Incidental Thyroid Nodules at Non FDG PET Nuclear Medicine Imaging: Evaluation of Prevalence and Malignancy Rate

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1 Nuclear Medicine and Molecular Imaging Original Research Yerubandi et al. Incidental Thyroid Nodules on Non-PET Nuclear Medicine Imaging Nuclear Medicine and Molecular Imaging Original Research Vijay Yerubandi 1 Bennett B. Chin 1 Julie A. Sosa 2,3 Jenny K. Hoang 1,4 Yerubandi V, Chin BB, Sosa JA, Hoang JK Keywords: incidental, incidentaloma, nuclear medicine, thyroid, thyroid nodule DOI: /AJR Received June 15, 2015; accepted after revision September 28, Department of Radiology, Duke University Medical Center, DUMC Box 3808, Erwin Rd, Durham, NC, 27710, Address correspondence to J. K. Hoang (jennykh@gmail.com). 2 Department of Surgery, Duke University Medical Center, Durham, NC. 3 Department of Medicine, Duke University Medical Center, Durham, NC. 4 Department of Radiation Oncology, Duke University Medical Center, Durham, NC. This article is available for credit. AJR 2016; 206: X/16/ American Roentgen Ray Society Incidental Thyroid Nodules at Non FDG PET Nuclear Medicine Imaging: Evaluation of Prevalence and Malignancy Rate OBJECTIVE. The purpose of this study was to estimate the prevalence of thyroid nodules detected incidentally on non FDG PET nuclear medicine imaging studies, the malignancy rate, and predictors of malignancy. MATERIALS AND METHODS. A retrospective review of more than 10 years of patient records at an academic medical center identified the cases of 31 patients with incidental focal radiotracer-avid thyroid findings on non FDG PET nuclear medicine studies who underwent biopsy or surgical excision. Statistical analysis of patient and imaging features was performed to identify features predictive of malignancy. Society of Radiologists in Ultrasound and American Thyroid Association biopsy criteria were applied to patients who had ultrasound images for review. RESULTS. Thirty-one patients had incidental thyroid findings on 99m Tc-sestamibi parathyroid scans (80.6%), 111 In-pentetreotide scans (16.1%), and 99m Tc-tetrofosmin cardiac scans (3.2%). These three types of scans accounted for 21,402 total examinations in the study period. Thus, the prevalence of incidental thyroid findings on non-pet nuclear medicine studies that were evaluated by pathologic examination was 0.14%. The malignancy rate was 16.1% (5/31). No clinical or imaging features were identified as predictive of malignancy. Society of Radiologists in Ultrasound and American Thyroid Association criteria were applied to 23 thyroid nodules with available ultrasound images. According to both sets of criteria, biopsy was recommended for 19 of 23 (82.6%) nodules, and one of three (33.3%) cases of thyroid cancer was missed. CONCLUSION. Most thyroid nodules incidentally detected on non FDG PET nuclear medicine studies are detected on 99m Tc-sestamibi parathyroid scans and 111 In-pentetreotide scans. Because these nodules are extremely rare and the malignancy rate is high, further evaluation of incidental focal radiotracer-avid thyroid findings with ultrasound is an appropriate recommendation. T hyroid nodules are a common incidental finding during imaging, especially on ultrasound and CT scans [1 5]. Among nuclear medicine studies, most incidental thyroid nodules are identified at 18 F-FDG PET [6 9]. Previous studies have shown that the prevalence of incidental thyroid nodules found with FDG PET is 1 2% and that the malignancy rate is 33 58% [6 9]. Increased radiotracer uptake in an incidental thyroid nodule is regarded as suspicious regardless of the sonographic findings because even FDG-avid nodules without suspicious sonographic findings have a fairly high malignancy rate of 11 13% [8, 9]. Given these results, further workup with thyroid ultrasound and fine-needle aspiration (FNA) is recommended for FDG-avid incidental thyroid nodules, according to the American College of Radiology (ACR) white paper on man- aging thyroid nodules incidentally detected at imaging [3]. Far less is known about incidental thyroid nodules with increased radiotracer uptake on non FDG PET nuclear medicine studies. The ACR white paper recommends that these nodules also be evaluated with ultrasound, but the literature on these nodules is limited to a few reports of incidental thyroid nodules and small studies of known thyroid nodules on 99m Tc-sestamibi or methoxyisobutylisonitrile (MIBI) and 111 In-pentetreotide scans [4, 10 16]. A 2014 review of 101 surgically managed incidental thyroid malignancies over a decade [4] revealed only one patient with cancer incidentally detected on a nuclear medicine study other than FDG PET, an 111 In-pentetreotide scan. It is not known how many benign nodules were evaluated in this period or whether malignancies were diagnosed that 420 AJR:206, February 2016

