Incidental Thyroid Nodules on Chest CT: Review of the Literature and Management Suggestions

Transcription

1 Special rticle Clinical Perspective hmed et al. Thyroid Nodules on Chest CT Special rticle Clinical Perspective Sameer hmed 1 Karen M. Horton 2 R. rooke Jeffrey, Jr. 3 Sheila Sheth 2 Elliot K. Fishman 4 hmed S, Horton KM, Jeffrey R Jr, Sheth S, Fishman EK Keywords: MDCT, nodules, thyroid DOI: /JR Received February 22, 2010; accepted after revision pril 28, Johns Hopkins University School of Medicine, altimore, MD. 2 Department of Radiology, Johns Hopkins Medical Institutions, 601 N Caroline St., JHOC 3253, altimore, MD ddress correspondence to K. M. Horton (kmhorton@jhmi.edu). 3 Department of Radiology, Stanford University Medical Center, Stanford, C. 4 The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, altimore, MD. JR 2010; 195: X/10/ merican Roentgen Ray Society Incidental Thyroid Nodules on Chest CT: Review of the Literature and Management Suggestions OJECTIVE. This article will review the current literature regarding the detection of thyroid nodules with an emphasis on CT diagnosis. We will also discuss management strategies. CONCLUSION. With advances in cross-sectional imaging, the detection of incidental thyroid nodules has increased significantly. Detection of thyroid nodules is common on chest CT that is being performed for unrelated reasons. The workup of these nodules can be timeconsuming and expensive. T he detection of thyroid nodules has increased dramatically over the past 50 years due to rapid advancements in imaging technology, especially CT, MRI, and ultrasound. Given recent improvements in MDCT, including improved resolution and thinner slice collimation, thyroid nodules are now commonly detected on chest and neck CT, typically as incidental, unsuspected findings. There is considerable variability in how radiologists report incidentally detected thyroid nodules and what follow-up recommendations, if any, they make. In addition, the risk of malignancy in these nodules remains low, yet many cases are still followed up with ultrasound and ultimately ultrasound-guided fine-needle aspiration (FN) biopsy, which at our institution averages more than $3000 in charges, including radiology and pathology charges. This improvement in technology has led to a particularly dramatic rise in the number of patients diagnosed with papillary microcarcinomas measuring less than 10 mm in diameter [1]. The recommended treatment of even small papillary thyroid carcinomas is thyroidectomy [1], which carries a small but significant risk of complications. fter surgery, patients receive lifelong thyroid hormone therapy. Despite an increase in surgeries to treat these small carcinomas, thyroid cancer specific mortality has not improved [1]. Ito et al. [2] showed that of 162 patients with papillary microcarcinomas followed without surgery, more than 70% of tumors either remained stable or decreased in size, even after 5 years or more, suggesting that overdiagnosis and overtreatment of thyroid disease is a significant concern, as noted by lack and Welch [3]. This article will review the current literature regarding the detection of thyroid nodules, with an emphasis on CT diagnosis. We will review case examples and discuss suggested guidelines for management of thyroid nodules detected on CT. Literature Review Thyroid carcinoma is the most frequent type of endocrine cancer in the United States, with 33,500 new cases diagnosed each year but only 1,500 deaths annually, mainly due to uncommon, aggressive forms of the disease [4]. The yearly incidence of differentiated thyroid cancers is increasing due, in part, to more frequent detection of small nonpalpable nodules on cross-sectional imaging examinations performed for unrelated indications [5]. The incidence and prevalence of unsuspected thyroid nodules varies with the population studied and the methods used for detection. The frequency of these incidentalomas has ranged from as low as 2% to as high as 67% [6 8]. The vast majority of cases are ultimately diagnosed as benign colloid nodules, cysts, or adenomas, whereas approximately 5% of nodules are malignant [9]. utopsy series report the highest prevalence of thyroid nodularity [10]. Mortensen et al. [11] examined 821 patients with no history of thyroid disease and reported nodules in 50% of thyroid glands. Nodules as small as 2 mm in diameter were detected, but it is unclear whether these are clinically relevant. This study showed 1066 JR:195, November 2010

