Nuclear Medicine and Molecular Imaging • Original Research Yerubandi et al. Incidental Thyroid Nodules on Non-PET Nuclear Medicine Imaging
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Nuclear Medicine and Molecular Imaging Original Research
Incidental Thyroid Nodules at Non–FDG PET Nuclear Medicine Imaging: Evaluation of Prevalence and Malignancy Rate Vijay Yerubandi1 Bennett B. Chin1 Julie A. Sosa2,3 Jenny K. Hoang1,4 Yerubandi V, Chin BB, Sosa JA, Hoang JK
Keywords: incidental, incidentaloma, nuclear medicine, thyroid, thyroid nodule DOI:10.2214/AJR.15.15192 Received June 15, 2015; accepted after revision September 28, 2015. 1 Department of Radiology, Duke University Medical Center, DUMC Box 3808, Erwin Rd, Durham, NC, 27710, Address correspondence to J. K. Hoang ([email protected]). 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; 206:420–425 0361–803X/16/2062–420 © American Roentgen Ray Society
420
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 99mTc-sestamibi parathyroid scans (80.6%), 111In-pentetreotide scans (16.1%), and 99mTc-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 99mTc-sestamibi parathyroid scans and 111In-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. 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 18F-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-
T
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 99mTc-sestamibi or methoxyisobutylisonitrile (MIBI) and 111In-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 111In-pentetreotide scan. It is not known how many benign nodules were evaluated in this period or whether malignancies were diagnosed that
AJR:206, February 2016
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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 nonPET 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 18F-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. 1—71-year-old woman with hyperparathyroidism and incidental finding of right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99mTc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99mTc-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. 2—36-year-old man with hyperparathyroidism and incidental right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99mTc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99mTc-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 2016 421
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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
422
Fig. 3—67-year-old man with history of carcinoid tumor and incidental right thyroid nodule. Delayed 24-hour anterior planar 111In-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. 4—56-year-old woman with history of cryptogenic cirrhosis and carcinoid tumor with incidental right thyroid nodule. Delayed 24-hour anterior planar 111In-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
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Nuclear Medicine and Molecular Imaging Original Research
Incidental Thyroid Nodules at Non–FDG PET Nuclear Medicine Imaging: Evaluation of Prevalence and Malignancy Rate Vijay Yerubandi1 Bennett B. Chin1 Julie A. Sosa2,3 Jenny K. Hoang1,4 Yerubandi V, Chin BB, Sosa JA, Hoang JK
Keywords: incidental, incidentaloma, nuclear medicine, thyroid, thyroid nodule DOI:10.2214/AJR.15.15192 Received June 15, 2015; accepted after revision September 28, 2015. 1 Department of Radiology, Duke University Medical Center, DUMC Box 3808, Erwin Rd, Durham, NC, 27710, Address correspondence to J. K. Hoang ([email protected]). 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; 206:420–425 0361–803X/16/2062–420 © American Roentgen Ray Society
420
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 99mTc-sestamibi parathyroid scans (80.6%), 111In-pentetreotide scans (16.1%), and 99mTc-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 99mTc-sestamibi parathyroid scans and 111In-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. 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 18F-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-
T
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 99mTc-sestamibi or methoxyisobutylisonitrile (MIBI) and 111In-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 111In-pentetreotide scan. It is not known how many benign nodules were evaluated in this period or whether malignancies were diagnosed that
AJR:206, February 2016
Downloaded from www.ajronline.org by Univ Of California-San Diego on 02/10/16 from IP address 132.239.1.230. Copyright ARRS. For personal use only; all rights reserved
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 nonPET 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 18F-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. 1—71-year-old woman with hyperparathyroidism and incidental finding of right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99mTc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99mTc-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. 2—36-year-old man with hyperparathyroidism and incidental right thyroid nodule on parathyroid scan. A, Immediate anterior planar 99mTc-sestamibi scintigram shows focal nodular uptake (arrow) in inferior aspect of right thyroid lobe. B, Delayed 2-hour anterior planar 99mTc-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 2016 421
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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
422
Fig. 3—67-year-old man with history of carcinoid tumor and incidental right thyroid nodule. Delayed 24-hour anterior planar 111In-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. 4—56-year-old woman with history of cryptogenic cirrhosis and carcinoid tumor with incidental right thyroid nodule. Delayed 24-hour anterior planar 111In-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
