Eur Radiol (2008) 18: 23812389 DOI 10.

1007/s00330-008-1032-8

BREAST

Gianfranco Scaperrotta Claudio Ferranti Claudia Costa Luigi Mariani Monica Marchesini Laura Suman Cristina Folini Silvana Bergonzi

Role of sonoelastography in non-palpable breast lesions

Received: 28 September 2007 Revised: 7 March 2008 Accepted: 30 March 2008 Published online: 4 June 2008 # European Society of Radiology 2008

G. Scaperrotta (*) Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy e-mail: gianfranco. scaperrotta@istitutotumori.mi.it Tel.: +39-223-902519 Fax: +39-223-902524

G. Scaperrotta . C. Ferranti . C. Costa . M. Marchesini . L. Suman . C. Folini . S. Bergonzi Department of Breast Imaging, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy L. Mariani Unit of Medical Statistics and Biometry, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

Abstract The purpose of this study was to evaluate the diagnostic utility of sonoelastography in differentiating benign from malignant non-palpable breast lesions. A total of 293 BIRADS 35 (Breast Imaging Reporting And Data System) impalpable breast lesions in 278 women was evaluated with B-mode ultrasound (US) and subsequently with sonoelastography (SE) before performing US-guided biopsy. Among the 293 lesions (size up to 2 cm), 110 (37.5%) were histologically malignant and 183 (62.5%) benign. Lesions that were malignant or showed atypical ductal hyperplasia

were referred for surgical excision, as well as 32 benign lesions showing discordance between US/SE results and histology. All other benign lesions had US follow-up at 6/12 months, showing stability. Overall performance of SE was lower than US, with sensitivity and specificity of 80% and 80.9%, respectively, for SE as compared with 95.4% and 87.4% for US. Statistical analysis showed no improvement in the joint use of SE and US over the use of US alone, whose performance, however, was very high in our study. SE is a simple, fast and non-invasive diagnostic method that may be a useful aid to US for less experienced radiologists in the assessment of solid non-palpable breast lesions, especially BI-RADS 3, where specificity was higher (88.7%). Keywords Sonoelastography . Breast ultrasound . Non-palpable breast lesions

Introduction
Breast ultrasonography (US) has become an invaluable tool for detection and imaging-guided biopsy of impalpable lesions, particularly in women with dense breasts. Technological improvements in transducer resolution and signal processing have enabled sensitivity of 8595% and specificity of 7680% to be achieved [1, 2]. US, however, is still strongly operator-dependant, and a correct diagnosis may be sometimes difficult because of the overlapping between the features of malignant and

benign breast lesions, although they have been described [35] and categorized [6]. Consequently, the diagnostic confirmation may often require image-guided biopsy procedures. Recently, a new ultrasound approach has been introduced, sonoelastography (SE), based on the principle that malignant tissue is harder than benign tissue. Elastography was introduced in 1991 [7] and started to be used in a clinical setting in 1997 [8]. Various methods have been tested before real-time free-hand SE was available, and Ueno and co-authors [9] have proposed

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simple interpretative criteria and a scoring system that classifies the lesions in the same way used by BI-RADS for classification of B-mode US images [6]. In preliminary papers authors have reported cases series including lesions up to 3 cm in diameter and sometimes palpable, with SE showing lower sensitivity, but greater specificity than US [911]. The reported sensitivity and specificity of SE range between 79100% and 7995%, respectively [4], and the exam is considered a promising opportunity because it is sufficiently easy to perform after an adequate training and takes only about 5 min after US assessment. We adopted a revised SE score system, based on a multicenter Italian Team of Study [12], which was used to evaluate 293 non-palpable breast lesions up to 2 cm in diameter before performing US-guided biopsy. The purpose was to determine the performance of the exam and estimate which role it may play in daily workup of nonpalpable lesions.