2 Thyroid Nodules on Chest CT an equal frequency of benign and malignant nodules, but most were asymptomatic microcarcinomas unrelated to the cause of death. Several ultrasound-based studies have reported on the frequency of incidental thyroid nodules. Steele et al. [12] retrospectively reviewed 2,004 bilateral carotid duplex sonography scans and reported thyroid nodules in 9% of patients (approximately 60% of nodules were detected in women). These patients did not have a history of thyroid nodules or known thyroid disease. In another study using this method of detection, Carroll [13] reported a 13% incidence (three men and six women) of asymptomatic thyroid nodules in a total of 67 patients without history of thyroid disease or head and neck radiation. Woestyn et al. [14] performed ultrasound examinations on 300 patients without any signs or symptoms of thyroid disease, asymmetry, or enlargement. Small, incidental echoic nodules were seen in 19% of patients (17% of men and 20% of women). study by artolotta et al. [15] in Italy examined 704 patients with high-resolution sonography and real-time spatial compound sonography. They reported an overall prevalence of 33%, with 60% of incidental nodules found in women. The highest reported frequency also was from an ultrasound-based study by Ezzat et al. [8] that detected unsuspected nodules in 67% of a total of 100 healthy patients. This is likely an overestimation of the prevalence because 84% of the subjects were women. These studies show that thyroid nodules are detected by ultrasound in a large proportion of patients, but the malignancy rates are still around 5% and the vast majority of these malignancies (75 80%) represent small papillary carcinomas [9]. limited number of CT- and MRI-based studies have examined the prevalence of incidental thyroid nodules. Yoon et al. [16] examined 734 patients without known thyroid disease using 16-MDCT contrast-enhanced scans of the neck and found thyroid nodules in 16% of the subjects. They also found that 9% of these incidentalomas were malignant, with some diagnostic CT features, such as nodular or rim calcifications, anteroposterior to transverse diameter ratio above 1.0, and mean attenuation value on contrast-enhanced scans greater than 130 HU. nother study by Youserm et al. [17] analyzed 123 CT scans of the head and neck and 108 MRI examinations and reported the prevalence of incidental thyroid nodules at 16%. Of the 14 patients evaluated for malignancy, none developed thyroid carcinoma by months of follow-up. Neither of these studies excluded patients with a history of neck radiation. Incidental thyroid nodules are detected least frequently in PET scans. Cohen et al. [6] reviewed all patients who underwent PET with use of 18 F-FDG at their institution and reported unsuspected nodules in 2% of patients. This large study of 4,525 subjects also included thyroid biopsy results for 15 patients with newly discovered nodules and 47% were found to be malignant. However, these patients were undergoing FDG PET for cancer staging, which introduces a potential selection and population bias. Patients with a history of neck radiation were not excluded, which likely contributed to a high rate of thyroid cancer. In addition, because PET is best at detecting active nodules, it is certainly more likely that nodules detected on PET will be malignant. Kang et al. [7] used FDG PET to examine 1,330 subjects and also identified thyroid incidentalomas in 2% of glands. Histologic diagnoses of PET-positive nodules were available for 15 glands by either sonography-guided core needle biopsy or surgical resection of the tumor, and approximately 26% tested positive for thyroid cancer. In both studies, the number of patients evaluated for malignancy was quite low compared with the total number of cases. FDG PET is a useful tool for detecting thyroid malignancies, with reported sensitivity of 75 90% and specificity of 90% [18, 19]. However, small nodules may be below the threshold for accurate detection. In summary, thyroid nodules are commonly detected as incidental findings on all imaging techniques including CT, sonography, MRI, and PET/CT. The chance of malignancy in these nodules is relatively low, depending on other risk factors and imaging characteristics. lso, most of these malignancies will be small papillary cancers [1]. Management Guidelines Incidentally detected thyroid nodules are a common clinical problem, and their management remains controversial. The majority of these nodules are either benign or small asymptomatic papillary cancers of questionable clinical significance. The challenge then becomes determining which nodules can be ignored, which should undergo biopsy, and which require surgical intervention. We will review major sets of guidelines established by the merican Thyroid ssociation (T), the National Comprehensive Cancer Network (NCCN), and the ritish Thyroid ssociation (T). Please note that there are many other guidelines available, such as guidelines by the Society of Radiologists in Ultrasound [20]. However, they are beyond the scope of this article but may be of interest to the reader. In 2006, T established guidelines for appropriate evaluation of incidentally discovered thyroid nodules [21]. They recommend that, in general, thyroid nodules 1 cm or larger should be further evaluated for malignancy. Nodules that are smaller than 1 cm may be considered for evaluation if a sonogram contains features indicative of malignancy, the patient has a history of head and neck radiation, or there is a family history of thyroid carcinoma. Thyroid nodules also