Fibroepithelial Lesions

7.1 FIBROADENOMA VS. HAMARTOMA

	Fibroadenoma	Hamartoma
Age	Any age, most frequent in women younger than 30 y old, frequently peri- and postpubertal adolescents	Any age, usually women in 4th or 5th decade
Presentation	Slow-growing, usually solitary, firm, mobile mass, typically less than 3 cm but may be larger	Soft palpable mass or asymptomatic, detected on imaging
Location	Anywhere in the breast or along the milk line	Anywhere in the breast
Imaging findings	Well-circumscribed, ovoid or multilobulated mass on mammogram; hypoechoic mass on ultrasound, wider than tall with distinct margins	Mammographically a well-circumscribed, round to oval mass containing fat and soft tissue with a thin, radiopaque pseudocapsule; by ultrasound, a circumscribed, round to oval mass, which may have intralesional heterogeneous echogenicity
Histology	1. Circumscribed, ovoid mass, smooth interface with surrounding mammary tissue, nonencapsulated (Fig. 7.1.1) 2. Ratio of stromal and glandular proliferation remains consistent throughout the lesion (Fig. 7.1.2) 3. Intracanalicular (glands compressed into cords by proliferating stroma) (Fig. 7.1.3) and pericanalicular (stroma surrounds epithelial elements with open lumina) patterns, admixed in most lesions; no clinical significance to patterns 3. Stroma uniform in cellularity and distribution, composed of mixture of collagen and bland, non-atypical stromal cells with ovoid nuclei (Fig. 7.1.3) 4. Rare stromal mitoses (less than 3 in 10 high-powered fields [HPF]) 5. The stroma may show a spectrum of changes, including multinucleated giant cells, myxoid change, PASH, hyalinization ± calcification, and rarely ossification 6. The epithelial component may show usual hyperplasia which is frequently mitotically active in adolescents, resembling gynecomastia	Lobulated mass incorporating normal mammary ducts, lobules and interlobular fibrous tissue within adipose tissue in varying proportions (Fig. 7.1.4) Ducts and lobular units have a normal architectural arrangement (Figs. 7.1.4 and 7.1.5) Demarcated from surrounding breast tissue by a thin, delicate capsule (Fig. 7.1.4) Epithelial elements may show fibrocystic changes Stroma may contain pseudoangiomatous stromal hyperplasia (PASH) or smooth muscle (myoid hamartoma) Not easily diagnosed on core needle biopsy as complete architecture lacking
Special studies	None to distinguish from mammary hamartoma	Should be interpreted in radiologic context, which is usually defining
Genetic abnormalities	Numerical abnormalities of chromosomes 16, 18, and 21; MED12 and RARA mutations	May be seen in association with Cowden’s syndrome. Aberrations involving 12q12-15 and 6p21 have been described.
Treatment	None required; may be excised for cosmesis if large or disfiguring	None necessary. Well-defined border/capsule usually allows for enucleation.
Clinical implication	Development of additional fibroadenomas	None. Rare local recurrences are of no consequence.

Figure 7.1.1 Fibroadenoma, showing sharp circumscription and a mixture of intracanalicular (top center) and pericanalicular (left lower) growth patterns.

Figure 7.1.2 The interface of the fibroadenoma with the adjacent normal mammary parenchyma is sharply circumscribed. The epithelium is evenly distributed with respect to the stroma.

Figure 7.1.4 Hamartomas are well-circumscribed, lobulated masses containing architecturally normal lobular units and terminal ducts admixed with mature adipose tissue. Note the thin fibrous capsule (top).

Figure 7.1.5 Segregation of the mature adipose tissue by encapsulation (upper right) is the defining feature of hamartoma.

Figure 7.1.3 The epithelium is focally compressed by the collagenous stroma containing paucicellular bland spindle cells. The stromal nuclei are nonoverlapping, evenly distributed, and lack atypia.

7.2 FIBROADENOMA VS. CELLULAR FIBROADENOMA

	Fibroadenoma	Cellular Fibroadenoma
Age	Any age, most frequent in women younger than 30 y old; frequently peri- and postpubertal adolescents	Women younger than 30 y
Presentation	Slow-growing, solitary, mobile mass, typically less than 3 cm but may be larger; occasionally multiple and/or bilateral	Solitary, firm, palpable, mobile mass, typically less than 3 cm but may be larger; occasionally multiple and/or bilateral; may have history of rapid growth, otherwise no clinical findings to distinguish from ordinary fibroadenoma
Location	Anywhere in the breast or along the milk line	Anywhere in the breast or along the milk line
Imaging findings	Well-circumscribed, ovoid or multilobulated mass on mammogram; hypoechoic mass on ultrasound, wider than tall with distinct margins	Well-circumscribed, ovoid or multilobulated mass on mammogram; hypoechoic mass on ultrasound, wider than tall with distinct margins; no imaging findings to distinguish fibroadenoma from cellular fibroadenoma
Histology	Circumscribed, ovoid mass; smooth interface with surrounding mammary parenchyma; nonencapsulated (Fig. 7.2.1) Proliferation of stromal and epithelial elements; ratio of stroma and glands remains relatively consistent throughout the lesion Two patterns, intracanalicular (glands compressed into cords by proliferating stroma) and pericanalicular (stroma surrounds epithelial elements with open lumina), are admixed in most lesions; no clinical significance to patterns. Intracanalicular pattern may mimic benign phyllodes tumor (Fig. 7.2.2) Stroma is uniform in cellularity and distribution, composed of a mixture of collagen and bland, non-atypical stromal cells with ovoid nuclei (Fig. 7.2.3) Little mitotic activity (<3/HPF)	Circumscribed, ovoid mass, smooth interface with surrounding mammary tissue, nonencapsulated (Fig. 7.2.4) Proliferation of stroma and epithelial elements; ratio of stroma and glands usually remains consistent throughout the lesion (Fig. 7.2.4); both intracanalicular and pericanalicular patterns common Increased stromal cellularity, but limited mitotic activity (usually <3/10 HPF) (Figs. 7.2.5 and 7.2.6) Stromal cells lack atypia (Fig. 7.2.6)
Special studies	None to distinguish from cellular fibroadenoma	None to distinguish from ordinary fibroadenoma
Genetic abnormalities	Numerical abnormalities of chromosomes 16, 18, and 21; MED12 and RARA mutations	Numerical abnormalities of chromosomes 16, 18, and 21; MED12 and RARA mutations
Treatment	None required; may be excised for cosmesis if large or disfiguring	None required; may be excised for cosmesis if large or disfiguring
Clinical implication	Development of additional fibroadenomas	The descriptors “giant” or “juvenile” fibroadenoma are clinical terms that describe rapid growth. The histologic correlate of these clinical terms is a cellular fibroadenoma that may show abundant hyperplasia that resembles gynectomastia. Mitotic activity in the epithelium and stroma (focally up to 5/10 HPF) is a result of hormonal stimulation and not an indication of aggressive clinical behavior.

