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ORIGINAL RESEARCH
Simple and Complex Fibroadenomas Are There Any Distinguishing Sonographic Features? Joana Pinto, MD, Ana Teresa Aguiar, MD, Hálio Duarte, MD, Filipa Vilaverde, MD, Ângelo Rodrigues, MD, José Luís Krug, MD
Objectives—Complex fibroadenomas are fibroadenomas harboring 1 or more complex pathologic features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm. No sonographic features have been clearly defined for the distinction of simple fibroadenomas from complex ones, which are associated with an increased cancer risk. We aimed to evaluate the accuracy of sonographic features for the prediction of complexity in fibroadenomas. Methods—A total of 252 fibroadenomas were found at consecutive percutaneous needle or excisional surgical biopsy. Sixty-three were excluded because their respective imaging examinations were not recorded on digital support and consequently were not available. According to histologic diagnoses, fibroadenomas (n = 189) were classified into simple (n = 159) and complex (n = 30). The size, number, and sonographic features were assessed, and their respective accuracy rates for prediction of complexity were analyzed. Results—All patients were women. Complex fibroadenomas presented more frequently as solitary nodules (n = 21 [70%]) and were significantly larger than simple fibroadenomas (1.9 versus 1.3 cm; P = .009). Image predictors of complexity were an irregular shape (P < .001), noncircumscribed contours (indistinct, angular, microlobulated, or spiculated; P < .001), a complex echo structure (P < .001), the presence of microcalcifications (P = .002), and posterior acoustic enhancement (P < .001). By logistic multivariate regression, a complex echo structure (odds ratio [OR], 9.5; 95% confidence interval [CI], 2.8–32.3), noncircumscribed contours (OR, 3.7; 95% CI, 1.1–12.8), and posterior acoustic enhancement (OR, 4.0; 95% CI, 1.1–14.6) were independent predictors of complexity. Receiver operating characteristic curve analysis showed that a complex echo structure was the most accurate sonographic finding for identification of complex fibroadenomas (area under the curve, 0.74). Received April 19, 2013, from the Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal (J.P., F.V., J.L.K.); and Instituto Português de Oncologia do Porto, Porto, Portugal (A.T.A., H.D., Â.R.). Revision requested June 5, 2013. Revised manuscript accepted for publication July 13, 2013. Address correspondence Joana Pinto, MD, Centro Hospitalar de Entre o Douro e Vouga, Rua Dr Cândido de Pinho, 4520-211 Santa Maria da Feira, Portugal. E-mail: [email protected] Abbreviations
BI-RADS, Breast Imaging Reporting and Data System doi:10.7863/ultra.33.3.415
Conclusions—Certain sonographic features are associated with complex fibroadenomas and can help the radiologist decide which ones require biopsy. Key Words—breast imaging; breast ultrasound; complex fibroadenomas; simple fibroadenomas; sonography
F
ibroadenomas are benign fibroepithelial tumors that develop in the terminal duct lobular unit.1,2 They are common lesions, particularly in women in their 20s and 30s.3 Complex fibroadenomas are a subtype of fibroadenomas harboring 1 or more complex pathological features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm.4 In the largest study conducted so far, Dupont et al5 concluded that the relative risk of developing invasive breast cancer in women with complex fibroadenomas was 3.1 times that of the general pop-
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:415–419 | 0278-4297 | www.aium.org
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Pinto et al—Sonographic Features of Simple and Complex Fibroadenomas
ulation, and some authors recommend surgical removal of complex fibroadenomas shortly after the diagnosis is made.6 In spite of this apparent increased risk of cancer, the imaging findings for complex fibroadenomas have rarely been studied, and no imaging features have been clearly defined for the distinction of simple fibroadenomas from complex ones. We aimed to evaluate the incidence and accuracy of several sonographic features, individually and in association, for the prediction of complexity in fibroadenomas.
