The Management Strategy of Benign Solitary Intraductal Papilloma on Breast Core Biopsy

The Management Strategy of Benign Solitary Intraductal Papilloma on Breast Core Biopsy

Accepted Manuscript The management strategy of benign solitary intraductal papilloma on breast core biopsy Dayoung Ko, Eunyoung Kang, So Yeon Park, Su...

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Accepted Manuscript The management strategy of benign solitary intraductal papilloma on breast core biopsy Dayoung Ko, Eunyoung Kang, So Yeon Park, Sun Mi Kim, Mijung Jang, Bo La Yun, Sumin Chae, Yerang Jang, Hye Jin Kim, Sung-Won Kim, Eun-Kyu Kim PII:

S1526-8209(16)30533-X

DOI:

10.1016/j.clbc.2017.03.016

Reference:

CLBC 599

To appear in:

Clinical Breast Cancer

Received Date: 4 December 2016 Revised Date:

14 March 2017

Accepted Date: 23 March 2017

Please cite this article as: Ko D, Kang E, Park SY, Kim SM, Jang M, Yun BL, Chae S, Jang Y, Kim HJ, Kim S-W, Kim E-K, The management strategy of benign solitary intraductal papilloma on breast core biopsy, Clinical Breast Cancer (2017), doi: 10.1016/j.clbc.2017.03.016. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT The management strategy of benign solitary intraductal papilloma on breast core biopsy

Chae1, Yerang Jang 1, Hye Jin Kim1, Sung-Won Kim4, Eun-Kyu Kim1

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Department of Surgery, Seoul National University College of Medicine, Seoul National University

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Bundang Hospital, Seongnam, Korea 2

Department of Pathology, Seoul National University College of Medicine, Seoul National University

Department of Radiology, Seoul National University College of Medicine, Seoul National University

Bundang Hospital, Seongnam, Korea

Department of Surgery, Daerim St. Mary’s Hospital, Seoul, Korea

Corresponding author:

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Bundang Hospital, Seongnam, Korea 3

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Dayoung Ko1, Eunyoung Kang1, So Yeon Park2, Sun Mi Kim3, Mijung Jang3, Bo La Yun3, Sumin

Eunyoung Kang, M.D., Ph.D.

Bundang Hospital

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Department of Surgery, Seoul National University College of Medicine, Seoul National University

82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea

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E-mail address: [email protected] Telephone number: +82-31-787-7102 Fax number: +82-31-787-4078

Conflicts of interest: none

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ACCEPTED MANUSCRIPT Abstract

Background: Intraductal papilloma (IDP) is well known as one of the common benign breast lesions requiring excision. However, treatment of IDP without atypia is controversial. The aim of our study

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was to determine the proper management of solitary IDP by core needle biopsy (CNB).

Patients and methods: We retrospectively reviewed patients with solitary IDP confirmed by CNB from March 2003 to March 2015. We collected data about final pathology after excision, as well as

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clinical, histological, and radiological findings at initial diagnosis. The final pathology was categorized as benign or malignant. We evaluated the rate of upgrade to malignancy and factors

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associated with malignancy.

Results: We identified 405 patients who presented benign solitary IDP by CNB. The mean age was 46.1 years (range, 15-86 years). In total, 135 patients underwent surgical excision and 211 underwent vacuum-assisted excision (VAE). Of 346 patients, malignant lesions were found in 8 patients (2.3%): 7 underwent surgical excision, and 1 underwent VAE. The size of IDP was only associated with

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cancer upgrade significantly (p = 0.003).

Conclusions: Our study shows that overall malignancy upgrade rate of benign solitary IDP after excision is very low (2.3%). Even when the size of IDP was less than 1 cm, the upgrade rate to cancer

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was only 0.9%. Therefore, for patients with small solitary IDP, we recommend close follow-up with

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ultrasound instead of excision.