2 Incidental Thyroid Nodules on Non-PET Nuclear Medicine Imaging were not treated surgically. Further knowledge of the outcomes of workup of incidental thyroid nodules detected on non-pet nuclear medicine studies would provide direction for the optimal plan for workup of incidental thyroid findings. The aim of this study was to estimate the prevalence of thyroid nodules detected incidentally on non FDG PET nuclear medicine imaging studies and their malignancy rate. A secondary aim was to determine predictors of malignancy. Our hypothesis was that incidental thyroid nodule detection with non FDG PET nuclear medicine imaging studies is a rare occurrence and that the malignancy rate is low. We additionally hypothesized that there would be no reliable predictors of malignancy after malignancy rates were compared on the basis of radiotracer type, patient characteristics, and suspicious sonographic characteristics. Materials and Methods Study Population A retrospective cohort study was conducted with the records of patients who underwent FNA or surgery for incidental thyroid findings on non- PET nuclear medicine imaging studies from January 1, 2004, to October 24, 2014, at our institution. Patients were identified via the Duke Enterprise Data Unified Content Explorer by query of all nuclear medicine reports for the term thyroid, which yielded 10,090 results. For the same data range, we searched for the term thyroid anywhere in a pathology report, which yielded 10,596 results. The presence of a pathology report indicated that the patient had undergone biopsy or surgery. The results from these two searches were filtered to establish a patient cohort that included only patients who had positive results in both searches, and this cohort contained 1850 patients. After exclusion of patients who underwent PET (almost entirely consisting of 18 F-FDG PET/CT) or studies performed for a thyroid abnormality, there were 84 patients. The medical records of these patients were reviewed for clinic notes and imaging and pathology results. This study was approved by the institutional review board with a waiver of the requirement to obtain informed consent for this retrospective analysis. To establish a cohort limited to radiotracer-avid focal and incidental findings, patients were further excluded for symptomatic or palpable thyroid findings (n = 15), imaging findings of diffuse thyroid uptake (n = 7), non radiotracer-avid thyroid nodule (n = 4), thyroid nodule previously investigated more than 3 months earlier or being evaluated with active surveillance (n = 20), and thyroid pathologic result A B Fig year-old woman with hyperparathyroidism and incidental finding of right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99m Tc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99m Tc-sestamibi scintigram from same examination as A shows persistent mild nodular uptake (arrow) in inferior aspect of right thyroid lobe. Uptake corresponds to thyroid nodules on SPECT/CT and subsequent thyroid ultrasound images. Final pathologic result after surgical excision was benign. A B Fig year-old man with hyperparathyroidism and incidental right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99m Tc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99m Tc-sestamibi scintigram shows persistent mild nodular uptake (arrow) in inferior aspect of right thyroid lobe. Uptake corresponds to thyroid nodules on SPECT/CT and subsequent thyroid ultrasound images. Final pathologic result after surgical excision was papillary carcinoma (T1N0M0). AJR:206, February

