Continuing Education Column Diagnostic pproaches to Patients with Thyroid Nodules Ho-Cheol Kang, MD Department of Internal Medicine, Chonnam National University Medical School E - mail : drkang@chonnam.ac.kr J Korean Med ssoc 2009; 52(4): 405-416 bstract Thyroid nodules are epidemic with the rising use of high-resolution thyroid ultrasonography for health screening. The primary aim in investigating a thyroid nodule is to exclude the possibility of malignancy, which occurs in about 5% of nodules. Initial history taking and physical examination should focus on the clinical risk factors associated with thyroid cancer. Measurement of thyroid stimulating hormone (TSH) is the only biochemical test routinely needed to exclude autonomously functioning nodules. Thyroid ultrasonography-guided fine needle aspiration biopsy (US-FN) is the most accurate standard diagnostic test for most thyroid nodules. Ultrasonographic features of nodules associated with increased risk of thyroid cancers include hypoechogenicity, microcalcification, irregular spiculated margin, taller-than-wide, Doppler signal in the nodules, and suspicious cervical lymphadenopathies. These findings are helpful in risk stratification of the nodules and in deciding which nodule should be sampled in multinodular goiters. The success of the procedure heavily depends on the experience and expertise of the clinicians. Knowledge on basic US-FN techniques and some tricks is very important to improve overall diagnostic yields. Practically critical issues related to US-FN are emphasized based on several guidelines and author's experiences. Keywords: Thyroid nodule; Thyroid cancer; Thyroid ultrasound; Fine-needle aspiration biopsy 405
Kang HC Table 1. Clinical risk factors for thyroid cancer Degree of suspicion High Moderate Low Signs and symptoms Rapid growth ge < 20 or > 60 y No Cervical lymph nodes Nodule > 4 cm and cystic suspicouis signs Fixation to tissue Male signs and Vocal cord paralysis Hard nodule Dubious nodule fixation Head and neck irradiation symptoms Percent of malignancy 71 14 11 406
Diagnostic pproaches to Thyroid Nodules Figure 1. Diagnostic algorithm for thyroid nodules (modified from Ref. 4). 407
Kang HC C D E Figure 2. () hypoechoic nodule has multiple internal microcalcifications, which is typical for thyroid papillary carcinoma, () 3D-recondtion US image shows solid hypoechoic nature of the tumor with multiple microcalcifications, (C, D) Surgical specimen shows a whitish to yellowish lobular nodule with multiple internal calcifications, (E) Pathologic examination confirms the diagnosis of thyroid papillary carcionoma with mutliple microcalcifications. The tumor has high cellularity and multiple psammoma bodies. C Figure 3. () hypoechoic nodule containing multiple internal microcalcifications is shown in right lobe of the thyroid, () 3D-image showing the microcalcifications in the nodule, (C) Multiple bilateral lymphadenopathies(ln) are evident in both internal jugular chains. 408
Diagnostic pproaches to Thyroid Nodules Table 2. Ultrasound features associated with thyroid cancer (modified from Ref. 8) US features Sensitivity (%) Specificity (%) Positive predictive value (%) Negative predictive value (%) Hypoechogenicity 26.5~87.1 43.4~94.3 11.4~68.4 73.5~93.8 Microcalcification 26.1~59.1 85.8~95.0 24.3~70.7 41.8~94.2 Irregular margins 17.4~77.5 38.9~85.0 9.3~60.0 38.9~97.8 or no halo Taller-than- wide 32.7 92.5 66.7 74.8 Solid 69.0~75.0 52.5~55.9 15.6~27.0 88.0~92.1 Doppler signal in 54.3~74.2 78.6~80.8 24.0~41.9 85.7~97.4 the nodule Figure 4. () panoramic thyroid US view of multifocal papillary carcinoma. hypoechoic nodule is seen in each lobe of the thyroid. Right lobe nodule has central dense calcification and ascoustic shadowing. oth nodules are tallerthan-wide and hypoechoic. () Schematic drawing of the US clearly shows the taller-than-wide nature of the nodules. 409
