Women s Imaging Original Research

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1 Women s Imaging Original Research Linda et al. Biopsy of Radial Scars Without Atypia Women s Imaging Original Research WOMEN S IMAGING Anna Linda 1 Chiara Zuiani 1 Alessandro Furlan 1 Viviana Londero 1 Rossano Girometti 1 Piernicola Machin 2 Massimo Bazzocchi 1 Linda A, Zuiani C, Furlan A, et al. Keywords: breast cancer, core needle biopsy, radial scar, mammography, sonography DOI: /AJR Received December 30, 2008; accepted after revision October 7, Institute of Radiology, Azienda Ospedaliero Universitaria, University of Udine, Via Colugna 50, Udine, UD 33100, Italy. Address correspondence to A. Linda (annalinda33@gmail.com). 2 Institute of Pathology, Azienda Ospedaliero Universitaria, University of Udine, Udine, Italy. AJR 2010; 194: X/10/ American Roentgen Ray Society Radial Scars Without Atypia Diagnosed at Imaging-Guided Needle Biopsy: How Often Is Associated Malignancy Found at Subsequent Surgical Excision, and Do Mammography and Sonography Predict Which Lesions Are Malignant? OBJECTIVE. The purposes of our study were to evaluate the surgical outcome of cases of radial scar without atypia diagnosed at imaging-guided percutaneous needle biopsy and to determine whether the mammographic and sonographic features are able to predict which lesions will be upgraded to malignancy at surgical excision. MATERIALS AND METHODS. The records of 4,458 consecutive imaging-guided biopsies were retrospectively reviewed. Surgical excision results were available in 62 cases in which radial scar was the highest-risk lesion at stereotactically guided or sonographically guided biopsy. The mammographic and sonographic images and surgical findings were reviewed. The underestimation rate of malignancy of percutaneous biopsy was calculated. Differences in mammographic and sonographic appearances between radial scars with and without associated malignancy were evaluated using the Fisher s exact test. RESULTS. The percutaneous malignancy underestimation rate was 8% (5/62): 9% (4/43) for sonography guided 14-gauge biopsies and 5% (1/19) for stereotactically guided 11-gauge vacuum-assisted biopsies (p = 1.000). Mammographic and sonographic appearances were not significantly different between radial scars with and those without associated malignancy. CONCLUSION. A percutaneous diagnosis of a radial scar does not exclude associated malignancy at surgical excision. Mammographic and sonographic features of a lesion diagnosed as a radial scar at percutaneous imaging-guided biopsy do not predict which lesions will have associated malignancy at surgery. Therefore, all patients with percutaneous diagnosis of a radial scar should undergo surgical excision regardless of mammographic and sonographic appearances, until further criteria can be determined. R adial scar of the breast has been previously described in the literature under several different names such as radial sclerosing lesion, scleroelastotic lesion, indurative mastopathy, nonencapsulated sclerosing lesion, sclerosing papillary proliferation, and, if larger than 1.0 cm, complex sclerosing lesion [1]. Radial scar is a benign breast lesion characterized by a central fibroelastotic core with ducts and lobules radiating outward, giving the lesion its characteristic stellate appearance [1]. The presence of glands trapped at the center of the lesion may cause the lesion to be mistaken for tubular carcinoma [2]. In addition, pathologic examination of a radial scar often reveals a diverse array of pathologic findings including typical epithelial hyperplasia, adenosis, papillomatosis, atypical epithelial hyperplasia, ductal carcinoma in situ (DCIS), and earlystage invasive carcinomas [3]. The presence of all stages of mammary carcinogenesis within or adjacent to radial scars has led some investigators to speculate that radial scar represents a stage in the development of invasive carcinoma [4, 5]. In fact, reports in the literature suggest that radial scar is associated with surrounding malignancy in 0 40% of the cases [6 16]. Because radial scar is associated with underlying malignancy, a percutaneous biopsy is deemed not reliable in ruling out malignant foci at the periphery of the lesion and surgical confirmation is considered mandatory by some investigators [6, 7]. Biopsy and pathologic criteria such as the absence of atypical hyperplasia in biopsy samples, retrieval of at least 12 specimens, and extensive sampling with vacuum-assisted large-core biopsy devices have been identified as factors that may spare a patient from undergoing surgical excision [7 9, 16]. To our knowledge, only a few reports in the literature have evaluated the potential 1146 AJR:194, April 2010

