Does Ultrasound Elastography Improve the Diagnostic Accuracy of Fine Needle Aspiration Cytology in Predicting Malignancy in Thyroid Nodules?

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1 Med. J. Cairo Univ., Vol. 82, No. 1, June: , Does Ultrasound Elastography Improve the Diagnostic Accuracy of Fine Needle Aspiration Cytology in Predicting Malignancy in Thyroid Nodules? OMNIA MOKHTAR, M.D.* and NEVEIN TAHON, M.D.** The Departments of Diagnostic Radiology* and Cytology**, National Cancer Institute, Cairo University, Cairo, Egypt Abstract Aim: The aim of this study was to correlate between real time ultrasound elastography (ultrasound strain imaging) and fine needle aspiration cytology in predicting malignancy in thyroid nodules. Patients and Methods: Prospective study included 96 patients with painless thyroid nodules, either solitary nodule or dominant nodule in the sitting of multinodular goiter who presented at Radiology Department, National cancer Institute, Cairo University. Conventional ultrasound and elastography were performed for all cases followed by FNAC and further pathological anylasis of excised lesion following surgery in suspicious cases. Results: Among the 96 studied cases, 35 (36.5%) had a final histopathological diagnosis of malignancy. The remaining 61 cases (63.5%) had a benign diagnosis on histopathological examination. 57 cases were classified by elastography as score 1 and 2 (negative), all of which were proved to be benign on histopathology (true negative) and no false negative cases. The remaining 39 cases were referred to surgery due to score 3,4, or 5. Of these 35 cases (89.7%) were proved to be malignant on histopathological reports (true positive) and 4 cases (10.3%) were diagnosed as benign (false positive). Conclusion: US-elastography is a promising technique that is easy and rapid to perform and can help to identify thyroid nodules that are likely to be malignant. Key Words: Thyroid nodule Elastography FNA cytology. Introduction THYROID nodules are common clinical presentation. They can be detected by palpation in 10% of women and 2% of men. The prevalence of thyroid nodules among population can be 60% or more if ultrasonography was used. These figures would have been much higher in areas of iodine deficiency [1]. Correspondence to: Dr. Omnia Mokhtar, The Department of Diagnostic Radiology, National Cancer Institute, Cairo University, Cairo, Egypt Thyroid nodules may be either a true solitary nodule or multinodular goiter. By far, the multinodular goiter is the most common thyroid disease encountered in clinical practice [2,3]. 10% to 15% of multinodular goiter may harbor a neoplasm, but of these 90% are benign and 10% are malignant, resulting in overall incidence of malignancy in multinodular goiter of 1% to 2% all over the world [3,4]. On the other hand, solitary thyroid nodule is far more likely to be a neoplasm, 90% of them were proved to be benign and 10% being malignant. About 50% of the clinically apparent solitary thyroid nodules turn out to be dominant nodule of multi-nodular goiter [5]. Solitary toxic nodules accounts for 4-7% of all solitary thyroid nodules. Percentage of malignancy is rare in hot nodules. Overall incidence of malignant hot nodules is 0.2% [6]. It is crucial to have a clear diagnostic approach to ensure patients presenting with thyroid nodules are managed appropriately and are not over or under-treated [4]. In the management of thyroid nodule, the primary challenge is to separate benign nodules (the majority) from malignant lesions (the minority) [5]. In the assessment of thyroid nodules, clinical evaluation is very important. One of the key features of the thyroid gland malignancy at palpation is the degree of firmness; malignant lesions tend to be much firmer or harder than benign one. However, this clinical parameter is highly subjective and dependent on the experience of the examiner. Thus it may be misleading. Some papillary carcinomas are cystic and soft, follicular carcinomas can be hemorrhagic and soft, and dystrophic calcification may render the benign nodules hard [5]. 427