On the scheduled day, for each patient the lesion/lesions was/were correctly identified with conventional B-mode US on the basis of previous mammographic and US studies, then a directed SE was performed on the region/ regions of interest (ROI). Finally, the lesions were submitted to US-guided 18- or 14-gauge core-needle biopsy (CNB) with an automatic short-throw (1.2 cm) biopsy gun (Pro-Mag). Only in 4 out of 293 cases, fineneedle aspiration citology (FNAC) was performed instead of CNB. Lesions that were malignant or showed atypical hyperplasia at CNB were referred for excision, while among lesions with benign CNB results 32 patients were referred for confirmatory open surgical biopsy, due to persistent risk of underestimation by discordance between US/SE results and histological diagnosis. The definitive histologic results were used as reference. Lesions with benign CNB results were submitted to US follow-up at 6 and 12 months. No significative changes concerning morphology and size of the lesions were found. Equipment

Materials and methods

Patients A prospective study was performed from January 2005 to May 2006 at the Breast Imaging Unit of the National Cancer Institute of Milan to assess the diagnostic capability of sonoelastography in non-palpable breast lesions prior to US-guided needle biopsy, with biopsy results as reference standard. Lesions that were clearly cystic or benign at B-mode US were excluded because we intended to enroll only lesions that could be liable to investigation (BI-RADS 3) or suspicious (BI-RADS 45) according to the Breast Imaging Reporting and Data System lexicon of the American College of Radiology [6]. Our study enrolled 278 women, aged from 29 to 82 years (mean of 53) with a total of 293 focal lesions, ranging from 3 mm to 20 mm in diameter. This number represents the set of eligible cases, after the exclusion of 17 cases because of unsatisfactory image quality (unacceptable elastographic image parameters). Lesions measuring more than 2 cm were also not included in the analysis. Among the lesions detected at conventional B-mode US, 165 were were classified as BI-RADS 3 being represented by developing or enlarging benign appearing masses. In the subset of 128 suspicious cases, classified as BI-RADS 4 or 5, 116 were represented by masses and 12 by focal architectural distortions. Most of the patients submitted to US-guided biopsy had previous mammography and/or ultrasound at our unit, but several women were referred to us on the basis of studies performed elsewhere. Pre-biopsy conventional US was performed using a digital electronic US unit LOGOS HiVision ESAOTE/HITACHI, with a linear array broad-band transducer with a frequency range of 614 MHz. Sonoelastography was performed with the same equipment, employing a dedicated software with an algorithm that in a very short time processes the radio-frequency impulses coming from the lesion and displays in real time and in color scale the degree of tissue strain in the ROI. Elastographic method After B-mode US detection of the lesion of interest, the patient remains in the supine position, and a stabilizer device is mounted on the probe to hold an homogeneous pressure on a wider area of the skins surface by minimizing lateral movements of the probe. Then the dual elastographic program starts, with the US monitor showing in real time the B-mode US image of the lesion on the right side and the same image with colorcoded elasticity features superimposed on the left side. The SE exam usually lasts on average 5 min, and motion images are obtained by applying a light constant pressure with the probe in contact with the skin perpendicular to the chest wall. In order to obtain correct elastographic images, attention must be paid to the definition of the ROI, which has to be sufficiently wide to include enough breast tissue surrounding the lesion so that data about the average strain of the tissue inside the region are available. The ROI usually must extend from the