2 Biopsy of Radial Scars Without Atypia role of mammographic and sonographic features in the management of radial scar diagnosed at percutaneous biopsy [8, 17 19]. In most of these studies, the data are based on small series and are limited because of the lack of criteria to separate radial scars with and those without surgical follow-up. The purposes of our study were, first, to evaluate the surgical outcome of cases of radial scar without atypia diagnosed at imaging-guided percutaneous needle biopsy and, second, to determine whether the mammographic and sonographic appearances are able to predict which lesions will be upgraded to malignancy at surgical excision. Materials and Methods The institutional review board granted permission for this retrospective cohort study, which was performed in a large university referral hospital for breast diseases. Patient Selection The study coordinator reviewed the histologic results of 4,458 consecutive imaging-guided needle biopsies of the breast performed at our institution from January 2000 to May Of these, 3,845 (86.3%) were performed under sonographic guidance, 607 (13.6%) were performed under stereotactic guidance, and six were performed under MR guidance (0.1%). Seventy-nine lesions (1.8%) diagnosed as radial scars at percutaneous biopsy were identified. The inclusion criteria for this study were, first, radial scar diagnosed as the highest-grade lesion at pathologic evaluation of biopsy specimens in the absence of any other high-risk lesion (i.e., atypical ductal hyperplasia or lobular neoplasia), DCIS, or invasive carcinoma; second, diagnostic surgical excision performed at the department of surgery at our hospital (it is our standard policy to recommend surgical excision of radial scars independently of the preoperative diagnostic judgment); and, third, pathologic analysis of percutaneous biopsy and surgical specimens performed at the department of pathology at our hospital. The exclusion criteria were, first, associated DCIS or invasive breast cancer in the same breast; and, second, absence of final pathology after surgical excision because of patient refusal to undergo the surgical procedure or referral to an outside hospital. Sixty-two lesions in 62 women (age range, years; mean age, 51 years) were included in our study group. The other 17 lesions were excluded: 14 as a result of absence of final pathology and three because of association with breast cancer in the same breast. Clinically, four women (6%) had mastalgia and 58 women (94%) had no specific symptoms. Of these 58 asymptomatic patients, five were being followed up for previous breast neoplasm and the remaining 53 were being screened for breast cancer. Imaging and Biopsy Techniques All 62 patients underwent mammographic examination. Images were obtained in two standard planes: mediolateral oblique and craniocaudal. Dedicated full-field equipment (Digital Device, Giotto IMS Srl) was used. Whole-breast sonography of all 62 women was performed using a broadband 5-12 MHz linear array transducer (HDI 5000, Advanced Technology Laboratories/Philips Healthcare), a broadband MHz linear transducer (Technos, Esaote), or a broadband MHz linear array transducer (iu22, Advanced Technology Laboratories/Philips Healthcare). We usually perform whole-breast sonography rather than targeted sonography guided by mammographic or clinical findings. All examinations were performed by one of four attending radiologists, each of whom had more than 10 years experience in breast imaging at the time of the study. Percutaneous biopsy was performed using stereotactic or sonographic guidance according to the judgment of the attending radiologist. In none of these cases was percutaneous biopsy performed under MR guidance. The biopsy procedures were performed by radiologists with years experience in breast imaging. In 43 of 62 lesions (69%), biopsy was performed under sonographic guidance using an automated biopsy gun (Magnum Biopsy Instrument, Bard) or a semiautomated biopsy gun (Precisa, Hospital Service SpA) with a 14-gauge, 15-cm-long needle (total running, 23 mm). A mean of five core samples (range, 3 8) were obtained per lesion. Nineteen lesions (31%) that were not visible on ultrasound were biopsied under stereotactic guidance using a digital prone table (Mammobed, Giotto, IMS Srl) and a directional vacuum-assisted biopsy device (Mammotome, Biopsy/Ethicon Endo-Surgery) with an 11-gauge needle. On average, 12 cores samples (range, 9 18) were obtained per lesion. In patients with mammographically detected microcalcifications, a specimen radiograph was obtained to confirm the presence of calcifications in each sample and a clip was left to mark the biopsy site. Imaging Interpretation All soft-copy mammographic