Figure 7.2.1 Fibroadenomas are nonencapsulated, stromal and epithelial proliferations that have a smooth interface with adjacent parenchyma.

Figure 7.2.2 The epithelium is evenly distributed in a paucicellular stroma. The different epithelial patterns are of no clinical significance in a fibroadenoma, although an intracanalicular pattern (left) can occasionally mimic benign phyllodes tumor.

Figure 7.2.4 Cellular fibroadenoma showing a smooth interface with adjacent connective tissue. There are a few foci of intracanalicular growth lacking distortion.

Figure 7.2.5 Stromal cellularity is increased but remains evenly distributed without stromal expansion in cellular fibroadenoma.

Figure 7.2.3 The stroma of this fibroadenoma is predominantly collagen, without increased stromal cellularity. The nuclei are bland and nonoverlapping.

Figure 7.2.6 Cellular fibroadenoma, consisting of prominent stromal cells that lack atypia and mitotic activity. Myoepithelial cells are evident.

7.3 CELLULAR FIBROADENOMA VS. BENIGN PHYLLODES TUMOR

	Cellular Fibroadenoma	Benign Phyllodes Tumor
Age	Women younger than 30 y	Generally a decade older than women with fibroadenomas, occasionally younger women
Presentation	Solitary, firm, palpable, mobile mass, typically less than 3 cm but may be larger; occasionally multiple and/or bilateral; no clinical findings to distinguish from benign phyllodes tumor	Solitary, firm, palpable, mobile mass, frequently larger than 5 cm; very rarely multiple and/or bilateral; no clinical findings to distinguish from cellular fibroadenoma
Imaging findings	Well-circumscribed, ovoid or multilobulated mass on mammogram; hypoechoic mass on ultrasound, wider than tall with distinct margins; no imaging findings to consistently distinguish fibroadenoma from benign phyllodes tumor	Round, oval or lobulated, well-circumscribed mass on mammogram, may have a radiolucent halo; on ultrasound, inhomogeneous, solid mass containing cleft-like cystic spaces with posterior acoustic enhancement
Histology	Circumscribed, ovoid mass, smooth interface with surrounding mammary parenchyma, nonencapsulated (Fig. 7.3.1) Proliferation of stroma and epithelial elements; ratio of stroma and glands usually remains consistent throughout the lesion (Fig. 7.3.2); both intracanalicular and pericanalicular patterns common Increased stromal cellularity, but limited mitotic activity (usually <3/10 HPF) (Figs. 7.3.3, 7.3.4, 7.3.5) Stromal cells lack atypia (Fig. 7.3.5)	Circumscribed, lobulated proliferations of epithelium and expanded stroma, classically with a leaf-like architecture (Figs. 7.3.6 and 7.3.7) The epithelium-bound leaf-like structures project into prominent epithelial-lined clefts formed by the expanded stroma (Figs. 7.3.7 and 7.3.8). Epithelial distribution fairly regular throughout the lesion. Stroma characterized by bland, spindled cells with mild atypia and mildly increased mitotic activity (usually <5/10 HPF) (Figs. 7.3.9 and 7.3.10); stroma may be condensed around epithelial clefts. Stromal expansion may be uniform or heterogeneous. Stromal overgrowth absent Squamous metaplasia common (rare in fibroadenoma) Distinction between benign phyllodes tumor and cellular fibroadenoma may be difficult with the limited sample provided by core needle biopsy
Special studies	None to distinguish from benign phyllodes tumor	None to distinguish from fibroadenoma
Genetic abnormalities	Numerical abnormalities of chromosomes 16, 18, and 21; MED12 and RARA mutations	Heterogeneous cytogenetic abnormalities. Mutations of MED12 and RARA, FLNA, SETD2, and KMT2D reported.
Treatment	None required; may be excised for cosmesis if large or disfiguring	Excision; circumscription of benign phyllodes tumor may result in positive margin due “shelling-out.” Clinical follow-up preferable to reexcision to maintain cosmesis.
Clinical implication	May develop additional fibroadenomas	Recurrence rates slightly higher than cellular fibroadenoma, approximately 10-15%