2 428 Does Ultrasound Elastography Improve the Diagnostic Accuracy US is the commonly used imaging modality, however no ultrasound feature has both high sensitivity and high specificity in detecting malignancy of thyroid nodules [7,8]. Fine needle aspiration cytology is the best single test used for differentiating malignant from benign thyroid nodules. FNAC has a sensitivity ranging from 65%-98% and specificity ranging from 72%- 100% [9]. Hence it distinguishes between patients that require clinical management or surgical excision and it assists in deciding the appropriate surgical procedure when necessary [10]. Cytology has certain limitations that restrict its use as a single diagnostic test in case of thyroid nodules. The major limitation of FNA cytology is that 10 to 20% of specimens are classified cytologically as indeterminate, i.e., inability to differentiate hypercellular follicular adenoma from well differentiated follicular carcinoma. This distinction is based on capsular or vascular invasion in histopathologic sections rather than cytologic criteria. Thus, a substantial proportion of nodules are not correctly diagnosed even in the hand of an experienced cytopathologist and these nodules still need to be excised for histolopathological final diagnoses [9,10]. During the last few years, ultrasound elastography (USE) has been added to the diagnostic investigation. It is used combined with US based upon the principle that the softer parts of tissues deform easier than the harder parts under compression, thus allowing a semi-quantitative determination of tissue elasticity [11]. This technology involves placing the probe and applying a uniform and slight pressure on the neck. A box, covering the target nodule and the immediate surrounding normal tissue, is highlighted on the scan image. Two ultrasound images, before and after tissue compression, are obtained. Dedicated software tracks the tissue displacement and displays this using a color scale ranging from red (highest elasticity corresponding to lowest risk of malignancy) over green (intermediate elasticity) to blue (lowest elasticity and corresponding to highest risk of malignancy). The results of this technique are scored by measuring the degree of distortion of the US beam under the application of an external force. Elastography has the advantage of being noninvasive and gives immediate information [2]. This technique has been extensively studied in breast lesions, prostate, pancreas, and lymph nodes [12,13]. Recent studies have evaluated the use of US elastography for detecting malignant thyroid nodules [2,14]. The aim of this study was to correlate between real time ultrasound elastography and fine needle aspiration cytology in predicting malignancy in thyroid nodules. Patients and Methods This prospective study included 96 patients, eighteen patients (18.8%) were males and 78 (81.2%) were females with male: female ratio of about 1: 4.3. Age range was 15 to 66 years and mean age of years. All patients had normal serum levels of thyroid hormones. Patients were presenting with painless thyroid nodules, either solitary nodule or dominant nodule in the sitting of multinodular goiter who presented at Radiology Department, National cancer Institute, Cairo University from January 2011 to July Conventional ultrasound was performed by using a digital electronic scanner with a frequency of MHz (EUB-7500; Hitachi Medical Corporation, Tokyo, Japan) in order to obtain B-mode. During B-mode ultrasound, thyroid gland lesions were identified and a region of interest for elastography was identified. After B-mode ultrasound, real-time strain imaging in the elasticity imaging mode, was performed for each region of interest that was selected during B-mode ultrasound. The ultrasound probe was placed on the fully extended neck and usual thyroid US study was done then the examined nodule is pressed with a stable light pressure, and a box was highlighted by the operator that included the nodule to be evaluated and sufficient surrounding thyroid tissue. The principle of ultrasound elastography is to acquire two ultrasonic images (before and after tissue compression by the probe) and track tissue displacement by assessing the propagation of the imaging beam. Dedicated software that able to provide an accurate measurement of tissue distortion was used. The elasticity software includes a scale for pressure monitoring. Optimally, to obtain images that were appropriate for analysis, we applied the probe with only light constant pressure which does not exceed 3 on the scale. We avoided using higher levels of pressure as the pattern of the elasticity image started to change markedly as the pressure increased. It is important that the level of pressure is maintained constant throughout the examination. B-mode images and elasticity images were displayed simultaneously side-by-side on the same screen to aid in lesion identification.

