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Malignant Lesions Initially Categorized as Probably Benign Breast Lesions: Retrospective Review of Ultrasonographic, Clinical and Pathologic Characteristics
Ultrasound in Med. & Biol., Vol. 36, No. 4, pp. 551–559, 2010 Copyright Ó 2010 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/10/$–see front matter
doi:10.1016/j.ultrasmedbio.2010.01.007
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Original Contribution MALIGNANT LESIONS INITIALLY CATEGORIZED AS PROBABLY BENIGN BREAST LESIONS: RETROSPECTIVE REVIEW OF ULTRASONOGRAPHIC, CLINICAL AND PATHOLOGIC CHARACTERISTICS HEE JUNG MOON, MIN JUNG KIM, JIN YOUNG KWAK, JUNG HYUN YOON, SOO JIN KIM, YU-MEE SOHN, and EUN-KYUNG KIM Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea (Received 11 September 2009; revised 14 January 2010; in final form 25 January 2010)
Abstract—The primary objective of this study was to review the ultrasonographic features of BI-RADS category 3 (‘‘probably benign’’) lesions that eventually proved to be malignant. A second objective was to investigate their clinical and pathologic features according to their palpability and time of biopsy. Thirty-two (0.8%) of 4000 women with lesions that were initially classified as ‘‘probably benign’’ proved to be malignant and formed the study group. The most common reason for a false negative assessment on ultrasound was a failure to recognize suspicious margin characteristics (28 of 32 malignancies, 87.5%). Malignancy was more frequent in palpable (2.4%, 21 of 859) than nonpalpable lesions (0.4%, 11 of 3141, p , 0.001). There was no statistical difference in the mean age, mean size of lesions, or tumor stage between patients who underwent early biopsy (n 5 19) or biopsy after 6 months (n 5 13). Twenty-nine of the lesions (90.6%) were retrospectively recategorized as BI-RADS 4, which calls for early biopsy. BI-RADS 3 lesions require especially careful assessment. (E-mail: [email protected]) Ó 2010 World Federation for Ultrasound in Medicine & Biology. Key Words: BI-RADS, Probably benign finding, Breast malignancy, Ultrasonography.
physicians. Several studies on malignant breast lesions initially categorized as probably benign on mammography have been performed (Lehman et al. 2008; Rosen et al. 2002; Sickles 1991; Varas et al. 1992, 2002; Yasmeen et al. 2003). However, there is no report about the US features of malignant breast lesions that were initially classified as category 3 on US to our knowledge. The objective of this study was to review the ultrasonographic features of BI-RADS category 3 (‘‘probably benign’’) lesions that eventually proved to be malignant. A second objective was to investigate their clinical and pathologic features according to their palpability and time of biopsy.
INTRODUCTION According to the American College of Radiology (ACR)Breast Imaging Reporting and Data System (BI-RADS) (American College of Radiology 2003), a solid mass with a circumscribed margin, oval shape and horizontal orientation on ultrasonography (US) is classified as a category 3, probably benign lesion and short-interval follow-up is recommended. Many authors have reported that US is very useful for differentiating benign from malignant lesions and it is reasonable to categorize probably benign lesions on US (Chala et al. 2007; Costantini et al. 2007; Graf et al. 2004, 2007; Hong et al. 2005; Kim EK et al. 2008; Leung and Sickles 2007; Rahbar et al. 1999; Stavros et al. 1995), because the negative predictive value is over 98% (Costantini et al. 2007; Raza et al. 2008; Stavros et al. 1995). However, about 2% of breast lesions categorized as probably benign may be finally diagnosed as malignant lesions and these cases frustrate both patients and
SUBJECTS AND METHODS Institutional Review Board approval was obtained for this retrospective study (IRB number, 4-2009-0177) and any informed patient consent was waived.
Address correspondence to: Eun-Kyung Kim, M.D., Department of Radiology, Yonsei University College of Medicine, 134 Seodaemun-ku, Shinchon-dong, 120-752 Seoul, South Korea. E-mail: [email protected]
Subjects Between October 2002 and July 2007, 13,734 women underwent 50,003 breast US examinations at 551
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our institution (referral center). Of those, 15,658 (31.3%, 15,658 of 50,003) of examinations in 4660 (33.9%, 4660 of 13,734) women were classified as category 3. Six hundred sixty women were excluded from this study; 267 were lost to follow-up; 215 were already under follow-up protocol after biopsy due to category 4a lesions on US; and 178 were already under follow-up protocol due to category 3 lesions on US. Based on reviews of medical records, imaging studies and pathology results of 4000 women with breast malignancies initially categorized as probably benign were investigated. Palpability of the lesions was determined by physical examination by clinicians and radiologists. Early US-guided biopsy (within 6 month after US examination) was performed in 1148 lesions of 1148 women at the physician’s or patient’s request, when either the physician or the patient wanted to confirm the breast lesion. US-guided biopsies were performed using a 14gauge automated core biopsy needle and a spring-loaded biopsy gun (Promac 2.2L; Manan Medical Products, Northbrook, IL, USA) in 735 women, vacuum-assisted US-guided biopsy (Mammotome, Ethicon Endo Surgery, Cincinnati, OH, USA) in 357 women and 23-gauge needle aspiration biopsy in 56 women. Of the 1148 women, 19 were diagnosed with breast malignancy. Of the remaining 2852 women with follow-up US, 331 women underwent late US-guided biopsy during follow-up because of an increase in size and/or change of breast lesion border characteristics (US-guided core biopsy in 177; vacuumassisted US-guided biopsy in 154). Eight women who underwent 6 to 12 months follow-up proved to have malignancy and five who underwent more than 12 months follow-up were diagnosed with malignancy. Finally, among the 4000 women with follow-up data of at least 6 months, a total of 32 lesions in 32 women (0.8%, 32 of 4,000 women) were included in this study (Fig. 1). Imaging methods All examinations included in this study were performed prospectively and interpreted by one of nine dedicated breast imaging radiologists with 1 to 11 years of experience. Prior to interpreting mammograms or performing US examinations, clinical information was available to the interpreting radiologist. Breast US examinations was performed using high-resolution US with 7-12 MHz linear array transducers (HDI 5000 or 3000; Philips-Advanced Technology Laboratories, Bothell, WA, USA; Logic 9; GE Medical Systems, Milwaukee, WI, USA). Compound imaging was used for all examinations performed with the HDI 5000 machine. All US examinations included bilateral whole-breast imaging and evaluation of any abnormalities found on clinical examination or mammogram. Mammograms
