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Original Research |
1 Department of Radiology, Hadassah-Hebrew University Medical Center, Kiryat
Hadassah, POB 12000, Jerusalem 91120, Israel.
2 Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem,
Israel.
3 Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem,
Israel.
Received January 4, 2007;
accepted after revision August 9, 2007.
Address correspondence to M. Sklair-Levy
(mirisl{at}hadassah.org.il)
Abstract
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MATERIALS AND METHODS. Complex fibroadenomas were diagnosed in 63 of 401 fibroadenomas (15.7%) found at consecutive percutaneous needle or excisional surgical biopsy. We evaluated the clinical and imaging presentations of complex fibroadenomas; compared pathology at core and excisional biopsy; and contrasted age, pathology, and size of complex and simple fibroadenomas using the Student's t test.
RESULTS. Patients with complex lesions were 18.5 years older (median age, 47 years; range, 21-69 years) than patients with noncomplex fibroadenomas (median age, 28.5 years; range, 12-86 years) (p < 0.001). Complex fibroadenomas were half the size (average, 1.3 cm; range, 0.5-2.6 cm) of noncomplex fibroadenomas (average, 2.5 cm; range, 0.5-7.5 cm) (p < 0.001). Only one malignancy, an invasive lobular carcinoma, was found in 63 complex fibroadenomas (1.6%). This patient had atypical lobular hyperplasia at core needle biopsy.
CONCLUSION. Approximately 16% of fibroadenomas are complex. Complex fibroadenomas are smaller and appear at an older age. At a mean follow-up of 2 years, we found a low incidence of malignancy in complex fibroadenomas. Women with complex fibroadenomas may therefore be managed with a conservative approach, similar to the approach now recommended for women with simple fibroadenomas.
Keywords: atypical lobular hyperplasia breast cancer breast sonography complex fibroadenoma core needle biopsy fibroadenoma mammography
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Fibroadenoma of the breast is the most common benign breast tumor in adolescent girls and young women. Fibroadenomas may occur at any age, but peak incidence falls during the second and third decades of life [1, 2]. They are stimulated by estrogen and progesterone, pregnancy, and lactation, and they undergo atrophic changes in menopause [1]. Most often they present as palpable breast masses measuring up to 3 cm [1, 2]. The epithelial elements of a fibroadenoma can exhibit a spectrum of proliferative lesions similar to those found elsewhere in the breast [1].
Although previous studies of patients with fibroadenoma show an elevated risk of breast carcinoma compared with women of similar age in the general population [3], malignant transformation from fibroadenoma to cancer is rare [3-9]. Therefore, the established management of biopsy-proven fibroadenomas is typically conservative, with observation by serial sonography or mammography to detect growth. Only a minority of women with these lesions undergo surgical excision [2, 3, 10].
The risk of developing breast carcinoma was found to be higher in patients with complex fibroadenoma than in those with noncomplex fibroadenomas. Dupont et al. [8] found that the cumulative risk of invasive breast carcinoma in women with complex fibroadenomas was 3.1 times that of women in the general population, compared with a relative risk of 1.89 times in women with noncomplex fibroadenomas [3].
Despite the elevated risk of malignancy, there is a lack of literature on this group of disorders, causing confusion about their management. The purpose of this study was to evaluate the incidence of complex fibroadenomas on biopsy, compare biopsy and excisional pathology, and propose decision criteria for managing patients with complex fibroadenomas of the breast.
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Women presenting to the breast imaging center are screened according to the following guidelines. All women receive a physical examination by a breast surgeon or gynecologist. Those older than 40 years undergo mammography, and women in this group with dense breasts, palpable lesions, or findings on mammography also undergo breast sonography. Women younger than 40 years begin their screening with sonography. Mammography is indicated in this group when sonography shows a suspicious finding, or when there is a palpable lesion that is not seen on sonography. MRI is performed for some women at high risk of disease.
Mammography was performed with screen-film (Mammomat 3000, Siemens Medical Solutions) until mid 2004. In mid 2004, we installed digital mammography (LoRad, Hologic). Sonography was performed using a linear transducer (7-12 MHz, ATL 3500, Philips Medical Systems).
Data on these patients, including lesion size and patient age, were retrieved retrospectively from imaging reports and patient files. Imaging studies were initially read by one of four experienced breast imaging radiologists. A single pathologist reviewed pathologic samples for all patients in the study.
We evaluated the presentation of complex fibroadenomas, including palpability, general appearance on mammography, and assessment according to the mammographic BI-RADS categories [11], and general sonographic appearance with assessment according to the sonographic BI-RADS categories. In addition, we compared core and excisional biopsy pathologic findings for complex fibroadenomas that were surgically excised after initial core needle biopsy.
Currently, most patients with solid lesions (mammography BI-RADS categories 3 or 4) are biopsied at our institution, generally using either mammography or sonography for guidance. The diagnosis for patients in this study was achieved by core needle biopsy using a 14-gauge cutting needle with an average of three specimens (range, 2-5 specimens) under sonographic guidance (41 patients, 65%), core needle biopsy using a 14-gauge cutting needle and a biopsy gun with an average of eight passes (range, 6-12 passes) under stereotactic guidance (five patients, 8%), or excisional surgical biopsy of a palpable lump (17 patients, 27%).
