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Fibroepithelial tumors

Fibroadenoma

Author: Gary Tozbikian, M.D.

Editorial Board Member: Kristen E. Muller, D.O.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 19 July 2021

Last staff update: 5 December 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Fibroadenoma of the breast pathology

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Table of Contents

Cite this page: Tozbikian G. Fibroadenoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastfibroadenoma.html. Accessed April 25th, 2024.

Definition / general

Benign biphasic tumor composed of a proliferation of both glandular epithelial and stromal components of the terminal duct lobular unit

Essential features

Most common breast tumor in adolescent and young women
Benign biphasic tumor comprised of glandular epithelium and specialized interlobular stroma of the terminal ductal lobular unit (Pathol Annu 1994;29:1)
Can show a spectrum of histologic appearances; generally uniform in stromal cellularity and distribution of glandular and stromal elements within a given lesion (an important distinction from phyllodes tumor)
Fibroadenomas with hypercellular stroma and prominent intracanalicular pattern can show morphologic overlap with benign phyllodes tumors, especially in needle biopsy specimens

Terminology

Fibroadenoma, usual type fibroadenoma, adult type fibroadenoma
Myxoid fibroadenoma
Juvenile fibroadenoma
Complex fibroadenoma

ICD coding

ICD-10: D24 - benign neoplasm of breast

Epidemiology

Most common benign tumor of the female breast
Most common breast tumor in adolescent and young women
Can occur at any age, median age of 25 years (J R Coll Surg Edinb 1988;33:16)
Juvenile fibroadenoma generally occurs in younger and adolescent patients < 20 years; reported in children at a very young age (Am J Surg Pathol 1985;9:730, Jpn J Clin Oncol 2011;41:260)
Complex fibroadenoma reported in older patients with median age between 35 - 47 years (Am J Clin Pathol 2001;115:736, AJR Am J Roentgenol 2008;190:214)
Myxoid fibroadenoma is associated with Carney complex (Am J Surg Pathol 1991;15:713)
Increased relative risk (1.5 - 2.0) of subsequent breast cancer; relative risk is higher (3.1) in complex fibroadenomas; no increased risk for juvenile fibroadenoma (N Engl J Med 1994;331:10, Int J Cancer 1994;57:681, Breast J 2017;23:182)

Sites

Breast
Can occur in axilla accessory breast tissue

Etiology

Increased risk associated with cyclosporine immunosuppression (Clin Nephrol 2004;61:151)

Clinical features

Often presents as painless, firm, mobile, slow growing mass
Usually solitary, can be multiple and bilateral
Usually less than 3 cm in diameter but may grow to large size (AJR Am J Roentgenol 2008;190:214)

Diagnosis

Histologic examination of involved tissue

Radiology description

Sonographically seen usually as a round or oval mass, smooth margins with hypo or isoechoic features (Radiology 1989;172:671, Invest Radiol 1986;21:34, AJR Am J Roentgenol 1983;140:369)
Can be associated with calcifications, especially in postmenopausal patients

Radiology images

Contributed by Mark R. Wick, M.D., Azadeh Khayyat, M.D. and Julie M. Jorns, M.D. (Case #533)

Mammogram

Images hosted on other servers:

Juvenile fibroadenoma

Case reports

12 year old girl with breast mass (Int J Surg Case Rep 2017;41:427)
16 year old girl with 28 cm left breast mass (BMJ Case Rep 2019;12:e227277)
17 year old girl with recurrent juvenile fibroadenoma (Medicine (Baltimore) 2018;97:e10765)
18 year old woman with mass in axilla accessory breast tissue (BMJ Case Rep 2015;2015:bcr2015209535)
35 year old woman with left breast mass (Breast Dis 2015;35:49)
37 year old woman with increased uptake of breast mass on PET scan (Clin Nucl Med 2017;42:145)
44 year old woman with bilateral breast masses (Oncol Lett 2015;10:1397)
Premenopausal woman with family history of breast cancer was found to have a subcentimeter mass with calcifications on mammogram (Case of the month #533)

Treatment

Management depends on patient risk factors and patient preference
Conservative management with close clinical followup, especially if concordant radiology findings (Br J Surg 1987;74:857)
Local surgical excision, especially if symptomatic (Am J Surg Pathol 1985;9:730)
If atypia / neoplasia is found within a fibroadenoma, the surgical and systemic therapeutic management is specific and appropriate to the primary atypical / neoplastic lesion

Gross description

Firm, well circumscribed, ovoid mass with bosselated surface, lobulations bulge above the cut surface, slit-like spaces
May have mucoid or fibrotic appearance; can be calcified

Gross images

Contributed by Gary Tozbikian, M.D.