Kang HC C D E Figure 5. case of mixed solid and cystic nodule with multple risky US features in solid portion. () lump in right side of the neck, () mixed solid-cystic nodule is seen in right lobe of the thyroid. (C) Typical multiple microcalcifications are observed in solid portion of the nodule. (D) Vascular signals are evident in solid portion of the nodule. US-FN was performed in the solid portion using capillary technique. (E) Cross sectioned specimen of resected mass shows the similar findings between US image and real mass. Cystic papillary was confirmed on pathologic examination. 410
Diagnostic pproaches to Thyroid Nodules Figure 6. Examples of suspicious lymphadenopathies (LP) suggesting metastases. () Round multiple LP, () Round LP with internal hyperechogenicity, (C) LP with cystic change, (D) LP with multiple microcalcifications. Figure 7. US-FN equipment is simple and inexpensive. Small needls (25~27 G) are critically important to improve diagnostic yield and to decrease the pain. C D 411
Kang HC Figure 8. Non-aspiration US-FN with 25-or 27-G needle. ngle correction is shown based on the location of the nodule. () more -vertical angle is used for a deep nodule. () less- vertical, more -obtuse angle is used for biopsy of a more superficial nodule. 412
Diagnostic pproaches to Thyroid Nodules C D Figure 9. Some tricks for difficut US-FN. () highly vascular nodule. Dopper vascualr mapping is helpful to avoid the puncture of vessels. () densely calcified nodule. When the calcified nodule cannot be penetrated with the needle, obtain the sample from the interface between the nodule and normal thyroid parenchyme. (C) nodule with thin eggshell calcification. Multiple breaks were seen after the US -FN. (D) mixed solid-cystic nodule. FN should be done in soloid portion. 413
Kang HC 11. Davies L, Welch HG. Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. JM 2006; 295: 2164-2167. 12. Cooper DS, Doherty GM, Haugen R, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver, Sherman SI, Tuttle RM. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16: 109-142. 13. Dean DS, Gharib H. Epidemiology of thyroid nodules. est Practice & Research Clinical Endocrinology & Metabolism 2008; 22: 901-911. 414
Diagnostic pproaches to Thyroid Nodules 14. Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med 2004; 351: 1764-71. 15. Fukada S. Toxic multinodular goiter. Nippon Rinsho 2006; 64: 2227-2232. 16. Gharib H, Papini E, Paschke R. Thyroid nodules: a review of current guidelines, practices, and prospects. Eur J Endocrinol 2008; 159: 493-505. 17. merican ssociation of Clinical Endocrinologists and ssociazione Medici Endocrinologi Medical Guidelines for clinical Practice for the Diagnosis and Management of thyroid nodules. Endocrine Practice 2006; 12: 63-102. 18. Frates MC, enson C, Charboneau JW, Cibas ES, Clark OH, Coleman G, Cronan JJ, Doubilet PM, Evans D, Goellner JR, Hay ID, Hertzberg S, Intenzo CM, Jeffrey R, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 2005; 237: 794-800. 