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were performed using dedicated equipment; a DMR (General Electric Medical Systems, Milwaukee, WI, USA) until April 2005 and the Lorad/Hologic Selenia full field digital mammography system (Lorad/Hologic, Danbury, CT, USA) after May 2005. Standard craniocaudal and mediolateral oblique views were routinely obtained and additional views were obtained as needed. Since 2000, we have categorized US examinations into one of five final assessments. A final assessment of category 3, probably benign on US, was based on our experience, ACR-BIRADS (American College of Radiology 2003) and criteria established in a study by Stavros et al. (Stavros et al. 1995). Category 3 was assessed when a solid mass showed an oval or gently lobulated shape, circumscribed margin and a parallel orientation. In cases of category 3 lesions, follow-up is scheduled at 6 months with US, at 12 months with both US and mammography and at 24 months with both US and mammography. If the lesion has demonstrated stability for 24 months, the final assessment is changed to category 2. Category 2 was initially classified when the lesion that lacked any suspicious findings were simple cysts or showed uniform or intense hyperechogenicity on US. Category 4 or 5 was classified when the lesion showed 1 or more suspicious findings viz.: round or irregular shape, microlobulated, indistinct, angular or spiculated margin, nonparallel orientation, echogenic halo, complex echogenicity, posterior shadowing, duct extension and microcalcifications within the mass on US (Kim EK et al. 2008). All final assessments were made in conjunction with mammograms, if available, and were based on the most suspicious features on mammogram or US. When more than one mass was found in both breasts, a single, final assessment was made based on the mass with the most suspicious features. Review of imaging findings For this study, two dedicated breast imaging radiologists with 6 and 11 years of experience independently and retrospectively reviewed all available breast US examinations and mammograms for 32 women with proven breast malignancies after initial probably benign categorization according to the ACR BI-RADS lexicon of US. Retrospective reviews of US images and mammograms were performed with digitized static images on a 5000-pixel monochrome liquid crystal display monitor (Senoadvantage) of a picture archiving and communicate system. The final categories of 32 malignancies were reassessed after reviewing 32 US examinations and 19 mammograms. Five mammograms performed at the time of initial category 3 assessment were not available for review because the mammograms were taken at a community clinic. Eight mammograms were excluded from the re-evaluation because they were performed after
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Fig. 1. Flow chart of the study population. F/U 5 follow-up. a Included in this study. b Six hundred sixty women were lost to follow-up.
the diagnosis of breast malignancy. The data independently evaluated by each radiologist were reviewed and, then, the two radiologists reached a consensus on lesion descriptors and final assessments for masses together. We evaluated missed suspicious US features for breast malignancies initially categorized as probably benign lesions. Clinical and pathologic characteristics between women with symptoms and those without and between women with early biopsy within 6 months after initial category 3 assessment and those with late biopsy during follow-up were also investigated. Statistical comparisons were performed using a t-test for parametric variables and a chi-square test or Fisher’s exact test for nonparametric variables. Statistical significance was assigned to p values less than 0.05. Data were analyzed using SAS software (SAS system for Windows, version 9.0, SAS Institute, Cary, NC, USA).
RESULTS Of 4000 women, 859 (21.5%) had palpable lumps. Breast malignancy was significantly more frequent in palpable lesions (21 of 859, 2.4%) than in nonpalpable lesions (11 of 3,141, 0.4%) (p , 0.001). Six hundred sixty three of 1148 lesions with early US-guided biopsy were palpable. Early biopsies were performed more frequently in palpable lesions (77.2%, 663 of 859) than nonpalpable lesions (15.4%, 485 of 3,141) (p 5 0.01).
The mean age of the 32 patients (0.8%, 32 of 4000) with breast malignancies was 45.4 years (range, 26 to 66 years). Among them, nine women were under 40 years of age. Mean size of the 32 breast malignancies was 15 mm (range, 4–51 mm; median, 13 mm). The pathologic diagnoses of 32 malignant lesions according to palpability and time of biopsy are listed in Table 1. Sixteen women underwent mastectomies, 10 underwent lumpectomy, three underwent wide excision, one received chemotherapy for breast lymphoma, and the status of two women [one ductal carcinoma in situ (DCIS) and one mucinous carcinoma] were unknown due to transfer to other hospitals. Missed suspicious US features In retrospective review of US features of 32 malignancies, only three fulfilled the published US criteria for the probably benign diagnosis (Table 2). The most commonly missed US feature was the margin characteristics (28 of 32 malignancies, 87.5%) (Figs. 2 and 3). With regard to shape, five malignancies had a round shape and four had irregular shapes (Fig. 4). Twenty-nine (90.6%) probably benign lesions were re-assessed as category 4, necessitating biopsy. A total of 19 mammograms were available for review. Ten showed negative findings and nine showed abnormalities. Abnormal mammographic findings included masses (n 5 5), focal asymmetry (n 5 3) and mass with microcalcifications (n 5 1). All
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Table 1. Final pathology of 32 malignancies initially assessed as probably benign lesions Clinical feature
Time of biopsy
Pathologic diagnosis
Palpable (n 5 21)
Nonpalpable (n 5 11)
Early biopsy (n 5 19)
Late biopsy (n 5 13)
Invasive ductal carcinoma, not otherwise specified (n 5 11) Ductal carcinoma in situ (n 5 8) Papillary carcinoma (n 5 3) Malignant phyllodes tumor (n 5 3) Medullary carcinoma (n 5 2) Mucinous carcinoma (n 5 2) Invasive apocrine carcinoma(n 5 1) Spindle cell sarcoma (n 5 1) Primary breast lymphoma (n 5 1)
8 (38.1)
3 (27.3)
6 (31.6)
5 (38.5)
3 (14.3) 3 (14.3) 3 (14.3)
5 (45.5)
5 (26.3) 2 (10.5) 1 (5.3) 1 (5.3) 2 (18.2)
3 (23.1) 1 (7.7) 2 (15.4) 1 (7.7)
2 (18.2) 1 (9.1)
1 (4.8) 1 (4.8) 1 (4.8) 1 (4.8)
1 (7.7) 1 (5.3) 1 (5.3)
The numbers in parentheses are percentages.