3 Yerubandi et al. not corresponding to a nodule detected at nuclear imaging (n = 7). The final patient cohort consisted of 31 patients with radiotracer-avid incidental thyroid findings and pathologic results. Clinical and Nuclear Medicine Imaging Data Data collected included patient factors (sex, age, history of nonthyroid malignancy) and imaging examination details (nuclear medicine examination, radiotracer type, indication for examination). Nuclear medicine imaging studies were performed according to department standard protocols at our institution. Imaging reports were reviewed to determine how the imaging findings were reported. The reporting styles were categorized into reported in the findings section only, reported in the impression section without management recommendation, and reported in the impression section with management recommendation. To estimate the proportion of non-pet nuclear medicine studies that resulted in workup for a thyroid abnormality, we discerned the total number of non-pet nuclear medicine studies performed at our institution in the study period from a combination of hospital billing data and nuclear medicine radiopharmacy records. Ultrasound Findings and Pathologic Workup The pathologic workup included biopsy, surgery, or both. For patients who had undergone ultrasound before the procedure, the ultrasound images were retrospectively evaluated at a PACS workstation by two radiologists (a board-certified radiologist with 13 years of experience and a 4th-year radiology resident). They looked for characteristics in the nodule corresponding to the location of the nuclear imaging finding and for additional thyroid nodules. Data collected included the largest nodule size and suspicious sonographic features that were criteria for biopsy according to the Society of Radiologists in Ultrasound (SRU) [17] and the American Thyroid Association (ATA) [18]. These features included solid versus cystic composition, hypoechogenicity, extrathyroidal extension and irregular margins, taller-than-wide shape, microcalcifications, and rim calcifications with an extrusive soft-tissue component. According to these criteria, the thyroid nodules were categorized as SRU positive or negative and ATA positive or negative. The cytologic results on nodules sampled by FNA were categorized according to the Bethesda thyroid cytopathology system (categories I VI) [19]. The final pathologic result was based on findings at examination of the surgical resection specimen if available and on FNA biopsy result if surgical resection was not performed. Location and the size of the nodule were matched with radiotracer uptake to ensure that they matched the Fig year-old man with history of carcinoid tumor and incidental right thyroid nodule. Delayed 24-hour anterior planar 111 In-pentetreotide scan shows focal abnormal uptake (arrow) in inferior aspect of right thyroid lobe. Uptake corresponds to thyroid nodule on SPECT/CT images. Final pathologic result after fine-needle aspiration was benign. pathologic findings. If a thyroid microcarcinoma coexisted with a benign radiotracer-avid nodule, the case was classified as benign. Outcome Measures and Statistical Analysis The primary outcome of interest was proportion of incidental thyroid nodules that were malignant. The characteristics of patients with malignant incidental thyroid nodules were compared with those of patients with nonmalignant results (benign and cytologic results of atypia or follicular lesion of undetermined importance). Either a chi-square test or a Fisher exact test was used for testing differences between categoric variables. The unpaired t test was used to test for differences in continuous variables. The prevalence of incidentally detected thyroid nodules evaluated by biopsy or pathologic analysis of the surgical specimen was calculated from the number of patients with incidental thyroid nodules detected on the included nuclear medicine studies divided by the total of number of examinations Fig year-old woman with history of cryptogenic cirrhosis and carcinoid tumor with incidental right thyroid nodule. Delayed 24-hour anterior planar 111 In-pentetreotide scan shows focal abnormal uptake (arrow) in inferior aspect of right thyroid lobe. Uptake corresponds to thyroid nodule