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ACCEPTED MANUSCRIPT Introduction

Papillary breast lesions are commonly diagnosed by core needle biopsy (CNB) and present various presentations from benign papilloma and atypical papilloma to invasive carcinoma.1 Benign

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papilloma is histologically composed of a fibrovascular core, a myoepithelial layer, and an outer layer of epithelium without atypical features. Atypical papilloma is characterized by the presence of a focal atypical epithelial proliferation such as atypical ductal hyperplasia or small foci of low grade ductal

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carcinoma in situ. Papillary breast lesion has received much attention in recent years due to its management, which is still controversial. In case of atypical papilloma, it is accepted that excision

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should be performed, since the cancer upgrade rate after excision has been reported to be 6.7-38.1%.2However, the management procedure for benign intraductal papilloma (IDP) without any symptoms

and atypia remains debatable. The importance of excision in IDP to exclude malignancy after excision has been reported by many researchers.3, 7-9 However, recent studies showed lower cancer upgrade rates in benign IDP without atypia and suggested observation without excision.10, 11

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Regarding IDP management, surgical excision is known as the standard method. Nonetheless, there have been attempts to utilize a vacuum-assisted device for IDP excision because it is less invasive. One study reported that vacuum-assisted excision (VAE) could acquire near-complete removal and

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replace surgical excision.12 Another review of 6-year VAE experience also suggested that VAE could be a substitute for surgery.13

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The aims of the present study were to evaluate the cancer upgrade rate of IDP without atypia after excision, to determine the predictors for cancer upgrade, and to evaluate the feasibility of VAE as a treatment option. Finally, this study could introduce a scheme how to approach the management of solitary benign papillary lesions.

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ACCEPTED MANUSCRIPT Patients and methods

We retrospectively reviewed the electronic medical records from March 2003 until May 2015 in Seoul National University Bundang Hospital and collected data about patients who were diagnosed

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with solitary papillary lesion including IDP, sclerosing papilloma, and papillary neoplasm at breast CNB. A total of 537 patients were identified, and 67 patients who had incidental findings with ductal carcinoma in situ (DCIS) or invasive cancer were excluded. Among 470 patients, 64 patients with a

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concurrent atypical lesion and 1 patient diagnosed with papillary carcinoma were excluded. Finally, 405 patients with benign solitary papilloma were included in our study subjects (Fig. 1). Among them,

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346 patients who underwent surgical excision or VAE were analyzed for calculating cancer upgrade rate. This study was approved by the institutional review board of Seoul National University Bundang Hospital (B-1512/328-124).

Data collection was performed for the information about age at diagnosis, symptoms, ultrasound finding (shape, size, distance from a nipple, and BI-RADS category), and pathological results of CNB.

breast radiologists.

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Ultrasound-guided CNB was performed using at least 5 times puncture to get an exact diagnosis by

In general, surgical management was recommended when patients complained of symptoms such as

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bloody nipple discharge and a palpable mass for symptom relief or when IDP was located near the skin or nipple. If VAE was technically possible, patients selected surgery and VAE. The VAE was

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performed by a breast-dedicated radiologist under ultrasound guidance. An 8-gauge or 11-gauge needle was utilized for ultrasound-guided VAE (Mammotome®: Devicor Medical Products, Cincinnati, OH, USA). After VAE, completion ultrasonography was performed routinely to confirm complete removal.

In our institution, pathological assessment of CNB and excision samples was performed by a single pathologist specialized in breast cancer, with over 15 years of experience. The final pathological results after excision were divided into 2 groups: a benign group that included non-proliferative

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ACCEPTED MANUSCRIPT lesions, proliferative lesions without atypia, and proliferative lesions with atypia; and the malignant group that was limited to only DCIS and invasive carcinoma. We have stratified the benign group into non-proliferative and proliferative lesions according to the changes in the surrounding tissue. Univariate analysis using the Fisher’s exact test was performed to identify the factors associated with

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cancer upgrade. To find predictors of cancer, multivariate analysis using the logistic regression model was also performed with variables that had a p-value < 0.1 using univariate analysis. Fisher’s exact test and t-test were used to assess the differences of patients and tumors characteristics between the

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p-value of < 0.05 was used to define statistical significance.