nine abnormalities on mammograms were visualized as masses on US and they were reassessed as category 4 on US. Clinical and pathologic characteristics Twenty-one (65.6%) of 32 malignancies were palpable. Clinical and pathologic characteristics according to palpability are summarized in Table 3. We could not evaluate the stage of 7 malignancies (three malignant phyllodes tumors, one sarcoma and one primary breast lymphoma) and that in two patients who were transferred to other hospitals. Among the remaining 25 malignancies, six (43%) of 14 palpable malignancies were in stage IIa,
whereas one (9%) of 11 nonpalpable malignancies were in stage IIa. However, there was no significant difference between the two groups (p 5 0.0900). The mean time interval of early biopsy from initial category 3 assessment was 3.4 days (range, 0–43 days). The mean time interval between initial category 3 assessment and late biopsy was 10.4 months (range, 6–25 months; median, 7 months). All 13 malignancies with late biopsy showed increased size during the follow-up period. The mean size increase was 7 mm (range, 4–18 mm; median, 6 mm). There was no statistical difference in mean age, mean size of lesions or tumor stage between early biopsy and late biopsy groups (Table 3).
Table 2. Missed US features of 32 malignancies initially categorized as probably benign lesions US features Shape Orientation Margin
Lesion boundary Echo pattern
Posterior acoustic features
Calcifications Special finding Recategorization The numbers in parentheses are percentages.
ACR-BIRADS lexicon
Number of malignancy (n 5 32) (%)
Oval Round Irregular Parallel Nonparallel Circumscribed Indistinct Angular Microlobulated Spiculated Abrupt interface Echogenic halo Anechoic Hyperechoic Complex Hypoechoic Isoechoic No posterior acoustic features Enhancement Shadowing Combined pattern Macrocalcifications Microcalcifications out of mass Microcalcifications in mass Ductal extension Category 3 Category 4
23 (71.8) 6 (18.8) 3 (9.4) 29 (90.6) 3 (9.4) 4 (12.5) 5 (15.6) 6 (18.8) 14 (43.8) 3 (9.4) 32 (100) 0 (0) 0 (0) 0 (0) 5 (15.6) 25 (78.1) 2 (6.3) 20 (62.5) 10 (31.3) 0 (0) 2 (6.3) 0 (0) 0 (0) 1 (3.1) 1 (3.1) 3 (9.4) 29 (90.6)
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Fig. 2. A 37-year-old woman with a palpable breast lump. Initial ultrasound (a; transverse and b; longitudinal a) showed a 9 mm mass, initially categorized as probably benign and 6-month follow-up was recommended. On review, the margin was microlobulated, which resulted in retrospective reassessment as category 4. The mammogram, which was not available for review, was negative on an out-side report. The 6-month follow-up US (c; transverse and d; longitudinal) showed a microlobulated mass that had enlarged to 12 mm and contained microcalcifications (arrow in b and c). Microcalcifications within the mass were also shown on the magnification view (d). US-guided 14-gauge needle core biopsy was performed and an invasive apocrine carcinoma was diagnosed (f, H&E stain 3100). A modified radical mastectomy was performed and the carcinoma was staged as T2N0.
There were two malignancies with false negative biopsies results, classified as late biopsy groups. One that showed fibrocystic change on early biopsy proved to be a phyllodes tumor on late biopsy. The lesion was confirmed as malignant phyllodes tumor by wide excision 25 months after the initial US. The other was an intraductal papilloma on late biopsy after 6-month follow-up US. The patient refused excision and the lesion turned out to be DCIS after 19 months from initial probably benign assessment. Of 13 malignancies, two were categorized
as probably benign despite size progression at the first 6-month follow-up US and showed a greater increase in size at the second 12-month follow-up US. Invasive ductal carcinoma, not otherwise specified, and papillary carcinoma were confirmed by late biopsy after the second follow-up US. Except two lesions with false negative biopsies and two lesions assessed as category 3 despite size progression at the first follow-up US, the other nine lesions proved to be malignancies on the first follow-up US and late biopsy. Excluding two malignancies with
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Fig. 3. A 46-year-old woman attended for a routine check-up. The mammogram showed extremely dense parenchyma and no abnormality (not shown). Transverse (a) and longitudinal (b) US images showed a 12 mm hypoechoic mass with an irregular shape and indistinct margin (arrow), which was initially categorized as probably benign. The lesion was retrospectively reassessed as category 4. Early US- guided 23-gauge needle aspiration biopsy was performed upon the physician’s request and the lesion was determined to be a mucinous carcinoma (c, H&E stain 3 100). A modified radical mastectomy was performed and the carcinoma was staged as T1N0.
false negative biopsies, the mean time interval between initial US and the late biopsy for the 11 malignancies was 8.3 months (range, 6–13 months). Seventy-three percent (8 of 11 with late biopsy) of malignancies were identified at 6 months and 27% (3 of 11) were identified at the 12-month follow-up.
DISCUSSION The probably benign assessment is proposed when the lesion has a likelihood of malignancy of less than 2%. Therefore, for probably benign lesions detected on mammograms, short-interval follow-up is recommended (Lindfors et al. 1998; Lindfors and Rosenquist 1994; Rubin 1999; Sickles 1999a, 1991, 1999b). Probably benign lesions detected on US are put on a similar follow-up protocol to those found on mammograms. Follow-up is scheduled at 6 months with US, at 12 months with both US and mammography and at 24 months with both US and mammography. If the lesion has
demonstrated stability for 24 months, the final assessment is changed to category 2. Some authors suggest that a 6-month diagnostic delay for false negative interpretations of lesions would have negligible impact on prognosis (Hall et al. 1988; Sickles et al. 1990) and malignant lesions that initially fulfilled the criteria for probably benign lesions could be rapidly identified with short-interval follow-up mammograms (Sickles 1991). All 13 malignancies with late biopsies showed an increase in size at the first follow-up US in this study. The interval change at first follow-up US was a key feature for re-assessment to category 4. There was no statistical difference in the pathologic stage between early biopsy and late biopsy groups. Moreover, there was no axillary lymph node metastasis in late biopsy group in this study. The mean time interval between initial US and malignancy diagnosis for the 11 malignancies was 8.3 months. Seventy-three percent of malignancies were identified at 6 months, which is comparable to the study conducted by Sickles et al. (Sickles 1991). Compliance is very important for the follow-up of probably benign
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Fig. 4. A 66-year-old woman had undergone a right mastectomy for breast cancer 5 years ago. The mammogram showed a 13 mm in size mass in the left breast (a) and ultrasound (b) showed an irregularly-shape, microlobulated margin and hypoechoic mass which was initially interpreted as category 3. The lesion was reassessed as category 4 due to microlobulated margin and suspicious ductal extension, retrospectively. After a 6-month follow-up, the lesion showed an increase in size (17 mm) and newly-developed pleomorphic microcalcifications on mammogram (c), and showed an increase in size on US and obvious ductal extension (d). Ductal carcinoma in situ was confirmed by US-guided 14-gauge needle core biopsy (e, H&E stain, 3100). A modified radical mastectomy was performed, and the tumor stage was T0N0.
