Jpn J Clin Oncol 2011;41(7)918 923 doi:10.

1093/jjco/hyr075 Advance Access Publication 21 June 2011

Preoperative Diagnosis of Ductal Carcinoma In Situ Arising Within a Mammary Fibroadenoma: A Case Report
Asako Ooe1,*, Sachiko Takahara1, Kazuhiro Sumiyoshi1, Hitoshi Yamamoto1, Eiichi Shiba1 and Jun Kawai2
1

Osaka Breast Clinic and 2Department of Pathology, Kansai Denryoku Hospital, Osaka, Japan

*For reprints and all correspondence: Asako Ooe, Osaka Breast Clinic, 1-3-4 Fukushima, Fukushima-ku, Osaka 553-0003, Japan. E-mail: obc@osaka-breast-clinic.com
Received December 6, 2010; accepted April 25, 2011

Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a broadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing broadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a denitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, conrming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type broadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses. Key words: ductal carcinoma in situ broadenoma vacuum-assisted core needle biopsy

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INTRODUCTION
Fibroadenomas of the breast are common tumors in young women. They can occur at any age, but peak incidence is typically in the second and third decades of life. Fibroadenomas are stimulated by estrogen and progesterone, pregnancy and lactation; additionally, they undergo atrophic changes during menopause. Fibroadenoma is a biphasic tumor composed of stromal and epithelial components. The epithelial elements of a broadenoma can exhibit a spectrum of proliferative lesions similar to those found elsewhere in the breast. Fibroadenomas are generally considered benign, and when a rare malignant change occurs, it usually takes the form of a sarcoma (1). Malignant changes within broadenoma are typically discovered incidentally following its excision. Here, we describe a case of ductal carcinoma in situ (DCIS) arising within a broadenoma that was diagnosed before operation. We were able to perform primary curative operation as the rst treatment.

CASE REPORT
A 46-year-old female was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. Core needle biopsies (CNBs) were obtained that showed broadenoma with borderline atypical ductal hyperplasia. She was recommended for tumor resection to obtain a denitive diagnosis at another clinic. She was referred to our clinic for further examination. The patient was evaluated for the same lump 5 years ago, at which time it was diagnosed by ultrasonography (US) as a benign tumor. She was pre-menopausal and had no history or family history of breast malignancy. Upon physical examination, the tumor (20 18 mm in size) was found to be located in the upper lateral quadrant of the right breast with an oval shape, smooth surface and clear margins. The tumor was also elastic, rm and freely movable. Axillary lymph nodes were not palpable. The left breast was unremarkable. On the basis of the physical examination results, we suspected the lump as a broadenoma. Mammography (MMG) revealed a 25 25 mm, well-

# The Author (2011). Published by Oxford University Press. All rights reserved.

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circumscribed, polygonal and relatively iso-dense mass without microcalcications or spiculations (Fig. 1). US also showed an oval and well-circumscribed heterogenous echoic mass with slit-like structures measuring 24 17 mm (Fig. 2A). The mass showed many high-echo spots and posterior acoustic echo enhancement. Doppler US showed an increase in vascularity (Fig. 2B). Magnetic resonance imaging (MRI) revealed early enhancement of the tumor following injection of gadolinium diethylenetriaminepentaacetic acid, suggesting a malignant pattern, showing well-circumscribed, polygonal and heterogeneously enhanced mass without daughter nodules or intraductal spread (Fig. 3). No distant metastasis was detected by computed tomography, and blood examination using tumor markers (carcinoembryonic antigen and carbohydrate antigen 15-3) revealed no abnormal ndings. US showed atypical ndings of broadenoma with a suspicion of malignancy. Information from the CNB was less informative; a US-guided 11 G vacuum-assisted CNB (Mammotomew) was performed to obtain additional histological information. All 12 fragment samples from the mass showed widespread and dense DCIS (cribriform and solid type) with numerous calcied bodies (Fig. 4). Intracanalicular and pericanalicular type of broadenoma in the background overlapped between the broadenoma and DCIS was found. The tumor was diagnosed as DCIS arising within a broadenoma. The stage was TisN0M0 0 (General Rules for Clinical and Pathological Recording of Breast Cancer of the Japanese Breast Cancer Society, 16 September 2008, 16th edition). The patient underwent breast-conserving surgery and sentinel lymph node biopsy. The negative margin of the resected specimen and no metastatic change in the sentinel

