Sonographic Findings in the Surgical Bed After Thyroidectomy

Article Sonographic Findings in the Surgical Bed After Thyroidectomy Comparison of Recurrent Tumors and Nonrecurrent Lesions Jung Hee Shin, MD, Boo-Kyung Han, MD, Eun Young Ko, MD, Seok Seon Kang, MD Objective. The purpose of this study was to assess the sonographic findings of recurrent tumors and nonrecurrent lesions mimicking recurrent tumors in the surgical bed after thyroidectomy for thyroid cancer. Methods. Fifty-eight patients who underwent sonography and sonographically guided fineneedle aspiration for evaluation of abnormal lesions in the surgical bed after thyroidectomy were included in this retrospective study. We compared the sonographic findings of recurrent tumors and nonrecurrent lesions, including lesion size, shape, margins, and echogenicity, presence or absence of microcalcification, and vascular flow signals. The reference standard was repeated sonographically guided fine-needle aspiration, surgery, or follow-up for at least 1 year. Results. Of 59 lesions in 58 patients, 20 were confirmed as recurrent tumors, and 36 were confirmed as nonrecurrent lesions in the surgical bed; 3 patients were lost to follow-up. On sonographic examination, the recurrent tumors diagnosed in 20 patients were oval in 70%, had well-defined margins in 100%, were hypoechoic in 70%, and had microcalcification in 10%. The average size was 0.7 cm (range, 0.4 2.1 cm). There was no statistical difference in sonographic findings between recurrent tumors and nonrecurrent lesions (P >.05). The 36 nonrecurrent lesions included remnant thyroidal tissue (n = 8), postoperative fibrosis (n = 7), suture granuloma (n = 7), strap muscle with a nodular contour (n = 4), reactive lymph nodes (n = 4), cysts (n = 3), tracheal cartilage (n = 2), and fat necrosis (n = 1). Conclusions. For lesions located in the surgical bed in patients after thyroidectomy, the distinction between recurrent thyroid cancer and nonrecurrent benign lesions cannot be made on the basis of the sonographic features. Fine-needle aspiration is helpful in determining the histologic nature of such lesions. Key words: recurrence; sonography; thyroid bed. Abbreviations DTC, differentiated thyroid cancer; FNA, fine-needle aspiration; Tg, thyroglobulin; TSH, thyrotropin; WBS, whole-body scanning Received March 16, 2007, from the Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Revision requested April 9, 2007. Revised manuscript accepted for publication May 22, 2007. Address correspondence to Boo-Kyung Han, MD, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea. E-mail: bkhan@smc.samsung.co.kr The disease-specific survival rate for differentiated thyroid cancer (DTC) is higher than 90% at 10 years. Five percent to 20% of patients with DTC have local or regional recurrences, which occur twice as frequently as distant metastases. Two thirds of the recurrences occur within the first decade after therapy, but others appear in later years. In most patients with DTC, recurrent disease is located in the neck. 1 3 After surgical treatment, patients with thyroid cancer are monitored closely for local recurrence or distant metastases. Accurate surveillance for possible recurrence in patients thought to be free of disease is a major goal of long-term follow-up. Postoperative assessment includes physical examination of the neck, neck sonography, chest 2007 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2007; 26:1359 1366 0278-4297/07/$3.50

Sonographic Findings in the Surgical Bed After Thyroidectomy radiography to detect lung metastases, iodine 131 whole-body scanning (WBS), tumor markers such as thyroglobulin (Tg) and anti-tg antibody for papillary and follicular carcinoma, and the calcitonin level for medullary carcinoma. According to recently published American and European consensus treatment guidelines for patients with DTC, neck sonography is recommended to evaluate the thyroid bed and nodal compartments at 6 to 12 months and then annually for at least 3 to 5 years, depending on the patient s risk for recurrent disease. 