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subcutaneous fat at the top to the anterior profile of the pectoral muscle at the bottom, with lateral borders set more than 5 mm from the lesions boundary. The exam is correctly performed checking the 15 LED scale that appears laterally on the right of the elastographic image that is indicative of proportionality between pressure and tissue strain. The color-coded image must be consistently overlapped with the B-mode US image, with a smooth appearance and without color flashes. The elasticity images are obtained according to a 256color scale ranging from red, indicative of the softest tissues that show the greatest strain, to blue for the hardest components that dont exhibit any strain, with green corresponding to the average strain observed in the ROI. To classify elastographic images, the 5-score system proposed by Ueno and co-workers [9] was considered, because it can be easily correlated to the 5-score BI-RADS classification, thus allowing a practical management of the lesions. However, a slight adjustment of Ueno scoring descriptors was undertaken according to the panel assessment of an Italian Multi-Centric Team of Study for Sonoelastography Evaluation in which we actively participated [12]. In the Ueno classification [9], score 1 indicated strain for the whole hypoechoic lesion, which appeared shaded in green. Score 2 indicated strain in most of the hypoechoic lesion, with a mosaic pattern of green and blue. Score 3 indicated strain (green) at the periphery of the lesion with a stiffness blue center. A score 4 indicated stiffness in the entire hypoechoic lesion, which was totally blue. Finally, score 5 indicated no strain in the entire hypoechoic lesions and in the surrounding area, both appearing blue. The Italian Team of Study classification [12] that we adopted differs from the above-mentioned one mainly for the score 1 lesions, which exhibit a typical three-layer feature (blue-green-red from the surface to the bottom) usually indicative of cystic lesions. This is a feature that Ueno and co-workers described in their preliminary report, but it is not referred to in their latest extensive paper [9]. In our classification, score 2 is a benign-like lesion almost entirely green with random blue points. A score 3 is a lesion predominantly green showing some blue spots, consistent with benignity. Score 4 is an almost entirely blue lesion with minimal green points at the periphery, suspect for malignancy. Score 5 is the same as in the Ueno classification, with an entirely blue lesion surrounded by a blue halo, consistent with malignancy (Fig. 1). Statistical methods Lesions were classified at US B-mode according to BIRADS (Breast Imaging Reporting and Data System). The

CHROMATIC CODE

ELASTOSONOGRAPHIC SCORE SCORE 1: Presence of chromatic tri-stratification (blue /green / red) SCORE 2: Prevalence of green, with in case some blue point, inconstant seat SCORE 3: Prevalently green, but with some blue spot. SCORE 4: Almost completely blue, with in case some green point, most of all in periphery SCORE 5: Completely blue, also with a blue peripheral glow around the nodule

ITALIAN TEAM OF STUDY Prevalently in the liquid forms

PREVALENTLY ELASTIC: prevalently in the benign forms

PREVALENTLY RIGID: prevalently in the malignant forms

Fig. 1 Sonoelastographic classification by the Italian Multi-Center Team of Study

correlation between US and SE scores was assessed by calculating the Kendalls tau-correlation coefficient: a 0 correlation coefficient denotes the lack of association between two scores, whereas a value of 1 would indicate perfect association. Considering each score level as a possible threshold for test positiveness, true positives (TP), true negatives (TN), false positives (FP) and false negatives (FN) were computed, and their frequency was used to obtain the estimates of sensitivity (TP/[TP+FN]), specificity (TN/ [TN+FP]), positive predictive value (PPV=TP/[TN+FN]) and negative predictive value (NPV=TN/[TN+FN]). Histology was used as reference for defining the lesion nature (benign, malignant). The overall diagnostic performance of the two methods under investigation, which is independent of the choice of a specific test threshold, was assessed by means of the Area under the ROC Curve (AUC-ROC), calculated nonparametrically as proposed by Hanley and McNeil [14]. An AUC-ROC of 1 indicates perfect discrimination between malignant and benign lesions, a value of 0.5 indicates the lack of discrimination, and values in between indicate partial discrimination that may vary from poor to strong. The comparison between the curves for US and ES, being derived from the same lesions, was performed as described in [15], whereas the remaining comparisons between independent sub-groups were carried out as described in [14]. Subgroup analyses were carried out in specific subsets, such as SE scores in the case of different US categories, or for lesions measuring up to 10 mm vs. 1120 mm. Furthermore, the AUC-ROC estimate for the joint use of US and ES was estimated by fitting a multiple logistic regression model in which the status of the lesion (benign or malignant) was entered as the response variable,

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whereas the US and SE scores were entered as the predictors.