lesions because malignancies can be detected without further delay (Leung and Sickles 2007). To achieve the greatest compliance, radiologists or technologists who have sufficient knowledge to confidently explain the goal of short-term follow-up mammography should recommend it to women just after completion of the
diagnostic work-up (Sickles 1999a) and a reminder system should be considered (Duijm et al. 1998). In probably benign lesions on US, the physician or technologists should confidently explain the importance of follow-up. The US BI-RADS lexicon by ACR is useful for differentiating benign from malignant solid masses
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Table 3. Clinical and pathologic characteristics of 32 malignancies according to symptoms Women with palpable lesions (n 5 21) Mean age (years) 42.7 (range, 26–62) Mean size (mm) 18 (range, 5–51) b Stage 0 (T0N0) 2 (9.5) I (T1N0) 6 (28.6) IIa T1 N1 1 (4.8) T2 N0 5 (23.8) NA 7c (33.3)
Women with nonpalpable Patients with early biopsy lesions (n 5 11) p value (n 519)a 52 (range, 40–66) 10 (range, 4–23) b
.0045 .0206 .0900
39.4 (range, 32–62) 12 (range, 5–51)
5 (45.5) 5 (45.5)
4 (21.1) 6 (31.6)
1 (9.1)
2 (10.5) 2 (10.5) 5d (26.3)
Patients with follow-up and late biopsy (n 5 13) 41 (range, 26–66) 8 (range, 4–23) b
r value .2481 .1721 .4916
3 (23.1) 2e (15.4)
NA 5 nonaccessible. The numbers in parentheses are percentages. a. Inclusion of two women without surgery and one breast lymphoma; b. The size at the time of the 6-month US follow-up recommendation; c. Three women had phyllodes tumors: one had a sarcoma, one had a primary breast lymphoma and two with DCIS and mucinous carcinoma on biopsy were referred to another hospital; d. Spindle cell sarcoma; Primary breast lymphoma; Malignant phyllodes tumor; two with DCIS and mucinous carcinoma on biopsy were referred to another hospital; e. Two malignant phyllodes tumors.
(Costantini et al. 2007, 2006; Hong et al. 2005; Kim EK et al. 2008). Identifying probably benign lesions using breast US is useful for reducing unnecessary biopsies (Chala et al. 2007) because of its high negative predictive value of 99.2% to 99.8% (Graf et al. 2007; Kim EK et al. 2008; Mainiero et al. 2005; Raza et al. 2008). In this study, the negative predictive value of probably benign lesions on US was 99.2%, comparable to previous studies. Graf et al. suggested that palpable probably benign lesions on US can be managed similarly to nonpalpable probably benign lesions (Graf et al. 2004). However, in a clinical setting, a large portion of palpable probably benign lesions undergo US-guided biopsy because of physicians’ or patients’ requests. In this study, early biopsies were performed more frequently in palpable lesions than nonpalpable lesions (p 5 0.01). Moreover, in 4000 women with probably benign lesions, breast malignancies were statistically more frequent in palpable lesions than in nonpalpable lesions (p ,0.001). Therefore, strict criteria should be applied to the probably benign categorization in palpable lesions. Stage IIa was substantially common in palpable lesions, although there was no statistical significance (p 5 0.0900). More data from a larger series may provide the statistical power needed to confirm the assertion that palpable malignancies would be in the more advanced stages than nonpalpable malignancies. The most commonly missed suspicious US feature was a noncircumscribed margin of the lesion. Only four (12.5%) of 32 lesions had the circumscribed margin. When published criteria were strictly applied, 29 (90.6%) of 32 malignancies were re-assessed as category 4 in this study. There are interobserver variabilities in using the ACR-BI-RADS US lexicon for solid masses on US. For interobserver agreements for sonographic descriptors, substantial agreement for lesion calcification and final assessment, moderate agreement for lesion shape, orientation, boundary and posterior acoustic
features, and fair agreement for lesion margin and echo pattern were obtained in our institution (Lee et al. 2008). Therefore, we have not investigated the interobserver variability in this study. Although the overall interobserver agreement with the ACR BI-RADS US lexicon is good and comparable to that of mammography, interobserver agreement for the margin was lower than for shape, orientation, echo pattern or posterior acoustic features (Lazarus et al. 2006; Lee et al. 2008). In clinical practice, a radiologist applies the published criteria as well as the standards based on their individual training and experiences. Therefore, subtle suspicious US features were sometimes ignored. Emphasis on the identification of subtle US features may result in an increase of category 4 classifications and increase in the sensitivity of US interpretation but may result in an increase of false positive interpretations and unnecessary biopsies. There were a few limitations to this study. First, this study was retrospective and we knew that the lesions were malignant. Therefore, bias in reviewing the US images could not completely be avoided. Second, 660 women were lost to follow-up and we followed US stability for at least 6 months in cases that did not undergo biopsy. Therefore, some slowly progressing cancers may have been missed in this study. Third, probably benign lesions with concomitant category 4 or 5 lesions in the remaining breasts were excluded. A recent study by Kim SJ et al. reported that the malignancy rate of probably benign lesions in patients with synchronous malignancy was 11.4% (Kim SJ et al. 2008). Probably benign lesions with concurrent category 4 and 5 lesions may have a higher malignancy rate and a large series study should be followed. Fourth, interobserver variability of this study was not evaluated. However, the interobserver variabilities in using the ACR-BI-RADS US lexicon has been studied in our institution (Lee et al. 2008) and the images were independently evaluated by each radiologist and, then, the two
BI-RADS category 3 lesions d H. J. MOON et al.
radiologists reached a consensus on lesion descriptors and final assessments for masses. In conclusion, the most commonly missed suspicious US feature was a noncircumscribed margin. The malignancy rate was significantly higher in palpable lesions than nonpalpable lesions. Therefore, attention should be paid in assessing the category 3 for palpable breast lesions. Acknowledgements—This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2009-0067048 and by a faculty research grant of Yonsei University College of Medicine for 2008 (No. 6-2008-0262) .