4,5 Although we expect that the routine use of neck sonography for postoperative follow-up will soon skyrocket, published data detailing sonographic findings of the surgical bed after thyroidectomy are few. The purpose of our study was to assess the sonographic findings of recurrent tumors and nonrecurrent lesions mimicking recurrent tumors in the surgical bed after thyroidectomy for thyroid cancer. Materials and Methods Study Population Institutional Review Board approval was obtained before the data of patients who underwent sonographically guided fine-needle aspiration (FNA) were reviewed. This retrospective study included 58 patients (8 men and 50 women; mean age, 48 years; range, 24 80 years) who underwent 60 sonographically guided FNA procedures for 59 abnormal lesions in the surgical bed and excluded 62 patients who underwent sonographically guided FNA of lymph nodes or lesions of the preserved contralateral lobe without abnormalities in the surgical bed. Of the 58 included patients, 1 patient underwent repeated sonographically guided FNA for a lesion, and another patient underwent sonographically guided FNA for bilateral lesions during this period. Fifty-six patients underwent total thyroidectomy, whereas surgery was not radical in 2 patients (unilateral lobectomy and subtotal lobectomy). None of the patients had distant metastases. Sonography and Sonographically Guided FNA Technique Neck sonography was performed in all patients before sonographically guided FNA. Experienced radiologists scanned the thyroid bed and neck nodal compartments with an HDI 5000 scanner (Philips Medical Systems, Bothell, WA) equipped with a commercially available 7- to 12-MHz linear transducer. Two radiologists (J.H.S. and B-K.H.) retrospectively reviewed the sonographic findings by consensus for lesion size, shape, margin, and echogenicity and the presence or absence of microcalcification. A uniform hyperechoic area may have been seen in the surgical bed between the carotid and the trachea. 6 If color Doppler sonography was available, the presence or absence of vascular flow signals within the lesions was assessed. On sonography, the longest diameter of the lesion was measured for size. The shape was classified as oval, round, triangular, irregular, or taller than wide in appearance. When clear demarcation was noted around more than 50% of the nodule, the margins of the lesion were categorized as well defined; when more than 50% of the border of the lesion was not clearly demarcated, the margins were considered poorly defined. The echogenicity categories were anechoic, hypoechoic, isoechoic, hyperechoic relative to the normal thyroid, and markedly hypoechoic relative to strap muscle. Microcalcification was defined as multiple punctate bright echoes with or without acoustic shadowing. Sonographically guided FNA was performed to examine any suspicious nodule in the surgical bed. The procedure was performed with or without local anesthesia using a 21- or 23-gauge needle attached to a 2- to 10-mL syringe. The aspirates were expressed onto frosted-end glass slides, immediately fixed in 95% alcohol, and stained with hematoxylin-eosin and Papanicolaou stains for analysis by 2 experienced pathologists. Results were classified as positive for carcinoma, benign, or inadequate. Patients with benign aspiration results but increased Tg levels, positive scan results, or both also underwent surgery. Among benign lesions, postoperative fibrosis was diagnosed when the lesion showed fibrous tissue on cytologic examination and disappeared on follow-up sonography. Strap muscle lesions were diagnosed if cytologic examination showed skeletal muscle fibers without any evidence of follicular cells. 1360 J Ultrasound Med 2007; 26:1359 1366

Shin et al Sonographic findings of recurrent tumors diagnosed by repeated sonographically guided FNA or surgery and nonrecurrent lesions mimicking recurrent tumors diagnosed by repeated sonographically guided FNA, surgery, or follow-up for at least 1 year were assessed. We compared the sonographic findings of both groups using the Fisher exact test or the χ 2 test. Results Of 59 lesions in 58 patients, 20 were confirmed as recurrent tumors, and 36 were confirmed as nonrecurrent lesions in the surgical bed; 3 patients were lost to follow-up. The follow-up period ranged from 6 months to 12 years after surgery (mean, 4.5 years). Twenty recurrent tumors in 20 patients were diagnosed by repeated surgical excision (n = 16) or repeated sonographically guided FNA (n = 4); these recurrences were proven to be papillary carcinoma in 18 cases and follicular carcinoma and medullary carcinoma in 1 case each. Thirty-six nonrecurrent lesions that were aspirated initially were proven by repeated surgical excision (n = 2), repeated sonographically guided FNA (n = 4), or follow-up sonography for at least 1 year (n = 30). Cytologic results of 60 sonographically guided FNAs from the surgical bed consisted