Results
At histology 110 lesions resulted in being malignant (37.5%) and 183 benign (62.5%) (Table 1). Lesion size was up to 5 mm in 66 cases (22.5%), 6 10 mm in 133 cases (45.4%), 1115 mm in 65 (22.2%) and 1620 mm in 29 cases (9.9%). Lesion size was not significantly different between the two subsets, with 122/183 (66%) benign lesions measuring up to 10 mm as compared with 77/110 (70%) malignant lesions. Patients with malignancy were on average older than women with benign diagnosis (mean age 60.1 years vs. 48.7). Among benign cases, apart from specific diagnoses like fibroadenoma or papilloma or cyst, the other cases were reported as fibrosclerosis, chronic mastitis and ANDI (Aberrations of Normal Development and Involution of breast parenchyma, according to the nomenclature by Hughes) [13]. The remaining five cases classified as other included two intramammary lymph nodes, one hemangioma and two cases reported as lipomatosis. Three lesions yielded atypical results at CNB. In one case subsequent excision with vacuum-assisted breast biopsy didnt confirm atypia or malignancy. The same occurred for another case that was submitted to surgical

Table 1 Histologic diagnoses in 293 non-palpable breast lesions Pathologic diagnosis Malignant lesions -Ductal invasive carcinoma -Lobular invasive carcinoma -Mucinous carcinoma -Tubular carcinoma -DCIS -LCIS Benign lesions -Fibroadenoma -Papilloma -ANDI -Atypical hyperplasia -Fibrosclerosis -Chronic mastitis -Cyst -Other No. of cases 110 78 16 4 3 8 1 183 58 9 54 2 36 14 5 5 Percent 37.5 26.6 5.5 1.4 1.0 2.4 0.3 62.5 19.8 3.0 18.6 0.7 12.3 4.8 1.6 1.6

biopsy. In the third case surgery revealed multifocal disease, so in our series we have considered this case as malignant despite the underestimation at CNB. Among the 293 non-palpable breast lesions, the relationship between US and SE scores is shown in Table 2. As suggested by the relatively high number of cases along the diagonal of the table, the scores of the two methods tended to be positively correlated. This was confirmed by an estimated Kendalls tau-correlation coefficient of 0.60 (standard error, 0.034). The distribution of US and SE scores separately for benign and malignant lesions is shown in Table 3, together with sensitivity and specificity. For US, high sensitivity and specificity were achieved with a threshold of 3, which is considering negative for malignancy a BI-RADS score 3 and as positive a score 4 or 5. Correspondent PPV and NPV (with 95% confidence limits) were 0.820 (0.7430.883) and 0.970 (0.9310.990). The AUC-ROC estimate was 0.926, indicating a strong and statistically significant (P<0.0001) overall diagnostic performance of the BI-RADS score. Also for SE a threshold of 3 yielded relatively high sensitivity and specificity estimates, which, however, were inferior to those obtained with US (0.80 vs. 0.95 for sensitivity, 0.81 vs. 0.87 for specificity). Corresponding PPV and NPV estimates were 0.715 (0.6270.793) and 0.871 (0.8110.917), respectively. The AUC-ROC estimate was 0.827, and the difference toward the corresponding estimate for US was statistically significant (P= 0.0012). Altogether, the above findings indicate that SE was able to discriminate between benign and malignant lesions, yet the performance was somewhat inferior to that of US. To investigate whether SE might add diagnostic information when combined with US, we assessed the performance of SE scores in the case of different US categories, namely BI-RADS 3 (mostly including benign lesions) or BI-RADS 45 (mostly including malignant lesions). The results in terms of sensitivity and specificity are shown in Table 4. No threshold choice was able to jointly yield high sensitivity and specificity either for BIRADS 3 or BI-RADS 45 lesions. AUC-ROC estimates for the two strata were 0.453 (P=0.7444) and 0.605 (P=

Table 2 Relationships between US and SE scores in 293 breast lesions US scores (BI-RADS) Sonoelastographic scores 12 3 4 5 Total 74 9 0 83 3 72 14 1 87 4 16 66 11 93 5 3 19 8 30 165 108 20 293 Total

