocrine malignancy, it accounts for the majority of deaths due to endocrine cancers (16). Although papillary thyroid cancer is considered to be relatively slow growing, certain variants have a poor prognosis (16). Another poor prognostic sign for thyroid cancer is diagnosis at an age older than 40 years for men and older than 50 years for women (16). Most patients undergoing PET/CT staging for newly diagnosed NSCLC are older individuals. However, even in older patients, treatment of papillary thyroid cancer has been shown to improve survival (16). Thus, we believe the cause of increased thyroid uptake in such individuals should be investigated.
Our study had several limitations. First, increased uptake of FDG in the thyroid of patients undergoing initial PET/CT staging of NSCLC is uncommon. Our study group was small (n = 6), representing only 4.3% of the larger group (n = 140) who underwent initial NSCLC staging with PET/CT. Perhaps a larger study group would have included some thyroid metastases, but our population reaffirms the findings that most patients with high FDG uptake in the thyroid will be found to have a primary thyroid malignancy (8,10,23), which should be investigated apart from the known cancer so that appropriate therapy can be initiated. Second, because of the retrospective nature of this study, two of the six patients with FDG uptake in the thyroid did not have histologic confirmation of the underlying cause; thus, metastatic disease in the thyroid may have been missed. Such a possibility is doubtful in one of the patients, because the thyroid gland had not changed at 1-year follow-up. The other patient was lost to follow-up. However, because the rate of malignant thyroid lesions in our study group was high, our findings do not support changing the recommendation that any abnormal uptake of FDG by the thyroid be examined at biopsy if an appropriate biopsy site can be localized.
In conclusion, focal thyroid FDG uptake found at initial PET/CT staging of NSCLC should be investigated and the foci should be examined at biopsy if possible because of the high likelihood of thyroid cancer. Accurate diagnosis of thyroid lesions, metastatic or otherwise, increases the likelihood of potentially curative therapy being undertaken for both the NSCLC and the thyroid disease.
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FOOTNOTES |
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Abbreviations: FDG = fluorodeoxyglucose • NSCLC = non–small cell lung cancer • SUV = standardized uptake value
2 Current address: Department of Diagnostic Radiology, Cheongju Saint Mary's Hospital, Chungbuk-do, South Korea 
The following authors have direct or indirect financial interest: B.S.S., GE Digital Radiography Medical Advisory Board; R.F.M, GE Medical Systems CT Medical Advisory Board; H.A.M., grants from GE Medical Systems and Astra Zeneca, consultant for Radiology Corp of America and GE Medical Systems, and speaker's bureau for Siemens, PETNET, and Cardinal Health; D.A.P., board of directors for Siemens and GE, honoraria from GE, Siemens, Corixa, and IDEC, research support from Corixa and IDEC, Corixa, Amersham, and GE Medical Systems.
Author contributions: Guarantor of integrity of entire study, E.M.M.; study concepts, all authors; study design, J.G.Y., E.M.M., R.F.M., M.T.T., H.A.M.; literature research, J.G.Y., E.M.M.; clinical studies, all authors; data acquisition, all authors; data analysis/interpretation, J.G.Y., E.M.M.; manuscript preparation and definition of intellectual content, J.G.Y., E.M.M., R.F.M.; manuscript editing, E.M.M.; manuscript revision/review, E.M.M., R.F.M.; manuscript final version approval, all authors
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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