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doi:10.1016/j.ultrasmedbio.2010.01.007
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Original Contribution MALIGNANT LESIONS INITIALLY CATEGORIZED AS PROBABLY BENIGN BREAST LESIONS: RETROSPECTIVE REVIEW OF ULTRASONOGRAPHIC, CLINICAL AND PATHOLOGIC CHARACTERISTICS HEE JUNG MOON, MIN JUNG KIM, JIN YOUNG KWAK, JUNG HYUN YOON, SOO JIN KIM, YU-MEE SOHN, and EUN-KYUNG KIM Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea (Received 11 September 2009; revised 14 January 2010; in final form 25 January 2010)
Abstract—The primary objective of this study was to review the ultrasonographic features of BI-RADS category 3 (‘‘probably benign’’) lesions that eventually proved to be malignant. A second objective was to investigate their clinical and pathologic features according to their palpability and time of biopsy. Thirty-two (0.8%) of 4000 women with lesions that were initially classified as ‘‘probably benign’’ proved to be malignant and formed the study group. The most common reason for a false negative assessment on ultrasound was a failure to recognize suspicious margin characteristics (28 of 32 malignancies, 87.5%). Malignancy was more frequent in palpable (2.4%, 21 of 859) than nonpalpable lesions (0.4%, 11 of 3141, p , 0.001). There was no statistical difference in the mean age, mean size of lesions, or tumor stage between patients who underwent early biopsy (n 5 19) or biopsy after 6 months (n 5 13). Twenty-nine of the lesions (90.6%) were retrospectively recategorized as BI-RADS 4, which calls for early biopsy. BI-RADS 3 lesions require especially careful assessment. (E-mail: [email protected]) Ó 2010 World Federation for Ultrasound in Medicine & Biology. Key Words: BI-RADS, Probably benign finding, Breast malignancy, Ultrasonography.
physicians. Several studies on malignant breast lesions initially categorized as probably benign on mammography have been performed (Lehman et al. 2008; Rosen et al. 2002; Sickles 1991; Varas et al. 1992, 2002; Yasmeen et al. 2003). However, there is no report about the US features of malignant breast lesions that were initially classified as category 3 on US to our knowledge. The objective of this study was to review the ultrasonographic features of BI-RADS category 3 (‘‘probably benign’’) lesions that eventually proved to be malignant. A second objective was to investigate their clinical and pathologic features according to their palpability and time of biopsy.
INTRODUCTION According to the American College of Radiology (ACR)Breast Imaging Reporting and Data System (BI-RADS) (American College of Radiology 2003), a solid mass with a circumscribed margin, oval shape and horizontal orientation on ultrasonography (US) is classified as a category 3, probably benign lesion and short-interval follow-up is recommended. Many authors have reported that US is very useful for differentiating benign from malignant lesions and it is reasonable to categorize probably benign lesions on US (Chala et al. 2007; Costantini et al. 2007; Graf et al. 2004, 2007; Hong et al. 2005; Kim EK et al. 2008; Leung and Sickles 2007; Rahbar et al. 1999; Stavros et al. 1995), because the negative predictive value is over 98% (Costantini et al. 2007; Raza et al. 2008; Stavros et al. 1995). However, about 2% of breast lesions categorized as probably benign may be finally diagnosed as malignant lesions and these cases frustrate both patients and
SUBJECTS AND METHODS Institutional Review Board approval was obtained for this retrospective study (IRB number, 4-2009-0177) and any informed patient consent was waived.
Address correspondence to: Eun-Kyung Kim, M.D., Department of Radiology, Yonsei University College of Medicine, 134 Seodaemun-ku, Shinchon-dong, 120-752 Seoul, South Korea. E-mail: [email protected]
Subjects Between October 2002 and July 2007, 13,734 women underwent 50,003 breast US examinations at 551
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our institution (referral center). Of those, 15,658 (31.3%, 15,658 of 50,003) of examinations in 4660 (33.9%, 4660 of 13,734) women were classified as category 3. Six hundred sixty women were excluded from this study; 267 were lost to follow-up; 215 were already under follow-up protocol after biopsy due to category 4a lesions on US; and 178 were already under follow-up protocol due to category 3 lesions on US. Based on reviews of medical records, imaging studies and pathology results of 4000 women with breast malignancies initially categorized as probably benign were investigated. Palpability of the lesions was determined by physical examination by clinicians and radiologists. Early US-guided biopsy (within 6 month after US examination) was performed in 1148 lesions of 1148 women at the physician’s or patient’s request, when either the physician or the patient wanted to confirm the breast lesion. US-guided biopsies were performed using a 14gauge automated core biopsy needle and a spring-loaded biopsy gun (Promac 2.2L; Manan Medical Products, Northbrook, IL, USA) in 735 women, vacuum-assisted US-guided biopsy (Mammotome, Ethicon Endo Surgery, Cincinnati, OH, USA) in 357 women and 23-gauge needle aspiration biopsy in 56 women. Of the 1148 women, 19 were diagnosed with breast malignancy. Of the remaining 2852 women with follow-up US, 331 women underwent late US-guided biopsy during follow-up because of an increase in size and/or change of breast lesion border characteristics (US-guided core biopsy in 177; vacuumassisted US-guided biopsy in 154). Eight women who underwent 6 to 12 months follow-up proved to have malignancy and five who underwent more than 12 months follow-up were diagnosed with malignancy. Finally, among the 4000 women with follow-up data of at least 6 months, a total of 32 lesions in 32 women (0.8%, 32 of 4,000 women) were included in this study (Fig. 1). Imaging methods All examinations included in this study were performed prospectively and interpreted by one of nine dedicated breast imaging radiologists with 1 to 11 years of experience. Prior to interpreting mammograms or performing US examinations, clinical information was available to the interpreting radiologist. Breast US examinations was performed using high-resolution US with 7-12 MHz linear array transducers (HDI 5000 or 3000; Philips-Advanced Technology Laboratories, Bothell, WA, USA; Logic 9; GE Medical Systems, Milwaukee, WI, USA). Compound imaging was used for all examinations performed with the HDI 5000 machine. All US examinations included bilateral whole-breast imaging and evaluation of any abnormalities found on clinical examination or mammogram. Mammograms
