Ductal carcinoma in situ, underestimation, ultrasound-guided core needle biopsy

Ductal carcinoma in situ diagnosed after an ultrasoundguided 14-gauge core needle biopsy of breast masses: Can underestimation be predicted preoperatively? Poster No.: C-0442 Congress: ECR 2010 Type: Scientific Exhibit Topic: Breast - US Authors: S. H. Park 1, E.-K. Kim 2, M. J. Kim 2, J. Y. Kwak 2, S. J. Kim 2 ; 1 2 Incheon/KR, Seoul/KR Keywords: Keywords: DOI: Ductal carcinoma in situ, underestimation, ultrasound-guided core needle biopsy Breast, Ultrasound 10.1594/ecr2010/C-0442 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 21

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Purpose BACKGROUND An ultrasound-guided core needle biopsy is an invaluable tool for the diagnosis of breast lesions. However, the possibility of inaccurate sampling with histologic underestimation of lesions, such as ductal carcinoma in situ (DCIS) has been unavoidable. Underestimation of DCIS occurs when a lesion is determined to be DCIS after a percutaneous breast biopsy and is subsequently shown to be invasive carcinoma following surgical excision. In a review of the literature, most prior studies of underestimating DCIS have been performed using stereotactic devices, However, underestimating DCIS after a US-CNB of a breast mass as compared to the use of a stereotactic biopsy has not been thoroughly evaluated. PURPOSE The purpose of this study is to determine the rate of underestimation of DCIS after an ultrasound-guided 14-gauge core needle biopsy of a breast masse and to compare the clinical and imaging characteristics between DCIS lesions and underestimated DCIS lesions identified following surgical excision. Page 3 of 21

Methods and Materials I. CASE SELECTION Between July 2005 and July 2007, 3124 ultrasound guided-14 gauge core needle biopsies (US-14G-CNBs) of breast masses were performed at the breast imaging center at our institution. Among the lesions, 78 lesions were pathologically-determined to be DCIS. Inclusion criteria was a histopathologically-proven pure DCIS without signs of microinvasion or invasive cancer, as determined by the use of light microscopy. DCIS with micro-invasion was defined as tumor cells, singly or in clusters, that infiltrated the periductal stroma or were seen as a projection of neoplastic cells through a disrupted basement membrane in continuity with the DCIS, measuring < 1 mm in the greatest dimension. Exclusion criteria: Excluding lesions with microinvasion (n = 9), 69 pure DCIS lesions in 60 patients that manifested as identifiable masses with or without calcifications as depicted on ultrasound (US) were included in the study population. Six patients had two separate lesions and one patient had four separate lesions. II.IMAGE AND CLINICAL ANALYSIS IMAGE ANALYSIS Two radiologists retrospectively reviewed the mammographic and sonographic findings of the DCIS lesions in consensus. 1. Mammography 2. US The mammographic characteristics of the lesions were classified as negative, calcifications only, a mass, a mass with calcifications, asymmetry, and asymmetry with calcifications. Page 4 of 21

Sonographic characteristics of size, shape, orientation, margin, lesion boundary, and echogenicity of the nodules according to the American College of Radiology Breast Imaging Reporting and Data System (BI- RADS ) lexicon were reviewed retrospectively. Lesion size : the maximum lesion diameter as measured on US. An abnormal lymph node was defined as a thickened or eccentrically bulging cortex with a diminished or absent hilum as depicted on US in accordance with previous reports. 3. Clinical review Clinical records for 60 patients were reviewed to determine age and symptoms at the time of presentation. BIOPSY PROCEDURE A US-14G-CNB was performed using a free hand technique and a highresolution sonography unit with a 7.5- or 12-MHz linear array transducer. All procedures were performed using an automated gun and 14-gauge Tru-Cut needles with a 22 mm throw. One of five radiologists specializing in breast imaging performed all of the biopsies. Prior to a biopsy, a breast US (including the bilateral axillae) was meticulously performed. A minimum of five biopsy samples were obtained with additional samples at the discretion of the radiologist. The pathologic results of the US-14G-CNBs for each case were retrospectively reviewed with the final pathology findings as determined after breast surgery. DATA ANALYSIS The results of the US-14G-CNBs were correlated with the subsequent surgical (lumpectomy or mastectomy) histologic findings. Axillary lymph node status was determined after a sentinel lymph node biopsy or axillary lymph node dissection. The rate of underestimation was defined as a diagnosis of DCIS after a US-14G-CNB with a pathologic diagnosis of invasive carcinoma following surgery. The underestimated group was defined as DCIS after a US-14G-CNB in which the cases were subsequently determined to be invasive ductal carcinoma (IDC) following surgical excision. Page 5 of 21