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VAE and surgery groups. All analyses were conducted using SPSS version 19 (IBM, Armonk, NY). A

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ACCEPTED MANUSCRIPT Results

Patients with core biopsy diagnosis of papillary lesion The mean age of 405 patients was 46.1 years (range 15-86). In total, 292 patients (72.1%) were

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identified on the screening examination, 72 (17.8%) patients presented nipple discharge, and 41 (10.1%) complained of a palpable mass. Ultrasound findings of target mass are presented in Table 1. Among patients who had an ultrasound initially, 80.9%, 6.7%, and 1.5% of cases showed BI-RADS

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C4a, C4b, and C4c, respectively. Radiological-pathological discordance was defined as when the lesion was confirmed to have benign histology after core needle biopsy, although it had moderate-to-

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high suspicion for cancer in radiology (C4b, C4c, or C5). The cases with radiological-pathological concordance (C3, C4a) were 371, whereas 34 cases showed discordant findings (C4b and C4c). The mean long diameter of the target mass was 1.0 cm (0.2-5.2 cm), and the mean distance between nipple and mass was 1.9 cm (0-11 cm). After classifying the shape, most of the patients showed noncystic hypoechoic masses, and 64 patients presented with an intraductal mass with ductal dilatation on

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ultrasound. On histopathological analysis on CNB specimens, proliferative lesions like columnar cell hyperplasia, complex fibroadenoma, florid ductal hyperplasia, nodular adenosis, pseudoangiomatous

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stromal hyperplasia, and usual ductal hyperplasia were accompanied with IDP in 159 cases (39.3%).

Patients with surgical or vacuum-assisted excision

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In our study, 346 patients underwent excision: 135 (33.5%) patients underwent surgical excision and 211 (52.0%) had VAE. Of the 346 patients who underwent excision, 8 patients (2.3%) were diagnosed with DCIS. In 7 cases, DCIS was located within papilloma, while it was identified adjacent to papilloma in 1 case. Figure 2 showed a representative example of upgraded intraductal papilloma after subsequent excision. The cancer upgrade rate was significantly higher among patients with a larger mass (Table 2). When the tumor size was more than 2 cm, the cancer upgrade rate was 15.8% (3 of 19), whereas when the tumor was less than 1 cm, the upgrade rate was only 0.9% (2 of 226). Age,

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ACCEPTED MANUSCRIPT symptoms, BI-RADS category, the distance between the nipple and mass, and the presence of other proliferative lesions did not have a significant effect on cancer upgrade. Using multivariate analysis, only mass size (≤1.0 cm vs. 1-2 cm: odds ratio [OR] = 4.16, 95% confidence interval [CI] 0.68-25.5;

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≤1.0 cm vs. >2 cm: OR = 48.23, 95% CI 5.88-395.53) was significantly associated with cancer upgrade.

To identify the pattern of IDP management, we compared the characteristics of patients according to

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excision methods (Table 3). Patients with surgical excision had significantly larger mass than patients with VAE (1.3 cm vs. 0.9 cm, p < 0.001), shorter distance from nipple (1.4 cm vs. 2.2 cm, p < 0.001),

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and had more symptoms (43% vs. 17%, p <0.001). There was a difference in cancer upgrade rate in accordance with the excision methods. The upgrade rate in the surgery group was 5.2% (7/135), which was higher than that (0.5%, 1/212) in the VAE group (p = 0.007). The difference indicated that more patients with a larger mass were included in the surgery group than in the VAE group.

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Follow-up of patients after excision

After excision, 293 patients were followed up, and the median follow-up period was 20.2 months (range 11-110). Among these patients, 23 and 5 patients were diagnosed with an additional papillary

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lesion in 116 patients in the surgery group and 177 patients in the VAE group, respectively. Only 4 of 28 patients had a true recurrence in the previous VAE site, and the other patients had new lesions

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occurred in other sites. All additional papillary lesions were excised and confirmed as benign lesions.

Follow-up of patients who did not undergo excision Twenty-seven patients who were diagnosed with IDP by CNB were followed up without excision, and the median follow-up time was 21.6 months (range 4.7-70.0 months). The mean age of these patients was 44.0 years (range 15-68 years), and the mean size of the mass was 0.97 cm (range 0.4-3.4 cm). Fifteen patients were found to have a mass at screening, and other patients had symptoms like

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ACCEPTED MANUSCRIPT nipple discharge and palpable mass. During the follow-up period, the additional papillary lesion was reported near the known lesion in 2 patients, and they underwent excision eventually. There was no cancer upgrade in the excisional specimen. Follow-up imaging studies of other patients showed

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stability of the lesions.

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ACCEPTED MANUSCRIPT Discussion

The management of IDP without atypia remains unclear. Therefore, we evaluated the cancer upgrade rate and predictors of malignancy for 346 patients who underwent surgical excision or VAE after

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diagnosis of IDP by CNB. After excision, 8 patients were diagnosed with cancer, and the overall cancer upgrade rate was 2.3%. The mass size was the only predictive factor for malignancy.