3 Omnia Mokhtar & Nevein Tahon 429 For each lesion examined, B-mode image of the examined nodule is assessed for echogenicity pattern, margin regularity and presence of microcalcifications then multiple frames of elasticity images is obtained. The elasticity image was matched with an elasticity color scale displayed on the computer monitor. The scale of the elasticity images ranged from red for components with greatest strain (i.e., softest components) to blue for those with no strain (i.e., hardest components). Green indicated average strain. To classify elasticity images, we evaluated the color pattern in the nodule. On the basis of the overall pattern, each image was given a score of five elasticity scores using Rago elasticity score (Figs. 1-3). score (1): The nodule is relatively homogenous and colored green (indicated elasticity in the whole nodule), score (2): The nodule is colored a mixture of green and blue (indicated elasticity in large parts in the nodule), score (3): The center of the nodule is colored blue and its periphery is colored green (indicated elasticity only at the peripheral part of the nodule with sparing of the center which is hard), score (4): The entire nodule is hard and displayed in blue (indicated no elasticity in the nodule), and score (5): No elasticity in the nodule and in the surrounding tissue which are displayed blue [12,15]. This technique is easy to perform and requires no more than 3-5min. Score (1) Score (2) Score (3) Score (4) Score (5) Fig. (1): Elastography scores according to rago criteria (Quoted from 15). (A) (B) Fig. (2): Thyroid nodule images obtained on US elastography with elasticity score 1 (A) and conventional US (B).

4 430 Does Ultrasound Elastography Improve the Diagnostic Accuracy (A) (B) Fig. (3): Thyroid nodule images obtained on US elastography with elasticity score 5 (A) and conventional US (B). The patients were referred to Cytology Unit for cytopathological diagnosis using FNA technique. Cytological specimens were evaluated blindly (without knowing the scores of elastography) and results classified into: Insufficient for diagnosis, benign, follicular lesion of undetermined significance, follicular neoplasm, suspicious for malignancy, and malignant sampling. All the studied patients underwent surgery, either due to compressive symptoms, cancer phobia due to family history of thyroid malignancy, or due to malignancy or suspicion of malignancy on FNAC and/or elastography. Patients with indeterminate cyologic results (follicular neoplasm) underwent surgery as the diagnostic accuracy of these thyroid lesions cannot rely solely on cytologic criteria. All these cases were evaluated for final histopathological diagnoses. The final diagnosis was based on the histopathologic examination of an excised thyroid nodule. Patients unfit for surgery as well as cases with insufficient cytological specimens were excluded from the study. No patient included in this series had a history of neck irradiation, previous diagnosis of thyroid malignancy, previous thyroid surgery, or toxic thyroid nodule confirmed by clinical evaluation. The results of elastography, fine needle aspiration cytology, and histopathology were statistically compared. Histopathology was taken as gold standard. Calculation of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy was done for elastography and fine needle aspiration cytology and then for the combined techniques. Statistically, fine needle aspiration specimens interpreted as benign or follicular lesion of undetermined significance (malignancy risk is 5% to 15%) were considered to be negative samples as both are not surgically resected. The false-negative cases were included those diagnosed as negative on fine needle aspiration cytology but confirmed as malignant upon surgical excision. The remaining categories; follicular neoplasm, suspicious for malignancy and malignant; were considered to be positive samples because they lead to a recommendation of surgery (i.e., they all have the same clinical impact). The false-positive category were included those cases that were diagnosed as positive on fine needle aspiration cytology and confirmed to be benign on histopathology. The use of the term positive is for statistical purposes only and does not indicate malignancy. Statistically, the elastography score 1 and 2, describing high elasticity, were strongly predictive of benignity with no need for surgical intervention, while score 3,4, and 5, describing nodules with low elasticity, were strongly predictive of malignancy. Results This study included 96 patients with thyroid nodules. A total of 59 patients (61.5%) had a solitary thyroid nodule and 37 patients (38.5%) had a dominant nodule in the setting of multinodular goiter. Among the 96 studied cases, 35 (36.5%) had a final histopathological diagnosis of malignancy: 31 were papillary carcinoma, 3 were minimally invasive follicular carcinoma, and one was medullary carcinoma. The remaining 61 cases (63.5%) had a benign diagnosis on histopathological exam-

