Ahead of print
DOI: 10.11152/mu-1408Fibroadenomas and breast carcinoma: a possible answer to a frequently asked question. A pictorial essay
Anca Ciurea¹, Hanelore Herta², Catalin Iacoban², Bogdan Fetica³, Liliana Rogojan², Cristiana Ciortea
2¹Department of Radiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, ²Emergency County Hospital,
³“Ioan Chiricuţă” Oncologic Institute, Cluj-Napoca, Romania
Received 13.01.2018 Accepted 17.03.2018 Med Ultrason
2018:0 Online first, 1-7
Corresponding author: Hanelore Herţa
Emergency County Hospital Cluj-Napoca, Department of Radiology
3-5 Clinicilor street, 400006 Cluj-Napoca Phone: 0040 756 430 483
E-mail: [email protected]
Introduction
Breast cancer is the second leading cause of cancer in women worldwide. The risk factors are diverse, from positive family history to hormonal changes, number of pregnancies, diet, and even the presence of benign breast lesions.
Fibroadenomas (FAs) are the most frequently en- countered benign breast lesions in young women and due to the age of the patients, they are usually diagnosed by ultrasound. Although they rarely undergo malignant transformation, the patients remain concerned about the possibility of malignant transformation.
The aim of this pictorial essay is to illustrate the appearance of classic and complex fibroadenomas, to discuss the risk factors and to highlight the imaging characteristics that raise the suspicion of malignant trans-
formation. In other words, we try to answer, according to our experience and literature data to a frequently asked question in daily practice: “Is there any risk that my fi- broadenoma will become malignant?”
Clinical examination
FAs are the most frequent benign solid lesions of the breast, with a prevalence of 15-23% [1] and a peak inci- dence during the third decade and a second smaller one in the fifth decade of life [2].
Usually FAs are asymptomatic but, in up to 20% of cases [3] they can be multiple and bilateral, increasing the possibility of clinical detection at palpation. FAs are generally no larger than 2-3 cm, except the juvenile giant subtypes. Gordon et al [4] reported a safe growth rate of 20% in all three dimensions over a period of 6 months, for all age groups.
The clinical presentation may vary because, on one hand, they are hormonally responsive lesions (they grow during pregnancy/lactation and involute in menopause) and, on the other hand, during their lifetime they suffer a broad spectrum of structural changes (from highly cellu- lar composition to hyalinization, sclerotic transformation or even calcification).
Abstract
Fibroadenomas (FAs) are the most frequently encountered benign breast lesions in young women and due to the age of the patients, they are usually diagnosed by ultrasound. Although they rarely undergo malignant transformation, the patients remain concerned about the possibility of malignant transformation.
The aim of this pictorial essay is to illustrate the appearance of classic and complex fibroadenomas, to discuss the risk fac- tors and to highlight the imaging characteristics that raise the suspicion of malignant transformation. In other words, we try to answer, according to our experience and literature data, to a frequently asked question in daily practice: “Is there any risk that my fibroadenoma will become malignant?”
Keywords: ultrasound; mammography; fibroadenoma; breast cancer
tumours. On gross examination they are round-oval, well-defined, encapsulated and usually lobulated lesions, clearly delineated from the surrounding tissues [5].
On microscopic examination, FAs are an admixture of stromal and cellular elements and arise from the terminal ductolobular unit, meaning that they are composed from stromal and epithelial cells normally found in the breast.
FAs that have in their structure cysts larger than 3 mm, areas of sclerozing adenosis, epithelial calcifications or papillary changes are classified as complex FAs [6].
Imaging
FAs may exhibit a range of different imaging char- acteristics, from classic appearance to complex forms, representing the most common cause of biopsy in ado- lescents and young females.
The classical mammographic appearance of a FA is a round-oval, well defined mass, possibly lobulated, isodense to the surrounding parenchyma and sometimes hard to distinguish from the dense breast tissue (fig 1).
