Are scintigraphy and ultrasonography necessary before fine-needle aspiration cytology for thyroid nodules? 29 ABSTRACT. Objective : To evaluate the effi cacy of scintigraphy, ultrasound and fi ne-needle aspiration in thyroid nodules and to establish the best diagnostic pathway in detecting thyroid cancer. Method: Two hundred and sixteen patients with thyroid nodules were examined using high-resolution ultrasonography, 99mTc thyroid scintigraphy and ultrasound-guided fi ne-needle aspiration. Of these, 113 patients subsequently underwent thyroidectomy. The remaining 103 were followed up for two years without any evidence of malig- nancy. Results : Cytopathology classifi ed 71% of the aspirate as benign, 3% as positive for malignancy, 21% as suspected neoplasia and 5% as unsatisfactory. Fine- needle aspiration cytology had a sensitivity of 87.5% and specifi city of 80% . On ultrasound 33% of malignant nodules were hypo-echoic and on scintigraphy 16% of solitary cold nodules were malignant. Neither test could reliably diagnose thyroid cancer. Conclusion: Ultrasound-guided fi ne-needle aspiration cytology should be the fi rst test performed in euthyroid patients with a thyroid nodule. Scintigraphy and ultrasound imaging should be reserved for follow-up studies and patients who have suppressed levels of thyroid stimulating hormone. Key words : thyroid nodule, ultrasonography, thyroid scintigraphy, fi ne-needle aspiration cytology. T he in v estig ation and management of nodular thyroid disease remains a clinical problem. It is more common in women, in older patients, follow- ing exposure to ionising radiation and in areas of iodine defi ciency.1–5 Clinically detectable thyroid nodules occur in approximately 4–10% of the population, but only 5–30% of those nodules are malignant.6,7 The apparent prevalence of thyroid nodules depends on the technique of detection, which ranges from 30–50% in different ultrasound series, to approximately 50% at autopsy.8–10 The most widely used screening procedure in the eval- uation of thyroid nodules was scintigraphy, and the radio- nuclides used were technetium pertechnetate (99mTc) and Iodine-123 (123I).2,10,11 The value of thyroid scintigraphy is in the identifi cation of cold nodules, because they are more likely to be malignant than functioning nodules. The inci- dence of malignancy in cold nodules is said to vary from 5 to 15% .1,12,13 High-resolution ultrasonography (US) categorises nod- ules as solid, cystic or mixed, with over 90% accuracy. squ journal for scientific research: medical sciences (2001), 1, 29 –33 ©sultan qaboos university Are scintigraphy and ultrasonography necessary before fi ne-needle aspi ration cytology for thyroid nodules? *Dilip K. Sankhla1 , Samir S. Hussein2, Haddia Bererhi3, Omeima El Shaf ie4, Nicholas J. Woodhouse4, V.Nirmala5 1Departments of Radiology, 2Nuclear Medicine, 3Medical Physics, 4Medicine and 5Pathology, Sultan Qaboos University Hospital, P.O. Box: 38, Al-Khod 123, Muscat, Sultanate of Oman. *To whom correspondence should be addressed. E-mail: dilipks@omantel.net.om s a n k h l a e t a l30 Despite such accuracy, current ultrasonography is unable to reliably separate benign thyroid nodules from malignant ones.2,12,14 Fine-needle aspiration (F NA) is a well-established diagnostic procedure often used as one of the initial screen- ing tests for patients with thyroid nodules. Several studies have shown that following the introduction of FNA , the number of thyroid surgical procedures has decreased by 50% while the percentage yield of cancer in operated patients has doubled.2,12–19 This paper presents an analysis of the results we obtained in Sultan Qaboos University Hospital using 99mTc- pertechnetate scintigraphy, US and ultrasound-guided F NA done at one sitting in patients with thyroid nodular disease. The analysis has been used to decide the best diagnostic approach to the management of thyroid nodules. M E T H O D A total of 216 patients seen in the thyroid clinic with nod- ular thyroid swelling were referred for investigation. All had high-resolution sonography, 99mTc-pertechnetate scinti- graphy and fi ne-needle aspiration under ultrasound guid- ance on the same day. The ages of the patients ranged from 17 to 88 years (mean 38 years) and 187 (87%) were women. t h e i n v e s t i g at i o n s th y roid scintigr a ph y was done after intra-venous injection of 80 MBq of 99mTc pertechnetate. Standard images were obtained after 20 minutes, anterior, both ante- rior oblique views, and one view with a marker over the abnormal area. high-r esolution sonogr a ph y was performed with a 7.5 MHz linear probe with the patient supine and the neck hyper-extended. fine needle aspir ation (F NA) was performed using ultrasound guidance to introduce a 23–25 gauge needle and a 10 ml disposable syringe. Aspiration was performed with short back and forth movements while suction was applied. Suction was released before the needle was removed from the lesion. The aspirate was expelled on to the glass slides and fi xed with 95% alcohol immediately. The rest of the specimen was rinsed in saline balanced solution. The