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were performed using dedicated equipment; a DMR (General Electric Medical Systems, Milwaukee, WI, USA) until April 2005 and the Lorad/Hologic Selenia full field digital mammography system (Lorad/Hologic, Danbury, CT, USA) after May 2005. Standard craniocaudal and mediolateral oblique views were routinely obtained and additional views were obtained as needed. Since 2000, we have categorized US examinations into one of five final assessments. A final assessment of category 3, probably benign on US, was based on our experience, ACR-BIRADS (American College of Radiology 2003) and criteria established in a study by Stavros et al. (Stavros et al. 1995). Category 3 was assessed when a solid mass showed an oval or gently lobulated shape, circumscribed margin and a parallel orientation. In cases of category 3 lesions, follow-up is scheduled at 6 months with US, at 12 months with both US and mammography and at 24 months with both US and mammography. If the lesion has demonstrated stability for 24 months, the final assessment is changed to category 2. Category 2 was initially classified when the lesion that lacked any suspicious findings were simple cysts or showed uniform or intense hyperechogenicity on US. Category 4 or 5 was classified when the lesion showed 1 or more suspicious findings viz.: round or irregular shape, microlobulated, indistinct, angular or spiculated margin, nonparallel orientation, echogenic halo, complex echogenicity, posterior shadowing, duct extension and microcalcifications within the mass on US (Kim EK et al. 2008). All final assessments were made in conjunction with mammograms, if available, and were based on the most suspicious features on mammogram or US. When more than one mass was found in both breasts, a single, final assessment was made based on the mass with the most suspicious features. Review of imaging findings For this study, two dedicated breast imaging radiologists with 6 and 11 years of experience independently and retrospectively reviewed all available breast US examinations and mammograms for 32 women with proven breast malignancies after initial probably benign categorization according to the ACR BI-RADS lexicon of US. Retrospective reviews of US images and mammograms were performed with digitized static images on a 5000-pixel monochrome liquid crystal display monitor (Senoadvantage) of a picture archiving and communicate system. The final categories of 32 malignancies were reassessed after reviewing 32 US examinations and 19 mammograms. Five mammograms performed at the time of initial category 3 assessment were not available for review because the mammograms were taken at a community clinic. Eight mammograms were excluded from the re-evaluation because they were performed after
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Fig. 1. Flow chart of the study population. F/U 5 follow-up. a Included in this study. b Six hundred sixty women were lost to follow-up.
the diagnosis of breast malignancy. The data independently evaluated by each radiologist were reviewed and, then, the two radiologists reached a consensus on lesion descriptors and final assessments for masses together. We evaluated missed suspicious US features for breast malignancies initially categorized as probably benign lesions. Clinical and pathologic characteristics between women with symptoms and those without and between women with early biopsy within 6 months after initial category 3 assessment and those with late biopsy during follow-up were also investigated. Statistical comparisons were performed using a t-test for parametric variables and a chi-square test or Fisher’s exact test for nonparametric variables. Statistical significance was assigned to p values less than 0.05. Data were analyzed using SAS software (SAS system for Windows, version 9.0, SAS Institute, Cary, NC, USA).
RESULTS Of 4000 women, 859 (21.5%) had palpable lumps. Breast malignancy was significantly more frequent in palpable lesions (21 of 859, 2.4%) than in nonpalpable lesions (11 of 3,141, 0.4%) (p , 0.001). Six hundred sixty three of 1148 lesions with early US-guided biopsy were palpable. Early biopsies were performed more frequently in palpable lesions (77.2%, 663 of 859) than nonpalpable lesions (15.4%, 485 of 3,141) (p 5 0.01).
The mean age of the 32 patients (0.8%, 32 of 4000) with breast malignancies was 45.4 years (range, 26 to 66 years). Among them, nine women were under 40 years of age. Mean size of the 32 breast malignancies was 15 mm (range, 4–51 mm; median, 13 mm). The pathologic diagnoses of 32 malignant lesions according to palpability and time of biopsy are listed in Table 1. Sixteen women underwent mastectomies, 10 underwent lumpectomy, three underwent wide excision, one received chemotherapy for breast lymphoma, and the status of two women [one ductal carcinoma in situ (DCIS) and one mucinous carcinoma] were unknown due to transfer to other hospitals. Missed suspicious US features In retrospective review of US features of 32 malignancies, only three fulfilled the published US criteria for the probably benign diagnosis (Table 2). The most commonly missed US feature was the margin characteristics (28 of 32 malignancies, 87.5%) (Figs. 2 and 3). With regard to shape, five malignancies had a round shape and four had irregular shapes (Fig. 4). Twenty-nine (90.6%) probably benign lesions were re-assessed as category 4, necessitating biopsy. A total of 19 mammograms were available for review. Ten showed negative findings and nine showed abnormalities. Abnormal mammographic findings included masses (n 5 5), focal asymmetry (n 5 3) and mass with microcalcifications (n 5 1). All
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Table 1. Final pathology of 32 malignancies initially assessed as probably benign lesions Clinical feature
Time of biopsy
Pathologic diagnosis
Palpable (n 5 21)
Nonpalpable (n 5 11)
Early biopsy (n 5 19)
Late biopsy (n 5 13)
Invasive ductal carcinoma, not otherwise specified (n 5 11) Ductal carcinoma in situ (n 5 8) Papillary carcinoma (n 5 3) Malignant phyllodes tumor (n 5 3) Medullary carcinoma (n 5 2) Mucinous carcinoma (n 5 2) Invasive apocrine carcinoma(n 5 1) Spindle cell sarcoma (n 5 1) Primary breast lymphoma (n 5 1)
8 (38.1)
3 (27.3)
6 (31.6)
5 (38.5)
3 (14.3) 3 (14.3) 3 (14.3)
5 (45.5)
5 (26.3) 2 (10.5) 1 (5.3) 1 (5.3) 2 (18.2)
3 (23.1) 1 (7.7) 2 (15.4) 1 (7.7)
2 (18.2) 1 (9.1)
1 (4.8) 1 (4.8) 1 (4.8) 1 (4.8)
1 (7.7) 1 (5.3) 1 (5.3)
The numbers in parentheses are percentages.
nine abnormalities on mammograms were visualized as masses on US and they were reassessed as category 4 on US. Clinical and pathologic characteristics Twenty-one (65.6%) of 32 malignancies were palpable. Clinical and pathologic characteristics according to palpability are summarized in Table 3. We could not evaluate the stage of 7 malignancies (three malignant phyllodes tumors, one sarcoma and one primary breast lymphoma) and that in two patients who were transferred to other hospitals. Among the remaining 25 malignancies, six (43%) of 14 palpable malignancies were in stage IIa,
whereas one (9%) of 11 nonpalpable malignancies were in stage IIa. However, there was no significant difference between the two groups (p 5 0.0900). The mean time interval of early biopsy from initial category 3 assessment was 3.4 days (range, 0–43 days). The mean time interval between initial category 3 assessment and late biopsy was 10.4 months (range, 6–25 months; median, 7 months). All 13 malignancies with late biopsy showed increased size during the follow-up period. The mean size increase was 7 mm (range, 4–18 mm; median, 6 mm). There was no statistical difference in mean age, mean size of lesions or tumor stage between early biopsy and late biopsy groups (Table 3).