The non-underestimated group consisted of accurately diagnosed cases of DCIS after a US-14G-CNB in which the cases were not invasive following surgical excision. The underestimated and non-underestimated groups were compared in terms of clinical symptoms, mammographic findings and sonographic characteristics, including axillary findings. STATISTICAL ANALYSIS Tests for statistical significance were performed with statistical software. A p < 0.05 was considered significant. Statistical comparisons were performed using the chi-squared test (Fisher's exact test) for categorical variables and the independent t-test for continuous variables. Confidence intervals were calculated according to the formula by developed by Berry. Page 6 of 21

Results I. UNDERESTIMATION RATE All 60 patients were women (age range, 24-88 years; mean age, 47.5 ± 11.3 years). Of the 69 DCIS lesions diagnosed after a US-14G-CNB, invasive carcinoma was diagnosed in 21 lesions in 19 patients following surgical excision (underestimated group). Thus, the rate of underestimation of DCIS in this study was 30.4% (95% confidence interval, 17.4%-38.0%). II. COMPARISONS OF THE UNDERESTIMATED AND NON-UNDERESTIMATED GROUPS Table 1. Comparisons of clinical findings in the underestimated and non- underestimated groups Clinical findings Age (mean ± standard deviation) Underestimated n = 21(%) Nonunderestimated n = 48(%) p-value 50.7 ± 11.6 46.1 ± 11.0 0.986 Symptom 10 (47.6) 36 (75) 0.129 Palpability 10 (47.6) 21 (43.8) Localized pain 0 (0) 7 (14.6) Nipple discharge 0 (0) 8 (16.7) Asymptomatic 11 (52.4) 12 (25.0) Table 2. Comparisons of mammographic findings in the underestimated and nonunderestimated groups Underestimated n = 21(%) Nonunderestimated p-value Page 7 of 21

n = 48(%) Mammographic finding 0.974 Negative 3 (14.3) 6 (12.5) Calcification only 7 (33.3) 19 (39.6) Mass 2 (9.5) 3 (6.3) Mass with 4 (19) 9 (18.8) calcifications Asymmetry 4 (19) 7 (14.6) Asymmetry with 1 (4.8) 4 (8.3) microcalcifications Table 3. Comparisons of sonographic findings in the underestimated and nonunderestimated groups Size (mean ± standard deviation) Sonographic findings Underestimated n 1 = 21(%) Nonunderestimated n = 48(%) p-value 2.3 ± 1.1 cm 1.6 ± 0.8 cm 0.151 Shape 0.210 Oval 4 (19) 19 (39.6) Round 2 (9.5) 2 (4.2) Irregular 15 (71.4) 27 (56.3) Orientation 0.276 Parallel 11 (52.4) 33 (68.8) Non-parallel 10 (47.7) 15 (31.3) Margin 0.103 Circumscribed 0 (0) 2 (4.2) Indistinct 4 (19) 16 (33.3) Page 8 of 21