Materials and Methods This retrospective study was approved by the Institutional Ethics Committee of our institution. On the basis of results of core needle or excisional surgical biopsy, we retrospectively identified 252 consecutive patients between February 2011 and August 2012 with the diagnosis of fibroadenoma. Of these, 63 were excluded because their imaging examinations were obtained before the existence of a picture archiving and communication system and consequently were not available on digital records. According to histologic diagnoses, the cases were classified into simple (n = 159) and complex (n = 30) fibroadenomas. At pathologic examination, fibroadenomas were diagnosed according to the definition of a benign fibroepithelial neoplasm,1 and complex fibroadenomas were identified in the presence of 1 or more of the following features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm.4 As our institution is a reference center for oncologic treatment, patients who are referred to our breast unit have already had an imaging screening examination with an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS)7 classification of at least category 3. Most patients with solid lesions (BI-RADS categories 3 and 4) underwent sonographically guided biopsy. The diagnosis of fibroadenoma was achieved by core needle biopsy using a 14-gauge cutting needle with an average of 4 specimens (range, 3–6 specimens) under sonographic guidance or excisional surgical biopsy of the nodule, according to the breast surgeon’s choice and the patients’ age, mass size, and other characteristics. The diagnosis of a complex fibroadenoma was obtained on the basis of core biopsy alone in 11 patients (36.7%), core and then excisional biopsy in 12 (40%), and excisional biopsy alone in 7 (23.3%). Sonography was performed with a linear transducer (7– 12 MHz; Xario Corevision Pro; Toshiba Medical Systems Co, Ltd, Tokyo, Japan). Patient files were consulted retrospectively to access patient demographic characteristics. Imaging studies were reviewed on a picture archiving and
416
communication system by a radiologist with 10 years of breast imaging experience to determine lesion characteristics. General sonographic appearances of all fibroadenomas were evaluated, including the size and number of nodules, and classified according to BI-RADS sonographic descriptors,7,8 considering the shape, margins, echo structure, orientation (parallel or not parallel to the skin surface), posterior acoustic features, and presence of calcifications (macrocalcifications or microcalcifications). Because patients that underwent biopsy did not systematically undergo mammography, we did not analyze mammographic features of the lesions. For statistical analysis, the SPSS version 17.0 statistical software package (IBM Corporation, Armonk, NY) was used. The χ2 test was used to compare categorical variables, expressed as percentages. Continuous variables, expressed as means, were compared using the Student t test for those with a normal distribution and the Mann-Whitney test otherwise. Multivariate stepwise logistic regression analysis was used to identify imaging features that were independently associated with the diagnosis of complex fibroadenoma. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of several sonographic features, isolated and in association. All P values were 2 sided, and P < .05 was considered statistically significant.
Results Of the 189 cases finally considered, 159 (84%) were simple fibroadenomas, and 30 (16%) were complex fibroadenomas. All patients sampled were women. Complex fibroadenomas were larger than simple fibroadenomas (1.9 versus 1.3 cm; P = .009). The mean age in the simple fibroadenoma group was 45 years (range, 19–84 years), and in the complex fibroadenoma group, it was 42 years (range, 22–70 years). There was no significant difference regarding the mean age between the groups (P = .255). The sonographic features of the nodules are shown in Table 1. Features that were present more frequently in complex than simple fibroadenomas included an irregular shape (P < .001), noncircumscribed contours (including indistinct, microlobulated, angular, and spiculated; P < .001; Figure 1), and a complex echo structure (presence of both anechoic and echogenic components; P < .001). The presence of posterior acoustic enhancement (P < .001; Figure 2) and microcalcifications (P = .002) were more common in complex fibroadenomas. On the contrary, both simple and complex fibroadenomas presented more frequently as single nodules (64% versus 70%) and with a parallel orientation to the skin surface (75.5% versus 73.3%).
