Definition
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• Benign biphasic tumor with epithelial and stromal components

Epidemiology
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• Usually women age 30 years or less

Sites
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• Often in upper outer quadrant

Etiology
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• Usually considered neoplastic; some believe it results from hyperplasia of lobular components

Clinical features
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• Most common benign tumor of female breast
• May have neoplastic stromal component with polyclonal epithelial component
• Hormonally responsive, grows during pregnancy and late luteal phase, regresses after menopause (Am J Epidemiol 2002;156:599)
• Associated with mildly increased risk of carcinoma, especially with ductal hyperplasia or family history of breast carcinoma
• Rarely coexists with DCIS (2%, Am J Clin Pathol 2001;115:736) or LCIS (Arch Pathol Lab Med 1984;108:590)
• Infarction is associated with pregnancy, lactation and fine needle aspiration (Arch Pathol Lab Med 1996;120:1069, Diagn Pathol 2013;8:38), but rarely is spontaneous (Pediatr Radiol 2004;34:988)
• "Fibroadenomatosis": multifocal disease, associated with cyclosporin A for kidney transplants (50% of females post-transplant, Ren Fail 2005;27:721, Arch Pathol Lab Med 2003;127:375)
• Association with EBV in immunosuppressed is controversial (Mod Pathol 2002;15:759, Mod Pathol 2003;16:1242)
• Xray: heavy, coarse calcifications

Case reports
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• 25 year old woman whose tumor had atypia due to chickenpox (Acta Cytol 2008;52:337)
• 35 year old woman with carcinoma developing in fibroadenoma (Cases J 2009;2:9348)
• 36 year old with coexisting invasive mucinous carcinoma (Pathologica 2008;100:199)
• 38 year old woman with coexisting hemangioma (Cases J 2009;2:7005)
• 49 year old woman whose tumor had bizarre stromal giant cells (Case of the Week #37)
• 51 year old woman with coexisting microinvasive ductal carcinoma (Acta Radiol 2006;47:643)
• 65 year old woman with coexisting adenoid cystic carcinoma (Ann Diagn Pathol 2005;9:157)
• 66 year old an with bilateral fibroadenomas with digital fibroma-like inclusions (Arch Pathol Lab Med 2007;131:1126)
• With coexisting phyllodes tumor, possibly due to transformation (Appl Immunohistochem Mol Morphol 2009;17:345)

Treatment
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• Excision (completely excise if 4 cm or more, enlarging over time and infiltrative border; after core biopsy, excise if cellular stroma found and phyllodes tumor cannot be excluded)
• May "recur" if adjacent fibroadenomatous hyperplasia is present
• Cryoablation (Am J Surg 2005;190:647)
• Anti-estrogens (World J Surg 2007;31:1178)

Clinical images
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Mammogram, courtesy of Dr. Mark R. Wick

Gross description
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• Sharply circumscribed with smooth, rounded border, freely movable spherical nodule, usually 3 cm or less
• Gray-white, bulging cut surface with numerous slits
• 20% multifocal

Gross images
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Courtesy of Dr. Mark R. Wick

   

Various images

       

Well circumscribed mass

Multiple fibroadenomas

Micro description
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• Rounded contour, overgrowth of fibrous and glandular tissue
• Intralobular stroma (delicate, cellular, myxoid or fibrotic) encloses glandular spaces; may infarct, become inflamed, calcify
• Pericanalicular: open glandular spaces vs intracanalicular: compressed glandular spaces [no clinical significance to this distinction]
• Glands have cuboidal/low columnar epithelium and adjacent myoepithelium, but no atypia
• 15% have apocrine metaplasia
• May have myxoid change (suggests Carney's syndrome), sclerosing adenosis, epithelial hyperplasia or other fibrocystic change
• May have adjacent fibroadenomatous change
• Rarely has pleomorphic, bizarre multinucleated giant cells (Arch Pathol Lab Med 2000;124:1721, Diagn Pathol 2008;3:33, Am J Surg Pathol 1986;10:823, Arch Pathol Lab Med 1994;118:912), squamous metaplasia, smooth muscle or adipose tissue, metaplastic cartilage, DCIS or LCIS
• Fibroadenoma phyllodes: rarely has focal leaf-like processes but otherwise typical fibroadenomatous stroma
• No necrosis, no elastic tissue, no anaplasia, no mitotic figures

Micro images
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Fibroblastic stroma surrounding compressed ducts

 

Intracananlicular pattern

 

Pericanalicular pattern

Mild hypercellularity

With apocrine change

   

Courtesy of Dr. Mark R. Wick

Containing DCIS, courtesy of Dr. Mark R. Wick

   

Infarcted fibroadenoma, contributed by Dr. Semir Vranic, University of Sarajevo (Bosnia)

   

With cystic changes

 

Atypical stromal cells

     

Epithelial hyperplasia

 

With atypical lobular hyperplasia

 

With LCIS

   

With DCIS

 

With infiltrating ductal carcinoma

 

With colloid (mucinous) carcinoma

       

Fibroadenoma with LCIS and invasive lobular carcinoma (contributed by Semir Vranic, MD)

Core biopsies

Digital fibroma like inclusions

Various immunostains

Fig 2: fibroadenoma
Fig 3: giant cells
Fig 4: vimentin

LMP1+ (EBV+) tumor

ER-beta staining of stromal cells (fig a-b)

With papillary carcinoma

 

With adenosis

Smooth muscle

Squamous metaplasia

Pericanalicular

 

Myxoid stroma

 

Bizarre stromal giant cells

   

Stromal edema

Virtual slides
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Videos
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Cytology description
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• Staghorn pattern of spindled or columnar epithelial cells and scattered crowded groups of epithelial cells (Am J Clin Pathol 1988;89:707); also multilayered fragments of epithelium (Acta Cytol 1997;41:1483)
• Rarely has bizarre multinucleated stromal giant cells (Acta Cytol 2002;46:535); may appear malignant (Chirurgia (Bucur) 2008;103:227)
• Myxoid fibroadenoma: highly cellular with moderate mucoid material and numerous bare nuclei

Cytology images
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Fig 1: multiple masses in mammogram
Fig 2/3: FNA shows sheets and clusters of ductal cells and myoepithelial cells with background myxoid stroma
Fig 4: classic features at core biopsy

Positive stains
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• PR (100%), ER-beta in stroma of cellular fibroadenomas (Mod Path 2006;19:599)
• Usually smooth muscle actin (weak in myxoid or sclerotic tumors)
• CD34

• AE1-AE3, CAM5.2, CK7, EMA

Electron microscopy description
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• Basal lamina around epithelial and endothelial cells

Molecular / cytogenetics description
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• Clonal chromosomal aberrations in 20%

Differential diagnosis
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• Cellular (juvenile) fibroadenoma: uniformly hypercellular stroma
• Hamartoma: more abundant adipose tissue; epithelial component is more disorganized
• Phyllodes tumor: at excision - more cellular stroma, stromal overgrowth (one low power field contains only stroma) with stromal condensation around ducts, leaf-like architecture, may be infiltrative; more mitotic figures, more Ki-67 staining (Am J Clin Pathol 2005;124:342)
• Phyllodes tumor: at core biopsy - increased stromal cellularity by 50% compared with typical fibroadenoma, stromal overgrowth (10x field with no epithelium), fragmentation, adipose tissue within stroma (Histopathology 2007;51:336)
• Papillary carcinoma: similar at FNA (Arch Pathol Lab Med 2000;124:1667)
• Tubular adenoma: lacks abundant stroma

Additional references
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• eMedicine
• Stanford University

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