on SPECT/CT images. Final pathologic result after surgical excision was papillary carcinoma (T1N0M0). performed with the study and radiotracer types over the established time period. The data were entered into a Microsoft Excel 2010 spreadsheet. Statistical analyses were performed with SAS software (Enterprise version 4.2, SAS Institute). All p values were two-sided, and p < 0.05 was considered statistically significant. Results Prevalence of Incidental Thyroid Findings and Malignancy Rate Thirty-one patients (25 women, 6 men; mean age, 62 years) with incidental thyroid findings on non FDG PET nuclear medicine studies underwent biopsy or surgery. The non-pet nuclear medicine studies were MIBI parathyroid scintigraphy (25 patients [80.6%]), 111 In-pentetreotide scans (five patients [16.1%]), and 99m Tc-tetrofosmin cardiac SPECT (one patient [3.2%]). Representative examples of benign and malignant 422 AJR:206, February 2016

4 Incidental Thyroid Nodules on Non-PET Nuclear Medicine Imaging incidentally detected thyroid nodules on MIBI parathyroid scans and 111 In-pentetreotide scans are shown in Figures 1 4. In the study period, our institution billed for 1200 parathyroid scintigraphic studies, In-pentetreotide scan studies, and 19,534 cardiac SPECT studies (any cardiac SPECT radiotracer). Based on a total of 21,402 examinations, the prevalence of performance of biopsy or surgery for an incidental thyroid finding on non-pet nuclear medicine studies was 0.14%. By study type, incidental thyroid findings that prompted biopsy or surgery were made on 2.08% of parathyroid MIBI scans, 0.75% of 111 In-pentetreotide scans, and 0.005% of cardiac SPECT scans. In the end, 5 of 31 (16.1%) of the radiotracer-avid thyroid nodules were malignant. All malignancies were surgically excised. All five malignancies were papillary thyroid carcinoma, and all were stage I except for one papillary thyroid carcinoma that was deemed stage III (T1N1aM0) after analysis of a thyroidectomy and central lymphadenectomy specimen that contained a single level VI cervical lymph node metastasis. Among the 26 patients without malignant radiotracer-avid thyroid nodules, 14 patients had benign results at surgical excision, and 10 patients underwent thyroid FNA without surgery. The Bethesda categories in these 10 FNA patients who did not undergo surgery were category II (benign) in seven patients and category III (atypia or follicular lesion of undetermined significance) in three patients. Two patients with benign radiotraceravid thyroid nodules had incidental papillary microcarcinomas in their surgical specimens that did not correspond to the abnormal radiotracer uptake that prompted further evaluation. These nodules in these patients were classified as benign for the purpose of this study. Clinical and Nuclear Medicine Imaging Predictors of Malignancy Table 1 compares the characteristics of patients with and those without thyroid cancer. There were no statistically significant differences in age (p = 0.12), sex (p = 0.24), or history of nonthyroid malignancy (p = 0.63). Three of 31 (9.7%) patients died in the study period, and all three had nonmalignant pathologic results. Thyroid findings were most commonly reported in the impression section without recommendations for workup (22/31 [71.0%]). Only 6 of 31 reports (19.4%) provided a recommendation for further evaluation. There was no difference in reporting style for patients who had thyroid TABLE 1: Characteristics of Patients With Incidental Thyroid Findings on Non FDG PET Nuclear Medicine Studies Characteristic All Patients malignancy compared with those with nonmalignant thyroid nodules (p = 1.0). Ultrasound Findings and Pathologic Workup Thyroid ultrasound images were available for retrospective radiologic review for Patients Without Cancer Patients With Cancer No. of patients Age (y) 0.12 Mean SD Sex 0.24 Women 25 (80.6) 22 (84.6) 3 (60.0) Men 6 (19.4) 4 (15.4) 2 (40.0) History of other malignancy (38.5) 3 (60.0) 0.63 Death 3 3 (11.5) Nuclear medicine study m Tc-sestamibi parathyroid scan (80.8) 4 (80.0) 111 In-pentetreotide scan 5 4 (15.4) 1 (20.0) 99m Tc-tetrofosmin cardiac SPECT 1 1 (3.8) 0 Reporting style 1.0 Only in findings of report 3 3 (11.5) 0 Findings and impression without (69.2) 4 (80.0) recommendations Recommendations for workup 6 5 (19.2) 1 (20.0) Workup Ultrasound (76.9) 3 (60.0) 0.58 Fine-needle aspiration (76.9) 3 (60.0) 0.58 Surgery (61.5) 5 (100.0) 0.14 Size of largest nodule on ultrasound 0.34 image (mm) Mean SD Ultrasound criteria for biopsy Society of Radiologists in Ultrasound (85.0) 2 (66.7) 0.45 American Thyroid Association (85.0) 2 (66.7) 0.45 Bethesda classification fine-needle 0.18 aspiration score I II (60.0) 1 (33.3) III 9 8 (40.0) 1 (33.3) IV V VI (33.3) Note Except for age and lesion size, values are numbers of patients with percentages in parentheses. 