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Pinto et al—Sonographic Features of Simple and Complex Fibroadenomas
Complex fibroadenomas were first described in 1994 by Dupont et al,5 who reported that 22% of proven fibroadenomas were complex. In our study, we found that 16% of all biopsy-proven fibroadenomas were complex. In our study, patients with complex fibroadenomas had a mean age of 42 years, a result concordant with the current literature, whereas patients with simple fibroadenomas
were much older than expected from previous studies.9 This discrepancy may have been due to a selection bias, as our institution is a tertiary referral oncologic hospital receiving patients with the highest risk, including older people. Young patients with recently noted nodules and no suspicious imaging findings may not be referred to our center or undergo biopsy but may receive follow-up instead. The mean size of the complex fibroadenomas tended to be in agreement with the findings of Sklair-Levy et al and was smaller than the average size reported in the literature for simple fibroadenomas.10 This finding is probably related to the fact that fibroadenomas tend to regress with age, becoming smaller over time and probably acquiring complex histopathologic characteristics during this period.11 In addition, simple fibroadenomas were smaller than expected.10 The fact that our patients with simple fibroadenomas were older than the usual population with simple fibroadenomas could explain why simple fibroadenomas were smaller than expected.
Table 1. Sonographic Features of Simple and Complex Fibroadenomas
Figure 1. Complex fibroadenoma (arrow) with noncircumscribed contours in a 43-year-old woman.
The multivariate stepwise logistic regression analysis showed that a complex echo structure, noncircumscribed contours, and posterior acoustic enhancement were independently associated with complex fibroadenomas (Table 2).Figure 3 shows the receiver operating characteristiccurve of several sonographic features for the diagnostic of complex fibroadenomas. We can observe that the most accurate finding for identification of complex fibroadenomas was the complex echo pattern of the nodule (area under the curve, 0.74).
Discussion
Sonographic Feature Number Single Multiple Shape Oval Round Irregular Contours Circumscribed Noncircumscribed Echo structure Anechoic Hyperechoic Hypoechoic Isoechoic Complex Posterior acoustic features None Enhancement Shadowing Combined pattern Orientation Parallel Not parallel Calcifications Macrocalcifications Microcalcifications Not detected
Simple
Complex
P
102 (64) 57 (36)
21 (70) 9 (30)
116 (73) 37 (23.3) 6 (3.8)
16 (53.3) 6 (20) 8 (26.7)
NS NS NS NS NS
ORIGINAL RESEARCH
Simple and Complex Fibroadenomas Are There Any Distinguishing Sonographic Features? Joana Pinto, MD, Ana Teresa Aguiar, MD, Hálio Duarte, MD, Filipa Vilaverde, MD, Ângelo Rodrigues, MD, José Luís Krug, MD
Objectives—Complex fibroadenomas are fibroadenomas harboring 1 or more complex pathologic features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm. No sonographic features have been clearly defined for the distinction of simple fibroadenomas from complex ones, which are associated with an increased cancer risk. We aimed to evaluate the accuracy of sonographic features for the prediction of complexity in fibroadenomas. Methods—A total of 252 fibroadenomas were found at consecutive percutaneous needle or excisional surgical biopsy. Sixty-three were excluded because their respective imaging examinations were not recorded on digital support and consequently were not available. According to histologic diagnoses, fibroadenomas (n = 189) were classified into simple (n = 159) and complex (n = 30). The size, number, and sonographic features were assessed, and their respective accuracy rates for prediction of complexity were analyzed. Results—All patients were women. Complex fibroadenomas presented more frequently as solitary nodules (n = 21 [70%]) and were significantly larger than simple fibroadenomas (1.9 versus 1.3 cm; P = .009). Image predictors of complexity were an irregular shape (P < .001), noncircumscribed contours (indistinct, angular, microlobulated, or spiculated; P < .001), a complex echo structure (P < .001), the presence of microcalcifications (P = .002), and posterior acoustic enhancement (P < .001). By logistic multivariate regression, a complex echo structure (odds ratio [OR], 9.5; 95% confidence interval [CI], 2.8–32.3), noncircumscribed contours (OR, 3.7; 95% CI, 1.1–12.8), and posterior acoustic enhancement (OR, 4.0; 95% CI, 1.1–14.6) were independent predictors of complexity. Receiver operating characteristic curve analysis showed that a complex echo structure was the most accurate sonographic finding for identification of complex fibroadenomas (area under the curve, 0.74). Received April 19, 2013, from the Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal (J.P., F.V., J.L.K.); and Instituto Português de Oncologia do Porto, Porto, Portugal (A.T.A., H.D., Â.R.). Revision requested June 5, 2013. Revised manuscript accepted for publication July 13, 2013. Address correspondence Joana Pinto, MD, Centro Hospitalar de Entre o Douro e Vouga, Rua Dr Cândido de Pinho, 4520-211 Santa Maria da Feira, Portugal. E-mail: [email protected] Abbreviations