and sonographic images were retrieved for retrospective independent interpretation by two radiologists with more than 10 years experience in breast imaging. The radiologists were aware of the study purpose but were blinded to the histologic diagnoses. Mammographic and sonographic images were presented randomly to each reader in separate sessions. Any discrepancy in opinion was resolved by consensus. With regard to mammography, the presence of a mass, including a mass with microcalcifications, or of microcalcifications or architectural distortion, including architectural distortion with microcalcifications, was noted. On the basis of sonography findings, lesions were classified as circumscribed or noncircumscribed masses. Reference Standard The study coordinator reviewed the surgical pathology report for each lesion and classified it according to the highest-grade lesion in one of the following categories: malignant (DCIS or invasive carcinoma), high risk (radial scar, atypical ductal hyperplasia, flat epithelial atypia, or lobular neoplasia), or benign (proliferative changes without atypia, other benign lesions). The final pathology results served as the reference standard. Statistical Analysis Data were entered into a computerized spreadsheet (Excel, Microsoft). The underestimation rate of malignancy of percutaneous biopsy was calculated according to the reference standard. For statistical evaluation of the differences in mammographic and sonographic appearances, radial scars eventually proved to contain malignant lesions were compared with radial scars without associated malignancy. The Fisher s exact test was used, and a p value of less than 0.05 was considered statistically significant. Results Final Pathology Results Of the 62 lesions, five (8%) proved to be malignant at surgical excision; 40 (65%), high risk; and the remaining 17 (27%), benign. Carcinomas associated with radial scars were three DCIS, two low-grade and one intermediate-grade DCIS; one grade 1 invasive ductal carcinoma, not otherwise specified; and one grade 2 invasive lobular carcinoma. Of the 40 high-risk lesions, 33 (82.5%) were radial scar, six (15%) were atypical ductal hyperplasia, and one (2.5%) was flat epithelial atypia. Of the 17 benign lesions, eight (47%) were fibrocystic changes, seven (41%) were sclerosing adenosis, and two (12%) were usual ductal hyperplasia. The percutaneous biopsy underestimation rate of malignancy was 8% (5/62): 9% (4/43) for sonography-guided 14-gauge biopsies and 5% (1/19) for stereotactically guided 11-gauge vacuum-assisted biopsies (p = 1.000). AJR:194, April

3 Linda et al. TABLE 1: Imaging and Biopsy Features of Five Lesions Diagnosed as Radial Scars Without Atypia at Percutaneous Biopsy Resulting in Malignancy at Surgical Excision Lesion No. Mammographic Appearance Lesion Sonographic Appearance A summary of all cases of malignant lesions diagnosed as radial scars without atypia at percutaneous biopsy is shown in Table 1. Mammographic Findings Thirty-eight (61%) of the 62 lesions were detected on mammography: 19 (50%) were shown as architectural distortions, 11 (29%) as calcifications, and eight (21%) as masses. Based on the results of surgical excision, three of five malignancies (60%) were detected on mammography. Malignancies were found in one of 19 architectural distortions (5%), in two of 11 lesions presenting as microcalcifications (18%), and in none of eight masses (0%) (p = 0.291). In the first case of microcalcifications, a hypoechoic mass was shown on sonography, and percutaneous biopsy was performed under sonographic guidance. In the second case, the only finding was a cluster of indeterminate microcalcifications (Fig. 1), and percutaneous biopsy was performed under stereotactic guidance with an 11-gauge vacuum-assisted biopsy device; 13 specimens were obtained. This lesion was upgraded to low-grade DCIS at surgical excision. Sonographic Findings Forty-five of 62 lesions (73%) were detected on sonography: 17 (38%) were categorized as a circumscribed mass and 28 (62%), as a noncircumscribed mass. Based on the results of surgical excision, four of five malignancies (80%) were detected on sonography. All four malignancies (14%) were found among noncircumscribed masses, whereas none (0%) was found among circumscribed masses (p = 0.281). One example of a noncircumscribed mass that was upgraded to malignancy, an intermediate-grade DCIS, at surgical excision is shown in Figure 2. Percutaneous biopsy was Size (mm) Type of Guidance Needle Size Biopsy performed under sonographic guidance using an automated biopsy gun with a 14-gauge needle, and five specimens were obtained. Discussion The use of percutaneous biopsy for the initial evaluation of clinically occult