require further evaluation in patients with regional lymphadenopathy, vocal cord paralysis, and physical interference with neck structures. Patients who fit the aforementioned criteria require an initial evaluation of serum thyroid-stimulating hormone (TSH). If TSH levels are not suppressed, then an ultrasound examination is recommended. FN biopsy, preferentially with ultrasound guidance, is a cost-effective procedure that should be used to test for malignancy; however, cystic nodules that yield nondiagnostic cytology should be followed through imaging or, in the case of firm nodules, surgery. If thyroid nodules are found to be malignant, the T strongly recommends surgery, but benign cytology does not require further diagnostic study or treatment. However, it is recommended that benign nodules be followed at 6- to 18-month intervals for evidence of growth. Thyroid glands with multiple nodules larger than cm require aspiration, but there are no specific recommendations regarding the number of nodules to be evaluated. ccording to the most recent guidelines established by the NCCN in 2009 [22], solitary nodules measuring greater than 1 cm in diameter in patients with certain risk factors should be further evaluated with measurement of TSH levels, neck ultrasound, and FN of nodules and clinically suspicious lymph nodes. Risk factors include age below 15 years and above 60 years, male sex, history of head and neck radiation, history of diseases associated with thyroid cancer (e.g., Gardner syndrome, Cowden syndrome, and Carney complex), and family history of thyroid cancer. Intranodular hypervascularity, irregular borders, and microcalcification seen on ultrasound are also important factors associated with malignancy [20]. Nodules that are very firm, have exhibited a pattern of rapid growth, or are invading other neck structures should be considered for surgery after FN. The NCCN also recommends that unsuspected nodules that measure less JR:195, November

3 hmed et al. than 1 cm in patients without the aforementioned risk factors should be monitored and followed-up clinically as indicated and a neck ultrasound may be considered. The T, in collaboration with the Royal College of Physicians, updated management guidelines in 2007 [23]. They did not recommend urgent referral to secondary care for the vast majority of incidental thyroid nodules. symptomatic nodules measuring less than 1 cm in unsuspected patients should be managed in primary care. If nodules are detected in a patient with a family history of thyroid cancer, history of neck irradiation, unexplained vocal abnormalities, painless growth of a palpable thyroid mass, cervical lymphadenopathy, or persistent neck pain, then it is necessary to further evaluate the condition. Initially, a thyroid function test should be performed, followed by FN biopsy. If aspiration does not yield a diagnosis after two attempts, core biopsy or surgical excision are suggested. In contrast to the T guidelines, the T does not recommend sonography for all patients under suspicion for thyroid cancer. However, ultrasound is recommended for biopsy and multinodular glands. Radioiodine isotope scanning is also not supported for diagnostic evaluation by the T, Fig year-old man who presented with shortness of breath and chest pain. Chest CT was ordered to evaluate for possible pulmonary embolism. Contrast-enhanced MDCT of chest was performed. Official CT report does not describe any thyroid nodules. and, xial () and coronal reformation () scans were reviewed as part of another study to determine prevalence of thyroid nodules on chest CT. Multiple nodules were noted (arrows); largest was described on left lobe, measuring 5 10 mm. When CT is performed for another indication, thyroid nodules can sometimes be overlooked by busy radiologists. Fig year-old man who was a smoker and presented with cough. Chest CT was ordered for suspected pneumonia. Official CT report does not describe any thyroid nodules but does note that thyroid is enlarged. This scan was reviewed as part of another study to determine prevalence of thyroid nodules on chest CT. and, xial images on repeat review show 2 1 cm nodule described in left lower pole. No nodules were seen at ultrasound. Clinical workup revealed top normal thyroid function tests. Due to artifact through thyroid from clavicles and from dense IV contrast material in subclavian veins, pseudolesions can be created. but the T does recommend its use for indeterminate cytology and suspicious lesions. Surgical intervention may be considered for malignant nodules. If a lesion is initially determined to be benign, FN biopsy should be repeated 3 6 months later to exclude the finite possibility of a false-negative diagnosis. ll of the aforementioned management guidelines include a size threshold of about 1 cm, above which a thyroid nodule requires clinical and usually imaging evaluation and likely biopsy. However, it is still unclear whether nodule size is predictive of malignancy. In one study, Papini et al. [24] correlated sonographic findings with the