Angular 0 (0) 0 (0) Microlobulated 13 (61.9) 29 (60.4) Spiculated 4 (19) 1 (2.1) Boundary 0.233 Abrupt 3 (14.3) 14 (29.2) Echogenic halo 18 (19.1) 34 (70.8) Echogenicity 0.365 Hyperechoic 0 (0) 0 (0) Isoechoic 3 (14.3) 4 (8.3) Hypoechoic 16 (76.2) 41 (85.4) Mixed echogenicity 2 (9.5) 3 (6.3) Microcalcification within the mass on US 11 (52.4) 28 (58.3) 0.793 Final assessment 0.148 4 12(57.1) 37(77.1) 5 9(42.9) 11(22.9) Abnormal lymph node in the axilla on US 1 Number of lesions 5/19(26.3) 2/41(4.9) 0.016 Two patients in the non-underestimated group (2/41 patients [4.9%]) and 5 patients in the underestimated group (5/19 patients [26.3%]) demonstrated the presence of abnormal axillary lymph nodes on US with a statistically significant difference (p = 0.016). However, there were no statistically significant differences between the underestimated and non-underestimated groups with respect to the mammographic findings, sonographic findings, size, age, and clinical symptoms, except for the presence of abnormal axillary lymph nodes depicted on US.(Figs: case 1 and case 2) Case 1. The underestimated group Page 9 of 21

Fig.: Case 1(a). Imaging findings are presented for a 42-year-old woman with invasive ductal carcinoma. Mammography demonstrates suspicious microcalcifications in the right breast(a). References: Department of Radiology, Breast Division, Gachon University Gil Hospital - Incheon/KR Page 10 of 21

Fig.: Case 1(b). Imaging findings are presented for a 42-year-old woman with invasive ductal carcinoma. Breast ultrasound reveals a 3 cm, irregularly-shaped and microlobulated margined hypoechoic mass with echogenic foci within the right upper outer quadrant (b). References: Department of Radiology, Breast Division, Gachon University Gil Hospital - Incheon/KR Page 11 of 21

Fig.: Case 1(c). Imaging findings are presented for a 42-year-old woman with invasive ductal carcinoma. Abnormal lymph nodes without fatty hilum in the right axilla are present (c). The patient underwent an ultrasound-guided 14-gauge core needle biopsy with a ductal carcinoma in situ identified based on the subsequent histology. However, invasive carcinoma was found following surgical excision with the presence of metastatic lymph nodes detected after axillary lymph node dissection. References: Department of Radiology, Breast Division, Gachon University Gil Hospital - Incheon/KR Case 2. The non-underestimated group Page 12 of 21

Fig.: Case 2(a). Imaging findings are presented for a 42-year-old woman with ductal carcinoma in situ. Ultrasound demonstrates an irregularly-shaped, hypoechoic mass in the right upper outer portion (a) with a normal appearing lymph node (arrows) in the right axilla (b). The pathologic findings following an ultrasound-guided 14-gauge core needle biopsy and surgical excision was consistent with ductal carcinoma in situ. References: Department of Radiology, Breast Division, Gachon University Gil Hospital - Incheon/KR Page 13 of 21

Fig.: Case 2(b). Imaging findings are presented for a 42-year-old woman with ductal carcinoma in situ. Ultrasound demonstrates an irregularly-shaped, hypoechoic mass in the right upper outer portion (a) with a normal appearing lymph node (arrows) in the right axilla (b). The pathologic findings following an ultrasound-guided 14-gauge core needle biopsy and surgical excision was consistent with ductal carcinoma in situ. References: Department of Radiology, Breast Division, Gachon University Gil Hospital - Incheon/KR III. RESULTS OF AXILLARY LYMPH NODES An axillary lymph node dissection or a sentinel lymph node biopsy was performed in 58 of 60 patients. In all 41 patients in the non-underestimated group, no axillary lymph node metastases were detected, whereas Page 14 of 21