23 of 31 (74.2%) patients, which allowed application of the SRU or ATA recommendations. This group included three of the five malignancies because two of the malignant thyroid nodules were not evaluated with ultrasound in the radiology department during p AJR:206, February

5 Yerubandi et al. the course of the workup. These patients underwent concomitant excision of the thyroid nodules during parathyroid surgery. There were no differences between the malignant and nonmalignant groups in mean size of thyroid nodules on ultrasound images (p = 0.34) (Table 1). Both the SRU and ATA categorization methods would have resulted in recommendations for biopsy of 19 of 23 (82.6%) of the incidentally identified thyroid nodules. One case (33%) of localized papillary thyroid cancer would have been missed according to each of the recommendations. Patients with thyroid cancer did not have differences in SRU or ATA criteria compared with those with nonmalignant thyroid nodules (p = 0.45 for both SRU and ATA). Discussion There have been multiple studies of the incidental detection of thyroid nodules during FDG PET, but to our knowledge, no studies have focused on the clinical significance of focal radiotracer uptake in the thyroid on non FDG PET nuclear medicine studies. Our study showed that incidental thyroid nodules on non FDG PET nuclear medicine studies that are evaluated with biopsy or surgery are rare: we identified only 31 cases in a search of more than a decade of records. However, when these nodules are identified, the malignancy rate is high at 16.1%. These results support the ACR white paper recommendations that increased radiotracer activity in thyroid nodules found on non FDG PET nuclear medicine studies merit further evaluation with ultrasound [3]. The current practice of workup of incidental thyroid nodules has been criticized for not being cost-effective [1, 3]. Thyroid nodules are present in as much as 50% of the population at autopsy, and the overwhelming majority of incidental thyroid nodules are benign [17, 20]. In addition, initiation of workup commonly leads to biopsy and surgery, but most small, localized differentiated thyroid cancers are typically indolent. A subset of papillary thyroid microcarcinomas are now being evaluated with careful surveillance without planned surgery [3, 21]. To improve selection for workup of incidental thyroid nodules detected on non FDG PET nuclear medicine studies, it is important to appreciate the risk or malignancy rate. To our knowledge, no previous studies have been conducted to evaluate the malignancy rate and outcomes of thyroid nodules incidentally detected on non FDG PET nuclear medicine studies, but two studies have been conducted to evaluate thyroid MIBI scanning of preoperative patients with known thyroid nodules. Kresnik et al. [11] performed MIBI scanning of the thyroid in 62 patients with known cold nodules on 99m Tc-pertechnetate scans. They found 23 were MIBI positive, of which five (22%) were malignant. Sathekge et al. [10] studied 71 patients with nodular thyroid glands; 32 had MIBI-positive results, and 21 (66%) MIBI-positive nodules were malignant. We found a lower malignancy rate of 16.0% for MIBI-positive nodules and an overall combined malignancy rate of 16.1% for incidental thyroid nodules detected on MIBI, 111 In-pentetreotide, and cardiac SPECT scans. The difference in MIBI-positive nodule rate could be related to a lower overall malignancy rate in our study, our broader study population without known thyroid nodules, and our use of a larger FOV (not optimized to study the thyroid). Our radiotracer-avid malignancy