results of ultrasound-guided FN biopsy and pathologic staging of resected carcinomas. They examined 494 patients and showed that the prevalence of malignancy was not significantly different between nodules greater or smaller than 1 cm (9% vs 7%). Sahin et al. [25] examined 207 patients with nodular goiter and showed that 21% of nodules smaller than 1 cm and 17% of nodules larger than 1 cm were malignant. These studies suggest that nodules smaller than 1 cm, many of which are detected on CT, MRI, and ultrasound, should not be dismissed clinically due to size alone. Even small nodules need clinical correlation with physical examination and an assessment of risk factors. In high-risk patients, even nodules smaller than 1 cm in size may need biopsy. Multinodular thyroid glands present another topic of controversy, and the current guidelines are not explicitly clear in their recommendations for dealing with these entities. However, several studies have examined malignancy in glands with multiple nodules. Sippel et al. [26] retrospectively reviewed the records of 325 patients who underwent thyroidectomy with an FN diagnosis of either follicular neoplasm, Hürthle cell neoplasm, or indeterminate. They showed that the risk of malignancy was lower in patients with multiple nodules compared with those with a solitary nodule (16% vs 28%). Frates et al. [27] showed that solitary nodules have a higher per-nodule likelihood of malignancy; however, this study only considered nodules larger than 1 cm in diameter. Other studies have shown that although solitary nodules are more likely to be malignant, multinodular glands still harbor a significant portion of thyroid carcinomas [24, 28]. pproximately two thirds of thyroid cancers are found in 1068 JR:195, November 2010

4 Thyroid Nodules on Chest CT the dominant nodule in patients with multiple nodules [20]. In general, the T and T suggest that sonographic features that are indicative of malignancy should be used to select nodules for biopsy from a multinodular gland. If suspicious features are not present, the larger nodules should be preferentially evaluated for malignancy. Incidental detection of nodules in patients with another known malignancy is also a clinical problem. In a study by Wilhelm et al. [29], 41 patients with a history of another C E known malignancy and an incidental thyroid nodule were evaluated. Thirty-five of the 41 patients met the criterion for biopsy, which was a nodule of 1 cm or greater. Twenty of these 35 had atypical biopsy results warranting surgical resection. Sixteen of these 20 underwent surgery. Pathology revealed four papillary thyroid cancers, four micropapillary thyroid cancers, two metastatic cancers, and seven benign nodules. One patient who did not fit their criteria of an abnormal biopsy also underwent surgical resection and Fig year-old man with history of lymphoma involving parotid gland. CT was ordered to evaluate for other sites of disease. and, Contrast-enhanced axial () and coronal reformation () images from MDCT of chest. Report described 1.9-cm nodule (arrows) in left thyroid lobe. C, Follow-up sonogram shows cm complex nodule (cursors) with cystic and solid components as well as increased vascularity. iopsy was recommended, but has not yet been performed. D F, Ultrasound also shows multiple other nodules (cursors) not reported on CT. Ultrasound is the technique of choice to characterize and measure thyroid nodules. Guidelines from various societies base biopsy recommendations on size and appearance of nodules on ultrasound as well as clinical history and risk factors. was found to have an incidental micropapillary cancer. Thus, there is still controversy regarding the management guidelines for thyroid nodules. However, the guidelines stress that clinical history is important (age, radiation, endocrine syndromes), laboratory analysis (TSH) is helpful, and the size and sonographic appearance of the nodule are important and help determine which nodules should be biopsied or followed. The guidelines do not directly address what to do with nodules detected on CT. D F JR:195, November

5 hmed et al. Fig year-old woman undergoing chest CT for evaluation of thoracic outlet syndrome. and, Contrast-enhanced axial with 5-mm slice thickness () and coronal reformation with mm slice thickness () images show 7-mm nodule in left lobe of thyroid (arrows) and sonography was recommended. C and D, Sonograms show mm 0.8 m cystic nodule with soft-tissue nodule (cursors). iopsy was performed and pathology revealed adenomatoid nodule. In retrospect, small solid nodule within cystic lesion can be seen on CT using thin slices. Characterizing incidentally detected thyroid nodule on routine chest CT using 3 to 5 mm slices can be difficult. Pitfalls in CT Detection of Thyroid Nodules dvancement in MDCT scanner technology has resulted in significant improvements in CT image resolution, now allowing submillimeter collimation. Small nodules are now commonly detected in the thyroid on examinations performed for other indications. s noted previously, on