Well circumscribed tumor with bulging cut surface

Microscopic (histologic) description

Well circumscribed, unencapsulated
Biphasic tumor, proliferation of both glandular and stromal elements
Glandular component
- 2 recognized growth patterns (of no clinical significance, both patterns may occur within a single lesion)
  - Intracanalicular: glands are compressed into linear branching structures by proliferating stroma
  - Pericanalicular: glands retain open lumens but are separated by expanded stroma
- Glandular elements have intact myoepithelial cell layer
- Often associated with usual type ductal hyperplasia, apocrine metaplasia, cyst formation or squamous metaplasia
- Rare mitotic activity can be observed in the glandular component, has no clinical significance
Stromal component
- Generally uniform cellularity within a given lesion
- Collagen and bland spindle shaped stromal cells with ovoid or elongated nuclei
- Usually no mitotic activity; rare mitotic activity may be present in young or pregnant patients (Breast J 2017;23:182)
- No stromal atypia
- Stroma may show myxoid change or hyalinization
- May show multinucleated giants cells (Am J Surg Pathol 1986;10:823, Arch Pathol Lab Med 1994;118:912)
- Rarely benign heterologous stromal elements (adipose, smooth muscle, osteochondroid metaplasia)
- Fibroadenomas may be involved by mammary neoplasia (e.g. invasive breast carcinoma, ductal carcinoma in situ, lobular carcinoma in situ) and atypical epithelial proliferations (e.g. atypical ductal hyperplasia, atypical lobular hyperplasia) often as a result of spread from an adjacent lesion
Variants
- Myxoid fibroadenoma
  - Similar structure but with prominent myxoid stromal change composed of abundant pale, blue-gray extracellular matrix material
- Complex fibroadenoma
  - Cysts > 3 mm, sclerosing adenosis, epithelial microcalcifications or papillary apocrine metaplasia (N Engl J Med 1994;331:10)
- Cellular fibroadenoma
  - Diffuse stromal hypercellularity
- Juvenile fibroadenoma
  - Increased stromal cellularity
  - Increased epithelial hyperplasia with gynecomastoid-like micropapillary projections
  - Fascicular stromal arrangement
  - Pericanalicular growth pattern
  - May show rapid growth and large size (Am J Surg Pathol 1985;9:730)

Microscopic (histologic) images

Contributed by Gary Tozbikian, M.D., Debra Zynger, M.D., Azadeh Khayyat, M.D. and Julie M. Jorns, M.D. (Case #533)

Fibroadenoma

Complex fibroadenoma

Myxoid fibroadenoma

Juvenile fibroadenoma

Cellular fibroadenoma

Fibroadenoma with ALH

Fibroadenoma with atypical ductal hyperplasia

Multinucleated stromal cells

Ductal carcinoma in situ (DCIS), solid type, with microcalcifications, confined to a fibroadenoma

Ductal carcinoma in situ (DCIS), solid type, with microcalcifications, confined to a fibroadenoma; lobular neoplasia (atypical lobular hyperplasia / lobular carcinoma in situ), with involvement of a fibroadenoma

Virtual slides

Contributed by Andrey Bychkov, M.D., Ph.D.

Fibroadenoma

Cytology description

Usual (adult type) fibroadenoma: biphasic population composed of abundant spindle stromal cells and naked nuclei, epithelium arranged in antler horn clusters or fenestrated honeycomb sheets (Am J Clin Pathol 1988;89:707, Acta Cytol 1991;35:695)
Myxoid fibroadenoma: high cellularity with stroma and epithelium embedded in myxoid background (Diagn Cytopathol 2001;25:278, Am J Clin Pathol 2003;120:194)

Cytology images

Contributed by Areej M. Al Nemer, M.D.

Branching sheets

Bare nuclei

Bland stromal fragments

Images hosted on other servers:

Diff-Quik

Pap

Positive stains

Stromal cells
- CD34
- Estrogen receptor beta (Mod Pathol 2006;19:599)
- Progesterone receptor (Cancer 1981;47:2016)
- Beta catenin (nuclear) (J Pathol 2003;200:627)
Epithelial cells
- AE1 / AE3, CK7, EMA, CAM5.2
- Estrogen receptor alpha

Negative stains

Stromal cells
- Cytokeratins
- Ki67 proliferation index is lower compared with phyllodes tumors but some overlap with benign phyllodes tumor (Am J Clin Pathol 2005;124:342, Histopathology 2010;57:220, Int J Surg Pathol 2008;16:137, Pathol Res Pract 1998;194:97)

