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Surgical excision outcome after radial scar without atypical proliferative lesion on breast core needle biopsy: a single institutional analysis
Annals of Diagnostic Pathology 21 (2016) 35–38
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Surgical excision outcome after radial scar without atypical proliferative lesion on breast core needle biopsy: a single institutional analysis☆ Yanjun Hou, MD, PhD a, Shveta Hooda, MD b, Zaibo Li, MD, PhD a,⁎ a b
Department of Pathology, Ohio State University Wexner Medical Center, Columbus, OH 43210 Department of Pathology, Ohio Valley Medical Center, Wheeling, WV 26003
a r t i c l e
i n f o
Available online xxxx Keywords: Radial scar Breast cancer Ductal carcinoma in-situ Atypical ductal hyperplasia
a b s t r a c t Radial scar (RS) has been recognized as a risk factor for developing breast cancer, and excision is recommended for patients with RS identified on core needle biopsy (CNB). However, recent literatures suggest that the increased risk may be caused by concurrent proliferative lesions on the biopsy, rather than radial scar itself. In this study, we investigated the follow-up excision (FUE) results for patients with RS on CNB with no history of a prior or a concurrent breast cancer or atypical proliferative lesions (APLs). A total of 113 RS cases including 32 cases with APLs or carcinoma and 81 cases without APLs on CNB were included in this study. Forty cases (49%) without APLs had FUE. No significant difference in radiologic and clinical findings was identified between cases with FUEs and cases without FUEs. Of the 40 cases with FUE, 9 cases (22.5%) were upgraded including 3 atypical ductal hyperplasias, 4 lobular neoplasias, 1 flat epithelial atypia, and 1 atypical apocrine adenosis. However, no case was upgraded to invasive carcinoma or ductal carcinoma in situ. All cases with mammotome CNBs were not upgraded. Our data suggest that conservative follow-up with imaging rather than surgical excisions may be more appropriate for patients with only RS on biopsy, especially for patients with mammotome CNBs. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Radial scar (RS) is characterized by a stellate configuration of fibroelastic core with entrapped ducts and lobules and is also referred as radial sclerosing lesion or complex sclerosing lesion [1,2]. The radiologic appearance of RS overlaps that of invasive carcinoma (IC), and it poses a challenge to radiologists [3-6]. RS has been found to be associated with both benign proliferative lesions and atypical/malignant proliferative lesions [7-12]. The management of patients with RS detected on image-guided core needle biopsies (CNBs) is still a matter of debate because the data from previous studies are conflicting in regard to whether these lesions are independent risk factors for malignancy [7-30]. However, many previous studies did not take into account patient's prior history of breast cancer or atypical proliferative lesions (APLs), which are associated with an increased risk for future breast carcinoma development [31,32]. Therefore, the increased rates of upgrade to malignancy on surgical excision after RS on CNBs found in some studies might be related to coexisting APLs or breast cancers. The aim of our study was to evaluate the surgical excision outcome of a consecutive
☆ Disclosure: All authors have no potential conflict of interest. ⁎ Corresponding author at: Department of Pathology, Ohio State University Wexner Medical Center, 410 W. 10th Ave, Columbus, OH 43210. Tel.: +1 614 366 4859; fax: +1 614 293 4715. E-mail address: [email protected] (Z. Li). http://dx.doi.org/10.1016/j.anndiagpath.2015.11.004 1092-9134/© 2015 Elsevier Inc. All rights reserved.
series of RS patients without any history of a prior or concurrent breast cancer or APLs over a period of 12 years at a single institution.
2. Methods and materials 2.1. Patient selection and data collection After institutional review board approval at The Ohio State University, a pathology archive database search was performed for a period of 12 years (January 2003 to December 2014). Although majority of the biopsies were performed using 14-gauge needles with 3 to 5 passes, some of the biopsies were done with 8-gauge mammotome needles. Biopsy specimens were received in 10% formalin and embedded in paraffin. Four levels of sections for each tissue block were obtained and stained with standard hematoxylin and eosin. Surgical excision specimens were also fixed in 10% formalin and embedded in paraffin. Most excisional specimens were submitted entirely for histologic examination. Radial scar was diagnosed based on the following criteria: a stellate lesion with central fibroelastotic zone of basophilic elastic material and radiating fibrous bands and dilated or compressed tubular structures with 2 cell layers (Fig. 1A). Cases were considered to be upgraded if follow-up excision (FUE) showed flat epithelial atypia (FEA) (Fig. 1B), atypical ductal hyperplasia (ADH) (Fig. 1C), and lobular neoplasia (LN) (atypical lobular hyperplasia [ALH] and lobular carcinoma in situ [LCIS]) (Fig. 1D).