lymph nodes were conrmed using frozen sections. A histological map of the breast-conserving surgery specimen consisted of ve serial sections (Figs 5 and 6). The specimen grossly appeared as a circumscribed white tumor. Histopathologically, serial sections #1 3 revealed the 23 mm-diameter tumor to be a broadenoma ( peri- and intracanalicular type) (Figs 6 and 7). Sections #2 4 showed another tumor measuring 15 mm in diameter to be DCIS nuclear grade I, a mainly solid and cribriform type that dominantly grew in a broadenoma and partially extended from the mass (Figs 6 and 7). There was no focus of inltrating malignant ductal epithelial cells in the surrounding stroma, as conrmed by immunohistochemical staining for smooth muscle actin (Fig. 8). Immunohistochemical staining showed 100% estrogen receptor positivity, a 50% progesterone receptor positivity and an 11% Ki67-labeling index (56/508). After surgery, the patient was treated with radiotherapy for the remnant right breast. Adjuvant hormone therapy with 20 mg/day of tamoxifen was started after radiation. The patient was disease-free 6 months after surgery.

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DISCUSSION
A carcinoma arising within a broadenoma is an uncommon occurrence. The incidence of carcinoma within broadenoma is between 0.0125 and 0.3% in a screened population, with a peak age of occurrence between 42 and 44 years (2,3). This corresponds to the peak age of lobular carcinoma in situ (LCIS) but is 20 years later than the peak age of broadenoma occurrence. Over 100 carcinoma cases arising within a broadenoma have been reported with the largest series of 105 cases by Diaz et al. (3). Two-thirds of carcinoma within broadenoma are lobular and one-third are ductal or mixed ductal and lobular. LCIS and DCIS exhibit an approximately equal frequency (4,5). Although carcinoma arising within a broadenoma is relatively rare, there are over 100 such cases reported in the literature. In very few of these 100 cases, tumorectomy was performed for the diagnosis of patients strongly suspected of having carcinoma. After unexpected histological diagnosis, secondary interventions for curative operation are generally performed. We want to emphasize that this is a rare report of a carcinoma arising within a broadenoma that was carefully diagnosed before curative operation. Therefore, we could directly perform radical operation without tumorectomy for denitive diagnosis. Fibroadenomas are not typically considered as a risk factor for carcinoma, although dissenting views do exist (6). The presence of a broadenoma in a woman with a positive family history may have greater clinical importance than broadenomas occurring in women with no additional risk factors (7,8). Most broadenoma cases showed cysts, sclerosing adenosis, epithelial calcications or papillary apocrine changes. These broadenomas are classied as complex and a long-term risk factor for breast cancer (9 11).

Figure 1. A well-circumscribed, polygonal, and relatively iso-density mass without microcalcications or spiculations (maximum diameter, 25 mm) is visible in the right mediolateral-oblique (MLO) and cranio-caudal (C-C) mammography.

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Ductal carcinoma in situ in a broadenoma

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Figure 2. Ultrasonography shows an oval and well-circumscribed mass with heterogenous internal echo (dimensions, 24 17 mm). The arrow indicates the direction of the probe in body mark. The arrow indicates the direction of the probe in body mark. (A). Doppler US shows an increase in vascularity (B).

Figure 3. Sagittal view of enhanced MRI shows well-circumscribed, polygonal and heterogeneously enhanced mass.

Figure 4. Samples from the mass show widespread and dense ductal carcinoma in situ (cribriform and solid type) with many calcied bodies overlapped between broadenoma and ductal carcinoma in situ (DCIS; H&E, 40).

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Figure 5. Histological map of partial mastectomy specimen consisting of ve serial sections. Shaded portion shows DCIS and blue solid line shows broadenoma.

Figure 6. The specimen grossly appeared as a circumscribed white tumor. Serial sections #13 reveal broadenoma (surrounded in a solid line), sections #2 4 show DCIS (shaded portion) and section #5 shows normal breast tissue only.

