diagnostic bene ts of ultrasound-guided biopsy versus ... · tic outcomes of ultrasound-guided core...

Diagnostic benefits of ultrasound-guidedbiopsy versus mammography-guided

biopsy for suspicious microcalcificationswithout definite breast mass

Min Jae Yun1, Keum Won Kim2,Jae Young Seo3 and Young Joong Kim4

1Dept. of Radiology, Asan medical center,88, Olympic-ro 43-gil, Sonpa-gu,

Seoul, 05505, South Korea2 3 4Dept. of Radiology,

Konyang University Hospital,College of Medicine,

Myunggok Medical Research Center,158 Gwanjeodong-ro, Seo-gu,Daejeon, 35365, South Korea

January 18, 2018

Abstract

The purpose of this report is to compare the diagnos-tic outcomes of ultrasound-guided core needle biopsy (US-CNB) versus mammograph-guided biopsy for suspicious mi-crocalcifications and to evaluate of the usefulness of US-CNB in the diagnosis of microcalcifications by comparinghistologic findings according to presence or absence of the le-sions on ultrasound. We retrospectively reviewed 178 casesof suspicious microcalcification on mammography withoutdefinite mass in 158 patients who underwent image-guidedbiopsies. Patients with US-visible calcifications underwent

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International Journal of Pure and Applied MathematicsVolume 118 No. 19 2018, 531-543ISSN: 1311-8080 (printed version); ISSN: 1314-3395 (on-line version)url: http://www.ijpam.euSpecial Issue ijpam.eu

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US-CNB (n=47) and ultrasound-guided localization exci-sion biopsy (US-LEB) (n=72), and those with US-invisiblelesions had mammography-guided localization excision biopsy(MG-LEB) (n=32) and stereotactic vacuum assisted biopsy(S-VAB) (n=27). Mammogram results and false negativerates were analyzed and histologic diagnoses and breastimaging reporting and data system (BI-RADS) categorieswere evaluated. Among all lesions, 119 of 178 (66.9%)were US-visible. US visibility was more frequently associ-ated with malignancy (27.7% vs 11.9%, p=0.012) and withhigher BI-RADS category (32.8% vs 15.3%, p=0.019). Theoverall false negative rate was 10.0% (4/40). Three of the4 false negative results occurred at US-CNB and 1 at S-VAB. The frequency of malignancy was significantly higherfor US-visible microcalcifications that were within a mass orassociated with ductal dilation (72.7% vs 17.5%, p<0.001).US-visible microcalcifications were associated with a higherBI-RADS category and a higher malignancy rate vs US-invisible lesions.

Key Words : Mammography, Calcification, Ultrasound,Needle biopsy, Breast cancer.

1 INTRODUCTION

Mammography is a sensitive test for the detection of microcalcifi-cations in the breast. Microcalcifications are detected at mammog-raphy in 30% to 50% of breast cancer cases, and calcifications arefound at histology in 60% to 80% of cases. Among patients withnon-palpable tumors, fully 42% had microcalcifications reported atmammography. Stereotactic vacuum assisted biopsy (S-VAB) ormammography-guided localization excision biopsy (MG-LEB) areusually recommended when microcalcifications are visible only onmammography.

There are disadvantages to S-VAB. It is costly and time-consuming,and it requires further exposure to ionizing radiation. In addi-tion, there are limitations in lesion localization and assessment ofbreast tissue thickness compared to other methods. Ultrasound(US)-guided techniques are more comfortable for patients, and theyare less time-consuming and less costly than mammography-guided

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methods. Also, there is no exposure to ionizing radiation and theyare real-time procedures, which both doctors and patients shouldprefer. Technical advances in ultrasonography including increasedresolution and the introduction of high-frequency transducers haveimproved US-detection of calcifications, and combining other imag-ing findings with microcalcifications on ultrasound may be helpful.

Current methods for the diagnosis of microcalcifications includeUS-guided core needle or vacuum-assisted biopsy (US-CNB; US-VAB), S-VAB, US- or MG-localization excision biopsy (LEB), andothers. The first purpose of this study was to compare the diagnos-tic accuracy of US-CNB, US-LEB, S-VAB, and MG-LEB in patientswith microcalcification. The second purpose of this study was toevaluate the usefulness of US-CNB in the diagnosis of microcalci-fications by comparing histologic findings according to presence orabsence of the lesions on ultrasound.

2 PROCEDURE FOR PAPER SUBMIS-

SION

Among 6230 patients who underwent mammography from March2013 to September 2016, 485 had BI-RADS category 4 or 5 tissuechanges, and 178 biopsies (158 patients), including 47 US-CNB, 72US-LEB, 27 S-VAB, and 32 MB-LEB, were performed for micro-calcifications on mammography with no additional findings [Figure1].