Table 2. Missed US features of 32 malignancies initially categorized as probably benign lesions US features Shape Orientation Margin
Lesion boundary Echo pattern
Posterior acoustic features
Calcifications Special finding Recategorization The numbers in parentheses are percentages.
ACR-BIRADS lexicon
Number of malignancy (n 5 32) (%)
Oval Round Irregular Parallel Nonparallel Circumscribed Indistinct Angular Microlobulated Spiculated Abrupt interface Echogenic halo Anechoic Hyperechoic Complex Hypoechoic Isoechoic No posterior acoustic features Enhancement Shadowing Combined pattern Macrocalcifications Microcalcifications out of mass Microcalcifications in mass Ductal extension Category 3 Category 4
23 (71.8) 6 (18.8) 3 (9.4) 29 (90.6) 3 (9.4) 4 (12.5) 5 (15.6) 6 (18.8) 14 (43.8) 3 (9.4) 32 (100) 0 (0) 0 (0) 0 (0) 5 (15.6) 25 (78.1) 2 (6.3) 20 (62.5) 10 (31.3) 0 (0) 2 (6.3) 0 (0) 0 (0) 1 (3.1) 1 (3.1) 3 (9.4) 29 (90.6)
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Fig. 2. A 37-year-old woman with a palpable breast lump. Initial ultrasound (a; transverse and b; longitudinal a) showed a 9 mm mass, initially categorized as probably benign and 6-month follow-up was recommended. On review, the margin was microlobulated, which resulted in retrospective reassessment as category 4. The mammogram, which was not available for review, was negative on an out-side report. The 6-month follow-up US (c; transverse and d; longitudinal) showed a microlobulated mass that had enlarged to 12 mm and contained microcalcifications (arrow in b and c). Microcalcifications within the mass were also shown on the magnification view (d). US-guided 14-gauge needle core biopsy was performed and an invasive apocrine carcinoma was diagnosed (f, H&E stain 3100). A modified radical mastectomy was performed and the carcinoma was staged as T2N0.
There were two malignancies with false negative biopsies results, classified as late biopsy groups. One that showed fibrocystic change on early biopsy proved to be a phyllodes tumor on late biopsy. The lesion was confirmed as malignant phyllodes tumor by wide excision 25 months after the initial US. The other was an intraductal papilloma on late biopsy after 6-month follow-up US. The patient refused excision and the lesion turned out to be DCIS after 19 months from initial probably benign assessment. Of 13 malignancies, two were categorized
as probably benign despite size progression at the first 6-month follow-up US and showed a greater increase in size at the second 12-month follow-up US. Invasive ductal carcinoma, not otherwise specified, and papillary carcinoma were confirmed by late biopsy after the second follow-up US. Except two lesions with false negative biopsies and two lesions assessed as category 3 despite size progression at the first follow-up US, the other nine lesions proved to be malignancies on the first follow-up US and late biopsy. Excluding two malignancies with
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Fig. 3. A 46-year-old woman attended for a routine check-up. The mammogram showed extremely dense parenchyma and no abnormality (not shown). Transverse (a) and longitudinal (b) US images showed a 12 mm hypoechoic mass with an irregular shape and indistinct margin (arrow), which was initially categorized as probably benign. The lesion was retrospectively reassessed as category 4. Early US- guided 23-gauge needle aspiration biopsy was performed upon the physician’s request and the lesion was determined to be a mucinous carcinoma (c, H&E stain 3 100). A modified radical mastectomy was performed and the carcinoma was staged as T1N0.
false negative biopsies, the mean time interval between initial US and the late biopsy for the 11 malignancies was 8.3 months (range, 6–13 months). Seventy-three percent (8 of 11 with late biopsy) of malignancies were identified at 6 months and 27% (3 of 11) were identified at the 12-month follow-up.
DISCUSSION The probably benign assessment is proposed when the lesion has a likelihood of malignancy of less than 2%. Therefore, for probably benign lesions detected on mammograms, short-interval follow-up is recommended (Lindfors et al. 1998; Lindfors and Rosenquist 1994; Rubin 1999; Sickles 1999a, 1991, 1999b). Probably benign lesions detected on US are put on a similar follow-up protocol to those found on mammograms. Follow-up is scheduled at 6 months with US, at 12 months with both US and mammography and at 24 months with both US and mammography. If the lesion has
demonstrated stability for 24 months, the final assessment is changed to category 2. Some authors suggest that a 6-month diagnostic delay for false negative interpretations of lesions would have negligible impact on prognosis (Hall et al. 1988; Sickles et al. 1990) and malignant lesions that initially fulfilled the criteria for probably benign lesions could be rapidly identified with short-interval follow-up mammograms (Sickles 1991). All 13 malignancies with late biopsies showed an increase in size at the first follow-up US in this study. The interval change at first follow-up US was a key feature for re-assessment to category 4. There was no statistical difference in the pathologic stage between early biopsy and late biopsy groups. Moreover, there was no axillary lymph node metastasis in late biopsy group in this study. The mean time interval between initial US and malignancy diagnosis for the 11 malignancies was 8.3 months. Seventy-three percent of malignancies were identified at 6 months, which is comparable to the study conducted by Sickles et al. (Sickles 1991). Compliance is very important for the follow-up of probably benign
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Fig. 4. A 66-year-old woman had undergone a right mastectomy for breast cancer 5 years ago. The mammogram showed a 13 mm in size mass in the left breast (a) and ultrasound (b) showed an irregularly-shape, microlobulated margin and hypoechoic mass which was initially interpreted as category 3. The lesion was reassessed as category 4 due to microlobulated margin and suspicious ductal extension, retrospectively. After a 6-month follow-up, the lesion showed an increase in size (17 mm) and newly-developed pleomorphic microcalcifications on mammogram (c), and showed an increase in size on US and obvious ductal extension (d). Ductal carcinoma in situ was confirmed by US-guided 14-gauge needle core biopsy (e, H&E stain, 3100). A modified radical mastectomy was performed, and the tumor stage was T0N0.