At pathology, fibroadenoma was diagnosed according to the accepted definition of a benign tumor arising from the epithelium and stroma of the terminal duct-lobule unit. The histologic hall-mark of fibroadenoma is concurrent proliferation of glandular or stromal elements [12]. Pathologic criteria for the diagnosis of complex fibroadenoma included one or more of the following: sclerosing adenosis, papillary apocrine metaplasia, a cyst 3 mm or larger, or epithelial calcification in a fibroadenoma [6].
Data Analysis
The relationships between age, pathologic diagnosis, and size of complex
and simple fibroadenomas were evaluated using the Student's t test. A
value for p of less than 0.05 was considered significant.
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On average, patients with complex lesions were 18.5 years older (median, 47 years; range, 21-69 years) than patients with simple fibroadenomas (median, 28.5 years; range, 12-86 years) (p < 0.001).
Presentation
In 22 patients, the fibroadenoma was seen on both mammography and
sonography, in seven on mammography alone, in 25 on sonography alone, and in
seven women the fibroadenoma was palpated and biopsied, but neither
mammography nor sonography was performed. In two patients who had a family
history of breast carcinoma with onset at an early age, the fibroadenoma was
first seen on MRI and then seen on targeted sonography. Data regarding imaging
studies performed and BI-RADS category 3 or 4 findings are summarized in
Table 1.
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A fibroadenoma was seen in 29 of 39 patients (74.4%) who underwent mammography, resulting in BI-RADS category 4 for these patients [11]. In 10 patients, the fibroadenoma was not seen on mammography due to high breast density.
On mammography, fibroadenomas presented as a well-defined mass in 23 of these 29 patients (79.3%). In four patients (13.8%), the lesion was characterized by coarse popcorn calcifications and coarse heterogeneous calcifications (Figs. 1A and 1B). In one patient, the lesion presented as a well-defined mass with associated coarse heterogeneous calcifications, and in one, as focal asymmetry.
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Diagnostic Findings on Core Needle and Excisional Biopsies
The diagnosis of complex fibroadenoma was obtained on the basis of core
needle biopsy alone in 23 women (36.5%), on the basis of core needle and then
excisional biopsy in 20 (31.7%), and on excisional biopsy alone in 20
(31.7%).
In 23 patients, the diagnosis of complex fibroadenoma was based on core needle biopsy alone, and the lesion was not excised. In 21 patients for whom follow-up was available, the mass appeared unchanged on mammography or sonography at a mean follow-up of 24.1 ± 11 months (range, 10-48 months) after biopsy. Two patients who arrived at our regional referral center from remote locations were lost to follow-up.
In 20 patients, excisional biopsy was performed after a diagnosis of complex fibroadenoma at core needle biopsy. After surgical excision, the diagnosis of complex fibroadenoma was changed to invasive lobular carcinoma in one patient and to benign phyllodes tumor in a second patient.
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The second patient was a 42-year-old woman. On routine screening mammography performed 2 years earlier, a 0.8-cm left breast lump had been detected in the lower inner quadrant. At that time, sonographically guided core needle biopsy revealed a complex fibroadenoma. The patient refused to undergo excisional biopsy and was referred for periodic follow-up. At her recent 2-year follow-up sonographic examination, the mass had grown to 1.4 cm, a 75% increase in maximum diameter; therefore, excisional biopsy was performed. Surgical pathology showed benign phyllodes tumor with extensive stromal myxoid changes (Fig. 2).
In 20 patients with a diagnosis of complex fibroadenoma, no core needle biopsy was performed, and the diagnosis was based solely on excisional biopsy.
Histology
The complex features of these fibroadenomas are summarized in
Table 2. Sclerosing adenosis
was the most frequent finding related to complexity; it was noted in 36
patients (57.1%). More than one complex feature occurred in 17 (27%) patients,
and 8% had more than two complex features.
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We found that complex fibroadenomas occurred in older patients (median age, 47 years) compared with simple fibroadenomas (median age, 28.5 years), with a highly significant p value of < 0.001. Complex fibroadenomas were also smaller than simple fibroadenomas, 1.3 cm compared with 2.5 cm, respectively (p < 0.001). This can be explained by the time needed for complex changes to develop in correlation with the older age of the patients. This finding is in agreement with other articles on the natural history of fibroadenomas, which are reported to regress and lose their cellularity with age, usually degenerating and becoming smaller over time [1, 2]. Regression of fibroadenomas may be explained by infarction, calcification, and hyalinization [2].
The appearance of fibroadenomas on imaging has been widely reported [14, 15]. In our study, we did not find mammographic or sonographic features that distinguish complex from simple fibroadenomas. Our experience confirmed reports in the literature [2] that the clinical, sonographic, and mammographic findings of complex fibroadenomas are usually similar to those of their simple counterparts. The decision whether to biopsy these breast lesions is based on BI-RADS criteria. Today most breast imaging experts biopsy all BI-RADS category 4 lesions and many BI-RADS category 3 lesions, although specific criteria vary between physicians and centers because formal guidelines have not been established. Imaging studies do not provide a clear differential diagnosis between benign and malignant lesions in many cases.