rate is lower than that for incidental thyroid nodules detected with FDG PET (33 58%), but it is higher than the malignancy rate for selected nodules evaluated with ultrasound (9 13%) and CT or MRI (0 11%) [6 9, 17, 22]. Thus, it seems that activity during nuclear medicine imaging is associated with a higher risk of malignancy than is a focal finding made on crosssectional images alone. The ACR white paper [3] recommends ultrasound and FNA of nodules that are FDG avid at PET and ultrasound workup for avid nodules in all other nuclear studies. The decision to biopsy a thyroid nodule that is not FDG avid at PET is based on the ultrasound findings. Our results agree with these recommendations. Although the malignancy rate in thyroid nodules on non-pet nuclear studies is high, it is still substantially lower than the FDG PET rate. In addition, we found no predictors of malignancy based on patient and nuclear medicine test results. If the SRU or ATA sonographic recommendations for biopsy had been followed, four biopsies (17.4%) could have been avoided, and one papillary thyroid cancer would have been missed. Another finding in our study that favors ultrasound workup of incidental thyroid nodules on non FDG PET nuclear imaging studies is that the number of nodules worked up is low in relation to the number of scans performed. The prevalence of incidental thyroid nodules on non-pet nuclear medicine studies that were evaluated with biopsy or surgery was 2% for parathyroid MIBI scans and less than 1% for all other studies; the next highest rate was 0.75% for 111 In-pentetreotide scans. These low rates are concordant with the findings in other studies of incidental thyroid nodules. Hobbs et al. [23] conducted a study that included 107 patients with incidental thyroid nodules who underwent biopsy in a 12-month period. The most common modality with which the nodules were detected was ultrasound (47 patients), followed by CT (37 patients), PET/CT (12 patients), and MRI (11 patients). No incidental thyroid nodules were detected on non FDG PET nuclear imaging studies. A review of 101 incidental thyroid malignancies over a decade at an academic center [4] revealed only one patient with an incidental cancer detected on a nuclear medicine study other than FDG PET ( 111 In-pentetreotide scan). Thus, recommending workup for all of these nodules would not add a substantial burden to the health care system as a whole [1]. There were several limitations to our study. First, our cohort was limited to patients with available pathologic results from FNA or surgical resection. This underestimates the prevalence of incidental thyroid nodules because some patients may have had reported findings that were not worked up or findings that were evaluated only with ultrasound. This selection bias could also potentially result in overestimation of the malignancy rate, because more suspicious nodules on ultrasound are more likely to be evaluated with FNA and surgery. Despite this, the malignancy rate seems to agree with the rates in other studies evaluating thyroid nodules on MIBI scans [11]. The second major limitation was the small sample size from a single center, which limited our ability to detect statistically significant differences in characteristics between malignant and nonmalignant thyroid nodules. However, given our findings of a higher malignancy rate in this cohort, it is unlikely that additional characteristics would prevent workup. Finally, most of the patients underwent parathyroid MIBI studies, and most would have undergone ultrasound for potential localization of the parathyroid lesion. Thus, the nuclear imaging finding did not necessarily lead to a change in management, because many of these patients would proceed along a localization algorithm anyway as part of their routine evaluation for primary hyperparathyroidism. Some patients had thyroid nodules removed in large part because they were already undergoing parathyroid surgery for the original indication of hyperparathyroidism. 424 AJR:206, February 2016