of 16 (27%) malignant, 33 (55%) benign, and 11 (18%) inadequate findings. The 11 patients with inadequate cytologic findings were later shown to have 2 recurrent tumors confirmed by surgery and 8 benign lesions confirmed by repeated sonographically guided FNA (n = 2) or follow-up (n = 6); 1 patient was lost to follow-up. Regarding the cytologic findings of benign and malignant, the performance of sonographically guided FNA for evaluating recurrences in the surgical bed was as follows: sensitivity, 79%; specificity, 97%; positive predictive value, 94%; and negative predictive value, 90%. Of the 20 patients with recurrent tumors, Tg or anti-tg antibody levels were increased in 12 (67%) of 18, and WBS findings were positive in 2 (29%) of 7. Sonographic findings of recurrent tumors and nonrecurrent lesions mimicking recurrent tumors are summarized in Table 1. On sonographic examination, the recurrent tumors diagnosed in 20 patients were oval in 70%, had well-defined margins in 100%, were hypoechoic in 70%, and had microcalcifications in 10%. The average size was 0.7 cm (range, 0.4 2.1 cm; Figure 1). There were no statistical differences in Table 1. Sonographic Findings of Recurrences and Nonrecurrent Lesions Mimicking Recurrent Tumors in 56 Cases Sonographic Finding Recurrences (n = 20) Nonrecurrent Lesions (n = 36) P Size, cm (range) 0.7 (0.4 2.1) 0.7 (0.3 3.1) Shape, n (%).413 Oval 14 (70) 21 (58) Round 3 (15) 4 (11) Triangular 0 (0) 5 (14) Irregular 2 (10) 2 (6) Taller than wide 1 (5) 4 (11) Echogenicity, n (%).403 Anechoic 0 (0) 1 (3) Isoechoic 0 (0) 4 (11) Hypoechoic 14 (70) 24 (67) Markedly hypoechoic 6 (30) 7 (19) Margin, n (%) Well-defined 20 (100) 36 (100) Poorly defined 0 (0) 0 (0) Calcification, n (%).356 Present 2 (10) 7 (19) Absent 18 (90) 29 (81) Vascular flow signals, n (%)*.659 Present 3 (23) 3 (15) Absent 10 (77) 17 (85) *Color Doppler sonography was available in 13 recurrences and 20 nonrecurrent lesions. J Ultrasound Med 2007; 26:1359 1366 1361

Sonographic Findings in the Surgical Bed After Thyroidectomy A B Figure 1. Recurrent tumor in the surgical bed after thyroidectomy in a 60-year-old woman. Transverse (A) and longitudinal (B) sonograms show a 0.4-cm well-defined taller-than-wide hypoechoic nodule. Sonographically guided FNA and repeated surgical excision revealed recurrent papillary carcinoma. the sonographic findings between recurrent tumors and nonrecurrent lesions mimicking recurrent tumors. Thirty-six nonrecurrent lesions mimicking recurrent tumors in the surgical bed included remnant thyroidal tissue (n = 8), postoperative fibrosis (n = 7), suture granuloma (n = 7), strap muscle with a nodular contour (n = 4), reactive lymph nodes (n = 4), cysts (n = 3), tracheal cartilage (n = 2), and fat necrosis (n = 1). On sonographic examination, remnant thyroidal tissues in 8 cases showed isoechoic (n = 4) or hypoechoic (n = 4) lesions that were oval (n = 5), triangular (n = 2), or taller than wide (n = 1) in the beds (Figure 2). All the nonrecurrent lesions with vascular flow signals were remnant thyroidal tissues. Postoperative fibrosis in 7 cases showed oval (n = 4), round (n = 1), or irregular (n = 2) hypoechoic (n = 6) or markedly hypoechoic (n = 1) lesions, with calcification in 1 case. Suture granuloma in 7 cases showed hypoechoic (n = 4) or markedly hypoechoic (n = 3) lesions with (n = 3) or without (n = 4) echogenic foci (Figure 3). Strap muscle lesions, which were seen in 4 cases, were irregular (n = 1), oval (n = 2), or round (n = 1) nodular lesions with (n = 2) or without (n = 2) echogenic foci thought to represent microcalcification (Figure 4). Four reactive lymph nodes showed hypoechoic (n = 3) or markedly hypoechoic (n = 1) nodules that were oval (n = 3) or taller than wide (n = 1). Tracheal cartilage in 2 cases showed hypoechoic lesions that were round or taller than wide (Figure 5). Three cases of cysts showed anechoic or markedly hypoechoic lesions with calcifications. Fat necrosis was located in the subcutaneous layer of the bed, depicted as an oval, heterogeneous, hypoechoic nodule (Figure 6). Figure 2. Remnant thyroid tissue mimicking a recurrent tumor in the surgical bed after thyroidectomy in a 33-year-old man. A transverse sonogram shows a 1.1-cm well-defined triangular isoechoic nodule. Sonographically guided FNA revealed benign follicular cells. This lesion had not changed on follow-up. 1362 J Ultrasound Med 2007; 26:1359 1366