neck CT and MRI examinations, 16% of patients had unsuspected thyroid nodules [16, 17]. The value of ultrasound characterization of thyroid nodules is well accepted and yields useful information that may help guide biopsy. However, the value of CT characterization is less well studied. There may be some diagnostic features, as noted by Yoon et al. [16] that suggest malignancy, such as nodular or rim calcifications, anteroposterior to transverse diameter ratio above 1.0, and mean attenuation value on contrast-enhanced scans greater than 130 HU. However, in a study by Shetty et al. [30] of nodules detected on CT with follow-up ultrasound, the authors found no reliable CT feature to help distinguish benign from malignant nodules. s noted in the article by Shetty et al. [30], thyroid nodules detected on chest CT are typically small and often too small to characterize accurately. Even larger incidental nodules detected on CT may be difficult to characterize C because the CT was not performed specifically to address the thyroid and the entire gland may not be imaged. For example, on chest CT, the patient s arms are positioned over the head, which often results in beam hardening artifact through the thyroid as a result of high-density IV contrast material in the subclavian veins. The clavicle can also cause artifact through the thyroid gland. These artifacts can obscure nodules or create pseudolesions. In addition, small nodules would be difficult to characterize on CT unless thin collimation and multiplanar reconstruction were available. Routine chest CT is usually performed with 3- to 5-mm slice thickness, not ideal for characterizing nodules less than 1 cm in size. In the study by Shetty et al. [30], 230 patients with abnormal findings in the thyroid on CT underwent ultrasound, and 118 ultimately underwent biopsy or resection. The CT and sonography images were reviewed and correlated. CT matched the sonography findings in 53% of patients. CT correctly identified the dominant nodule but missed the multinodularity in 30% of patients. CT overestimated the number of nodules in 2.2% and was falsepositive for lesions in 4.3%. The prevalence of malignancy in these incidentally detected nodules was 3.9%, with a 7.4% rate of malignant potential [30]. The authors also report that although nodules may appear homogeneously cystic on CT, on sonography the same nodules may appear as complex cystic or solid nodules of varying echogenicity. No simple density threshold on CT could distinguish simple cysts from complex cystic or solid nodules. The authors do not address whether the size reported on the CT correlated with the size reported on sonography. ecause CT underestimated the number of nodules relative to sonography in several cases, the authors suggested that sonography is a useful followup study after incidental detection of a thyroid nodule on CT. The authors state Our results suggest that every incidental abnormality of the thyroid detected on CT deserves additional clinical or imaging evaluation to exclude the possibility of malignancy [30]. In our experience the significance of incidentally detected thyroid nodules differs depending on the appearance of the nodule as well as patient medical history and demographics (Figs. 1 4). Conclusions Thyroid nodules are being detected with increased frequency on contrast-enhanced MDCT examinations of the chest performed for unrelated reasons. However, there is considerable variability in how radiologists report incidentally detected thyroid nodules and what follow-up recommendation they make. D 1070 JR:195, November 2010

6 Thyroid Nodules on Chest CT This variability in part is related to the fact that there are no well-established criteria on CT to help distinguish benign from malignant nodules, especially when nodules measure less than 1 cm in size. Most of the guidelines established by various societies rely on clinical history, ultrasound features, and biopsy for cytopathology to determine which nodules should be left alone, followed, or resected. ccording to the literature, nodules measuring 1 cm or greater detected on CT or smaller nodules with worrisome CT features, such as calcifications or invasion of surrounding structures, should probably be referred for ultrasound evaluation and ultimately FN biopsy. Detailed clinical correlation is also important to identify risk factors such as age, history of head and neck radiation, endocrine syndromes, family history of thyroid cancer, cervical adenopathy, and so on. In patients with multiple nodules, clearly dominant nodules should probably be handled the same because CT gives limited information about the internal characteristics of nodules. However, there is still uncertainly in how to handle a small nodule of less than 1 cm detected incidentally on chest CT. Should all patients be referred for follow-up ultrasound evaluation? That seems excessive and expensive, especially because small nodules are common and the vast majority of the nodules smaller than 1 cm are benign. However, the studies summarized in this