breast lesions is now widespread and is a practical alternative to open surgical biopsy for many patients. In previous studies, investigators have reported high rates of concordance between the histologic findings of percutaneous biopsy and surgical biopsy [20]. Exceptions are lesions that have high-risk histology results; this heterogeneous group of lesions includes atypical ductal hyperplasia, lobular neoplasia, papillary lesions, fibroepithelial lesions, mucocelelike lesions, columnar cells lesions, and radial scars [21]. Diagnoses of these lesions based on percutaneous biopsy are considered to be unreliable because of the risk that the lesions will be upgraded to malignancy at surgical excision; therefore, Vacuum-Assisted Device No. of Samples Surgical Results 1 a Calcifications 5 Stereotactic 11-gauge Yes 13 DCIS (low grade) 2 Calcifications Mass 15 Sonographic 14-gauge No 6 DCIS (low grade) 3 Architectural distortion Mass 22 Sonographic 14-gauge No 5 ILC 4 b Mass 10 Sonographic 14-gauge No 5 DCIS (intermediate grade) 5 Mass 9 Sonographic 14-gauge No 5 IDC Note Dash ( ) indicates no relevant findings, DCIS = ductal carcinoma in situ, ILC = invasive lobular carcinoma, IDC = invasive ductal carcinoma. a See Figure 1. b See Figure 2. A when encountered in biopsy specimens, they raise repeated management questions [22]. In lesions diagnosed as radial scars at percutaneous biopsy, underestimation of malignancy occurs not only because of sampling error (i.e., sampling only the region of radial scar in a lesion containing both radial scar and carcinoma), but also because of diagnostic error resulting from of the difficulty in differentiating radial scar from carcinoma, particularly of tubular histotype [6]. Studies addressing the issue of invasive carcinoma or in situ carcinoma occurring after a percutaneous diagnosis of radial scar have reported variable underestimation rates, ranging from 0 to 40% [6 16] (Table 2). Such variability is attributable primarily to limited study cohort sizes, differences in inclusion criteria, and possible biases with regard to the selection of lesions to undergo surgical excision. Furthermore, in some of these reports, the authors did not provide complete methodologic, radiologic, or clinical details. Fig year-old woman with radial scar without atypia found at stereotactically guided 11-gauge vacuumassisted biopsy that was upgraded to low-grade ductal carcinoma in situ at excisional biopsy (lesion 1 in Table 1). A, Magnification mammogram shows clustered amorphous calcifications (arrow). B, Radiograph of biopsy specimens shows calcifications (arrow) in one of 13 specimens. B 1148 AJR:194, April 2010

4 Biopsy of Radial Scars Without Atypia TABLE 2: Frequency of Malignancy in Lesions Yielding Radial Scars at Percutaneous Biopsy Malignancy Underestimation Rate, % (No. of Lesions Upgraded/Total No. of Lesions) Study [Reference No.] No. of Radial Scars at Core Biopsy (No. of Surgically Excised Lesions) Despite being included among the lower published malignancy underestimation rates, the 8% (5/62) incidence of carcinoma at surgical excision in this study shows that percutaneous biopsy of a radial scar is not reliable for diagnosis and should prompt surgical excision with pathologic examination of the entire lesion. Regarding the histologic features of the five cancers detected at surgical excision, none was a tubular carcinoma. This finding suggests that underestimation was mainly due to sampling error rather than diagnostic error. The results of our study confirm previous findings that DCIS arising in radial scars are likely to be of low or intermediate grade and that invasive carcinomas are likely to be grade 1 or 2 [23]. Three of the five malignancies were low- or intermediate-grade DCIS. This finding raises the question of overdiagnosis of slow-growing lesions that do not necessarily progress to invasive malignant disease. Therefore, a diagnostic delay due to a noninvasive management decision (imaging follow-up) of these cases likely would not have had a significant impact on patient prognosis [24]. Nevertheless, studies have shown that most of the malignant foci are contained within the confines of radial scars [6, 25, 26]; therefore, significant progression Type of Core Needle Biopsy Needle Size No. of Lesions would be required before changes in lesion size or contour will become apparent. In comparing the data from our study with the data from previous studies, it is necessary to consider that all patients with percutaneous diagnosis of radial scar in association with atypia (i.e., lobular neoplasia, atypical ductal hyperplasia, or both) were excluded from our evaluation, whereas in many published studies this exclusion criterion is not explicitly