A. Imaging TechniquesDigital mammography with standard craniocaudal and medi-

olateral oblique (CC and MLO) views and magnification for mi-crocalcifications was performed with a Lorad/Hologic Selenia full-field digital mammography system (Lorad/Hologic, Danbury, CT,USA). High-resolution ultrasonography (iU22, Philips Medical Sys-tems, Bothell, WA, USA, or Logiq 9, GE Medical Systems, Milwau-kee, WI, USA) was performed with 12-MHz linear transducers by 3radiologists with breast imaging experience of 2 to 13 years. All pa-tients underwent ultrasonography prior to biopsy. Imaging findingswere retrospectively reviewed by 2 radiologists.

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B. Biopsy TechniquesAll biopsies were performed by 3 radiologists with 2 to 13 years

of experience. US-CNB or US-LEB was performed when there wascalcification on mammography with no other finding and microcal-cification could be relatively well observed with ultrasound. Whennecessary, radiopaque markers were attached to the skin aboveUS-visible microcalcifications and mammography was performed toconfirm the match. US-CNB was performed with a 14-gauge coreneedle (Stericut; TSK Laboratory, Tochigi, Japan). For US-LEB,the guidewire was placed in the target lesion under US guidance,localization was confirmed by mammography, and the specimenmammography was performed after excision to confirm inclusion ofthe target lesion.

Patients underwent mammography-guided procedures when mi-crocalcifications were not visible on ultrasound. The biopsy methodwas determined by the location of the lesion and the clinical charac-teristics of the patient. S-VAB was performed with 8- or 11-gaugeneedles, lateral view, with the patient in a lateral decubitus posi-tion. For MG-LED, the horizontal and vertical coordinates of thetarget lesion were obtained using windowed compression paddles,the needle was inserted vertically, and the position of the needle

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was confirmed using 90-degree direction mammography. Specimenmammography was performed in all cases to confirm the presenceof microcalcifications.

The histology reports were compared with mammography andultrasound findings. A benign diagnosis of a BI-RADS category4c or 5 lesion was regarded as imaging-pathology discordance, andrebiopsy was recommended in these cases. Further measures afterbenign diagnoses of BI-RADS category 4b lesions were determinedaccording to imaging findings, histologic findings, and clinical find-ings. Surgical resection was recommended for atypical ductal hy-perplasia (ADH), atypical lobular hyperplasia (ALH), lobular car-cinoma in situ (LCIS), papillary lesions, and radial scar. Patientswith imaging-pathology concordance and benign lesions were fol-lowed at 6-month or 1-year intervals according to histologic findings.

C. Data analysisAge, breast parenchymal pattern, microcalcification features,

BI-RADS category, and histologic findings were analyzed accordingto biopsy method. We evaluated rates of malignancy, histologicalunderestimation, and false-negative diagnoses, as detected in pa-tients who underwent follow-up procedures or were monitored bymammography for at least 1 year after the initial diagnosis. Theratio of benign lesions to malignant lesions according to the pres-ence of US-visible microcalcifications was also investigated and theinvasiveness of malignant lesions was characterized. The accuracyof US-CNB and S-VAB was compared, and for CNB, the ratio ofbenign lesions to malignant lesions according to the presence ofassociated findings and invasiveness was analyzed. Statistical anal-yses were performed with SPSS 20.0 software (SPSS Inc., Chicago,IL, USA). The chi-square test was performed and p-values <0.05were considered statistically significant.

3 RESULTS

The average age of the 158 patients was 49.5 years (range 27 to77). Of the total 178 lesions, 106 (59.6%) were associated withheterogeneous density patterns, and heterogeneous density patternswere observed most frequently in all biopsy groups. The extent of

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microcalcification in the US-CNB group was significantly greaterthan that observed in the other groups (p<0.001). There were nosignificant differences according to the distribution pattern or shapeof microcalcifications. Overall, BI-RADS category 4a lesions weremost common (130/178, 73.0%), and among 15 BI-RADS category5 lesions (15/178, 8.4%), 14 were US-visible and 12 were evaluatedby US-CNB.

