Fibroepithelial Lesions

Clinical Presentation and Imaging Features

Fibroadenomas are more common in premenopausal women, most frequently in women aged 20 to 30 years, but they may be present at any age. Fibroadenomas usually present as a well-defined, mobile mass on physical examination or a well-defined, solid, hypoechoic mass on ultrasound ( Fig. 12.1 ).

Gross Pathology

Fibroadenomas are grossly well-circumscribed masses with smooth or lobulated contours. When sectioned, they typically show a bulging, tan-white cut surface ( Fig. 12.2A ). They can often be surgically excised in their entirety, in which case they appear grossly to bear a thin fibrous rim, although they are usually unencapsulated (see Fig. 12.2B ). They range in size from less than 1 cm to larger than 4 cm in greatest dimension. Most often they are 3 cm or less, and the larger tumors are more common in adolescent females.

Some fibroadenomas, particularly if histologically myxoid, can show a gelatinous cut surface or may be partially cystic (see Fig. 12.2C ).

Microscopic Pathology

Fibroadenomas are composed of both epithelium and stroma and demonstrate well-circumscribed, lobulated or smooth borders. The arrangement of the epithelium within the tumor results in one of two growth patterns. The intracanalicular growth pattern consists of compressed ducts, forming thin clefts throughout the lesion. Such a pattern can be prominent and form leaflike arrangements simulating the architecture seen in phyllodes tumors, especially in hyalinizing or hyalinized lesions (see Fig. 12.2D and E ). The pericanalicular growth pattern , in contrast, demonstrates open ductal lumens with stroma growing around the tubules (see Fig. 12.2F to J ). Most fibroadenomas show both patterns ( Figs. 12.3 and 12.4 ).

The epithelium in fibroadenomas can be inactive or show variable levels of hyperplasia, metaplasia, and adenosis (see Fig. 12.4C ). The term complex fibroadenoma is used when extensive sclerosing adenosis, fibrocystic change, and/or hyperplasia are present ( Figs. 12.5 and 12.6 ), with cysts 3 mm or larger, papillary apocrine metaplasia, and epithelial calcifications. Complex fibroadenomas are associated with a slightly increased risk of subsequent development of breast cancer as compared with simple fibroadenomas (see “Treatment and Prognosis”). Fibroadenomas demonstrating florid or prominent adenosis may resemble tubular adenomas ( Fig. 12.7 ). Lactational change often occurs in fibroadenomas of pregnant or breastfeeding women. When the fibroadenoma shows diffuse lactational change, the term lactating adenoma is frequently used ( Fig. 12.8B ).

The stroma in fibroadenomas is variable in morphology and cellularity. Simple fibroadenomas show collagenized stroma with low cellularity. Some fibroadenomas will have partial or complete hyalinization of the stroma (i.e., hyalinized fibroadenomas) ( Figs. 12.9 to 12.12 ). The stroma may be myxoid; patients with Carney complex more often demonstrate myxoid fibroadenomas ( Fig. 12.13 ). Stroma identical to that seen in pseudoangiomatous stromal hyperplasia is a frequent finding ( Fig. 12.14 ). Regardless of the nature of the stroma, the cellularity is almost always homogeneous throughout; in other words, there is generally a lack of significant regional variation in cellularity. This is an important differentiating feature when distinguishing between a cellular fibroadenoma and a phyllodes tumor (see “Phyllodes Tumor” ). Fibroadenomas with increased stromal cellularity ( Fig. 12.15 ) are more common in women younger than 30 years old and have been traditionally termed juvenile fibroadenomas . Juvenile fibroadenomas often show prominent epithelial hyperplasia and characteristically lack epithelial and stromal mitoses, although mitotic figures can be observed (see Fig. 12.15A and B ). Cellular fibroadenomas may grow to reach large sizes; when larger than 5 cm or greater than 500 g, the term giant fibroadenoma has been used. Giant fibroadenomas are uncommon and represent 0.5% to 2% of all fibroadenomas. They are more common in young Black women and have been postulated to result from abnormal estrogen exposure, as evidenced by their increased frequency during pubescence and pregnancy.

The stromal cells in fibroadenomas, reflective of their fibroblastic and/or myofibroblastic differentiation, are positive for actin and CD34 by immunohistochemistry (IHC) and have also been reported to be variably CD10+, which has been traditionally used by some in breast pathology as a myoepithelial cell marker.

Multinucleated stromal giant cells have been infrequently described in benign breast stroma, and were originally documented by Rosen. In his report, the giant cells were visible at low (×10) magnification, were dispersed rather than aggregated, demonstrated scanty cytoplasm and hyperchromatic nuclei, and were not associated with adjacent carcinoma. Similarly, multinucleated stromal giant cells have been reported in fibroadenomas. Although the multinucleated giant cells are often pleomorphic, the stroma in these cases generally lack mitotic activity and these multinucleated giant cells are thought to be of no clinical significance. The presence of mitoses, especially atypical mitotic figures, and/or atypia in nonmultinucleated stromal cells should raise suspicion of a phyllodes tumor, although both usual and atypical mitotic figures have been reported in otherwise benign fibroadenomas. Rarely, fibroadenomas demonstrate spontaneous infarction.

The stroma in fibroadenomas may show differentiation other than that of fibroblasts or myofibroblasts. Although it has been reported that most fibroepithelial lesions with adipocytic differentiation represent phyllodes tumors, it is not infrequent to encounter benign adipocytes in fibroadenomatous stroma in routine practice ( Fig. 12.16A to C ).

Although relatively uncommon, carcinoma may arise in or extend to involve fibroadenomas. The incidence of carcinoma within fibroadenomas is reported to range from 0.0125% to 0.3% in a screened population, and most commonly occurs in women in their early 40 s. Lobular neoplasia in the form of lobular carcinoma in situ (LCIS) more commonly arises in fibroadenomas than does ductal neoplasia, with greater than 50% of affected fibroadenomas showing LCIS in published reports ( Fig. 12.17 ). Approximately one-third of carcinomas within fibroadenomas are ductal or mixed ductal and lobular (see Fig. 12.17A and B ).