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Table 3 Performance of US and SE in 293 breast lesions Method US Score 3 4 5 12 3 4 5 Benign no. 160 23 0 75 73 30 5 Malignant no. 5 85 20 8 14 63 25 Sensitivity 95.4% Specificity 87.4% AUC-ROC 0.926 Standard error 0.017

SE

80.0%

80.9%

0.827

0.026

0.0979), indicating the lack of significant discrimination between benign and malignant lesions within each stratum. However, the specificity of SE in the subsets of BI-RADS 3 lesions was 88.7%, superior to the figure of 80.9% of the whole series. The AUC-ROC for the joint use of US and SE information was 0.925, a figure indicating no gain over the use of US scores alone (0.926, as shown in Table 3). Table 5 shows the performance of the joint use of US and SE versus histological results. Both examinations were concordant and correct in 142 TN and 87 TP lesions, for an accuracy of 78.1% (229 out of 293 cases). Both examinations were concordant but wrong in 4 FN and 17 FP cases, for an error rate of 7.2% (21 out of 293 cases). The subset of four FN both at US and SE included two cases of ductal invasive carcinoma, one case of mucinous carcinoma and one case of lobular carcinoma in situ (LCIS) associated with atypical ductal hyperplasia (ADH) that was found at subsequent surgical excision. In the subset of 17 both US and SE false-positive cases, we found 10 chronic mastitis, many of them with giant plurinucleate granulomatous cells and hemosiderin or cholesterol crystals, diagnoses that didnt warrant further excision (Fig. 2). Of the remaining seven cases, yielding six reports of fibroadenoma or adenosis, and one case of papilloma at CNB, three underwent confirmatory surgery

and four had a 612 month ultrasound follow-up that excluded significant changes. The numbers in Table 5 show that US improvement resulting from SE examination was negligible, because elastography allowed to recognize 1 out of 5 US FN and 6 out of 23 US FP, respectively (Fig. 3). Therefore, of the 43 lesions where the two methods were discordant, SE was more accurate than US only in seven cases. (Fig. 4) We also explored the diagnostic performance of SE in small (up to 10 mm) or larger lesions (1120 mm), and the results are shown in Table 6. A slightly better overall performance was observed in the first case (AUC-ROC, 0.841) versus the second (0.787), yet the difference was not statistically significant (P=0.37). An opposite behavior was observed for US (not shown), for which a slight decay in the diagnostic performance was associated with small lesion size (AUC-ROC, 0.90). In any case, the above effects were too small to be considered of practical importance.

Discussion
The first clinical results of SE were published in 1997 2001 [8, 16], but only in 20032004 the development of US equipment with dedicated software for real time processing enabled SE utilization simultaneously with routine US examinations [17, 18]. The scoring system

Table 4 Performance of SE in 165 US BI-RADS 3 lesions and in 128 BI-RADS 45 lesions SE Score US score 3 12 3 4 5 12 3 4 5 Benign no. 71 71 15 3 4 2 15 2 Malignant no. 3 1 1 0 5 13 62 25 Sensitivity 20.0% Specificity 88.7% AUC-ROC 0.453 Standard error 0.144

US score 45

82.8%

26.1%

0.605

0.064

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Table 5 Joint results of US and SE versus histological diagnosis in 293 lesions Histological diagnosis Benign Malignant US/ SE neg 142 4 US neg/ SE pos 18 1 US pos/ SE neg 6 18 US/ SE pos 17 87

initially proposed by Ueno and co-workers [9] was useful to compare the results of the preliminary studies. The ability of SE to evaluate the mechanical properties of different tissues is a useful diagnostic tool that provides further information about breast lesions in addition to the well-known morphologic parameters such as shape, orientation, margins, internal structure and the presence of calcifications. These additional findings may be very useful in distinguishing malignant from benign non-palpable solid lesions; as well, the stiffness of a mass as perceived at palpation plays an important role in the clinical assessment. Changes in elastic properties between normal tissue, fibroadenoma and cancer have been reported in previous papers [19, 20], assessing that neoplastic lumps are significantly harder than fibroadenomas. We should recognize, however, that both fibroadenoma and cancer may have variable features when we consider different stages of development and involution for the former and different histological subtypes for the latter. The infiltrating lobular carcinoma, for instance, may have a permeative growth pattern without mass formation, while mucinous, medullary and papillary carcinomas usually exhibit round shapes and circumscribed margins and are often, but not always soft tumors (Fig. 5). In all of them a fibrous desmoplastic reaction is usually absent [21]. It is from this perspective that Ueno and co-workers in their paper divided malignant lesions in scirrhous and non-scirrhous types, the former