Fibroadenoma is one of the most common benign breast tumors. On the other hand, carcinoma arising within a broadenoma is rare. Hence, histological examination is not necessary for the diagnosis of all types of broadenomas, considering the extremely low possibility of carcinoma arising within a broadenoma. For the detection of a broadenoma, US ndings seem more useful than MMG or MRI ndings because US examinations can be easily performed non-invasively and repeatedly. Typically, US shows a broadenoma as an oval or lobulated mass with a circumscribed

margin, homogeneous hypoechogenecity and a relatively low depth:width ratio. Doppler US often shows marginal vascularities surrounding the mass, and slightly increased vascularity in broadenomas is different from those in cancers that show vascular inltration into the mass. For a case that shows the above-mentioned clinical ndings, cytological diagnosis is recommended for denitive diagnosis. In contrast, complex broadenoma sometimes shows a relatively high depth:width ratio, partially irregular margins and increased vascularity in the mass. For diverse lesions,

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Figure 7. Postoperative H&E staining of the resected specimen. Histologic features of the tumor show DCIS nuclear grade I, mainly solid and cribriform type ( 100).

Figure 8. Immunohistochemistry for smooth muscle actin ( 100). There was no focus of inltrating island of malignant ductal epithelial cells in the surrounding stroma.

histological diagnosis is recommended and cytological diagnosis is considered insufcient. A carcinoma arising in a broadenoma may be considered as a chance occurrence, because the epithelial component of a broadenoma is subject to the same stimuli as the rest of the breast parenchyma (12,13). Azzopardi et al. states that carcinoma involving a broadenoma may be related to one of the following: arising in the adjacent breast tissue engulfing and inltrating a broadenoma; in the crevices of a broadenoma as well as in the adjacent breast tissue; and carcinoma restricted entirely, or at least dominantly, to a broadenoma. The presented case corresponded to the third criteria. The biological behavior of carcinoma arising within a broadenoma does not differ from that of breast carcinoma unrelated to broadenoma (2). It may be difcult to suggest

that a malignant change has occurred in a broadenoma since clinical and radiological signs may be masked, particularly in the cases of carcinoma in situ. Because of the heterogeneity of the lesion, ne needle aspiration cytology (FNAC) and CNB are not always sufcient to exclude malignancy in benign breast lesions that are at risk of developing cancer, as shown in our case, and open biopsy is often mandatory (7). In the present case, carcinoma arising within a broadenoma showed heterogeneous echo pattern, with slit-like structures. One side of the mass showed low echogenicity and the other side showed high echogenicity (Fig. 2). On the basis of this observation, we speculated that the mass was divided into two major components and was not a homogenous lesion. Four CNB specimens were obtained from another clinic. The amount of tumor cells in each specimen might have been inadequate for histological analysis. A variety of histological ndings were possible, such as complex broadenoma, broadenomatosis, DCIS (cribriform type) and atypical ductal hyperplasia. Pathologists speculated that the mass was a broadenoma with ductal hyperplasia, only DCIS, or borderline atypical ductal hyperplasia without the involvement of stroma. Hence, obtaining a consistent histological diagnosis was very difcult. In such cases, a tumorectomy is routinely performed for obtaining a denite diagnosis. However, the patient was unwilling to undergo tumorectomy for the denite diagnosis of the mass. Therefore, US-guided vacuum-assisted CNBs were performed. According to the US ndings, the mass was speculated to comprise two different components. We collected samples from the high and low echogenicity areas of the mass via the caudal approach. In all, 12 samples were obtained from the three parts of the mass, i.e. the caudal outer rim, cranial outer rim and internal part, with four samples from each part. All the 12 samples from the mass showed DCIS in the background of broadenoma. The tumor was diagnosed as DCIS arising within a broadenoma. Although tumorectomy is considered more reliable for histological diagnosis compared with a US-guided vacuum-assisted CNB, one can perform the latter procedure when a patient is unwilling to undergo tumorectomy. In such cases, the site for tumor sampling should be carefully determined using imaging ndings. When an US-guided vacuum-assisted CNB seems inadequate for obtaining a denite diagnosis, surgical open biopsy should be considered as the next step to avoid the risk of pathological overdiagnosis or underdiagnosis. We used a US-guided vacuum-assisted CNB to obtain enough information for diagnosis. A US-guided vacuum-assisted CNB is a new biopsy technique that uses a suction system to obtain a larger tissue sample than can be obtained by a CNB single insertion. The US-guided 11 G vacuum-assisted CNB probe obtains 100 mg of tissue per sample, whereas the 14 G core probe obtains samples with an average weight of 15 mg, which is approximately oneseventh of the US-guided vacuum-assisted CNB specimen (14). Providing a denitive diagnosis before operation