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Y. Hou et al. / Annals of Diagnostic Pathology 21 (2016) 35–38
Fig. 1. Representative images of RS, ADH, LCIS, and IC. Radial scar (A); FEA (B); ADH (C); LCIS (D).
A total of 113 cases were interpreted as RS with or without other benign or malignant lesions. Thirty-two cases with a diagnosis of RS were excluded from this study due to concurrent or prior diagnosis of FEA, ADH, LN, ductal carcinoma in situ (DCIS), or IC. The details are summarized in Table 1. The remaining 81 cases of radial scar without any other concurrent or prior APLs were included in this study. Medical records were reviewed for patient age, symptoms, and radiologic results (microcalcification, distortion, mass, etc). The American College of Radiology Breast Imaging, Reporting and Data System (BI-RADS) score was also recorded.
2.2. Statistical analysis Data were entered using Microsoft Excel spreadsheet software (Microsoft, Redmond, WA). Mean, median, and SD were calculated. Fisher exact test was used to compare the difference. All the analyses were done using the SAS 9.3 system (SAS Institute, Cary, NC), and P b .05 was considered statistically significant.
Table 1 Excluded cases: 32 due to concurrent or prior history of atypical proliferative lesions or carcinomas.
FEA ADH LN (ALH and LCIS) DCIS IDC Total Abbreviation: IDC, invasive ductal carcinoma.
Concurrent
Prior
4 5 6 7 7 29
0 0 0 2 1 3
3. Results The mean age of all patients (81 cases) in this study was 52.6 years (range, 24-75 years). All patients were rendered a BI-RADS score of 4 (suspicious abnormality: a biopsy should be considered) on mammography before CNBs. Biopsy methods included ultrasound guided (47 cases) and stereotactic guided (34 cases). Microcalcification was detected in 42 patients including 26 (65%) in cases with FUE and 16 (39%) in cases without FUE. Forty-nine cases with distortion or mass on radiologic imaging were deemed as targeted lesions, including 18 (45%) in cases with FUE and 31 (76%) in cases without FUE. Eight-gauge mammotome core biopsy was performed in 18 cases, including 8 in cases with FUE and 10 in cases without FUE (Table 2). Follow-up excision was performed in 40 cases (49%), and the other 41 cases did not have any FUE. Significantly more cases with microcalcification and fewer cases with distortion/mass were found in the group with FUE than in the group without FUE, indicating that surgical excision was less likely performed for targeted lesions (distortion/mass lesions) (Table 2). Significant lesions on FUE were divided into 5 categories: IC, DCIS, ADH (with/without LN), LN alone, and FEA. Of the 40 cases with RS on
Table 2 Age and radiological findings of cases with/without FUE.
Average age BI-RADS ≥4 Microcalcification Distortion/mass Mammotome Bx
Cases with FUE ex: n = 40
Cases without FUE ex: n = 41
Total, n = 81
P
53.2 (39-70) 40 (100%) 26 (65%) 18 (45%) 8 (20%)
52.0 (24-75) 41 (100%) 16 (39%) 31 (76%) 10 (24%)
52.6 (24-75) 81 (100%) 42 (52%) 49 (60%) 18 (22%)
NS NS .02 .005 NS
Note: Some cases have overlapping radiologic findings. Abbreviations: NS, not statistically significant; Bx, biopsy.
Y. Hou et al. / Annals of Diagnostic Pathology 21 (2016) 35–38 Table 3 Significant lesions found on FUE in patients with RS diagnosed on CNBs. Lesions
Case no.