The risk that malignant transformation will occur in any fibroadenoma is low and has been reported to be 0.0125-0.3% [1, 4-9]; the risk of transformation specifically in complex fibroadenomas has not been reported. However, there are numerous reports that the general risk of developing cancer in the breast parenchyma is elevated among women with both simple and complex fibroadenomas [3-9]. Patients with fibroadenoma are 1.3-2.1 times more likely than women in the general population to develop breast cancer. Risk is further elevated for women with complex fibroadenomas, who are 3.1-3.72 times more likely to develop breast cancer than women in the general population [2, 3, 8].
Among 63 complex fibroadenomas, we found one invasive lobular carcinoma, for an incidence of 1.6%. This breast carcinoma occurred in a 64-year-old patient. The lesion shown on this patient's mammogram was considered BI-RADS category 4 because of an increased number of calcifications in comparison with her previous study, so core needle biopsy was performed. She was diagnosed with ALH at the initial core biopsy.
Lobular carcinoma in situ (LCIS) and ALH are considered marker lesions that indicate an elevated risk for developing breast carcinoma in the future [16, 17]. Foster et al. [18] recently reported that 17% of lesions in patients with LCIS or ALH on core needle biopsy were upgraded to invasive cancer or ductal carcinoma in situ (DCIS) after excision, a rate similar to the upgrade rate in patients with atypical ductal hyperplasia. On the basis of this and other reports, new guidelines for the management of patients with ALH or LCIS who are diagnosed on percutaneous core needle biopsy are emerging, suggesting excisional biopsy is appropriate when LCIS or ALH is diagnosed at core needle biopsy [18-20].
Current management of patients with histologically proven fibroadenoma varies among physicians. Especially in young women, the trend is toward more conservative management when lesions appear benign based on clinical and imaging criteria and there is a histologic diagnosis of fibroadenoma on core needle biopsy [3].
After biopsy, most of these lesions are benign. Lesions biopsied with sufficient tissue obtained, and concordant results with clinical findings and imaging, are recategorized as BI-RADS category 2. Patients having these benign lesions can return to routine screening.
For BI-RADS category 3 lesions (probably benign), the recommendation is 6-month sonographic surveillance if the lesion was seen on sonography (to avoid unnecessary ionizing radiation), or mammographic surveillance if the lesion was seen only on mammography. The relevant imaging studies are repeated at 12 months, 24 months, and in some institutions, 36 months, after which the patient goes back to routine screening for both palpable [21] and nonpalpable [22] lesions.
Fibroadenomas may fluctuate in size. In a study of acceptable growth rates for fibroadenomas at long-term follow-up, Gordon et al. [23] found that fibroadenoma volume may increase up to 16% per month in women younger than 50 years, and up to 13% per month in women 50 years old and older, or up to 20% in maximal dimension over 6 months for women of all ages. Growth of this magnitude does not necessarily indicate progression to phyllodes or malignancy; however, excision is recommended for growth beyond this limit [23].
In contrast, Greenberg et al. [2] recommend excisional biopsy for all fibroadenomas that exhibit rapid growth. In support of this approach, note that distinguishing between fibroadenoma and phyllodes on the basis of even core needle biopsy can be challenging [1]. We found phyllodes tumor in one complex fibroadenoma that exhibited rapid growth at the 2-year follow-up sonography in our study.
Literature on management of complex fibroadenomas is scarce. Carter et al. [3] found that the presence of atypia in a fibroadenoma does not increase the risk of future breast carcinoma in long-term follow-up and recommended against excisional biopsy. We found only one study, by Greenberg et al. [2], that recommends excisional biopsy shortly after diagnosis of a complex fibroadenoma.
On the basis of our experience in 63 patients, we believe that complex fibroadenomas can be managed with the same guidelines as those used for simple fibroadenomas. In the absence of atypical findings, the lesions should be monitored on mammography and sonography biannually for 2 years, and annually thereafter. When histopathology on core biopsy reveals a higher-risk lesion, such as ALH, we believe that excisional biopsy is indicated to rule out malignancy.
Our study is limited by the small number of patients with the diagnosis of complex fibroadenoma who underwent core needle or excisional biopsy for comparison, and by the incomplete follow-up of patients who underwent only core needle biopsy. We continue to follow these patients to ensure early detection of any change in lesion size.
In conclusion, in this study 15.7% of fibroadenomas were complex. They appeared at an older age and were associated with a low incidence of malignancy at a mean follow-up of 2 years. Women with complex fibroadenomas may therefore be managed with a conservative approach, similar to the approach now recommended for women with simple fibroadenomas. Larger studies are indicated to validate these findings.
Acknowledgments
We thank Shifra Fraifeld, our research associate in the Department of
Radiology, for her editorial assistance in the preparation of this
manuscript.
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