A proliferative lesion of the breast is considered to be excised if there are possibilities of malignancy

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or under-diagnosis for malignant lesion. In previous studies, the range of cancer upgrade rate of IDP was from 3.1% to 9.0%.3-5, 7, 8, 14 Surgical excision for IDP was accepted to exclude malignancy.

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Several studies presented significant upgrade rate. Rizzo et al. reviewed 234 IDP patients without atypia who underwent surgical excision.3 In this study, 21 (9.0%) cases were upgraded to DCIS or invasive ductal carcinoma. A study that evaluated 200 patients with IDP by CNB also reported that 104 patients underwent excision and 9 of them (8.7%) were diagnosed with breast cancers.7 However, more recent studies reported lower upgrade rates, which were from 0% to 3.8%, in benign papilloma

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patients without atypia compared to previous studies.10, 11, 15, 16 In our study, the overall cancer upgrade rate after excision was only 2.3%, which showed good agreement with recent results. Many studies have reported predictive factors for cancer upgrade. Older age, microcalcification on

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CNB, larger size, palpable mass, nipple discharge, radiological-pathological discordance, and higher BI-RADS score were reported as predictors for cancer upgrade.8, 14, 17, 18 The relationship between

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target mass size and cancer upgrade were examined in some studies. Chang et al. performed a prospective study for 100 lesions in 87 patients diagnosed with benign papilloma on CNB, which analyzed cancer upgrade rates of 2 groups divided by mass size of 1.5 cm. A significantly higher upgrade rate was observed in patients with a mass of ≥1.5 (15.0%) cm than that in patients with a mass of <1.5 cm (1.25%; p = 0.026).19 Another study that utilized the size of 1.3 cm as a cut-off value also reported higher upgrade rate in patients with larger mass (< 1.3 cm vs. ≥ 1.3 cm: OR 3.409, p =

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ACCEPTED MANUSCRIPT 0.06).15 Our study also showed that the mass size was a predictive factor for upgrade. The upgrade rate of patients having a mass of ≤ 1 cm was 0.9% while patients with a mass between 1 cm and 2 cm had an upgrade rate of 3.0%. Furthermore, the cancer upgrade rate was significantly increased

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when the size was greater than 2 cm (15.8%). Radiological-pathological concordance was reported as a significant cancer predictor in a study that evaluated 230 IDP cases.15 Significantly higher upgrade rate was observed in discordant cases (50%) compared to that of concordant cases (1.8%; p <0.001). In our study, there was no significant

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difference in cancer upgrade rate between the concordant cases and discordant cases. Age, symptoms, and distance from nipple were also considered predictors by previous studies. One

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study that analyzed 160 CNB-diagnosed benign papillomas showed that patients with a palpable mass of IDP without atypia had a higher risk of cancer upgrade.18 Youk et al. suggested that predictive factors for malignancy were larger mass size, shorter distance from the nipple, and older age.14 However, in our study, age, symptoms, and distance from nipple were not revealed as predictive

multivariate analysis.

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factors. Only mass size of IDP was significantly associated with cancer upgrade in both univariate and

According to BI-RADS category, benign breast lesions that have <3% possibility of malignancy can

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be observed with close clinical follow-ups. In our study, we observed a 0.9% of cancer upgrade among patients with solitary benign IDP without atypia, which was less than 1 cm. Therefore, we

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suggest close observation with ultrasound and physical examination in patients with small benign IDP without atypia, while in patients with IDP larger than 1 cm, we recommend excision (Fig. 3). Regarding the method of excision, surgical excision is known as a traditional and gold standard of treatment. Recently, many centers utilize the vacuum-assisted device. One study reviewed 49 benign papillary lesions that were proven by a vacuum-assisted biopsy. As they showed no cancer upgrade after surgical excision, they suggested that vacuum-assisted biopsy is enough for excision.20 In our study, the cancer upgrade in the VAE group was only 0.5%, and the additional papillary lesion occurred in a small number of cases (2.8%) among 177 patients who were followed up after VAE.