Fig. 3 Fibroadenoma with elasticity score 2. On conventional Bmode image, the lesion was classified as BI-RADS 4

including invasive ductal and tubular carcinomas [9]. These peculiarities are reflected in different features both at US B-mode and at SE examinations and are responsible for diagnostic inaccuracies. If we consider for instance the four FN results both at US and SE [Table 5], we should be aware that ultrasonographic and elasticity features of the mucinous carcinoma may be benign-like, especially if the stromal pattern is poor, and that in situ carcinomas often lack ultrasonographic conspicuousness or typical features. Therefore, an actual error occurred only for two ductal invasive carcinomas, one measuring 610 mm and the second more than 15 mm in diameter. Even in the subset of 17 FP results both at US and SE, interpretative difficulties may occur in many instances, especially in the chronic mastitis group, leading to upgrading and worsening in classification both at ultrasound and at elastography. US B-mode was superior to SE both in sensitivity (95.4% vs. 80%) and specificity (87.4% vs. 80.9%). Our results are similar to those reported by Thomas et al. [11], who in 300 patients with histologically confirmed breast

Fig. 2 Right: on conventional B-mode image, a lesion classified as BI-RADS 4. Left: on elasticity image, the hypoechoic lesion was entirely blue (score 4). Histology: chronic mastitis with macrophages and giant plurinucleate cells

Fig. 4 Ductal infiltrating carcinoma with atypical US features (BIRADS 3) and sonoelastography SCORE 4

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Table 6 Performance of SE in 199 breast lesions measuring up to 10 mm and in 94 lesions measuring 1120 mm SE score Lesions up to 10 mm 12 3 4 5 12 3 4 5 Benign no. 54 43 21 4 21 30 9 1 Malignant no. 5 7 45 20 3 7 18 5 Sensitivity 84.4% Specificity 79.5% AUC-ROC 0.841 Standard error 0.030

Lesions 1120 mm

69.7%

83.6%

0.787

0.052

lesions (168 benign, 132 malignant) reported sensitivity and specificity, respectively, of 94% and 83% for US Bmode vs. 82% and 87% for elastography. They found, however, a superiority of elastography in BI-RADS 3 lesions and in fatty breasts. A French multi-center prospective study [22] with 345 breast lesions reported for elastography a sensitivity of 79.5%, a specificity of 93%, a PPV of 85.3%, a NPV of 89.8% and an accuracy of 88.4%. Sensitivity increased to 90% and specificity decreased to 72% when the cut-off for malignancy was lowered and BI-RADS 3 lesions were considered malignant. Giuseppetti et al. [10] in a study of 91 breast lesions (26 measuring more than 2 cm) reported a sensitivity of 79% and a specificity of 89%. However, when only lesions up to 2 cm were analyzed, the values increased to 86% and 100%, respectively. The authors emphasize the influence of histological subtype and size of cancers on the performance of elastography. Ueno and co-authors [9] in their case series of 111 breast lesions measuring up to 3 cm, all cyto/histologically