Shin et al Figure 3. Suture granuloma mimicking a recurrent tumor in the surgical bed after thyroidectomy in a 32-year-old man. A transverse sonogram shows a 0.8-cm well-defined oval hypoechoic nodule with suture materials, which were misdiagnosed as microcalcification. Although sonographically guided FNA revealed foreign body granuloma, repeated surgical excision was performed because of clinical suspicion. Discussion Initial follow-up for low-risk patients with DTC ( 85% of postoperative patients) who have undergone total or near-total thyroidectomy and iodine 131 ablation should be based on thyrotropin (TSH)-suppressed Tg measurements and neck sonography, followed by TSH-stimulated serum Tg measurements if the TSH-suppressed Tg level is undetectable. 7,8 Diagnostic WBS should be used only when indicated and has limited sensitivity to detect persistent disease or recurrence. 9,10 Sonography is very useful in predicting and localizing recurrences when diagnostic WBS and Tg measurement results are negative or divergent and can be helpful as a guide for FNA to confirm these lesions. 6 In our study, sonographically guided FNA was a sensitive (79%) and specific (97%) test for diagnosing indeterminate lesions in the surgical bed. Nodal metastasis at the time of the original surgery for papillary or medullary carcinoma has not been shown to influence the overall survival rate. 11 13 However, recurrence of papillary carcinoma in the thyroid bed, especially in older patients with extrathyroidal disease, is associated with significantly increased thyroid cancer mortality. 14,15 Early detection of local recurrences in patients with invasive disease may provide an opportunity for more successful surgery or radiation therapy. Until now, because no specific criteria have existed to distinguish between recurrent tumors and nonrecurrent lesions on sonography, aspiration or surgical excision of any abnormal nodule in the surgical bed has been justified to confirm a recurrence or persistent disease. We were disappointed that we also failed to discover critical Figure 4. Strap muscle mimicking a recurrent tumor in the surgical bed after thyroidectomy in a 45-year-old woman. Transverse (A) and longitudinal (B) sonograms show a 0.6-cm well-defined oval hypoechoic nodule with echogenic foci misinterpreted as microcalcification. Repeated sonographically guided FNA revealed skeletal muscle fragments. A B J Ultrasound Med 2007; 26:1359 1366 1363

Sonographic Findings in the Surgical Bed After Thyroidectomy A B Figure 5. Tracheal cartilage mimicking a recurrent tumor in the surgical bed after thyroidectomy in a 44-year-old woman. Transverse (A) and longitudinal (B) sonograms show a 0.5-cm taller-than-wide hypoechoic nodule in the far medial portion of the left bed. Sonographically guided FNA revealed the cartilage. This lesion was not detected as a suspicious lesion on follow-up sonography. criteria for sonographic findings to differentiate between recurrent tumors and nonrecurrent lesions. Reasons for this failure in our study include the fact that these lesions were so small (average size, 0.7 cm in both groups) that it was difficult to define an exact sonographic feature. Also, aspiration was performed for lesions that had findings similar to the general sonographic findings accepted for malignancy, especially those for papillary carcinoma, including microcalcification, irregular margins, hypoechogenicity or marked hypoechogenicity, and a shape that was taller than wide. 16 18 Most recurrent tumors in our series showed well-defined oval hypoechoic nodules as a nonspecific finding. We found that microcalcification was uncommon (10%) in recurrent tumors compared with the frequency seen in original papillary carcinoma. When sonographically guided FNA was performed on a nodule with punctate echogenic foci thought to be suggestive of microcalcification, cytologic results more frequently revealed nonrecurrent lesions such as suture granuloma, strap muscle, postoperative fibrosis, and degenerated cysts than recurrent tumors, but this trend was not statistically significant (P =.356). In previous reports, cases misdiagnosed as recurrent tumors in the surgical bed included normal residual thyroids, parathyroid glands, suture granuloma, and lymph nodes. 6,19,20 We also found strap muscle, tracheal cartilage, pyramidal lobes, postoperative fibrosis, cysts, and fat necrosis. The strap muscle contained skeletal muscle fragments on cytologic examination and did not change or lost its edematous nodular contour on follow-up. Pyramidal lobes were located in the center of the surgical bed and were longitudinally oval. Computed tomography had Figure 6. Fat necrosis mimicking a recurrent tumor in the surgical bed after thyroidectomy in a 47-year-old man. A neck sonogram shows a 0.5-cm heterogeneous hypoechoic nodule in the subcutaneous layer of the surgical bed. Sonographically guided FNA revealed adipose tissue. On follow-up sonography, this lesion had disappeared. 1364 J Ultrasound Med 2007; 26:1359 1366