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ACCEPTED MANUSCRIPT Therefore, VAE could be safely used for management of IDP if it was technically possible. Although there is a limitation of being a single center and retrospective review study, which leads to the possibility of bias, our research was performed in a large study population. We believe that it is sufficient to identify the predictors of cancer upgrade and to find a subgroup for conservative

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management. In addition, in our hospital, all breast lesions were reviewed by a single breast-dedicated pathologist, which could increase the accuracy of diagnosis. Because papillary lesion of breast presents in various forms, the roles of pathologists and radiologists have been emphasized. A study

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that evaluated the diagnosis accuracy of papillary lesions between breast pathologists and non-breast pathologists showed that the diagnosis alteration from CNB to excision was significantly less in breast

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pathologists than in non-breast pathologists.21 Furthermore, because each CNB was performed using at least 5 times of puncture by breast-dedicated radiologists, we could avoid the under-sampling of mass, and the diagnosis accuracy could increase.

In conclusion, the present study provides insight into the management of small (≤1 cm) solitary

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benign papillary lesions that can be followed-up with imaging and physical examination without excision. Moreover, our results demonstrate the feasibility of using VAE instead of surgical excision

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when needed.

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ACCEPTED MANUSCRIPT References

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Valdes EK, Feldman SM, Boolbol SK. Papillary lesions: a review of the literature. Ann Surg Oncol. 2007;14:1009-1013. Nakhlis F, Ahmadiyeh N, Lester S, Raza S, Lotfi P, Golshan M. Papilloma on Core Biopsy:

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Rizzo M, Linebarger J, Lowe MC, et al. Management of papillary breast lesions diagnosed on

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core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up. J. Am. Coll. Surg. Vol 214: Elsevier; 2012:280-287.

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Mercado CL, Hamele-Bena D, Oken SM, Singer CI, Cangiarella J. Papillary lesions of the breast at percutaneous core-needle biopsy. Radiology. 2006;238:801-808. Irfan K, Brem RF. Surgical and mammographic follow-up of papillary lesions and atypical

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Papillomas of the Breast at Core Needle Biopsy. American Journal of Roentgenology. Vol

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Tatarian T, Sokas C, Rufail M, et al. Intraductal Papilloma with Benign Pathology on Breast

Core Biopsy: To Excise or Not? Ann Surg Oncol. Vol 23: Springer International Publishing; 2016:1-7. 10.

Swapp RE, Glazebrook KN, Jones KN, et al. Management of benign intraductal solitary

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ACCEPTED MANUSCRIPT papilloma diagnosed on core needle biopsy. Ann Surg Oncol. Vol 20: Springer-Verlag; 2013:1900-1905. 11.

Nayak A, Carkaci S, Gilcrease MZ, et al. Benign Papillomas Without Atypia Diagnosed on Core Needle Biopsy: Experience From a Single Institution and Proposed Criteria for Excision.

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Cassano E, Urban LA, Pizzamiglio M, et al. Ultrasound-guided vacuum-assisted core breast biopsy: experience with 406 cases. Breast Cancer Res Treat. 2007;102:103-110.

Maxwell AJ. Ultrasound-guided vacuum-assisted excision of breast papillomas: review of 6years experience. Clin Radiol. 2009;64:801-806.

Youk JH, Kim E-K, Kwak JY, Son EJ, Park B-W, Kim S-I. Benign Papilloma without Atypia

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Diagnosed at US-guided 14-gauge Core-Needle Biopsy: Clinical and US Features Predictive of Upgrade to Malignancy 1. Radiology. Vol 2582011:81-88. 15.

Kim S-Y, Kim E-K, Lee HS, et al. Asymptomatic Benign Papilloma Without Atypia _ Which Subgroup can be Managed by Observation. Ann Surg Oncol. Vol 23: Springer International

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Publishing; 2016:1860-1866.

Pareja F, Corben AD, Brennan SB, et al. Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: Rate of upgrade to carcinoma at

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Li X, Weaver O, Desouki MM, et al. Microcalcification is an important factor in the

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management of breast intraductal papillomas diagnosed on core biopsy. Am J Clin Pathol. 2012;138:789-795.

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Jung S-Y, Kang H-S, Kwon Y, et al. Risk Factors for Malignancy in Benign Papillomas of the Breast on Core Needle Biopsy. World J Surg. Vol 34: Springer-Verlag; 2010:261-265.