speci- mens were sent to the cytopathology laboratory for cyto- logical evaluation. R E S U LT S scintigr a ph y showed that 124/216 (57%) patients had solitary cold nodules, 64/216 (30%) had multiple cold lesions, and 28/216 (13%) had no nodule. sonogr a ph y showed 118/216 (55%) patients to have soli- tary lesions, 81/216 (38%) with multiple lesions and 17/216 (7%) without nodules [Table1]. fine-needle aspir ation results of the 216 patients were grouped as benign (cyst, nodule, lymphocytic thy- roiditis, sub-acute thyroiditis), malignant (papillary, med- ullary, anaplastic, lymphoma), suspicious neoplasia (follicu- lar lesion, follicular neoplasm, hurthle cell neoplasm) and inconclusive (foam cell, cyst fl uid, few follicular cells, too much blood). Fine needle aspirates were reported as show- ing benign cells in 154/216 (71%) patients, malignant in 6/216 (3%), ‘suspicious’ cells in 46/216 (21%) and were inconclusive in 10/216 (5%) [Table 2]. surgery was performed in 113 patients, because the cytol- ogy result was malignant, suspicious or inconclusive or the patient had a large thyroid mass. The remaining 103 patients were followed up clinically and with US to see any change in nodule size. No patient of this group showed any sign of malignancy during a two year follow up. In the operated group, 16/113 (14%) had a malignant lesion (12 papillary, 2 follicular, 1 medullary, 1 lymphoma) Table 1. Comparison between results of high resolution ultrasonography (US) and scintigraphy S c i n t i g r a p h y US (%) Solitary Multiple No Nodule Solitary 118 (55) 93 13 12 Multiple 81 (38) 27 47 7 No Nodule 17 (7) 4 4 9 Total 216 (100%) 124 (57%) 64 (30%) 28 (13%) Table 2. Results of fine-needle aspiration cytology (FNAC) of thyroid nodules Histology in Operated Patients Cytological Diagnosis FNAC (%) Benign Malignant (%) Benign 154 (71) 53 2 (1.3) Malignant 6 (3) 1 5 (83.3) Suspicious 46 (21) 37 9 (20) Inconclusive 10 (5) 6 0 (0) Total 216 97 16 (14) s c i n t i g r a p h y a n d u l t r a s o n o g r a p h y 31 and 97/113 (86%) were benign. Of the 64 patients who had a solitary nodule on US, 13/64 (20%) had malignant lesions on histology [Figure 1]. Out of the 71 solitary lesions detected on scintigraphy, 11/71 (16%) were malignant on histology [Figure 2]. Eleven percent of the hyper-echoic and 33% hypo-echoic nodules were malignant. Six patients who did not show a defi nite nodule on US examination had abnormal scintigraphy. On histology, 3 patients showed fea- tures of Hashimoto’s thyroiditis and 3 had multi nodular goitre [Table 3]. For analysis the inconclusive cytology group (10 cases) were excluded in statistical calculations. The cytological diagnosis of 206 patients was true positive in 14/206 (6.8%), false negative in 2/206 cases (1%), true negative 152/206 (73.7%) and false positive in 38/206 cases (18%) with a sensitivity of 87.5% and specifi city of 80%. D I S C U S S I O N Historically, thyroid scintigraphy using 99mTc or 123I has been the foundation for assessment of the thyroid nodule.10,11 Nodules detected by thyroid scintigraphy are classifi ed as cold (hypo functioning), hot (hyper functioning) or inde- terminate. Generally, 85% of thyroid nodules are cold, 10% are indeterminate and 5% are hot. 85% of cold nodules, 90% of indeterminate nodules and 95% of hot nodules are benign.1 The incidence of malignancy in cold nodules varies from 5% to 15%.1,12,13 Therefore, although most thy- roid nodules are cold, most cold lesions are benign. We observed similar fi ndings: 16% of solitary cold lesions and 11% multiple cold lesions were malignant. While we detected 118 solitary lesions on US, only 93 soli- tary cold lesions were demonstrated on scintigraphy. The remainder were multiple lesions (13 cases) with no nodule being shown in 12 cases. It has also been observed by Solbiati et al20 that US is more sensitive than scintigraphy in detecting nodules. 99mTc-pertechnetate thyroid scintigraphy cannot truly differentiate benign or malignant nodules and cannot be used as the basis for recommending treatment of the nodule, including thyroid surgery. Certainly, not all patients with thyroid nodules require thyroid scintigra- phy, but it is helpful in cases having suspicious or inconclu- sive cytology on FNA , and in cases with clinical evidence of thyrotoxicosis or having suppressed thyroid stimulating hormone (TSH ). Misken and Rosen21 described the use of US to exam- ine the thyroid in 1973. Originally, US was primarily used to distinguish between cystic and solid thyroid lesions. However, the development of high-resolution, real time, hand-held sonographic probes has allowed the collection of information that enhances clinical examination. US can confi rm the presence of a lesion and defi ne its characteris- tics better than manual palpation.8 Sonography has dem- onstrated that non-palpable thyroid nodules are 4 times more common than those which are detected clinically.8 Unfortunately, US characteristics such as size, echogenic- ity, and the presence of a halo sign cannot truly differen- tiate between benign and malignant. Hyper-echoic solid nodules are usually benign (96%), but sclerosing papillary neoplasms can also have this appearance. Mixed lesions rep- resent solid lesions that have undergone variable degrees of cystic degeneration and are benign in 85% of cases. The rare cystic lesions with smooth wall and echo-free, are almost always benign. Hypo-echoic nodules are more likely to be malignant than benign, 63% of hypo-echoic lesions rep- resenting malignancy in one series.20 In the present series, 33% of hypo-echoic nodules and 11% of hyper-echoic nod- ules were malignant. US is useful to guide the needle for F NAC of a thyroid nodule although it does not differenti- ate benign and malignant nodules. It improves the quality of diagnosis in preoperative assessment of thyroid nodules Table 3. Correlation between ultrasonography (US) texture and histology H i s t o l o g y Nodule Echotexture No. Cases Benign Malignant Hyperechoic 27 24 3 (11) Hypoechoic 6 4 2 (33) Cystic 8 7 1 (13) Mixed 66 56 10 (15) No Nodule 6 6 0 (0) Total 113 97 16 (14) N o o f p a ti e n ts Figure 1. Correlation between number of nodules on ultrasonography and histology 51 39 3 13 0 10 20 30 40 50 60 Single Multiple Benign Malignant s a n k h l a e t a l32 to select patients for surgery. It may have a more important role in the follow up of a nodule to assess its size and echo pattern once a decision is made not to operate. It can also be most useful in the long-term follow-up of patients with thyroid cancer by detecting small nodules that could repre- sent recurrence of cancer.3, 22, 23 The present study shows that F NAC has a high sensi- tivity of 87.5% and specifi city of 80%. On reviewing other large series of thyroid FNAC, the sensitivity of thyroid F NA ranges from 65% to 99% and its specifi city from 72% to 100%.15,17,24–29 Several F NA B series and reviews have been performed to establish the effi cacy of this procedure. In Caruso’s24 report on ten series with 9,119 patients, results of needle biopsy were benign in 74%, suspicious and inad- equate in 22%, and malignant in 4%. Gharib25 evaluated seven series with a total of 18,183 F NA where 69% were benign, 27% were suspicious and inconclusive and only 4% were malignant. The suspicious or inconclusive groups were approximately equally divided. Of the suspicious group of nodules, 10–30% were ultimately malignant. Overall, 70% of patients had a defi nitive diagnosis of either benign or malignant disease by FNA . In the present series, 20% of nodules in the suspicious group were malignant on histology . In 216 patients (operated and non-operated), the false negative rate was 1% and the false positive rate 18%, considering both the malignant and suspicious categories as positive. However, it is diffi cult to know the true frequency of false negative results because only a small percentage of patients (approximately 10%) with benign cytological fi ndings undergo surgery.12 The reported false negative rate ranges from 1% to 11%.24,25 Because F NA is considered a screening procedure, particular attention should be given to minimizing false-negative diagnosis, even at the expense of accepting false-positive diagnosis.30 The F NA remains the fi rst test in majority of cases for the evaluation of thyroid nodule. We believe that ultrasound-guided fi ne-aspiration cytology is the most effective method available. Ultrasound- guidance allows continuous visualization of the needle during insertion and sampling which results in pin-point accuracy with a high level of safety. It also permits mul- tiple sampling of the same lesion which reduces the risk of obtaining an inadequate sample.22,23 The following thy- roid malig nancies can be diagnosed by FNA : papillary, fol- licular variant of papillary, medullary, anaplastic, thyroid lymphoma, and metastases to the thyroid. Follicular carci- noma, Hurthle cell carcinoma and some cases with cellular atypia cannot be diagnosed by FNAC. Ultrasound-guided F NAC has reduced the cost for evaluation and treatment of thyroid nodules and has improved yield of cancer found at surgery. Due to the wide spread acceptance and low morbidity of FNA , it has virtually replaced large needle (16–18 gauge) or cutting needle (14 gauge) biopsy procedure for sampling the thy- roid. Its use should reduce the number of imaging proce- dures needed. C O N C L U S I O N Thyroid nodules are common and only a small percentage is malignant. The initial evaluation of thyroid nodules should effectively select patients for surgery who are likely to have malignancy. It appears from this study that Ultra- sound-guided F NAC should be the fi rst test performed in an euthyroid patient with a thyroid nodule as it is safe, inex- pensive, and has a high sensitivity. US is indicated in thyroid nodules with non-suspicious cytological fi ndings for follow up and is also useful in fol- low-up cases of thyroid malignancies. Thyroid scintigra- phy should be reserved for patients with indeterminate or inconclusive fi ndings on cytology, those with thyrotoxicosis and patients with suppressed TSH . a c k n ow l e d g e m e n t s The authors thank Professor William D. 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