%
ADH AAA LN FEA Cases with upgrade Cases without upgrade Total
3 1 4 1 9 31 40
7.5% 2.5% 10% 2.5% 22.5% 77.5% 100.00%
CNB, no IC or DCIS was identified on FUE. Nine cases (22.5%) were upgraded on FUEs, including 3 ADH, 4 LN, 1 FEA and 1 atypical apocrine adenosis (AAA) (Table 3). Next, the demographic features and radiologic findings were evaluated for any significant difference between cases with an upgrade and the cases without an upgrade. The only variable with a significant difference between these 2 groups is the mammotome biopsy, which was performed only in the group without upgrade. All other variables including age and radiologic findings did not show any significant difference between these 2 groups (Table 4). 4. Discussion Radial scar occurs in 8% to 16% of women and in up to 42% of the contralateral breast from patients with a history of invasive ductal carcinoma based on autopsy studies [33-35]. However, the true relationship between RS and malignancy is difficult to assess. During the pre-CNB era (no routine presurgical CNB), the radiologically detected RS associated malignancy rate ranged from 10% to 41% on lesion excision [7,10,11,36-40]. However, the underlying RS-associated malignancy rate does not address the question of how to manage patients with RS identified on CNBs currently, especially when no current/prior atypia/ cancer is present. Several studies had investigated this issue during last decade, and 1 recent meta-analysis demonstrated an overall malignancy upgrade rate of 10.5% for CNB-confirmed RS on excision, including 27% for RS with epithelial atypia (27%) vs 7.5% for RS without atypia [13,14,19,30]. One recent study with 53 CNB-confirmed RS cases demonstrated a careful radiologic-pathologic correlation lowered the malignancy upgrade rate to 2% on excision [30]. Our recent study from University of Pittsburgh Magee Womens Hospital also demonstrated a low malignancy upgrade rate of 0.9% on excision in CNB-confirmed RS patients without any concurrent/prior APL/cancer [41]. Current study from an academic medical center demonstrated no malignancy upgrade on FUE after RS on CNBs without current/prior atypia/cancer. The reason leading to nonmalignancy upgrade in our study may be case selection bias. All cases with current/prior history of breast cancer or APLs (including ADH, LN, and FEA) were excluded from current study cohort. Our recent study and other studies have revealed that history of breast cancer or APLs plays an important role in subsequent development of breast carcinoma or APLs [31,32]. Therefore, the high malignancy upgrade rates in previous studies may be caused by the presence of history of breast cancer/atypia in some cases from their study cohorts. In consistent with this hypothesis, a Table 4 Demographic, clinical, and radiologic findings in cases with/without upgrade on FUE.
Average age (range) (y) Radiologic findings Microcalcification Distortion/Mass BI-RADS ≥4 Mammotome Bx
Not upgraded (n = 31)
Upgraded (n = 9)
Total (n = 40)
P
53.2 (39-69)
53.4 (41-70)
53.2 (39-70)
NS
21 (67.7%) 13 (28.8%) 31 (100%) 8 (26%)
5 (57.8%) 5 (25.0%) 9 (100%) 0 (0%)
26 (65.0%) 18 (45.0%) 40 (100%) 8 (20%)
NS NS NS .044
37
large study from Vanderbilt University with a long-term follow-up demonstrated that the presence of RS in a benign breast biopsy mildly elevated the risk of IC risk, but this risk was largely attributed to the coexistent proliferative disease, especially atypical hyperplasia [12]. Furthermore, both study from Memorial Sloan Kettering Cancer Center and our recent study from University of Pittsburgh Magee Womens Hospital found similar low malignancy upgrade rate (2% and 0.9%, respectively) on FUE for RS without atypia on CNBs [30,41]. Although no malignancy was identified in current study, the upgrade rate to APLs (including ADH, LN, and FEA) was considerably high (22.5%), which was consistent with the results from Memorial Sloan Kettering Cancer Center study (22.6%) and our recent study from University of Pittsburgh Magee Womens Hospital (26%) [30,41]. Multiple variables were investigated to identify possible factors that would predict the presence APLs on FUE, and the only variable with a significant relationship to the upgrade was the absence of mammotome biopsies, indicating the importance of larger biopsies in reducing falsenegative rate with CNBs. Knowing the outcomes of patients who did not undergo FUE for their RSs on CNBs is important for the optimal management of these patients. Approximately half of RS patients did not undergo FUEs in our study cohort. By searching our pathology archive data, we did not find any subsequent malignant lesions during a follow-up period of up to 11 years. The findings were consistent with previous study by Resetkova et al [42], which found no subsequent carcinomas at a median follow-up of 29 months in 46 patients who did not have their RS excised. In the study of Brenner et al [16], no carcinoma was found in 55 patients who did not undergo excision with a follow-up of at least 48 months. Similarly, Sohn et al [43] did not find any carcinoma in 10 patients with a mean follow-up of 47 months. Therefore, it may be acceptable to closely monitor patients by radiology if a surgical excision is not desired. In summary, no