5 Omnia Mokhtar & Nevein Tahon 431 ination: 39 were hyperplastic nodules (nodular goiter) and 22 were follicular adenoma. FNAC results were interpreted as benign in 34 cases (35.4%), follicular lesion of undetermined significance in 13 cases (13.5%), follicular neoplasm in 18 cases (18.8%), suspicious for malignancy in 6 cases (6.3%), and positive for malignancy in 25 cases (26.0%) (Table 1). In thyroid nodules interpreted cytologically as benign When these cases were compared with their corresponding histopathological diagnosis, 32 cases (94.1%) were confirmed as nodular goiter, 1 case (2.9%) was follicular adenoma, and 1 case (2.9%) was papillary thyroid carcinoma (Table 1). The papillary carcinoma case was small and cystic, yielding 4cc of dark brown liquid with near total collapse of the clinically felt nodule. The exact lesion might be missed during aspiration. 13 cases were reported cytologicaly as follicular lesion of undetermined significance. Ten out of these 13 cases (76.9%) were diagnosed histopatho- logically as follicular adenoma and 3 cases (23.1%) were nodular goiter (Table 1). 18 thyroid smears were interpreted on fine needle aspiration cytology as follicular neoplasm. Eleven cases of which (61.1%) were diagnosed histopathologically as follicular adenoma, 3 cases (16.7%) as nodular goiter, 3 cases (16.7%) as minimally invasive follicular carcinoma, and 1 case (5.6%) as follicular variant of papillary carcinoma (Table 1). Five out of the 6 smears (83.3%) that were demonstrated cytologic features suspicious for malignant neoplasm, were confirmed after the resection as being malignant, papillary carcinoma in 4 cases (66.7%) and medullary carcinoma in one case (16.7%). The remaining case (16.7%) was proved histopathologically as nodular goiter. The 25 cases (100%) that interpreted cytologically as papillary carcinoma were confirmed on histopathological examination (Table 1). Table (1): Cytological diagnoses of the 96 included cases compared with the corresponding histopathological diagnoses. Cytological diagnoses No Histopathological diagnoses No (%) Remarks Benign 34 Nodular goiter 32 (94.1%) TN Follicular adenoma 1 (2.9%) TN Papillary carcinoma 1 (2.9%) FN Follicular lesion of US 13 Nodular goiter 3 (23.1%) TN Follicular adenoma 10 (76.9%) TN Follicular neoplasm 18 Follicular adenoma 11 (61.1%) FP Nodular goiter 3 (16.7%) FP Follicular carcinoma 3 (16.7%) TP Papillary carcinoma 1 (5.6%) TP Suspicious for malignancy 6 Papillary carcinoma 4 (66.7%) TP Medullary carcinoma 1 (16.7%) TP Nodular goiter 1 (16.7%) FP Malignant 25 Papillary carcinoma 25 (100%) TP TP : True positive cases. FP : False positive cases. FN : False negative. TN: True negative cases. US : Undetermined significance. Of the included 47 cases cytologically diagnosed as negative, 46 cases (97.9%) were proved to be benign on histopathology (true negative) and one case (2.1%) was papillary carcinoma (false negative). Of the remaining 49 cytologically positive cases, 34 cases (69.4%) were proved to be malignant (true positive) and 15 cases (30.6%) were diagnosed as benign on histopathological reports (false positive) (Table 2). Thus FANC achieved sensitivity of 97.1%, specificity of 75.4%, positive predictive value (PPV) of 69.4%, negative predictive value of 97.9%, and total diagnostic accuracy of 83.3%. Forty six out of 61 cases (75.4%) with a final histopathological diagnosis of benign nodule had a negative cytological diagnosis, while 34 out of 35 cases (97.1%) with a final histopathological