BI-RADS, Breast Imaging Reporting and Data System doi:10.7863/ultra.33.3.415
Conclusions—Certain sonographic features are associated with complex fibroadenomas and can help the radiologist decide which ones require biopsy. Key Words—breast imaging; breast ultrasound; complex fibroadenomas; simple fibroadenomas; sonography
F
ibroadenomas are benign fibroepithelial tumors that develop in the terminal duct lobular unit.1,2 They are common lesions, particularly in women in their 20s and 30s.3 Complex fibroadenomas are a subtype of fibroadenomas harboring 1 or more complex pathological features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm.4 In the largest study conducted so far, Dupont et al5 concluded that the relative risk of developing invasive breast cancer in women with complex fibroadenomas was 3.1 times that of the general pop-
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:415–419 | 0278-4297 | www.aium.org
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Pinto et al—Sonographic Features of Simple and Complex Fibroadenomas
ulation, and some authors recommend surgical removal of complex fibroadenomas shortly after the diagnosis is made.6 In spite of this apparent increased risk of cancer, the imaging findings for complex fibroadenomas have rarely been studied, and no imaging features have been clearly defined for the distinction of simple fibroadenomas from complex ones. We aimed to evaluate the incidence and accuracy of several sonographic features, individually and in association, for the prediction of complexity in fibroadenomas.
Materials and Methods This retrospective study was approved by the Institutional Ethics Committee of our institution. On the basis of results of core needle or excisional surgical biopsy, we retrospectively identified 252 consecutive patients between February 2011 and August 2012 with the diagnosis of fibroadenoma. Of these, 63 were excluded because their imaging examinations were obtained before the existence of a picture archiving and communication system and consequently were not available on digital records. According to histologic diagnoses, the cases were classified into simple (n = 159) and complex (n = 30) fibroadenomas. At pathologic examination, fibroadenomas were diagnosed according to the definition of a benign fibroepithelial neoplasm,1 and complex fibroadenomas were identified in the presence of 1 or more of the following features: epithelial calcifications, apocrine metaplasia, sclerosing adenosis, and cysts larger than 3 mm.4 As our institution is a reference center for oncologic treatment, patients who are referred to our breast unit have already had an imaging screening examination with an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS)7 classification of at least category 3. Most patients with solid lesions (BI-RADS categories 3 and 4) underwent sonographically guided biopsy. The diagnosis of fibroadenoma was achieved by core needle biopsy using a 14-gauge cutting needle with an average of 4 specimens (range, 3–6 specimens) under sonographic guidance or excisional surgical biopsy of the nodule, according to the breast surgeon’s choice and the patients’ age, mass size, and other characteristics. The diagnosis of a complex fibroadenoma was obtained on the basis of core biopsy alone in 11 patients (36.7%), core and then excisional biopsy in 12 (40%), and excisional biopsy alone in 7 (23.3%). Sonography was performed with a linear transducer (7– 12 MHz; Xario Corevision Pro; Toshiba Medical Systems Co, Ltd, Tokyo, Japan). Patient files were consulted retrospectively to access patient demographic characteristics. Imaging studies were reviewed on a picture archiving and
416
communication system by a radiologist with 10 years of breast imaging experience to determine lesion characteristics. General sonographic appearances of all fibroadenomas were evaluated, including the size and number of nodules, and classified according to BI-RADS sonographic descriptors,7,8 considering the shape, margins, echo structure, orientation (parallel or not parallel to the skin surface), posterior acoustic features, and presence of calcifications (macrocalcifications or microcalcifications). Because patients that underwent biopsy did not systematically undergo mammography, we did not analyze mammographic features of the lesions. For statistical analysis, the SPSS version 17.0 statistical software package (IBM Corporation, Armonk, NY) was used. The χ2 test was used to compare categorical variables, expressed as percentages. Continuous variables, expressed as means, were compared using the Student t test for those with a normal distribution and the Mann-Whitney test otherwise. Multivariate stepwise logistic regression analysis was used to identify imaging features that were independently associated with the diagnosis of complex fibroadenoma. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of several sonographic features, isolated and in association. All P values were 2 sided, and P < .05 was considered statistically significant.