Malignancy was confirmed by biopsy in 6.9% (9/130) of BI-RADS category 4a lesions, 37.5% (6/16) of category 4b lesions,76.5% (13/17) of category 4c lesions, and 80.0% (12/15) of category5 lesions. Malignancy rates according to biopsy method were: US-CNB 40.4% (19/47); US-LEB 19.4% (14/72); S-VAB 14.8% (4/27);and MG-LEB 9.4% (3/32). Rates of invasive cancer were 21.1%(4/19) in US-CNB, 21.4% (3/14) in US-LEB, 50.0% (2/4) in S-VAB, and 0.0% (0/3) in MG-LEB. Overall, there were more US-visible lesions in high BI-RADS category (32.8% vs 15.3%, p=0.019)and the malignancy rate among US-visible lesions was significantlyhigher (27.7% vs 11.9%, p=0.012), although there was no significantdifference in the number of invasive cancers [Table 1]. US-visiblemicrocalcifications within a mass or associated with duct ectasia[Figures 3] had a significantly higher rate of malignancy (65.5% vs16.7%, p<0.001) compared to US-visible microcalcifications alone[Figure 2], but there were no significant differences in invasivenessbetween the groups [Table 2].

TABLE I

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TABLE II

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The sensitivity and accuracy of US-CNB were 84.2% and 93.6%,respectively, and the sensitivity and accuracy of S-VAB were 75.0%and 96.3% [Table 3]. The overall false negative rate was 10.0%(4/40), and among the 4 false negatives, 3 lesions were initiallyidentified as benign at US-CNB and 1 at S-VAB. Thus, the falsenegative rate for US-CNB was 15.8% (3/19), and the false negativerate for S-VAB was 25% (1/4). The final histopathologic resultshowed ductal carcinoma in situ (DCIS) in 3 cases and microinva-sive ductal carcinoma in the fourth.

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TABLE III

4 DISCUSSION

Microcalcification is one of the most important mammographicfindings in non-palpable early breast cancer. Ultrasound can fur-ther characterize 23 to 45% of these microcalcifications, which mayappear echogenic foci located within a mass or duct, in associationwith internal microlobulation, or distributed in a branch pattern.Microcalcifications in the presence of a mass or ductal ectasia on ul-trasound are more strongly associated with invasive tumors. In thisstudy, we examined the diagnostic accuracy of US-CNB, US-LEB,S-VAB, and MG-LEB and compared the diagnostic performance ofUS-CNB and S-VAB, both of which had relatively high accuracy(US-CNB, 93.6%; S-VAB, 96.3%) [Table 4]. US-CNB and S-VABboth obtain similar tissue amounts, and can be expected to havesimilar accuracy. Other recent studies have shown that US-VABand US-CNB also have similar accuracy (94% to 99%) for breastlesions with microcalcification.

Three of the total 4 false negative results in this study were ob-tained at US-CNB. In these 3 cases, US showed microcalcificationwith mass. Because of the imaging-pathology discordance, follow-up US-LEB was performed in all 3 cases, leading to diagnoses ofDCIS in 2 and microinvasive ductal carcinoma in the other. Thefourth false negative result occurred after S-VAB. The initial diag-nosis was fibrocystic change, but because of an imaging-pathologydiscordance, a follow-up US-LEB was performed, and the final di-agnosis was DCIS. Thus, although US-CNB can be regarded as a

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viable method for diagnosis of microcalcifications, it must be em-phasized excisional biopsy should always be recommended in casesof imaging-pathology discordance.

In this study, US-visible microcalcifications were associated withhigher BI-RADS category (32.8% vs 15.3%, p=0.019) and the ma-lignancy rate among US-visible lesions was significantly higher (27.7%vs 11.9%, p=0.012) compared to US-invisible microcalcifications, asother recent studies have shown as same results. The frequency ofmalignancy was significantly higher for US-visible microcalcifica-tions that were within a mass or associated with ductal dilation.

This study has several limitations. First, it was conducted ata single institution, and the number of patients is relatively small.Second, diagnostic accuracy was compared only for US-CNB vsmammographic S-VAB, while the recently reported US-VAB wasnot included. However, comparison of US-CNB and S-VAB con-firmed the diagnostic usefulness of US-CNB. It is necessary to studyand compare additional biopsy methods in multicenter studies thatinclude more ultrasound findings and more patients. Finally, ul-trasound and US-guided procedures are operator-dependent, so thediagnosis of microcalcifications or the success rate of the proceduremay vary, and we did not assess inter-observer variability in thisstudy. However, all retrospective imaging evaluations were per-formed by 2 radiologists in consensus.

5 CONCLUSION

US-CNB is an accurate and acceptable diagnostic technique for US-visible microcalcifications. US-visible microcalcifications are associ-ated with higher BI-RADS category and higher rates of malignancycompared to US-invisible microcalcifications. The frequency of ma-lignancy was significantly higher for US-visible microcalcificationsthat were within a mass or associated with ductal dilation.

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