article suggest that CT characterization of nodules does not correlate well with the number of nodules or nodule characteristics found on ultrasound. It is also debatable whether the measurements of nodules detected on CT actually correlate with lesion measurements on sonography. For example, if CT shows a 7-mm nodule, will sonography show the same nodule to measure 1 cm? t this point, given the limitations of CT, it is probably prudent to report all thyroid nodules detected on CT. However, it is probably not reasonable to advise a follow-up ultrasound examination in every patient. In addition, it should be noted that radiologists typically have limited access to clinical information and the medical history of these patients. It is really the clinicians who should decide which patient needs to undergo ultrasound evaluation once a clinical examination and assessment of risk factors is considered. 2. Ito Y, Uruno T, Nakano K, et al. n observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13: lack WC, Welch HG. dvances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med 1993; 328: National Cancer Institute Website. NCI Cancer ulletin for February 19, ncicancerbulletin/nci_cancer_ulletin_021908/ page3. ccessed June 25, Chen Y, Jemal, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, Cancer 2009; 115: Cohen MS, rslan N, Dehdashti F, et al. Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose positron emission tomography. Surgery 2001; 130: Kang KW, Kim SK, Kang HS, et al. Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18 F-fluorodeoxyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subjects. J Clin Endocrinol Metab 2003; 88: Ezzat S, Sarti D, Cain DR, raunstein GD. Thyroid incidentalomas: prevalence by palpation and ultrasonography. rch Intern Med 1994; 154: Desser TS, Kamaya. Ultrasound of thyroid nodules. Neuroimaging Clin N m 2008; 18: , vii 10. Dean DS, Gharib H. Epidemiology of thyroid nodules. est Pract Res Clin Endocrinol Metab 2008; 22: Mortensen JD, Woolner L, ennett W. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15: Steele SR, Martin MJ, Mullenix PS, zarow KS, ndersen C. The significance of incidental thyroid abnormalities identified during carotid duplex ultrasonography. rch Surg 2005; 140: Carroll. symptomatic thyroid nodules: incidental sonographic detection. JR 1982; 138: Woestyn J, fschrift M, Schelstraete K, Vermeulen. Demonstration of nodules in the normal thyroid by echography. r J Radiol 1985; 58: artolotta TV, Midiri M, Runza G, et al. Incidentally discovered thyroid nodules: incidence, and greyscale and colour Doppler pattern in an adult population screened by real-time compound spatial sonography. Radiol Med 2006; 111: Yoon DY, Chang SK, Choi CS, et al. The prevalence and significance of incidental thyroid nod- 1997; 18: Feine U, Lietzenmayer R, Hanke JP, Held J, Wohrle H, Muller-Schauenburg W. Fluorine-18- FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med 1996; 37: Grunwald F, Kalicke T, Feine U, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: results of a multicentre study. Eur J Nucl Med 1999; 26: Frates MC, enson C, Charboneau JW, et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 2005; 237: Cooper DS, Doherty GM, Haugen R, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16: National Comprehensive Cancer Network Website. Thyroid Carcinoma. ccessed June 25, ritish Thyroid ssociation Website. ritish Thyroid ssociation guidelines for the management of thyroid cancer. ccessed June 25, Papini E, Guglielmi R, ianchini, et al. Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-doppler features. J Clin Endocrinol Metab 2002; 87: Sahin M, Sengul, erki Z, Tutuncu N, Guvener ND. Ultrasound-guided fine-needle aspiration biopsy and ultrasonographic features of infracentimetric nodules in patients with nodular goiter: correlation with pathological findings. Endocr Pathol 2006; 17: Sippel RS, Elaraj DM, Khanafshar E, Kebebew E, Duh QY, Clark OH. Does the presence of additional thyroid nodules on ultrasound alter the risk of malignancy in patients with a follicular neoplasm of the thyroid? Surgery 2007; 142: ; discussion, Frates MC, enson C, Doubilet PM, et al. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab 2006; 91: Deandrea M, Mormile, Veglio M, et al. Fineneedle aspiration biopsy of the thyroid: comparison between thyroid palpation and ultrasonography. Endocr Pract 2002; 8: Wilhelm SM, Robinson V, Krishnamurthi SS, Reynolds HL. Evaluation and management of incidental thyroid nodules in patients with another primary malignancy. Surgery 2007; 142: ; References 1. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, JM 2006; 295: ules identified on computed tomography. J Comput ssist Tomogr 2008; 32: Youserm DM, Huang T, Loevner L, Langlotz CP. Clinical and economic impact of incidental thyroid lesions found with CT and MR. JNR discussion, Shetty SK, Maher MM, Hahn PF, Halpern EF, quino SL. Significance of incidental thyroid lesions detected on CT: correlation among CT, sonography, and pathology. JR 2006; 187: JR:195, November