Shin et al advantages over sonography in confirming pyramidal lobes. Postoperative fibrosis disappeared or had unclear morphologic characteristics over time. Reactive lymph nodes might be detected in the far inferior portion of the surgical bed, an area that is not included in the surgical field. Tracheal cartilage was commonly located in the far medial portion of the bed, which was predominantly on the left side because of a spaceoccupying area anterior to the esophagus. When misdiagnosed tracheal cartilage is aspirated, a cough can occur. Cysts disappeared after aspiration or were confirmed as degenerated cysts arising from remnant tissue after subtotal thyroidectomy. It is important to image in multiple planes to correctly diagnose lesions mimicking recurrent tumors at the time of sonographic examination. Awareness of this potential pitfall can lead to correlation of sonographic findings with those of other imaging modalities, such as computed tomography, WBS, and positron emission tomography, or laboratory assessment. In such cases, precise localization with sonographically guided FNA is essential to prevent misdiagnosis as a recurrent tumor and to avoid repeated surgical excision. Our study had the following limitations. First, although nonrecurrent lesions mimicking recurrent tumors were initially aspirated, most cases were confirmed by follow-up, not by repeated surgical excision. Second, in our series, the sensitivity of laboratory findings and WBS was not accurately comparable with that of sonography because those examinations were not permitted in all patients. In our series, given undetectable Tg levels, sonography might show much smaller neoplastic foci (0.4 cm) in the surgical bed. An undetectable Tg level or negative WBS findings will not necessarily exclude recurrent tumors in the surgical bed. Therefore, the diagnostic procedures of reference can be sonography and sonographically guided FNA of any suspicious lesion. In conclusion, for lesions located in the surgical bed in patients who previously underwent thyroidectomy, the distinction between recurrent thyroid cancer and nonrecurrent benign lesions cannot be made on the basis of the sonographic features. Fine-needle aspiration is helpful in determining the histologic nature of such lesions. References 1. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998; 338:297 306. 2. Mazzaferri EL. An overview of the management of papillary and follicular thyroid carcinoma. Thyroid 1999; 9:421 427. 3. Mazzaferri EL, Kloos RT. Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001; 86:1447 1463. 4. Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006; 16:109 142. 5. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154:787 803. 6. Simeone JF, Daniels GH, Hall DA, et al. Sonography in the follow-up of 100 patients with thyroid carcinoma. AJR Am J Roentgenol 1987; 148:45 49. 7. Schlumberger M, Berg G, Cohen O, et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 2004; 150:105 112. 8. Mazzaferri EL, Robbins RJ, Spencer CA, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 2003; 88:1433 1441. 9. Torlontano M, Crocetti U, D Aloiso L, et al. Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer. Eur J Endocrinol 2003; 148:19 24. 10. Pacini F, Molinaro E, Castagna MG, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003; 88:3668 3673. 11. Cady B, Sedgwick CE, Meissner WA, Bookwalter JR, Romagosa V, Werber J. Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma. Ann Surg 1976; 184:541 553. 12. Mazzaferri EL, Young RL, Oertel JE, Kemmerer WT, Page CP. Papillary thyroid carcinoma: the impact of therapy in 576 patients. Medicine (Baltimore) 1977; 56:171 196. 13. Frazell EL, Foote FW Jr. Papillary thyroid carcinoma: pathological findings in cases with and without clinical evidence of cervical node involvement. Cancer 1955; 8:1164 1166. 14. McConahey WM, Hay ID, Woolner LB, van Heerden JA, Taylor WF. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 1986; 61:978 996. J Ultrasound Med 2007; 26:1359 1366 1365

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