Calcifications are often found within a degenerated FA and are subdivided into two classical benign patterns: pe- ripheral, “rim” like calcifications, elliptical in shape and central, coarse calcifications with “popcorn” appearance [7] (fig 2). Sometimes in the early development of epi- thelial calcification, it can be challenging to distinguish them from the subtle, punctate pleomorphic malignant calcifications, especially when an associated mass is not visible. If the benign calcification patterns are present, no further follow-up is needed [3].
Magnetic resonance imaging (MRI) features is cor- related with pathology. The high cellular FAs, also called myxoid, have higher water content showing hypointense signal on T1 weighted images and hyperintense signal on T2 weighted images. Sometimes the differentiation be- tween a myxoid FA and a cystic lesion can be made only in the presence of fine internal septations within the FAs, easily depicted on T2 sequences [8]. The fibrotic FAs have poor water content, showing isointense T1 signal and hypointense T2 signal. There are also partially fibrot- ic FAs, with hypointense T2 signal dropping only in the sclerotic areas. The enhancement pattern also follows the
histologic subtypes, the myxoid masses typically show- ing rapid and strong enhancement, due to their high cel- lular component, conversely to fibrotic masses that show
Fig 1. Mammographic appearance of a fibroad-enoma (arrows) on 2D (a) and 3D (mammogra- phy): oval, well defined mass, isodense to the surrounding parenchyma.
Fig 2. Multiple fibroadenomas on mammogra- phy, with typical “pop corn” calcifications.
Fig 3. MRI (T1 contrast enhanced, substrac- tion image) shows in the left breast a typical fibroadenoma: an oval enhancing mass with hypoenhancing septations.
little or no contrast enhancement. The internal septations are usually hypoenhancing structures [9] (fig 3).
Classical FAs appear at ultrasound (US) as parenchi- mal masses with benign features (fig 4). They are well- circumscribed and oval in shape, with the long axis parallel to the skin surface, homogeneous, hypo- or iso- echoic, surrounded by a thin echogenic capsule. Fine fibrous internal septations may be visible and also a few discrete lobulations. The posterior echogenicity is normal or increased, with thin edge shadows, an excep- tion being the calcified masses that demonstrate acous- tic shadowing [7]. The majority exhibit blood flow on Doppler examination, showing a feeding vessel and capsular or segmental vessels within the internal septa- tions. Furthermore, FAs are soft, compressible masses, with uniformly low elasticity values at shear wave elas- tography (average 28 kPa, range 18 to 44 kPa) [10].
Not all FAs exhibit benign features on US, therefore further biopsy is required in order to confirm their be- nign nature.
Complex FAs exhibit on ultrasound less reliable char- acteristics (fig 5) that exclude the possibility of “probably benign”/BIRADS 3 categorization and require further bi- opsy. These findings include: small epithelial calcifica- tions, often without acoustic shadowing, angular or ir- regular margins, heterogeneous internal echotexture and
discrete cystic changes or hyperechoic foci relying on their different histologic patterns [7].
FAs and breast cancer
Being a proliferation of the normal cells of the breast, fibroadenomas may suffer the same changes such as breast parenchyma, including the development of malig- nancy. The literature data is limited regarding the cor- relation of these two entities, with a reported incidence between 0.125% and 0.02% [11].
A carcinoma within a FA is considered when the neo- plastic transformations are entirely encased within the FA or when the carcinoma is focally involving the FA. There are situations when the carcinoma appears in the prox- imity of FAs but not within the FA, with possible con- sequent invasion (fig 6). Therefore, in the cases of FAs focally involved by carcinoma, the question is whether the cancer developed within or in the proximity of the FA (fig 7).
Back in 1994 DuPont et al observed that special concerns should be given to certain groups considered at risk, such as women with adjacent proliferative dis- ease, long history of fibroadenoma (FA), breast cancer in a first-degree relative and the presence of BRCA1 gene.
Also they reported an incidence of complex FAs of ap-
Fig 4. Typical ultrasound appearance of a fibroadenoma: oval circumscribed hypoechoic mass, with the long axis parallel to the skin, homogeneous, surrounded by a thin echogenic capsule (a). On Doppler examination segmental vessels are visible (b) and on sonoelastography the lesion has the same elasticity as the surrounding parenchyma (c).Fig 5. Complex fibroadenoma appearing on ultrasound as a lobulated mass with heterogeneous internal echotexture and small cystic inclusions (a). The lesion presents intense blood supply (b) and a mosaic pattern (score 2) on elastography (c).
legal implication of delayed breast cancer detection.