6 432 Does Ultrasound Elastography Improve the Diagnostic Accuracy diagnosis of carcinoma had a positive cytological diagnosis (p<0.005). Among the 39 cases with histopathological diagnosis of nodular goiter, 35 cases (89.7%) were correctly diagnosed by cytology as being negative. The last 4 cases were over diagnosed cytologically as being positive, follicular neoplasm in 3 cases (7.7%) and suspicious for malignancy in one case (2.6%); achieving 89.7% diagnostic accuracy. Regarding to the 22 follicular adenoma cases 11 cases (50%) revealed negative cytological result and 11 cases (50%) showed positive results, achieving 50% diagnostic accuracy. Of the 31 nodules with final hiatopathological diagnosis of papillary carcinoma, 30 cases (96.8%) were positive on cytology and one case (3.2%) was negative achieving 96.8% diagnostic accuracy. All the 3 nodules (100%) with final diagnosis of minimally invasive follicular carcinoma gave positive cytological reports. The only medullary carcinoma case was positive on cytology (Table 1). Table (2): Relation between final histopathological diagnoses and cytological results of the 96 studied cases. Cytological results Histopathological diagnoses Positive Negative Positive 34 (69.4%) 15 (30.6%) 49 (TP) (FP) Negative 1 (2.1%) 46 (97.9%) 47 (FN) (TN) TP : True positive cases. FP : False positive cases. FN : False negative. TN: True negative cases. Total On US nodule irregularity and presence of microcalcifications are strong predictive factors of malignancy especially if combined with hypoechogenicity on US elastography, score 1 was found in 6 cases (6.3%), score 2 in 51 cases (53.1%), score 3 in 5 cases (5.2%), score 4 in 15 cases (15.6%), and score 5 in 19 cases (19.8%) (Table 3). The results of US elastography were then compared with their corresponding histopathological diagnosis. All cases with US elasography score 1 and 2 (100%) were confirmed as benign on histopathological diagnosis. Two of the 5 cases (40%) with elastography score 3 were malignant on histopathology, while 3 cases (60%) were benign. Of score 4, 14 out of 15 cases (93.3%) were malignant and the remaining one case (6.7%) were benign on final histopathology. All cases with elastography score 5 (100%) were malignant (Table 3). Table (3): Elastography scores of the 96 included cases compared with the corresponding histopathological diagnoses. Elastography No score Histopathological diagnoses No (%) Remarks Score (1) 6 Nodular goiter 4 (66.7%) TN Follicular adenoma 2 (33.3%) TN Score (2) 51 Nodular goiter 35 (86.6%) TN Follicular adenoma 16 (31.4%) TN Score (3) 5 Follicular adenoma 3 (60%) FP Papillary carcinoma 2 (40%) TP Score (4) 15 Follicular adenoma 1 (6.7%) FP Papillary carcinoma 12 (80%) TP Follicular carcinoma 2 (13.3%) TP Score (5) 19 Papillary carcinoma 17 (89.5%) TP Follicular carcinoma 1 (5.3%) TP Medullary carcinoma 1 (5.3%) TP TP : True positive cases. FN: False negative cases. FP : False positive cases. TN : True negative cases. All the included 57 cases with elastography score 1 and 2 (negative) were proved to be benign on histopathology (true negative) and no false negative cases. The remaining 39 cases were referred to surgery either due to score 3,4, or 5. Of these 35 cases (89.7%) were proved to be malignant on histopathological reports (true positive) and 4 cases (10.3%) were diagnosed as benign (false positive) (Table 4). Thus US elastography achieved sensitivity of 100%, specificity of 93.4%, positive predictive value (PPV) of 89.7%, negative predictive value of 100%, and total accuracy of 95.8%. Fifty seven out of 61 cases (93.4%) with a final histopathological diagnosis of benign nodule had US elastography score 1 and 2, while all cases (100%) with a final histopathological diagnosis of malignant nodule had score 3, 4, and 5 (p<0.0001). Table (4): Relation between final histopathological diagnoses and elastography results of the 96 studied cases. Elastography results Histopathological diagnoses Positive Negative Positive 35 (89.7%) 4 (10.3%) 39 (TP) (FP) Negative 0 57 (100%) 57 (FN) (TN) TP : True positive cases. FP : False positive cases. FN : False negative. TN: True negative cases. Total

7 Omnia Mokhtar & Nevein Tahon 433 The 39 cases with histopathological diagnosis of nodular goiter were correctly showed negative score (1,2), achieving 100% diagnostic accuracy. Among the 22 follicular adenoma cases 18 cases were correctly scored as score 1,2, while 4 cases were over-scored as score 3,4, achieving 81.8% diagnostic accuracy. All the 31 nodules with final hiatopathological diagnosis of papillary carcinoma were correctly scored as score 5, score 4, and score 3; achieving 100% diagnostic accuracy. The 3 nodules with final diagnosis of minimally invasive follicular carcinoma were correctly scored as score 4 and score 5. The only medullary carcinoma case had score 5 (Table 3). The elastography scores were compared with the results of FNAC. In the 18 nodules with cytological report of follicular neoplasm (indeterminate