Fig. 5 Right: hypoechoic lesion BI-RADS 4. Left: totally blue sonoelastographic image coherent with malignancy (Score 4). Histology: mucinous cancer with high stromal component

confirmed, reported a sensitivity of 86.5%, a specificity of 89.8% for SE as compared with correspondent values of 96.2% and 62.7% for conventional US when the malignancy cut-off point was set between BI-RADS category 3 and 4, similarly to our study. These different results for SE in the literature probably reflect the experience gained by the operators, even though the case selection plays a most important role. Conventional US is operator-dependant, and there may be an inter-observer variability. However, all studies agree that SE requires training and practice to learn the appropriate technique. In particular, in our experience, most of the cases that were excluded from the analysis because of unacceptable image parameters belonged to the initial period of the learning curve. A light constant perpendicular compression of the US probe on the breast surface overlying the lesion is mandatory to obtain correct elasticity images. When the operator is well trained, the SE can be performed straightforwardly after the US conventional study, and it needs only a short extra time of 5 min on average. Unlike other published papers, our cases are composed exclusively of impalpable breast lesions up to 2 cm in diameter with histological correlation, and our results indicate that the role of sonoelastography is ancillary to conventional US, whose performance was overall better. Among US B-mode scores, the cancer rate of BI-RADS 3 lesions was 3% (5 out of 165), value that was not statistically different from the 2% established threshold. It can be attributed to chance fluctuations and not to systematic over-estimation. In score-4 lesions, 85 cancers were found in 108 cases (78.7%), for a total of 23 FP results, while all 20 BI-RADS score-5 lesions yielded cancer (100%). Among SE scores, the cancer rate for score-4 lesions was 67.7% (63 out of 93) and for score 5 was 83.3% (25 out of 30), for a total of 35 FP results. On the other hand, there were 22 FN results in 170 score 13 negative examinations (12.9%). This value is comparable to that found by Ueno and co-workers [9], and we agree with their recommendations

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about caution in deciding to withdraw a scheduled needle biopsy on the basis of a negative elasticity score. These authors reported two cancers in 15 score-3 cases (13%) and 5 malignant lesions in 24 score-2 cases (20.8%). In our cases we found 8 cancers in 77 score-2 lesions (10.4%) and 14 in 87 score-3 examinations (16.1%). In our study the joint use of US and SE showed no statistically significant improvement over the use of US scores alone. Table 5 shows that adding SE exam to US assessment was negligible in the 43 lesions where the two methods were discordant. In this setting, SE allowed to correctly estimate 1 out of 5 US FN and 6 out of 23 FP results, so SE was more accurate than US only in 7 cases. We have to recognize that the performance of US assessment was very high in our cases [Table 3], probably because of the experience gained working in a Breast Imaging Unit of a cancer center. In this situation it may be more difficult for a new method such as SE to achieve a substantial improvement in the diagnostic setting, though the specificity of SE was increased (88.7% instead of 80.9%) in the subset of BI-RADS 3 lesions. Probably different considerations may be valid either in a general radiological practice where radiologists may not be breast-dedicated or in centers where breast units exist, but the volume of diagnostic examinations and surgical treatments is not so wide and organized to gather a substantial audit. In our opinion, if the performance of US is not very high, then SE may play a more important role in the assessment of non-palpable breast lesions. We are aware that the performance of SE in our study doesnt seem so effective in comparison with other papers, but this probably may reflect the case selection of only

small impalpable breast lesions and the presence of some particular entities, such as the chronic mastitis group, which may affect the results. SE is a new method that needs to be fully validated. All preliminary reports passed through a learning curve, providing a categorization of breast lesions that served as a cornerstone for subsequent studies such as ours and so SE needs to be more extensively evaluated to reveal its ultimate potential.

Conclusions
Sonoelastography is a simple, non-invasive diagnostic examination that provides information about the stiffness of a mass, thus completing the morphological assessment by US B-mode. This may be useful to further characterize non-palpable breast lesions, especially for the BI-RADS 3 category, where follow-up or biopsy is the common option, in the attempt to decrease the number of unnecessary biopsies. Caution must be paid, however, before deciding to avoid a scheduled biopsy on the basis of a negative elastographic score, because of the considerable amount of FN results reported in our cases as well as in other published reports. In our opinion SE may play an important adjunctive role in helping the decision making by less-experienced or non breast-dedicated radiologists, because we must recognize that the diagnostic accuracy of conventional US with modern equipment is already very high, especially in expert hands, and SE has to be more extensively evaluated to fill the gap.

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