malignancy was identified on excision in CNBconfirmed RS patients without concurrent/prior atypia/cancer, although APLs were identified in a considerable portion of patients (22.5%). Moreover, all patients with mammotome biopsy-confirmed RS did not find any upgrade lesions. Because the management for atypical lesions identified on excision is just follow-up, our data suggest that conservative followup with imaging rather than surgical excisions may be more appropriate for these patients, especially for patients with mammotome biopsy. References [1] Hamperl H. Strahlige narben und obliterienrende mastopathie: Beitrage Zur pathologischen histoloie der mamme. Virchows Arch A Pathol Anat Histol 1975; 369:55–68. [2] Eusebi V, Millis RR. Epitheliosis, infiltrating epitheliosis, and radial scar. Semin Diagn Pathol 2010;27:5–12. [3] Meyer JE, Christian RL, Lester SC, et al. Evaluation of nonpalpable solid breast masses with stereotaxic large-needle core biopsy using a dedicated unit. Am J Roentgenol 1996;167:179–82. [4] Ciatto S, Morrone D, Catarzi S, et al. Radial scars of the breast: review of 38 consecutive mammographic diagnoses. Radiology 1993;187:757–60. [5] Orel SG, Evers K, Yeh IT, et al. Radial scar with microcalcifications: radiologicpathologic correlation. Radiology 1992;183:479–82. [6] Mitnick JS, Vazquez MF, Harris MN. Differentiation of radial scar from scirrhous carcinoma of the breast: mammographic-pathologic correlation. Radiology 1989;173: 697–700. [7] Sloane JP, Mayers MM. Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age. Histopathology 1993;23:225–31. [8] Jacobs TW, Byrne C, Colditz G, et al. Radial scars in benign breast-biopsy specimens and the risk of breast carcinoma. N Engl J Med 1999;340:430–6. [9] Mokbel K, Price RK, Mostafa A, et al. Radial scar and carcinoma of the breast: microscopic findings in 32 cases. Breast 1999;8:339–42. [10] Farshid G, Rush G. Assessment of 142 stellate lesions with imaging features suggestive of radial scar discovered during population-based screening for breast cancer. Am J Surg Pathol 2004;28:1626–31. [11] Fasih T, Jain M, Shrimankar J, Staunton M, Hubbard J, Griffith CD. All radial scars/ complex sclerosing lesions seen on breast screening mammograms should be excised. Eur J Surg Oncol 2005;31:1125–8. [12] Sanders ME, Page DL, Simpson JF, et al. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Carcinoma 2006;106:1453–61.
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[13] Jackman RJ, Nowels KW, Rodriguez-Soto J, et al. Stereotactic, automated, large-core needle biopsy of nonpalpable breast lesions: false-negative and histologic underestimation rates after long-term follow-up. Radiology 1999;210:799–805. [14] Philpotts LE, Shaheen NA, Jain KS, Carter D, Lee CH. Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle biopsy: clinical importance. Radiology 2000;216(3):831–7. [15] Kirwan SE, Denton ER, Nash RM, et al. Multiple 14G stereotactic core biopsies in the diagnosis of mammographically detected stellate lesions of the breast. Clin Radiol 2000;55:763–6. [16] @Brenner RJ, Jackman RJ, Parker SH, et al. Percutaneous core needle biopsy of radial scars of the breast: when is excision necessary? Am J Roentgenol 2002;179:1179–84. [17] Cawson JN, Malara F, Kavanagh A, et al. Fourteen-gauge needle core biopsy of mammographically evident radial scars: is excision necessary? Cancer 2003;97:345–51. [18] Brodie C, O’Doherty A, Quinn C. Fourteen-gauge needle core biopsy of mammographically evident radial scars. Cancer 2004;100:652–3. [19] Dillon MF, McDermott EW, Hill A, et al. Predictive value of breast lesions of “uncertain malignant potential” and “suspicious for malignancy” determined by needle core biopsy. Ann Surg Oncol 2006;14:704–11. [20] Lopez-Medina A, Cintora E, Mugica B, et al. Radial scars diagnosed at stereotactic core-needle biopsy: surgical biopsy findings. Eur Radiol 2006;16:1803–10. [21] Doyle EM, Banville N, Quinn CM, et al. Radial scars/complex sclerosing lesions and malignancy in a screening programme: incidence and histological features revisited. Histopathology 2007;50:607–14. [22] @Lieske B, Ravichandran D, Alvi A, et al. Screen-detected breast lesions with an indeterminate (B3) core needle biopsy should be excised. Eur J Surg Oncol 2008;34:1293–8. [23] El-Sayed ME, Rakha EA, Reed J, et al. Predictive value of needle core biopsy diagnoses of lesion of uncertain malignant potential (B3) in abnormalities detected by mammographic screening. Histopathology 2008;53:650–7. [24] Hayes BD, O’Doherty A, Quinn CM. Correlation of needle core biopsy with excision histology in screen-detected B3 lesions: the Merrion Breast Screening Unit experience. J Clin Pathol 2009;62:1136–40. [25] Rajan S, Wason AM, Carder PJ. Conservative management of screen-detected radial scars: role of mammotome excision. J Clin Pathol 2011;64:65–8. [26] Rakha EA, Lee AHS, Jenkins JA, et al. Characterization and outcome of breast needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening. Int J Cancer 2011;129:1417–24. [27] Rakha EA, Ho BC, Naik V, et al. Outcome of breast lesions diagnosed as lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4) on needle core biopsy, including detailed review of epithelial atypia. Histopathology 2011;58:626–32.