cytology), the score 2, describing high elasticity, being found in 10 of 14 benign nodules on histology and in no malignant nodules; and score 3, 4, and 5, describing low elasticity, was found in the 4 malignant nodules and in 4 out of the 14 benign nodules (p<0.0005). The elastography scoring was efficient in differentiating benign from malignant in indeterminate cytological result. For the 31 nodules with suspicious or malignant cytological reports, score 2, describing benignity, was found in one case, which was follicular adenoma on histopathology; while score 3,4,5, describing malignancy, were scored in the remaining 30 nodules, that were malignant on histopathology (p<0.0005). The elastography scoring was highly efficient in differentiating benign from malignant in suspicious or malignant cytological result. Among the 47 cases with benign cytological reports, 46 nodules had score 1,2 and the only case that falsely diagnosed on cytology as being benign was correctly had score 4 by elastography (p<0.0001). The elastography scoring was highly efficient in differentiating benign from malignant in benign cytological result (Table 5). Figs. (4-7) show varieties of our cases. Table (5): Relation of cytological results with elasticity scores of the 96 studied thyroid nodules in relation to the final histopathological diagnosis. Cytological results Elasticity score Pathological diagnosis Benign Malignant Total Benign Score Score 2 Score Indeterminate Score Score Score Score Suspicious 1 5 Score Score Score Score Malignant Score Score Fig. (4): 35-year-old male with right Lobe mixed solid and cystic nodule with suspicious solid component within. Score 3 on elastography, proved by pathology to be papillary carcinoma.

8 434 Does Ultrasound Elastography Improve the Diagnostic Accuracy Fig. (5): 61-year-old male with suspicious left lobe nodule score 4 on elastography proved pathologically to be papillary carcinoma. Fig. (6): 28-year-old female with right lobe nodule score 2 on elastography proved pathologically to be follicular adenoma. Fig. (7): 50-year-old female with right Lobe nodule score 3 on elastography proved pathologically to be papillary carcinoma.

9 Omnia Mokhtar & Nevein Tahon 435 Discussion The elasticity of tissues has been studied by several authors with different approaches [16]. US elastography is a dynamic technique that evaluates the degree of distortion of a tissue under the application of an external force, and is based upon the principle that the softer parts of tissues deform easier than the harder parts under compression, thus allowing an objective determination of tissue consistency [17,18]. Malignant lesions are often associated with changes in the mechanical properties of a tissue, and US elastography has been used to differentiate cancers from benign lesions in prostate, breast, pancreas, and lymph nodes [12,13]. In our study we have used the freehand compression applied on the neck region that was standardized by real-time measurement on a numerical scale, rendering highly reproducible real-time determination of tissue elasticity. This technical implementation minimizes the artifacts reported by Lyshchik et al., [19], and reduces the interobserver and intraobserver variability. This technique is easy to perform and requires no more than 3-5min of additional examination time to conventional US, so it can be done during routine US thyroid evaluation. In our study group, all the included 57 cases with elastography score 1,2 (negative) were proved to be benign on histopathology (true negative) and no false negative cases. The remaining 39 cases were referred to surgery either due to score 3,4, or 5. Of these 35 cases (89.7%) were proved to be malignant on histopathological reports (true positive) and 4 cases (10.3%) were diagnosed as benign (false positive). Thus US elastography achieved sensitivity of 100%, specificity of 93.4%, positive predictive value (PPV) of 89.7%, negative predictive value of 100%, and total accuracy of 95.8%. These results matches with results of T. Rago, F. Santini et al., [16], who found that the highest elasticity scores, indicative of a greater nodular consistency, were invariably associated with malignancy with minimal loss of sensitivity (specificity 100%, sensitivity 93.4%). The possibility to select the area of US elastography analysis allowed a correct scoring, even of these small nodules, independently from the position of the nodule within the thyroid lobe. Therefore, USE can be used to increase both the