6 Incidental Thyroid Nodules on Non-PET Nuclear Medicine Imaging In summary, incidental thyroid nodules on non FDG PET nuclear medicine studies that are worked up with pathologic analysis are extremely rare. When detected, the thyroid nodules are usually noted on MIBI parathyroid and 111 In-pentetreotide scans. As seen for incidental detection of thyroid nodules at FDG PET, the malignancy rate is higher than that for incidental nodules seen at CT, MRI, and ultrasound. The ACR white paper recommendations for further evaluation with ultrasound are appropriate. References 1. Youserm DM, Huang T, Loevner LA, Langlotz CP. Clinical and economic impact of incidental thyroid lesions found with CT and MR. AJNR 1997; 18: Nguyen XV, Choudhury KR, Eastwood JD, et al. Incidental thyroid nodules on CT: evaluation of 2 risk-categorization methods for work-up of nodules. AJNR 2013; 34: Hoang JK, Langer JE, Middleton WD, et al. Managing incidental thyroid nodules detected on imaging: white paper of the ACR Incidental Thyroid Findings Committee. J Am Coll Radiol 2015; 12: Bahl M, Sosa JA, Nelson RC, Esclamado RM, Choudhury KR, Hoang JK. Trends in incidentally identified thyroid cancers over a decade: a retrospective analysis of 2,090 surgical patients. World J Surg 2014; 38: Bahl M, Sosa JA, Nelson RC, Hobbs HA, Wnuk NM, Hoang JK. Thyroid cancers incidentally detected at imaging in a 10-year period: how many cancers would be missed with use of the recommendations from the Society of Radiologists in Ultrasound? Radiology 2014; 271: Soelberg KK, Bonnema SJ, Brix TH, Hegedus L. Risk of malignancy in thyroid incidentalomas detected by 18 F-fluorodeoxyglucose positron emission tomography: a systematic review. Thyroid 2012; 22: Shie P, Cardarelli R, Sprawls K, Fulda KG, Taur A. Systematic review: prevalence of malignant incidental thyroid nodules identified on fluorine-18 fluorodeoxyglucose positron emission tomography. Nucl Med Commun 2009; 30: Kwak JY, Kim EK, Yun M, et al. Thyroid incidentalomas identified by 18 F-FDG PET: sonographic correlation. AJR 2008; 191: Choi JS, Choi Y, Kim EK, et al. A risk-adapted approach using US features and FNA results in the management of thyroid incidentalomas identified by 18 F-FDG PET. Ultraschall Med 2014; 35: Sathekge MM, Mageza RB, Muthuphei MN, Modiba MC, Clauss RC. Evaluation of thyroid nodules with technetium-99m MIBI and technetium- 99m pertechnetate. Head Neck 2001; 23: Kresnik E, Gallowitsch HJ, Mikosch P, Gomez I, Lind P. Technetium-99m-MIBI scintigraphy of thyroid nodules in an endemic goiter area. J Nucl Med 1997; 38: Villa G, Ratto GB, Carletto M, et al. The incidental discovery of follicular thyroid cancer with In-111 pentetreotide scintigraphy in a patient with carcinoid tumor of the lung. Clin Nucl Med 2003; 28: Görges R, Kahaly G, Muller-Brand J, et al. Somatostatin receptor status in non-medullary thyroid carcinoma. Nuklearmedizin 1999; 38: Gorges R, Kahaly G, Muller-Brand J, Macke H, Roser HW, Bockisch A. Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid 2001; 11: Forssell-Aronsson EB, Nilsson O, Bejegard SA, et al. 111 In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors. J Nucl Med 2000; 41: Treglia G, Caldarella C, Saggiorato E, et al. Diagnostic performance of (99m)Tc-MIBI scan in predicting the malignancy of thyroid nodules: a meta-analysis. Endocrine 2013; 44: Frates MC, Benson CB, Charboneau JW, et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 2005; 237: Haugen BR, Alexander EK, Bible KC, et al American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2015 Oct 14 [Epub ahead of print] 19. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009; 132: Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15: Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 2010; 34: Nam-Goong IS, Kim HY, Gong G, et al. Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings. Clin Endocrinol (Oxf) 2004; 60: Hobbs HA, Bahl M, Nelson RC, et al. Incidental thyroid nodules detected at imaging: can diagnostic workup be reduced by use of the Society of Radiologists in Ultrasound recommendations and the three-tiered system? AJR 2014; 202:18 24 FOR YOUR INFORMATION This article is available for CME and Self-Assessment (SA-CME) credit that satisfies Part II requirements for maintenance of certification (MOC). To access the examination for this article, follow the prompts associated with the online version of the article. AJR:206, February