stated. Brenner et al. [8], Resetkova et al. [9], and Becker et al. [16] concluded that lesions without associated atypia at percutaneous biopsy performed with a vacuum-assisted device are amenable to followup instead of surgical excision in view of the low risk of malignancy. However, our results contradict their conclusions. Limited or partial sampling of correctly targeted imaging lesions has been identified as the most important cause of underestimation [27] and the amount of tissue obtained per biopsy has become a matter of concern. Compared with automated or semiautomated biopsy guns, vacuum-assisted biopsy devices provide pathologists with large individual samples obtained with larger needles, thereby inherently improving the architectural definition of difficult-to-diagnose lesions such as radial scars. Lomoschitz et al. Radial Scars With Atypia at Core Biopsy Radial Scars Without Atypia at Core Biopsy López-Medina et al. [6] 43 (43) Large core 14-gauge (2/5) 16 (6/38) 19 (8/43) Cawson et al. [7] 62 (62) Large core 14-gauge 62 NA NA 6 (4/62) Brenner et al. [8] 157 (102) Large core 14- and 12-gauge (1/7) 9 (5/58) 9 (6/65) Overall VAB 11- and 14-gauge (7/22) 0 (0/70) 8 (7/92) Resetkova et al. [9] 80 (19) VAB 11- and 9-gauge 80 0 (0/14) 0 (0/66) 0 (0/80) Dahlstrom et al. [10] 6 (3) Large core 14-gauge 6 0 (0/6) 0 (0/6) Lee et al. [11] 4 (4) Large core 14-gauge 4 25 (1/4) 25 (1/4) Meyer et al. [12] 4 (4) Large core 14-gauge 4 0 (0/4) 0 (0/4) Jackman et al. [13] 5 (5) Large core 14-gauge 5 40 (2/5) 40 (2/5) Philpotts et al. [14] 9 (8) Large core 14-gauge 4 0 (0/1) 0 (0/3) 0 (0/4) VAB 11-gauge 5 0 (0/1) 0 (0/4) 0 (0/5) Apesteguía et al. [15] 2 (2) VAB 11-gauge 2 0 (0/2) 0 (0/2) Becker et al. [16] 161 (90) Large core 14-gauge (6/24) 5 (5/100) 9 (11/124) VAB 11-gauge (2/12) 0 (0/25) 5 (2/37) This study 62 (62) Large core 14-gauge 43 9 (4/43) 9 (4/43) Note Dash ( ) indicates no cases. VAB = vacuum-assisted biopsy, NA = not available. VAB 11-gauge 19 5 (1/19) 5 (1/19) [28] reported that the highest diagnostic yield at stereotactically guided vacuum-assisted biopsy can be achieved with 12 specimens per lesion and that this yield is not improved with more than 12 specimens. Indeed, the malignancy underestimation rate in our series was lower using stereotactically Fig year-old woman with family history of breast cancer with radial scar without atypia found at 14-gauge biopsy. Lesion was upgraded to intermediate-grade ductal carcinoma in situ at excisional biopsy (lesion 4 in Table 1). Sonogram shows 10-mm oval hypoechoic mass with parallel orientation and no vascularity in lower outer quadrant of left breast. Bilateral mammograms (not shown) were negative. AJR:194, April

5 Linda et al. guided 11-gauge vacuum-assisted biopsy devices than using sonography-guided 14-gauge automated or semiautomated guns. However, a falsenegative result occurred. Notably, one lesion in which a vacuum-assisted device was used to obtain 13 specimens was underestimated (Fig. 1). This result does not seem to substantiate the findings of Brenner et al. [8] and Becker et al. [16] who reported that a diagnosis of radial scars without atypia at vacuum-assisted biopsy (using 14- or 11-gauge needle) with at least 12 specimens is reliable and that surgical excision is not required (Table 2). Nevertheless, in those series, an average of 14 and 32 cores per targeted lesion, respectively, were obtained. Resetkova et al. [9] had that same finding using an 11- or 9-gauge needle (Table 2). To our knowledge, our case is the first reported case of underestimation with a vacuum-assisted device. However, we must emphasize that the overall vacuum-assisted biopsy underestimation rate obtained by combining our results with those of the three mentioned literature references is only 0.6% (1/180). In addition, our unique case of underestimation with a vacuum-assisted biopsy device is likely to be explained by inaccurate sampling of the radiologic lesion. In fact, a specimen radiograph obtained after the procedure showed a few calcifications, suggesting that the mammographic lesion was not entirely removed and that residual microcalcifications were left after vacuum-assisted biopsy (Fig. 1). A complementary explanation for this unusual occurrence might be that the diagnostic quality of sampling in this setting is reflected not only in the amount of sampling relative to the extent of the lesion (the more extensive the sampling, the lower the likelihood of underestimation) but also in the extent of the malignant disease relative to the extent of the entire lesion. In fact, López-Medina et al. [6] showed that the proportion of the radial scar volume involved by carcinoma ranged from 3.7% to 16.2% (mean, 8.3%) and was located invariably at the