19. Kim W, Kim TW, Kwon HS, Moon WJ, Lee J, Choi YS, KIm SK, Kim SW, Chung KW, aeck JH, Kim I, Park DJ, Na DG, Choe JH, Chung JH, Jung HS, Kim JH, Nam KH, Chang HS, Chung WY, Hong SW, Hong SJ, Lee JH, Yi KH, Jo YS, Kang HC, Song M, Park JW, Yoon JH, Kang SJ, Lee KW. Management guidelines for patients with thyroid nodules and thyroid cancer. J Korean Endocr Soc 2007; 22: 157-187. 10. Mazzaferri EL. Management of a Solitary Thyroid Nodule. N Engl J Med 1993; 328: 553-559. 11. Mandel SJ. 64-year-old woman with a thyroid nodule. JM 2004; 292: 2632-2642. 12. Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules. nn Intern Med 2005; 142: 926-931. 13. rignardello E, Corrias, Isolato G, Palestini N, Cordero di Montezemolo L, Fagioli F, occuzzi G. Ultrasound Screening for Thyroid Carcinoma in Childhood Cancer Survivors: Case Series. J Clin Endocrinol Metab 2008; 93: 4840-4843. 14. ui, Mazzaferri E. CME New Paradigms in the Diagnosis and Management of Thyroid Nodules. The Endocrinologist 2007; 17: 35. 15. Cases J, Surks MI. The changing role of scintigraphy in the evaluation of thyroid nodules. Seminars in Nuclear Medicine 2000; 30: 81-87. 16. Hegedus L, onnema SJ, ennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003; 24: 102-132. 17. Kang KW, Kim S-K, Kang H-S, Lee ES, Sim JS, Lee IG, Jeong S-Y, Kim SW. Prevalence and Risk of Cancer of Focal Thyroid Incidentaloma Identified by 18F -Fluorodeoxyglucose Positron Emission Tomography for Metastasis Evaluation and Cancer Screening in Healthy Subjects. J Clin Endocrinol Metab 2003; 88: 4100-4104. 18. Kim JM, Ryu J-S, Kim TY, Kim W, Kwon GY, Gong G, Moon DH, Kim SC, Hong SJ, Shong YK. 18F-Fluorodeoxyglucose Positron Emission Tomography Does Not Predict Malignancy in Thyroid Nodules Cytologically Diagnosed as Follicular Neoplasm. J Clin Endocrinol Metab 2007; 92: 1630-1634. 19. Marqusee E, enson C, Frates MC, Doubilet PM, Larsen PR, Cibas ES, Mandel SJ. Usefulness of ultrasonography in the management of nodular thyroid disease. nn Intern Med 2000; 133: 696-700. 20. Levine R. Something old and something new: a brief history of thyroid ultrasound technology. Endocr Pract 2004; 10: 227-233. 21. Mandel SJ. Diagnostic use of ultrasonography in patients with nodular thyroid disease. Endocr Pract 2004; 10: 246-252. 22. Solbiati L, Osti V, Cova L, Tonolini M. Ultrasound of thyroid, parathyroid glands and neck lymph nodes. Eur Radiol 2001; 11: 2411-2424. 23. Ross DS. Nonpalpable Thyroid Nodules-Managing an Epidemic. J Clin Endocrinol Metab 2002; 87: 1938-1940. 24. Gharib H, Papini E. Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin North m 2007; 36: 707-735, vi. 25. askin HJ. Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and multinodular goiters. Endocr Pract 2004; 10: 242-245. 26. Can S, Peker K. Comparison of palpation-versus ultrasoundguided fine-needle aspiration biopsies in the evaluation of thyroid nodules. MC Res Notes 2008; 1: 12. 27. Il Seong Nam-Goong HYK, Gyungyub Gong, Ho Kyu Lee, Suck Joon Hong, Won ae Kim, Young Kee Shong. Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings. Clinical Endocrinology 2004; 60: 21-28. 28. ndreas Machens H -JgH, Henning Dralle,. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer 2005; 103: 2269-2273. 29. Mazzaferri EL, Sipos J. Should ll Patients with Subcentimeter Thyroid Nodules Undergo Fine-Needle spiration iopsy and Preoperative Neck Ultrasonography to Define the Extent of Tumor Invasion? Thyroid 2008; 18: 597-602. 30. Hoang JK, Lee WK, Lee M, Johnson D, Farrell S. US Features of thyroid malignancy: pearls and pitfalls. Radiographics 2007; 27: 847-860; discussion 861-865. 31. Kim E-K, Park CS, Chung WY, Oh KK, Kim DI, Lee JT, Yoo HS. New Sonographic Criteria for Recommending Fine- Needle spiration iopsy of Nonpalpable Solid Nodules of the Thyroid. m. J. Roentgenol 2002; 178: 687-691. 415