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enables initial curative surgery and eliminates the need for a second operation, increasing a patients quality of life. Surgical management depends on the stage at presentation and the presence of axillary or distant metastasis. Prognosis depends on the grade and stage at presentation but broadenoma may attract early attention, leading to early detection and good outcome. In the present case, according to the imaging and pathological ndings, the high echoic part of the mass seemed more like a DCIS and was situated closer to the head and slightly lateral to the broadenoma. As mentioned above, if a mass speculated as a broadenoma shows typical imaging ndings, cytological evaluation is recommended to avoid unnecessary biopsy examination. On the other hand, a histological examination should be performed in the case that shows atypical US ndings.

References
1. Azzopardi JG, Ahmed A, Mills RR. Problems in breast pathology. In: Bennigton JC, editors. Major Problems in Pathology. Edinburgh: WB Saunders Company Ltd 1979;325 8. 2. Pick PW, Iossides IA. Occurrence of breast carcinoma within a broadenoma. A Review. Arch Pathol Lab Med 1984;108:590 6. 3. Diaz NM, Palmer JO, McDivitt RW. Carcinoma arising within broadenomas of the breast. A clinicopathologic study of 105 patients. Am J Clin Pathol 1991;95:614 22. 4. Kurosumi M, Itokazu R, Mamiya Y, Kishi K, Takayama S, Nagasawa M, et al. Invasive ductal carcinoma with a predominant intraductal component arising in a broadenoma of the breast. Pathol Int 1994;44:874 7. 5. Gashi-Luci LH, Limani RA, Kurshumliu FI. Invasive ductal carcinoma within broadenoma: a case report. Cases J 2009;2:174 7. 6. Dent DM, Cant PJ. Fibroadenoma. World J Surg 1989;13:706 10. 7. Kuijper A, Preisler-Adams SS, Rahusen FD, Gille JJ, van der Wall E, van Diest PJ. Multiple broadenomas harbouring carcinoma in situ in a woman with a family history of breast/ovarian. Cancer 2002;55: 7957. 8. Chintamani, Khandelwal R, Tandon M, Yashwant K, Kulshreshtha P, Aeron T, et al. Carcinoma developing in a broadenoma in a woman with a family history of breast cancer: a case report and review of literature. Cases J 2009;2:934851. 9. Tissier F, De Roquancourt A, Astier B, Espie M, Clot P, Marty M, et al. Carcinoma arising within mammary broadenomas. A study of six patients. Ann Pathol 2000;20:110 4. 10. Kuijper A, Mommers EC, van der Wall E, van Diest PJ. Histopathology of broadenoma of the breast. Am J Clin Pathol 2001;115:736 42. 11. Sklair-Levy M, Sella T, Alweiss T, Craciun I, Libson E, Mally B. Incidence and management of complex broadenomas. Am J Roentgenol 2008;190:214 8. 12. Netto D, Satchidanand SK, Gaeta JK. Carcinoma arising in broadenomas: report of two cases and a review of the literature. J Surg Oncol 1980;13:36772. 13. Carter BA, Page DL, Schuyler P, Parl FF, Simpson JF, Jensen RA, et al. No elevation in long-term breast carcinoma risk for women with broadenomas that contain atypical hyperplasia. Cancer 2001;92: 30 6. 14. Parker SH, Klaus AJ. Performing a breast biopsy with a directional, vacuum-assisted biopsy instrument. Radiographics 1997;17: 123352.

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CONCLUSIONS
This case highlights the rare association of two common breast diseases and the value of histological examination for the diagnosis of malignancy. Progress in imaging instruments has allowed the detection of even small breast lesions. As in our presented case, one should be aware of broadenoma progression capabilities whether US and MMG reveal malignancy. Histological examination is recommended because of the heterogeneity of the lesion and because FNAC is not always a reliable diagnostic tool.

Conict of interest statement

None declared.