periphery of the lesion. As a consequence, even very extensive sampling might theoretically miss malignant foci [23]. Further investigation with a larger patient database and with correlation between complete removal of the radiologically targeted lesion and underestimation is necessary to clarify this issue. In our series, mammographic and sonographic appearances were not able to predict which radial scars diagnosed at percutaneous biopsy would be malignant at surgical excision. In particular, underestimation of malignancy occurred in two of 11 cases (18%) presenting as microcalcifications, which were diagnosed as radial scars without atypia at percutaneous biopsy but proved to be lowgrade DCIS at surgical excision. This result confirms the findings of Becker et al. [16], who reported that two of 37 radial scars (5%) without atypia diagnosed at percutaneous biopsy and presenting as microcalcifications were upgraded to malignancy at surgery. On the contrary, this finding is in contrast with the results of Brenner et al. [8] and Resetkova et al. [9]; in their studies, those investigators found no case of underestimation among 28 radial scars without atypia and among 55 radial scars (with and without atypia) presenting as microcalcifications, respectively. With regard to sonographic lesions, of the 17 circumscribed masses, none was found to be malignant at excision. However, this malignancy rate was not statistically different from that found in noncircumscribed lesions (4/28), possibly because of small sample size. Although further studies are necessary to support these findings, our results show that even calcifications should be excised when wellperformed percutaneous biopsy shows radial scar regardless of its association with atypia. When pathology results from percutaneous biopsy yield radial scar that was not suspected on imaging, it is difficult to determine if the lesion biopsied is an atypical-looking radial scar or if a microscopic radial scar was biopsied in proximity to the lesion being targeted. According to Cawson et al. [7] and Hassell et al. [19], up to one third of radial scars found on percutaneous biopsy are incidental to the lesion being targeted. One might speculate that incidental radial scars are at the highest risk of underestimation; that is, the suspicious radiologic lesion and the target for the biopsy are located in the immediate vicinity of the radial scar but are not part of the radial scar. Therefore, the diagnosis of radial scar is likely to be based just on a limited percentage of the sampled tissue. This partial and peripheral sampling of the lesion will not allow malignant foci to be reliably excluded and surgical excision will be required. Our study has some limitations. First, it is a retrospective study with a limited sample size. Second, heterogeneous biopsy technique was used: 19 lesions were biopsied with an 11-gauge vacuum-assisted device, and 43 with a 14-gauge automated or semiautomated needle biopsy. Third, the pathologic slides of core specimens were not retrospectively reviewed by a pathologist and the original pathologic interpretation has been accepted. In conclusion, our results showed that, first, a diagnosis of a radial scar based on percutaneous biopsy does not exclude associated malignancy at subsequent surgical excision; and, second, mammographic and sonographic appearances of a lesion diagnosed as a radial scar at imaging-guided percutaneous biopsy are not able to predict which lesions will have associated malignancy at subsequent surgical excision. Our results suggest that surgical excision is required for lesions yielding radial scars at percutaneous biopsy regardless of the mammographic and sonographic appearance. Acknowledgments We thank Dianne Georgian-Smith, Harvard Medical School, Boston, MA, for her insightful comments; Joel D. Kochanski, Maury Regional Medical Center, Columbia, TN, for his assistance with manuscript preparation; and Giovanni Brondani, Institute of Radiology, Azienda Ospedaliero Universitaria, Udine, Italy, for his assistance with preparation of the figures. References 1. Rosen PP. Radial sclerosing lesions. In: Rosen PP, ed. Rosen s breast pathology. Philadelphia, PA: Lippincott-Raven, 1997: Schnitt SJ, Connolly JL. Pathology of benign breast disorders. In: Harris J, Morrow M, Hellman S, eds. Diseases of the breast. Philadelphia, PA: Lippincott-Raven, 1996: Kennedy M, Masterson AV, Kerin M, Flanagan F. Pathology and clinical relevance of radial scars: a review. J Clin Pathol 2003; 56: Mokbel K, Price RK, Mostafa A, et al. Radial scar and carcinoma of the breast: microscopic findings in 32 cases. Breast 1999; 8: Jacobs TW, Schnitt SJ, Tan X, Brown LF. 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