[28] Bianchi S, Giannotti E, Vanzi E, et al. Radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy: analysis of 49 cases from a single centre and review of the literature. Breast 2012;21:159–64. [29] Andacoglu O, Kanbour-Shakir A, Teh YC, et al. Rationale of excisional biopsy after the diagnosis of benign radial scar on core biopsy: a single institutional outcome analysis. Am J Clin Oncol 2013;36:7–11. [30] Conlon N, D'Arcy C, Kaplan JB, et al. Radial scar at image-guided needle biopsy: is excision necessary? Am J Surg Pathol 2015 Jun;39(6):779–85. [31] Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow up study. Cancer 1985;55:2698–708. [32] Li Z, Fadare O, Hameed O, Zhao C, Desouki MM. Incidental atypical proliferative lesions in reduction mammoplasty specimens in patients with a history of breast cancer. Hum Pathol 2014;45:104–9. [33] Nielsen M, Jensen J, Andersen JA. An autopsy study of radial scar in the female breast. Histopathology 1985;9:287–95. [34] Bhatal PS, Brown RW, Lesueur GC, et al. Frequency of benign and malignant breast lesions in 207 consecutive autopsies in Australian women. Br J Cancer 1985;51:271–8. [35] Nielsen M, Christensen L, Andersen J. Radial scars in women with breast cancer. Cancer 1987;59:1019–25. [36] Manfrin E, Remo A, Falsirollo F, et al. Risk of neoplastic transformation in asymptomatic radial scar: analysis of 117 cases. Breast Cancer Res Treat 2008;107:371–7. [37] Frouge C, Tristant H, Guinebretiere JM, et al. Mammographic lesions suggestive of radial scars: microscopic findings in 40 cases. Radiology 1995;195:623–5. [38] Alleva DQ, Smetherman DH, Farr Jr GH, et al. Radial scar of the breast: radiologicpathologic correlation in 22 cases. Radiographics 1999;19:S27–37. [39] King TA, Scharfenberg JC, Smetherman DH, et al. A better understanding of the term radial scar. Am J Surg 2000;180:428–33. [40] Patterson JA, Scott M, Anderson N, et al. Radial scar, complex sclerosing lesion and risk of breast cancer. Analysis of 175 cases in Northern Ireland. Eur J Surg Oncol 2004;30:1065–8. [41] Li Z, Ranade A, Zhao C. Pathologic findings of follow-up surgical excision for radial scar on breast core needle biopsy. Hum Pathol 2016;48:76–80. http://dx.doi.org/ 10.1016/j.humpath.2015.06.028. [42] Resetkova E, Edelweiss M, Albarracin CT, et al. Management of radial sclerosing lesions of the breast diagnosed using percutaneous vacuum-assisted core needle biopsy: recommendations for excision based on seven years' of experience at a single institution. Breast Cancer Res Treat 2011;127:335–43. [43] Sohn VY, Causey MW, Steele SR, et al. The treatment of radial scars in the modern era: surgical excision is not required. Am Surg 2010;76:522–5.
Contents lists available at ScienceDirect
Annals of Diagnostic Pathology
Surgical excision outcome after radial scar without atypical proliferative lesion on breast core needle biopsy: a single institutional analysis☆ Yanjun Hou, MD, PhD a, Shveta Hooda, MD b, Zaibo Li, MD, PhD a,⁎ a b
Department of Pathology, Ohio State University Wexner Medical Center, Columbus, OH 43210 Department of Pathology, Ohio Valley Medical Center, Wheeling, WV 26003
a r t i c l e
i n f o
Available online xxxx Keywords: Radial scar Breast cancer Ductal carcinoma in-situ Atypical ductal hyperplasia
a b s t r a c t Radial scar (RS) has been recognized as a risk factor for developing breast cancer, and excision is recommended for patients with RS identified on core needle biopsy (CNB). However, recent literatures suggest that the increased risk may be caused by concurrent proliferative lesions on the biopsy, rather than radial scar itself. In this study, we investigated the follow-up excision (FUE) results for patients with RS on CNB with no history of a prior or a concurrent breast cancer or atypical proliferative lesions (APLs). A total of 113 RS cases including 32 cases with APLs or carcinoma and 81 cases without APLs on CNB were included in this study. Forty cases (49%) without APLs had FUE. No significant difference in radiologic and clinical findings was identified between cases with FUEs and cases without FUEs. Of the 40 cases with FUE, 9 cases (22.5%) were upgraded including 3 atypical ductal hyperplasias, 4 lobular neoplasias, 1 flat epithelial atypia, and 1 atypical apocrine adenosis. However, no case was upgraded to invasive carcinoma or ductal carcinoma in situ. All cases with mammotome CNBs were not upgraded. Our data suggest that conservative follow-up with imaging rather than surgical excisions may be more appropriate for patients with only RS on biopsy, especially for patients with mammotome CNBs. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Radial scar (RS) is characterized by a stellate configuration of fibroelastic core with entrapped ducts and lobules and is also referred as radial sclerosing lesion or complex sclerosing lesion [1,2]. The radiologic appearance of RS overlaps that of invasive carcinoma (IC), and it poses a challenge to radiologists [3-6]. RS has been found to be associated with both benign proliferative lesions and atypical/malignant proliferative lesions [7-12]. The management of patients with RS detected on image-guided core needle biopsies (CNBs) is still a matter of debate because the data from previous studies are conflicting in regard to whether these lesions are independent risk factors for malignancy [7-30]. However, many previous studies did not take into account patient's prior history of breast cancer or atypical proliferative lesions (APLs), which are associated with an increased risk for future breast carcinoma development [31,32]. Therefore, the increased rates of upgrade to malignancy on surgical excision after RS on CNBs found in some studies might be related to coexisting APLs or breast cancers. The aim of our study was to evaluate the surgical excision outcome of a consecutive
☆ Disclosure: All authors have no potential conflict of interest. ⁎ Corresponding author at: Department of Pathology, Ohio State University Wexner Medical Center, 410 W. 10th Ave, Columbus, OH 43210. Tel.: +1 614 366 4859; fax: +1 614 293 4715. E-mail address: [email protected] (Z. Li). http://dx.doi.org/10.1016/j.anndiagpath.2015.11.004 1092-9134/© 2015 Elsevier Inc. All rights reserved.
series of RS patients without any history of a prior or concurrent breast cancer or APLs over a period of 12 years at a single institution.
2. Methods and materials 2.1. Patient selection and data collection After institutional review board approval at The Ohio State University, a pathology archive database search was performed for a period of 12 years (January 2003 to December 2014). Although majority of the biopsies were performed using 14-gauge needles with 3 to 5 passes, some of the biopsies were done with 8-gauge mammotome needles. Biopsy specimens were received in 10% formalin and embedded in paraffin. Four levels of sections for each tissue block were obtained and stained with standard hematoxylin and eosin. Surgical excision specimens were also fixed in 10% formalin and embedded in paraffin. Most excisional specimens were submitted entirely for histologic examination. Radial scar was diagnosed based on the following criteria: a stellate lesion with central fibroelastotic zone of basophilic elastic material and radiating fibrous bands and dilated or compressed tubular structures with 2 cell layers (Fig. 1A). Cases were considered to be upgraded if follow-up excision (FUE) showed flat epithelial atypia (FEA) (Fig. 1B), atypical ductal hyperplasia (ADH) (Fig. 1C), and lobular neoplasia (LN) (atypical lobular hyperplasia [ALH] and lobular carcinoma in situ [LCIS]) (Fig. 1D).
36
Y. Hou et al. / Annals of Diagnostic Pathology 21 (2016) 35–38
Fig. 1. Representative images of RS, ADH, LCIS, and IC. Radial scar (A); FEA (B); ADH (C); LCIS (D).
A total of 113 cases were interpreted as RS with or without other benign or malignant lesions. Thirty-two cases with a diagnosis of RS were excluded from this study due to concurrent or prior diagnosis of FEA, ADH, LN, ductal carcinoma in situ (DCIS), or IC. The details are summarized in Table 1. The remaining 81 cases of radial scar without any other concurrent or prior APLs were included in this study. Medical records were reviewed for patient age, symptoms, and radiologic results (microcalcification, distortion, mass, etc). The American College of Radiology Breast Imaging, Reporting and Data System (BI-RADS) score was also recorded.
2.2. Statistical analysis Data were entered using Microsoft Excel spreadsheet software (Microsoft, Redmond, WA). Mean, median, and SD were calculated. Fisher exact test was used to compare the difference. All the analyses were done using the SAS 9.3 system (SAS Institute, Cary, NC), and P b .05 was considered statistically significant.
Table 1 Excluded cases: 32 due to concurrent or prior history of atypical proliferative lesions or carcinomas.
FEA ADH LN (ALH and LCIS) DCIS IDC Total Abbreviation: IDC, invasive ductal carcinoma.