However the “in situ” forms are reported more com- mon than invasive forms, 66.9% representing lobular carcinoma in situ (LCIS), 12.4% ductal carcinoma in situ (DCIS), 11% invasive ductal carcinoma (IDC), and 3.4%
invasive lobular carcinoma (ILC)) [13]. Malignant trans- formation is suggested by several altered features such as: texture, margins, shape, growth or even regression, vascularization, mobility, compressibility and surround- ings.
On mammograms, the detection of new pleomorphic microcalcifications or indistinct margins within a known FA raises the suspicion of malignancy (fig 8). However, the US examination can be more helpful. It offers a more conspicuous lesion characterization such as elevated size, amorphous/irregular shape and contour, changes in echotexture, increase color-flow signals within the mass and even changes in elasticity. US can also depict new calcifications inside the FA, any new calcifications needing to be further morphologically analyzed by mam- mography (fig 9). Nevertheless, there are cases when a carcinoma within a FA looks indistinguishable from the complex FAs (fig 10).
In cases of malignant transformation, it is not uncom- mon to have two or more malignant lesions in the same or in both breasts, a fact that supports the affirmation of
Fig 6. Mammography of the right breast. A ma-lignant mass (short arrow) is seen in the prox- imity of a fibroadenoma (long arrow).
Fig 7. Ultrasound of a 57 year old patient. A le- sion with benign features, histologically proved to be a fibroadenoma (long arrow) is focally involved by a pathologically proved invasive ductal carcinoma (short arrow).
Fig 8. Mammography of the right breast in cranio-caudal projection (a) and enlarged view (b). In the retroareolar region there is a circumscribed mass with new pleomorphic associated microcalcification that raised the suspicion of associated malignancy. On the pathology specimen an IDC NST (circle) is seen inside a fibroadenoma (rectangle).
Fig 9. In a) the mammography of a 56 year old patient shows an oval, circumscribed, homogeneous mass, proved to be a fibroad- enoma. Three years later, the same lesion shows dimensional regression, with newly appeared pleomorphic calcifications within the lesion (b). In the same breast, a second mass is seen, with spiculated contour, highly suggestive for malignancy. On ultrasound, the known fibroadenoma, with changed features appears as a lobulated mass, inhomogeneous due to hyperechoic spots representing the microcalcifications (c) and on Doppler ultrasound it shows circumferential vascularisation (d). The newly appeared mass is irregular and non-circumscribed, with angulated margins and hyperechoic rim (e), with plunging blood vessel (f). The pathology specimen shows an IDC with large tubular malignant structures (g) in the fibroadenoma (h) and an IDC (i) with cords (in oval) and nests (rec- tangle) pattern in the second, newly appeared lesion.
Fig 10. A 50 year old patient, with a known fibroadenoma in her left breast, presents for the screening mammography. On the mammog- raphy in medio-lateral projection (a), the fibroadenoma (arrows) presents as an oval, circumscribed mass, with benign features. On ultra- sound (b), the lesion appears isoechoic, inhomogeneous due to small cystic areas inside, ill defined and oriented perpendicular to the skin, resembling a complex fibroadenoma. After the ultrasound examination the lesion was classified as suspicious and rebiopsy was indicated.
At pathology, the lesion was proved to be a fibroadenoma with a IDC within (c). In the same breast, better visible on the mammography in cranio-caudal projection (d) there is a second mass, with spiculated countour. On ultrasound (e) the mass has malignant features (irregular shape, non-circumscribed contour) and after biopsy it was proved to be a NST (circle) and micropapillary (square) IDC (f).
DuPont that women with adjacent proliferative disease are more prone to develop a breast cancer within the fi- broadenoma (fig. 11) [2].