Kang HC 32. Moon W - J, Jung SL, Lee JH, Na DG, aek J-H, Lee YH, Kim J, Kim HS, yun JS, Lee DH, For the Thyroid Study Group KSoN-, Head, Neck Radiology. enign and Malignant Thyroid Nodules: US Differentiation-Multicenter Retrospective Study. Radiology 2008; 247: 762-770. 33. Hegedus L. Thyroid ultrasound. Endocrinol Metab Clin North m 2001; 30: 339-360, viii-ix. 34. runese L, Romeo, Iorio S, Napolitano G, Fucili S, Zeppa P, Vallone G, Lombardi G, ellastella, iondi, Sodano. Thyroid -flow twinkling sign: a new feature of papillary cancer. Eur J Endocrinol 2008; 159: 447-451. 35. Rago T, Santini F, Scutari M, Pinchera, Vitti P. Elastography: New Developments in Ultrasound for Predicting Malignancy in Thyroid Nodules. J Clin Endocrinol Metab 2007; 92: 2917-2922. 36. Won ae Kim S -MH, Tae Yong Kim, Il Seong Nam-Goong, Gyungyub Gong, Ho Kyu Lee, Suck Joon Hong, Young Kee Shong,. Ultrasonographic screening for detection of thyroid cancer in patients with Graves disease. Clinical Endocrinology 2004; 60: 719-725. 37. huja, Chick W, King W, Metreweli C. Clinical significance of the comet-tail artifact in thyroid ultrasound. J Clin Ultrasound 1996; 24: 129-133. 38. Kang HC, Kim HK. Comet-tail artifact. J Korean Thyroid ssoc 2008; 1: 78-79. 39. raga M, Cavalcanti TC, Collaco LM, Graf H. Efficacy of Ultrasound-Guided Fine-Needle spiration iopsy in the Diagnosis of Complex Thyroid Nodules. J Clin Endocrinol Metab 2001; 86: 4089-4091. 40. D. N. Poller ES, C. Yiangou,. Thyroid FNC cytology: can we do it better? Cytopathology 2008; 19: 4-10. 41. Suen KC. Fine-needle aspiration biopsy of the thyroid. CMJ 2002; 167: 491-495. 42. lexander EK. pproach to the Patient with a Cytologically Indeterminate Thyroid Nodule. J Clin Endocrinol Metab 2008; 93: 4175-4182. 43. Tublin ME, Martin J, Rollin LJ, Pealer K, Kurs-Lasky M, Ohori NP. Ultrasound-guided fine-needle aspiration versus fineneedle capillary sampling biopsy of thyroid nodules: does technique matter? J Ultrasound Med 2007; 26: 1697-1701. 44. Degirmenci, Haktanir, lbayrak R, car M, Sahin D, Sahin O, Yucel, Caliskan G. Sonographically guided fineneedle biopsy of thyroid nodules: the effects of nodule characteristics, sampling technique, and needle size on the adequacy of cytological material. Clinical Radiology 2007; 62: 798-803. 45. elfiore, La Rosa GL. Fine-needle aspiration biopsy of the thyroid. Endocrinol Metab Clin North m 2001; 30: 361-400. 46. Castro MR, Gharib H. Thyroid fine-needle aspiration biopsy: progress, practice, and pitfalls. Endocr Pract 2003; 9: 128-136. 47. Rausch P, Nowels K, Jeffrey R, Jr. Ultrasonographically guided thyroid biopsy: a review with emphasis on technique. J Ultrasound Med 2001; 20: 79-85. 48. ellantone R, Lombardi CP, Raffaelli M, Traini E, De Crea C, Rossi ED, Fadda G. Management of Cystic or Predominantly Cystic Thyroid Nodules: The Role of Ultrasound-Guided Fine- Needle spiration iopsy. Thyroid 2004; 14: 43-47. 49. aloch ZW, LiVolsi V. Fine-needle aspiration of thyroid nodules: past, present, and future. Endocr Pract 2004; 10: 234-241. Peer Reviewers Commentary 416