Concurrent
Prior
4 5 6 7 7 29
0 0 0 2 1 3
3. Results The mean age of all patients (81 cases) in this study was 52.6 years (range, 24-75 years). All patients were rendered a BI-RADS score of 4 (suspicious abnormality: a biopsy should be considered) on mammography before CNBs. Biopsy methods included ultrasound guided (47 cases) and stereotactic guided (34 cases). Microcalcification was detected in 42 patients including 26 (65%) in cases with FUE and 16 (39%) in cases without FUE. Forty-nine cases with distortion or mass on radiologic imaging were deemed as targeted lesions, including 18 (45%) in cases with FUE and 31 (76%) in cases without FUE. Eight-gauge mammotome core biopsy was performed in 18 cases, including 8 in cases with FUE and 10 in cases without FUE (Table 2). Follow-up excision was performed in 40 cases (49%), and the other 41 cases did not have any FUE. Significantly more cases with microcalcification and fewer cases with distortion/mass were found in the group with FUE than in the group without FUE, indicating that surgical excision was less likely performed for targeted lesions (distortion/mass lesions) (Table 2). Significant lesions on FUE were divided into 5 categories: IC, DCIS, ADH (with/without LN), LN alone, and FEA. Of the 40 cases with RS on
Table 2 Age and radiological findings of cases with/without FUE.
Average age BI-RADS ≥4 Microcalcification Distortion/mass Mammotome Bx
Cases with FUE ex: n = 40
Cases without FUE ex: n = 41
Total, n = 81
P
53.2 (39-70) 40 (100%) 26 (65%) 18 (45%) 8 (20%)
52.0 (24-75) 41 (100%) 16 (39%) 31 (76%) 10 (24%)
52.6 (24-75) 81 (100%) 42 (52%) 49 (60%) 18 (22%)
NS NS .02 .005 NS
Note: Some cases have overlapping radiologic findings. Abbreviations: NS, not statistically significant; Bx, biopsy.
Y. Hou et al. / Annals of Diagnostic Pathology 21 (2016) 35–38 Table 3 Significant lesions found on FUE in patients with RS diagnosed on CNBs. Lesions
Case no.
%
ADH AAA LN FEA Cases with upgrade Cases without upgrade Total
3 1 4 1 9 31 40
7.5% 2.5% 10% 2.5% 22.5% 77.5% 100.00%
CNB, no IC or DCIS was identified on FUE. Nine cases (22.5%) were upgraded on FUEs, including 3 ADH, 4 LN, 1 FEA and 1 atypical apocrine adenosis (AAA) (Table 3). Next, the demographic features and radiologic findings were evaluated for any significant difference between cases with an upgrade and the cases without an upgrade. The only variable with a significant difference between these 2 groups is the mammotome biopsy, which was performed only in the group without upgrade. All other variables including age and radiologic findings did not show any significant difference between these 2 groups (Table 4). 4. Discussion Radial scar occurs in 8% to 16% of women and in up to 42% of the contralateral breast from patients with a history of invasive ductal carcinoma based on autopsy studies [33-35]. However, the true relationship between RS and malignancy is difficult to assess. During the pre-CNB era (no routine presurgical CNB), the radiologically detected RS associated malignancy rate ranged from 10% to 41% on lesion excision [7,10,11,36-40]. However, the underlying RS-associated malignancy rate does not address the question of how to manage patients with RS identified on CNBs currently, especially when no current/prior atypia/ cancer is present. Several studies had investigated this issue during last decade, and 1 recent meta-analysis demonstrated an overall malignancy upgrade rate of 10.5% for CNB-confirmed RS on excision, including 27% for RS with epithelial atypia (27%) vs 7.5% for RS without atypia [13,14,19,30]. One recent study with 53 CNB-confirmed RS cases demonstrated a careful radiologic-pathologic correlation lowered the malignancy upgrade rate to 2% on excision [30]. Our recent study from University of Pittsburgh Magee Womens Hospital also demonstrated a low malignancy upgrade rate of 0.9% on excision in CNB-confirmed RS patients without any concurrent/prior APL/cancer [41]. Current study from an academic medical center demonstrated no malignancy upgrade on FUE after RS on CNBs without current/prior atypia/cancer. The reason leading to nonmalignancy upgrade in our study may be case selection bias. All cases with current/prior history of breast cancer or APLs (including ADH, LN, and FEA) were excluded from current study cohort. Our recent study and other studies have revealed that history of breast cancer or APLs plays an important role in subsequent development of breast carcinoma or APLs [31,32]. Therefore, the high malignancy upgrade rates in previous studies may be caused by the presence of history of breast cancer/atypia in some cases from their study cohorts. In consistent with this hypothesis, a Table 4 Demographic, clinical, and radiologic findings in cases with/without upgrade on FUE.