Molecular / cytogenetics description

MED12 exon 2 mutations in usual (adult type) fibroadenoma; likely a driver genetic event (NPJ Breast Cancer 2016;2:16035, Nat Genet 2014;46:877, Histopathology 2015;67:719)
Myxoid fibroadenomas lack MED12 mutations (Histopathology 2017;71:626)
RARA mutations (Nat Genet 2015;47:1341, J Pathol 2016;238:508)
Cellular variant of fibroadenoma shows higher rates of mutation in PIK3CA and MAP3KI (Mod Pathol 2021;34:1320)
Fewer mutations (e.g. MED12, TERT promoter, RB1, EGFR) compared with benign phyllodes tumor (Mod Pathol 2021;34:1320)

Videos

Fibroadenoma

Sample pathology report

Breast, right, 2:00 zone 2, ultrasound guided core biopsy:
- Fibroadenoma

Differential diagnosis

Phyllodes tumor:
- Well developed leaf-like architecture, with accompanied increased stromal cellularity
- Prominent mitotic activity ≥ 3/10 high power fields or the finding of 3 or more characteristic histologic features (stromal overgrowth, fat infiltration, stromal fragmentation, subepithelial stromal condensation, stromal nuclear pleomorphism) is predictive of phyllodes tumor (versus fibroadenoma) in core biopsy specimens (Am J Clin Pathol 2014;142:362)
Hamartoma of breast:
- Integral adipose component
- Disordered but morphologically normal appearing ducts and lobules
Tubular adenoma:
- Prominent pericanalicular adenosis-like epithelial proliferation with little intervening stroma
Fibroadenomatoid changes (sclerosing lobular hyperplasia, fibroadenomatoid mastopathy):
- Generally does not form a clinically dominant mass
- Individual lobule or few groups of lobules with collagenized interlobular stroma and loss of interlobular stromal mucopolysaccharides (Hum Pathol 1984;15:336, Pathology 1987;19:393, Malays J Pathol 1991;13:101)
Myxoma:
- Lacks glandular elements (versus myxoid fibroadenoma)

Board review style question #1

A 13 year old girl presents with a firm, palpable 3.5 cm breast mass. She undergoes an ultrasound guided biopsy and subsequent local excision showing a fibroepithelial lesion with circumscribed borders, uniformly increased stromal cellularity, glandular proliferation with pericanalicular growth pattern and prominent gynecomastoid-like usual type ductal hyperplasia. Rare mitotic activity (< 1/10 high power fields) is identified. Stromal cytologic atypia is not present. What is the correct diagnosis?

Fibroadenoma
Juvenile fibroadenoma
Myxoid fibroadenoma
Phyllodes tumor (benign)
Phyllodes tumor (borderline)

Board review style answer #1

B. Juvenile fibroadenoma. The clinical presentation and histologic features are characteristic of a juvenile fibroadenoma.

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Reference: Fibroadenoma

Board review style question #2

A 25 year old woman presents with a 3 cm breast mass. An ultrasound guided biopsy shows a fibroepithelial lesion. Which histologic feature is consistent with a diagnosis of fibroadenoma?

Circumscribed borders
Marked stromal cytologic atypia
Stromal condensation around glandular structures
Stromal mitotic activity (7 - 8/10 high power fields)
Stromal overgrowth

Board review style answer #2

A. Circumscribed borders. Fibroadenomas generally show noninfiltrative, circumscribed borders. The histologic features in answer choices B, C, D and E are observed in phyllodes tumors.

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Reference: Fibroadenoma

Board review style question #3

Which of the following is true about the breast lesion shown above?

Displays infiltrative margins
Most common benign tumor arising in the breast
Occurs primarily in postmenopausal women
Often has a brisk mitotic rate
Stromal overgrowth is a key finding

Board review style answer #3

B. Most common benign tumor arising in the breast. This is a fibroadenoma.

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Reference: Fibroadenoma

Board review style question #4

Fibroadenomas harbor epithelial atypia or malignancy at approximately what rate?

0.2%
2%
20%
50%

Board review style answer #4

B. 2%. The classification and behavior of fibroepithelial tumors of the breast including fibroadenoma and phyllodes tumor is driven by the stroma. However, epithelial changes may be seen and are thought to occur by chance or are driven by unrelated risk factor(s). Thus, epithelial atypia and malignancy is uncommon, with a recent large study by Krishnamurthy et al. showing a rate of ~2% (Breast Dis 2019;38:97). See Case #533 for more information.

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Reference: Fibroadenoma

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