sensitivity and the specificity of US for the detection of malignant thyroid nodules, and so it seems to have great potential as a new tool for the diagnosis of thyroid cancer [20]. Although presently, FNA remains the most important procedure for the diagnostic management of thyroid nodules, yet a substantial proportion (up to 20%) of cytological specimens yield indeterminate results [21] and the distinction between benign and malignant lesions can only be made on histological criteria. In follicular lesions, conventional echographic patterns were found to be of minor relevance for predicting carcinoma [16]. These results have been confirmed in a series done by Rago T., et al., [22], containing 32 patients with indeterminate nodules on cytology, seven of whom resulted to have a papillary or follicular thyroid carcinoma on histology. The predictivity of US elastography in this subgroup of patients was highly rewarding, scores 4-5 being found in six of seven patients having a final diagnosis of malignancy and a score of 1-3 in all 25 patients with a histological diagnosis of benign lesion. In our study, the elastography scores were compared with the results of FNAC. In the 18 nodules with cytological report of follicular neoplasm (indeterminate cytology), the score 2, describing high elasticity, being found in 10 of 14 benign nodules on histology and in no malignant nodules; and score 3,4, and 5, describing low elasticity, was found in the 4 malignant nodules and in 4 out of the 14 benign nodules (p<0.0005). The elastography scoring was efficient in differentiating benign from malignant nodules in indeterminate cytological result. For the 31 nodules with suspicious or malignant cytological reports, score 2, describing benignity, was found in one case, which was follicular adenoma on histopathology; while score 3,4,5, describing malignancy, were scored in the remaining 30 nodules, that were malignant on histopathology (p<0.0005). The elastography scoring was highly efficient in differentiating benign from malignant nodules in suspicious or malignant cytological result. Among the 47 cases with benign cytological reports, 46 nodules had score 1 and 2 and the only case that falsely diagnosed on cytology as being benign was correctly had score 4 by elastography (p<0.0001). The elastography scoring was highly efficient in differentiating benign from malignant in benign cytological result. On the other hand, conventional US maintains a pivotal importance to define which nodules are suitable for the US elastographic characterization. Indeed, nodules in which US reveals the presence

10 436 Does Ultrasound Elastography Improve the Diagnostic Accuracy of calcified shell have to be excluded from the US elastographic evaluation because the US beam does not cross the calcification, and the probe compression does not result in tissue strain deformation. Similarly, in cystic nodules, US elastography cannot give useful information, the main determinant of nodule stiffness being the fluid content, and not the solid wall [23,24]. For this reason, we selected 96 patients who had solid nodules for the analysis. Only in 5 cases, anechoic lacunae were present within the nodule that occupied less than 20% of the nodule volume. Further studies will be necessary to understand whether US elastographic measurements can give reliable results in nodules that are greater than 20% cystic. One other limitation of this technique is that the nodule to be examined must be clearly distinguishable from other nodules present in the thyroid, to select it for the US elastography measurement. Thus, multinodular goiters with coalescent nodules in most cases are not suitable for this analysis. In conclusion, US elastography seems to have great potential as a new tool for the diagnosis of thyroid cancer, especially in nodules with indeterminate cytology. It can also used as a guide to select suspicious nodule for targeting by biopsy in cases with multiple nodules. Larger prospective studies are needed to confirm our results and establish the diagnostic accuracy of this technique and to determine its ability to replace FNAC in the future. References 1- ASTERIA C., GIOVANARDI A., PIZZOCARO A., et al.: US elastography in the differential diagnosis of benign and malignant thyroid nodules. Thyroid, 18 (5): , BASHARAT R., BUKHARI M.H., SAEED S. and HA- MID T.: Comparison of fine needle aspiration cytology and thyroid scan in solitary thyroid nodule. Pathology Res. 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