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Chang JM, Moon WK, Cho N, et al. Risk of carcinoma after subsequent excision of benign papilloma initially diagnosed with an ultrasound (US)-guided 14-gauge core needle biopsy: a prospective observational study. Eur Radiol. Vol 20: Springer-Verlag; 2010:1093-1100.

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Chang JM, Han W, Moon WK, et al. Papillary Lesions Initially Diagnosed at Ultrasoundguided Vacuum-assisted Breast Biopsy: Rate of Malignancy Based on Subsequent Surgical Excision. Ann Surg Oncol. Vol 18: Springer-Verlag; 2011:2506-2514. Jakate K, De Brot M, Goldberg F, Muradali D, O'Malley FP, Mulligan AM. Papillary lesions

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diagnoses. Am J Surg Pathol. 2012;36:544-551.

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of the breast: impact of breast pathology subspecialization on core biopsy and excision

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ACCEPTED MANUSCRIPT Figure legends

Figure 1. Case flow of our study

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Figure 2. A representative example of upgraded intraductal papilloma after subsequent excision.

(A) This case was diagnosed as benign intraductal papilloma using core needle biopsy, and there was no atypical epithelial proliferation. (B) Subsequent excision revealed solid proliferation of atypical

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cells, that is, low grade ductal carcinoma in situ, in the lower portion of the lesion.

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Figure 3. Management scheme for benign solitary papilloma without atypia on core needle biopsy

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ACCEPTED MANUSCRIPT Table 1. Clinical, radiological, and histological characteristics of patients

Mean Age, years (range)

46.1

(15-86)

Laterality (right) Symptom Screening (no symptom) Nipple discharge Palpable mass Radiological findings (ultrasound) BI-RADS category C3 C4a C4b C4c Character Intraductal mass Solid and cystic mass Noncystic mass Mean size, cm Distance from nipple, cm Histological findings Another proliferative lesions without atypia Absence Presence

183

45.2

292 72 41

72.1 17.8 10.1

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44 327 27 6

10.9 80.9 6.7 1.5

64 19 322 1.0 1.9

15.8 4.7 79.5 (0.23-4.30) (0-11.00)

246 159

60.7 39.3

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%

Clinical findings

N 405

ACCEPTED MANUSCRIPT Table 2. Clinical, radiological, and histological characteristics of patients Surgery (n=135) N

%

p-value

(22-80) 38.2

46.1 115

(22-75) 61.8

0.758 0.741 <0.001

57.0 25.2 17.8

175 26 10

82.9 12.3 4.7

11.9 74.1 11.9 2.2

19 181 9 2

19.3 5.2 75.6 (0.23-5.20) (0.00-8.00)

30 7 174 0.87 2.22

14.2 3.3 82.5 (0.30-2.40) (0.00-11.00)

61.5 38.5

129 82

61.1 38.9

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%

0.023

9.0 85.8 4.3 0.9

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N Clinical findings Mean Age, years (range) 45.8 Laterality (right) 71 Symptom Screening (no symptom) 77 Nipple discharge 34 Palpable mass 24 Radiological findings (ultrasound) BI-RADS category C3 16 C4a 100 C4b 16 C4c 3 Character Intraductal mass 26 Solid and cystic mass 7 Noncystic mass 102 Mean size, cm 1.26 Distance from nipple, cm 1.38 Histological findings Another proliferative lesions without atypia Absence 83 Presence 135 Abbreviation: VAE, vacuum-assisted excision

VAE (n=211)

0.287

< 0.001 < 0.001 1.000

ACCEPTED MANUSCRIPT Table 3. Cancer upgrade according to characteristics of patients Total N

N

Cancer upgrade %

p-value

256 90

5 3

2.0 3.3

252 60 34

7 0 1

2.8 0.0 2.9

35 281 25 5

2 4 2 0

5.7 1.4 8.0 0.0

227

2

0.9

100 19

3 3

56 14 276

1 0 7

Age (years)

0.433

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134 212

3 5

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>1.0, ≤2.0 >2.0 Character Intraductal mass Solid and cystic mass Noncystic mass Another proliferative lesions Presence Absence

0.067

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≤1.0

0.423

3.0 15.8

1.000

1.8 0.0 2.5

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≤50 >50 Symptoms Screening Nipple discharge Palpable mass BI-RADS C3 C4a C4b C4c Mass size

2.2 2.4

1.000

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