lesions because malignancies can be detected without further delay (Leung and Sickles 2007). To achieve the greatest compliance, radiologists or technologists who have sufficient knowledge to confidently explain the goal of short-term follow-up mammography should recommend it to women just after completion of the
diagnostic work-up (Sickles 1999a) and a reminder system should be considered (Duijm et al. 1998). In probably benign lesions on US, the physician or technologists should confidently explain the importance of follow-up. The US BI-RADS lexicon by ACR is useful for differentiating benign from malignant solid masses
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Table 3. Clinical and pathologic characteristics of 32 malignancies according to symptoms Women with palpable lesions (n 5 21) Mean age (years) 42.7 (range, 26–62) Mean size (mm) 18 (range, 5–51) b Stage 0 (T0N0) 2 (9.5) I (T1N0) 6 (28.6) IIa T1 N1 1 (4.8) T2 N0 5 (23.8) NA 7c (33.3)
Women with nonpalpable Patients with early biopsy lesions (n 5 11) p value (n 519)a 52 (range, 40–66) 10 (range, 4–23) b
.0045 .0206 .0900
39.4 (range, 32–62) 12 (range, 5–51)
5 (45.5) 5 (45.5)
4 (21.1) 6 (31.6)
1 (9.1)
2 (10.5) 2 (10.5) 5d (26.3)
Patients with follow-up and late biopsy (n 5 13) 41 (range, 26–66) 8 (range, 4–23) b
r value .2481 .1721 .4916
3 (23.1) 2e (15.4)
NA 5 nonaccessible. The numbers in parentheses are percentages. a. Inclusion of two women without surgery and one breast lymphoma; b. The size at the time of the 6-month US follow-up recommendation; c. Three women had phyllodes tumors: one had a sarcoma, one had a primary breast lymphoma and two with DCIS and mucinous carcinoma on biopsy were referred to another hospital; d. Spindle cell sarcoma; Primary breast lymphoma; Malignant phyllodes tumor; two with DCIS and mucinous carcinoma on biopsy were referred to another hospital; e. Two malignant phyllodes tumors.
(Costantini et al. 2007, 2006; Hong et al. 2005; Kim EK et al. 2008). Identifying probably benign lesions using breast US is useful for reducing unnecessary biopsies (Chala et al. 2007) because of its high negative predictive value of 99.2% to 99.8% (Graf et al. 2007; Kim EK et al. 2008; Mainiero et al. 2005; Raza et al. 2008). In this study, the negative predictive value of probably benign lesions on US was 99.2%, comparable to previous studies. Graf et al. suggested that palpable probably benign lesions on US can be managed similarly to nonpalpable probably benign lesions (Graf et al. 2004). However, in a clinical setting, a large portion of palpable probably benign lesions undergo US-guided biopsy because of physicians’ or patients’ requests. In this study, early biopsies were performed more frequently in palpable lesions than nonpalpable lesions (p 5 0.01). Moreover, in 4000 women with probably benign lesions, breast malignancies were statistically more frequent in palpable lesions than in nonpalpable lesions (p ,0.001). Therefore, strict criteria should be applied to the probably benign categorization in palpable lesions. Stage IIa was substantially common in palpable lesions, although there was no statistical significance (p 5 0.0900). More data from a larger series may provide the statistical power needed to confirm the assertion that palpable malignancies would be in the more advanced stages than nonpalpable malignancies. The most commonly missed suspicious US feature was a noncircumscribed margin of the lesion. Only four (12.5%) of 32 lesions had the circumscribed margin. When published criteria were strictly applied, 29 (90.6%) of 32 malignancies were re-assessed as category 4 in this study. There are interobserver variabilities in using the ACR-BI-RADS US lexicon for solid masses on US. For interobserver agreements for sonographic descriptors, substantial agreement for lesion calcification and final assessment, moderate agreement for lesion shape, orientation, boundary and posterior acoustic
features, and fair agreement for lesion margin and echo pattern were obtained in our institution (Lee et al. 2008). Therefore, we have not investigated the interobserver variability in this study. Although the overall interobserver agreement with the ACR BI-RADS US lexicon is good and comparable to that of mammography, interobserver agreement for the margin was lower than for shape, orientation, echo pattern or posterior acoustic features (Lazarus et al. 2006; Lee et al. 2008). In clinical practice, a radiologist applies the published criteria as well as the standards based on their individual training and experiences. Therefore, subtle suspicious US features were sometimes ignored. Emphasis on the identification of subtle US features may result in an increase of category 4 classifications and increase in the sensitivity of US interpretation but may result in an increase of false positive interpretations and unnecessary biopsies. There were a few limitations to this study. First, this study was retrospective and we knew that the lesions were malignant. Therefore, bias in reviewing the US images could not completely be avoided. Second, 660 women were lost to follow-up and we followed US stability for at least 6 months in cases that did not undergo biopsy. Therefore, some slowly progressing cancers may have been missed in this study. Third, probably benign lesions with concomitant category 4 or 5 lesions in the remaining breasts were excluded. A recent study by Kim SJ et al. reported that the malignancy rate of probably benign lesions in patients with synchronous malignancy was 11.4% (Kim SJ et al. 2008). Probably benign lesions with concurrent category 4 and 5 lesions may have a higher malignancy rate and a large series study should be followed. Fourth, interobserver variability of this study was not evaluated. However, the interobserver variabilities in using the ACR-BI-RADS US lexicon has been studied in our institution (Lee et al. 2008) and the images were independently evaluated by each radiologist and, then, the two
BI-RADS category 3 lesions d H. J. MOON et al.
radiologists reached a consensus on lesion descriptors and final assessments for masses. In conclusion, the most commonly missed suspicious US feature was a noncircumscribed margin. The malignancy rate was significantly higher in palpable lesions than nonpalpable lesions. Therefore, attention should be paid in assessing the category 3 for palpable breast lesions. Acknowledgements—This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2009-0067048 and by a faculty research grant of Yonsei University College of Medicine for 2008 (No. 6-2008-0262) .
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