Average age (range) (y) Radiologic findings Microcalcification Distortion/Mass BI-RADS ≥4 Mammotome Bx
Not upgraded (n = 31)
Upgraded (n = 9)
Total (n = 40)
P
53.2 (39-69)
53.4 (41-70)
53.2 (39-70)
NS
21 (67.7%) 13 (28.8%) 31 (100%) 8 (26%)
5 (57.8%) 5 (25.0%) 9 (100%) 0 (0%)
26 (65.0%) 18 (45.0%) 40 (100%) 8 (20%)
NS NS NS .044
37
large study from Vanderbilt University with a long-term follow-up demonstrated that the presence of RS in a benign breast biopsy mildly elevated the risk of IC risk, but this risk was largely attributed to the coexistent proliferative disease, especially atypical hyperplasia [12]. Furthermore, both study from Memorial Sloan Kettering Cancer Center and our recent study from University of Pittsburgh Magee Womens Hospital found similar low malignancy upgrade rate (2% and 0.9%, respectively) on FUE for RS without atypia on CNBs [30,41]. Although no malignancy was identified in current study, the upgrade rate to APLs (including ADH, LN, and FEA) was considerably high (22.5%), which was consistent with the results from Memorial Sloan Kettering Cancer Center study (22.6%) and our recent study from University of Pittsburgh Magee Womens Hospital (26%) [30,41]. Multiple variables were investigated to identify possible factors that would predict the presence APLs on FUE, and the only variable with a significant relationship to the upgrade was the absence of mammotome biopsies, indicating the importance of larger biopsies in reducing falsenegative rate with CNBs. Knowing the outcomes of patients who did not undergo FUE for their RSs on CNBs is important for the optimal management of these patients. Approximately half of RS patients did not undergo FUEs in our study cohort. By searching our pathology archive data, we did not find any subsequent malignant lesions during a follow-up period of up to 11 years. The findings were consistent with previous study by Resetkova et al [42], which found no subsequent carcinomas at a median follow-up of 29 months in 46 patients who did not have their RS excised. In the study of Brenner et al [16], no carcinoma was found in 55 patients who did not undergo excision with a follow-up of at least 48 months. Similarly, Sohn et al [43] did not find any carcinoma in 10 patients with a mean follow-up of 47 months. Therefore, it may be acceptable to closely monitor patients by radiology if a surgical excision is not desired. In summary, no malignancy was identified on excision in CNBconfirmed RS patients without concurrent/prior atypia/cancer, although APLs were identified in a considerable portion of patients (22.5%). Moreover, all patients with mammotome biopsy-confirmed RS did not find any upgrade lesions. Because the management for atypical lesions identified on excision is just follow-up, our data suggest that conservative followup with imaging rather than surgical excisions may be more appropriate for these patients, especially for patients with mammotome biopsy. References [1] Hamperl H. Strahlige narben und obliterienrende mastopathie: Beitrage Zur pathologischen histoloie der mamme. Virchows Arch A Pathol Anat Histol 1975; 369:55–68. [2] Eusebi V, Millis RR. Epitheliosis, infiltrating epitheliosis, and radial scar. Semin Diagn Pathol 2010;27:5–12. [3] Meyer JE, Christian RL, Lester SC, et al. Evaluation of nonpalpable solid breast masses with stereotaxic large-needle core biopsy using a dedicated unit. Am J Roentgenol 1996;167:179–82. [4] Ciatto S, Morrone D, Catarzi S, et al. Radial scars of the breast: review of 38 consecutive mammographic diagnoses. Radiology 1993;187:757–60. [5] Orel SG, Evers K, Yeh IT, et al. Radial scar with microcalcifications: radiologicpathologic correlation. Radiology 1992;183:479–82. [6] Mitnick JS, Vazquez MF, Harris MN. Differentiation of radial scar from scirrhous carcinoma of the breast: mammographic-pathologic correlation. Radiology 1989;173: 697–700. [7] Sloane JP, Mayers MM. Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age. Histopathology 1993;23:225–31. [8] Jacobs TW, Byrne C, Colditz G, et al. Radial scars in benign breast-biopsy specimens and the risk of breast carcinoma. N Engl J Med 1999;340:430–6. [9] Mokbel K, Price RK, Mostafa A, et al. Radial scar and carcinoma of the breast: microscopic findings in 32 cases. Breast 1999;8:339–42. [10] Farshid G, Rush G. Assessment of 142 stellate lesions with imaging features suggestive of radial scar discovered during population-based screening for breast cancer. Am J Surg Pathol 2004;28:1626–31. [11] Fasih T, Jain M, Shrimankar J, Staunton M, Hubbard J, Griffith CD. All radial scars/ complex sclerosing lesions seen on breast screening mammograms should be excised. Eur J Surg Oncol 2005;31:1125–8. [12] Sanders ME, Page DL, Simpson JF, et al. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Carcinoma 2006;106:1453–61.
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