FIBROADENOMA is a circumscribed benign neoplasm of the terminal duct lobular unit with biphasic proliferation of

epithelial and stromal components.

Fibroadenomas usually present as painless, solitary, firm, slow- growing, mobile, well-defined nodules < 3 cm.
Mammography shows nodular densities or calcified nodules. Multiple synchronous or metachronous fibroadenomas can
be unilateral or bilateral. Symptomatic fibroadenomas are rare in older women. Giant (> 5 cm) fibroadenomas are
uncommon, but may occasionally occur in adolescent girls, leading to distortion of the breast. Fibroadenomas may also
develop in men with gynaeco- mastia {2124}. Juvenile fibroadenomas occur more commonly but not exclusively in
adolescents; they can be large and grow rapidly {2240}.
Epidemiology
Fibroadenomas are rare before menarche and are most common in adolescent girls and women aged < 35 years, except for
complex fibroadenomas, which tend to occur about two decades later {1462,1958}. Juvenile fibroadenomas are relatively
more common in young African-Americans {1800,621}.
Etiology
Most fibroadenomas are sporadic. A small proportion of myxoid fibroadenomas occur in women with Carney complex
{292}. Ciclosporin immunosuppression has been associated with the development of multiple large fibroadenomas in
adolescent girls and young women {173,909,107,2047}; in this setting, the lesions stop growing or regress after therapy is
switched to tacrolimus {909}.

Pathogenesis
Fibroadenomas are hormone-sensitive and may grow rapidly during pregnancy. The epithelium and stroma are non-
clonal, but monoclonality has been demonstrated in areas of stromal expansion {1072}. Numerical abnormalities of
chromosomes 16, 18, and 21 have been reported {119}, but no consistent aberrations are found {1230}.
Macroscopic appearance
Fibroadenomas are solid, ovoid, and well circumscribed, usually < 3 cm. Sectioning reveals a uniform rubbery, lobulated,
whorled, greyish-white cut surface with intervening slit-like spaces. A glistening surface or calcifications may be noticed.
Histopathology
Fibroadenoma may show a pericanalicular pattern with stromal cells growing around open ducts in a circumferential
fashion and/or an intracanalicular pattern with stromal compression of ducts into clefts. These patterns may be seen singly
or in combination. The pericanalicular pattern is more common in juvenile fibroadenoma. The stromal component is
usually of uniformly low cellularity and lacks atypia, but it may sometimes exhibit focal or diffuse hypercellularity
(especially in women aged < 20 years), bizarre multinucleated giant cells, extensive myxoid change {292,1244}, or
hyalinization with dystrophic calcifications, and rarely ossification in postmenopausal women. Lipomatous, smooth
muscle, and osteochondroid metaplasia may occur. Mitoses are uncommon but may be present in fibroadenomas in young
or pregnant patients. Epithelial squamous and apocrine metaplasia, epithelial apical snouts, focal fibrocystic changes,
sclerosing adenosis, usual ductal hyperplasia, and even extensive myoepithelial proliferation can occur {1073}. Atypical
ductal/lobular hyperplasia and ductal/lobular carcinoma in situ may infrequently involve fibroadenomas {1073,1990}.
When atypical hyperplasia is confined to the fibroadenoma, there is reportedly no increased subsequent cancer risk {295}.
Invasive carcinoma may also involve fibroadenomas, often as a result of secondary involvement.
Juvenile fibroadenomas often show a pericanalicular growth pattern with a uniform mild to moderate increase in stromal
cellularity, with stromal cells in fascicular arrangements and no substantial nuclear atypia, accompanied by usual ductal
hyperplasia {2062,1800}, most commonly of gynaecomastoid type. Mitotic activity in the stromal component is usually
low: < 2 mitoses per 10 high-power fields (< 1 mitosis/mm2) {1800,621}.
The diagnosis of fibroadenoma on core biopsy is reliable and accurate; however, the finding of a cellular fibroepithelial
lesion on core biopsy may prompt consideration of phyllodes tumour. In such cases, surgical excision is usually
advocated. A molecular test that may distinguish fibroadenoma from phyllodes tumour on core biopsy has been reported
{2043}.
Complex fibroadenomas have one or more of the following features: cysts > 3 mm, sclerosing adenosis, epithelial
calcifications, and papillary apocrine metaplasia {554}. They are present in 3-4% of benign breast biopsies {1462,966},
account for 16-23% of all fibroadenomas {554,1958}, and are smaller than other fibroadenomas {1958}. Complex
fibroadenomas without atypia carry a slightly increased relative risk (2.27-3.1 times the risk in the general population) for
developing subsequent breast carcinoma {1462,554,1958}.
Cellular fibroadenomas have a pericanalicular growth pattern, mildly to moderately increased stromal cellularity, and
usually < 1 stromal mitosis/mm2 (< 2 mitoses per 10 high-power fields), but they lack the following features: stromal
nuclear atypia, exaggerated intracanalicular architecture, periductal subepithelial stromal condensation, and intratumoural
heterogeneity {2029}.
Juvenile fibroadenomas are most common in adolescent girls or young women, and they can be very large, causing breast
distortion. Stromal cellularity is mild to moderate, with fascicular arrangement and no substantial nuclear atypia. There is
usually < 1 stromal mitosis/mm2 (< 2 mitoses per 10 high-power fields) {2062,1800,621}. Usual ductal hyperplasia is
common {2062, 1800}.
Cytology
Cytological aspirates from fibroadenomas typically yield cellular sheets with antler- or staghorn-shaped epithelial clusters,
with a clean background containing bipolar nuclei, giving an appearance of sesame seeds strewn among epithelial
fragments {2030}. The epithelial clusters often show admixed myoepithelial nuclei {1280,207}. Stromal clumps can be
associated with myxoid material. Rarely, multinucleated giant cells may be discerned {2134}. The presence of usual
ductal hyperplasia within the fibroadenoma can result in the presence of larger branched proliferative epithelial aggregates
in the aspirates. Occasionally the aspirates may show high cellularity, and isolated single epithelial cells with mild nuclear
atypia may be seen, resulting in an atypical or even false positive malignant diagnosis.
Diagnostic molecular pathology
Not clinically relevant
Essential and desirable diagnostic criteria
Essential: circumscribed biphasic tumour; intracanalicular and/ or pericanalicular growth pattern; no stromal overgrowth;
absence of well-developed fronds; no stromal atypia; low mitotic activity in the stromal component.
Staging
Not clinically relevant Prognosis and prediction
Most fibroadenomas do not recur after complete surgical excision. In adolescents, there is a tendency for one or more new
lesions to develop at another site or close to the site of the previous surgical treatment {936}. Complex fibroadenomas are
associated with a minimal increase in relative cancer risk {554}.