Results Of the 189 cases finally considered, 159 (84%) were simple fibroadenomas, and 30 (16%) were complex fibroadenomas. All patients sampled were women. Complex fibroadenomas were larger than simple fibroadenomas (1.9 versus 1.3 cm; P = .009). The mean age in the simple fibroadenoma group was 45 years (range, 19–84 years), and in the complex fibroadenoma group, it was 42 years (range, 22–70 years). There was no significant difference regarding the mean age between the groups (P = .255). The sonographic features of the nodules are shown in Table 1. Features that were present more frequently in complex than simple fibroadenomas included an irregular shape (P < .001), noncircumscribed contours (including indistinct, microlobulated, angular, and spiculated; P < .001; Figure 1), and a complex echo structure (presence of both anechoic and echogenic components; P < .001). The presence of posterior acoustic enhancement (P < .001; Figure 2) and microcalcifications (P = .002) were more common in complex fibroadenomas. On the contrary, both simple and complex fibroadenomas presented more frequently as single nodules (64% versus 70%) and with a parallel orientation to the skin surface (75.5% versus 73.3%).
J Ultrasound Med 2014; 33:415–419
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Pinto et al—Sonographic Features of Simple and Complex Fibroadenomas
Complex fibroadenomas were first described in 1994 by Dupont et al,5 who reported that 22% of proven fibroadenomas were complex. In our study, we found that 16% of all biopsy-proven fibroadenomas were complex. In our study, patients with complex fibroadenomas had a mean age of 42 years, a result concordant with the current literature, whereas patients with simple fibroadenomas
were much older than expected from previous studies.9 This discrepancy may have been due to a selection bias, as our institution is a tertiary referral oncologic hospital receiving patients with the highest risk, including older people. Young patients with recently noted nodules and no suspicious imaging findings may not be referred to our center or undergo biopsy but may receive follow-up instead. The mean size of the complex fibroadenomas tended to be in agreement with the findings of Sklair-Levy et al and was smaller than the average size reported in the literature for simple fibroadenomas.10 This finding is probably related to the fact that fibroadenomas tend to regress with age, becoming smaller over time and probably acquiring complex histopathologic characteristics during this period.11 In addition, simple fibroadenomas were smaller than expected.10 The fact that our patients with simple fibroadenomas were older than the usual population with simple fibroadenomas could explain why simple fibroadenomas were smaller than expected.
Table 1. Sonographic Features of Simple and Complex Fibroadenomas
Figure 1. Complex fibroadenoma (arrow) with noncircumscribed contours in a 43-year-old woman.
The multivariate stepwise logistic regression analysis showed that a complex echo structure, noncircumscribed contours, and posterior acoustic enhancement were independently associated with complex fibroadenomas (Table 2).Figure 3 shows the receiver operating characteristiccurve of several sonographic features for the diagnostic of complex fibroadenomas. We can observe that the most accurate finding for identification of complex fibroadenomas was the complex echo pattern of the nodule (area under the curve, 0.74).
Discussion
Sonographic Feature Number Single Multiple Shape Oval Round Irregular Contours Circumscribed Noncircumscribed Echo structure Anechoic Hyperechoic Hypoechoic Isoechoic Complex Posterior acoustic features None Enhancement Shadowing Combined pattern Orientation Parallel Not parallel Calcifications Macrocalcifications Microcalcifications Not detected
Simple
Complex
P
102 (64) 57 (36)
21 (70) 9 (30)
116 (73) 37 (23.3) 6 (3.8)
16 (53.3) 6 (20) 8 (26.7)
NS NS NS NS NS