metastatic axillary lymph nodes in 3 of 17 patients were present in the underestimated group after surgery. This difference was statistically significant (p = 0.02 by Fisher's exact test). Among the seven patients determined to have abnormal axillary lymph nodes on US, two patients in the underestimated group were shown to have lymph node metastasis following surgery. The sensitivity and positive predictive value (PPV) of the axillary US findings with the histopathologic correlation of lymph node metastasis in the study were 66.7% (2/3) and 28.6% (2/7), respectively. IV. COMPARISONS OF PREVIOUSLY REPORTED DATAS Variable DCIS underestimation rates ranging from 5%-44% have been reported and most biopsies have been performed using stereotactic devices with directional vacuum-assisted biopsy in addition to automated large-core needle biopsy. However, US-14G-CNB rates of underestimating DCIS have not been evaluated as compared to the use of a stereotactic biopsy. We identified the rates of DCIS underestimation after a US-guided-CNB that ranged from 20%-66.7% in 10 studies in the literature review (Table 4) and the original aim of these studies was to evaluate the accuracy of a USguided-CNB and not to determine rates of DCIS underestimation Table 4. Reported ductal carcinoma in situ underestimation rates after an ultrasoundguided 14-gauge core needle biopsy Study Target Core needle size Smith et al., Sonographically 2001 3 visible mass subtracting calcifications only Schoonjans et Palpable and al., 2001 24 non-palpable sonographically visible breast masses Buchberger et al., 2002 23 Breast masses and calcifications DCIS for CNB/ Total number of biopsied cases Total number underestimated 14- ACN 5/128(1%) 1/5(20%) 14- ACN 9/424(2.1%) 5/9(55.5%) 14- ACN 10/590(1.7%) 3/10(30%) Page 15 of 21

Philpotts et al., Sonographically 2003 25 visible breast lesions (primarily breast masses) Pijnappel et al., Breast mass 2004 26 and calcifications only Crystal et al., Sonographically 2005 27 visible breast masses Sauer et al., Palpable or 2005 28 non-palpable, sonographically visible breast masses Cho et al., 2005 29 Sonographically visible breast mass (n=551) and calcifications (n=11) Youk et al., Sonographically 2008 5 visible breast masses (palpable or non-palpable) subtracting calcifications only Schueller et al., Sonographically 2008 30 visible, nonpalpable breast masses Current study, 2009 Sonographically visible breast mass (palpable or nonpalpable) 14- ACN 2/181(1.1%) 1/2(50%) 14 or 18 ACN 8/128 (6.3%) 5/8(62.5%) 14- ACN 6/715(0.8%) 4/6(66.7%) 14- ACN 19/962(2.0%) 11/19(57.9%) 14- ACN 10/562(1.8%) 5/10(50%) 14- ACN 126/2420(5.2%) 36/126(29%) 14- ACN 52/1061(4.9%) 19/52(36.5%) 14- ACN 69/3124 (2.2%) 21/69 (30.4%) Page 16 of 21

subtracting calcifications only ACN: automated core needle, DCIS: ductal carcinoma in situ, CNB: core needle biopsy Higher rates of DCIS underestimation determined with the use of US guidance as compared with stereotactic biopsy techniques may be explained as most US-guided biopsy procedures are performed on a mass and the underestimation of invasive cancer is more frequent for a mass than for a microcalcification. Some investigators have reported that 90% of carcinomas that present as microcalcifications alone were non-infiltrating, whereas 84% of carcinomas that present as a mass were invasive. In the present study, the rate of DCIS underestimation was 30.4% (21 of 69 lesions), which is within the range of previously published results. Page 17 of 21

Conclusion It would be useful to identify the pre-operative factors that could predict the presence of occult invasion within DCIS lesions. The ability to identify patients pre-operatively who have a high possibility of having a co-existing invasive carcinoma might allow sentinel lymph node mapping and needle aspiration or a biopsy to be performed prior to the initial surgical excision. In conclusion, the rate of underestimating DCIS for the use of a US-14G- CNB of breast masses in this study was 30.4%. Based on our results, it would seem difficult for radiologists to predict a possible pathologic underestimation by relying on the imaging and clinical findings of the breast lesion. However, the presence of abnormal axillary lymph nodes on US may be a useful factor to predict DCIS underestimation using a US-14G-CNB. Page 18 of 21

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Personal Information Sung Hee Park, M.D. Department of Diagnostic Radiology Gachon University Gil Hospital Incheon South Korea E-mail: shpark@gilhospital.com pshee11@medimail.co.kr Page 21 of 21