Conclusion
The management of newly detected solid lesions differs, from triple assessment to short-term follow up. These approaches allow the identification of four possible outcomes: the malignancy simulators (malig- nant lesions may mimic FAs), to detect rapid growth in some special histological types (juvenile FAS), to suspect the phyllodes tumors that may be identical on imaging to FAs and to diagnose the early malignant changes.
FAs, being a proliferation of normal cells of the breast, suffer the same changes as the breast itself. They can increase their size in certain physiological situa- tions (menstruation, pregnancy, lactation), can be pain- ful, may regress after menopause and can develop ma-
lignant transformation. Even though there is a very low incidence, every radiologist should be aware of the pos- sibility that FAs could suffer malignant alterations and give special attention to any changes that appear even in a pathologically proven FA.
References
1. Hua B, Xu JY, Jiang L, Wang Z. Fibroadenoma with an unexpected lobular carcinoma in situ: A case report and re- view of the literature. Oncol Lett 2015;10:1397-1401.
2. Dupont WD, Page DL, Parl FF, et al. Long-Term Risk of Breast Cancer in Women with Fibroadenoma. N Engl J Med 1994;331:10-15.
3. Chu B, Crystal P. Imaging of fibroepithelial lesions: a picto- rial essay. Can Assoc Radiol J 2012;63:135-145.
4. Gordon PB, Gagnon FA, Lanzkowsky L. Solid breast masses diagnosed as fibroadenoma at fine-needle aspiration biopsy: acceptable rates of growth at long-term follow-up.
Radiology 2003;229:233-238.
Fig 11. A 73 year old patient is referred for the diagnosis of a 10 cm palpable lump in her right breast. On mammography, the patient presents in her left breast (a) a circumscribed oval mass with associated benign calcifications, in the periphery with the presence of a second lesion, spiculated, with associated architectural distorsion. At ultrasound (b) a hypoechoic oval lesion with benign features in seen (circle). The lesion is in contact with and involved by a second mass (dot), with spiculated contour and architectural distortion (attraction of Cooper ligaments – arrows). The spiculated lesion in the left breast was proved to be an IDC (c) with cribriform (circle) and tubular pattern (square). In the right breast, on mammography (d), corresponding to the palpable lump, there were no significant findings but the ultrasound (e) revealed a 7 mm suspicious mass and a few areas of discrete shadowing. The biopsy performed from the lesion in the right breast (f) revealed an ILC with diffuse pattern (rectangle).
5. Goel NB, Knight TE, Pandey S, Riddick-Young M, de Pare- des ES, Trivedi A. Fibrous lesions of the breast: imaging- pathologic correlation. Radiographics 2005;25:1547-1559.
6. Neal L, Tortorelli CL, Nassar A. Clinician’s guide to imag- ing and pathologic findings in benign breast disease. Mayo Clin Proc 2010;85:274-279.
7. Stavros AT (ed). Breast Ultrasound. Lippincott Williams &
Wilkins, 2004:1030.
8. Fischer U (ed). Practical MR Mammography: High-Reso- lution MRI of the Breast. Thieme, 2012:392.
9. Park EK, Cho KR, Seo BK, et al. Radiologic Findings of Ductal Carcinoma in Situ Arising Within a Juvenile Fi- broadenoma: Mammographic, Sonographic and Dynamic Contrast-Enhanced Breast MRI Features. Iran J Radiol 2015;12:e17916.
10. Wang ZL, Li JL, Li M, Huang Y, Wan WB, Tang J. Study of quantitative elastography with supersonic shear imaging in the diagnosis of breast tumours. Radiol Med 2013;118:583- 590.
11. Ooe A, Takahara S, Sumiyoshi K, Yamamoto H, Shiba E, Kawai J. Preoperative diagnosis of ductal carcinoma in situ arising within a mammary fibroadenoma: a case report. Jpn J Clin Oncol 2011;41:918-923.
12. Sklair-Levy M, Sella T, Alweiss T, Craciun I, Libson E, Mally B. Incidence and management of complex fibroad- enomas. AJR Am J Roentgenol 2008;190:214-218.
13. Wu YT, Chen ST, Chen CJ, et al. Breast cancer arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment policy. World J Surg Oncol 2014;12:335.
