Fibrocystic changes

Usual ductal hyperplasia

Editorial Board Member: Gary Tozbikian, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Sofia Lérias, M.D.
Melinda Lerwill, M.D.

Last author update: 11 February 2021
Last staff update: 25 April 2022

Copyright: 2002-2023,, Inc.

PubMed Search: Usual ductal hyperplasia[TIAB] free full text[SB]

Sofia Lérias, M.D.
Melinda Lerwill, M.D.
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Cite this page: LĂ©rias S, Lerwill M. Usual ductal hyperplasia. website. Accessed September 27th, 2023.
Definition / general
  • Benign intraductal proliferation of progenitor epithelial cells with varying degrees of solid or fenestrated growth
Essential features
  • Component of fibrocystic changes
  • Mild cytologic variability
  • Streaming growth pattern with fenestrated spaces and lack of cellular polarity
  • Immunoreactive for high molecular weight cytokeratins
  • Associated with slight increase in subsequent breast cancer risk (1.5 - 2 times)
  • Also called epithelial hyperplasia, intraductal hyperplasia, hyperplasia of usual type, ductal hyperplasia without atypia, epitheliosis
ICD coding
  • ICD-10: N60.99 - unspecified benign mammary dysplasia of unspecified breast
  • ICD-11: GB20.Y - other specified benign breast disease
  • Terminal duct lobular units
  • Occasionally, extralobular ducts
  • Proliferation of CK5+ progenitor cells that can differentiate along glandular or myoepithelial lineages; glandular progenitor cells appear to predominate and show intermediate levels of differentiation (J Pathol 2002;198:458)
  • No specific etiologic factors
Clinical features
  • No specific clinical findings
  • Diagnosis by histologic examination of tissue removed via biopsy or surgical excision
Radiology description
  • No specific mammographic findings; occasional examples are associated with microcalcifications
  • Can involve an underlying lesion (e.g. radial scar or papilloma) that is identified on imaging
  • May show enhancement on magnetic resonance imaging (Arch Pathol Lab Med 2017;141:1513)
Prognostic factors
Case reports
  • No treatment necessary
Gross description
  • No macroscopic findings
Microscopic (histologic) description
  • Proliferation of cells of luminal and myoepithelial lineages, occasionally with intermixed apocrine cells
  • Cytologic features (Semin Diagn Pathol 2004;21:10)
    • Mild variation in cellular and nuclear size and shape
    • Relatively small ovoid nuclei with frequent elongated or asymmetrically tapered (pear shaped) forms
    • Lightly granular euchromatic chromatin and small nucleoli
    • Frequent longitudinal nuclear grooves (coffee bean-like) and occasional nuclear pseudoinclusions
    • Many examples demonstrate cellular maturation, where the cells shrink as they progress from a basal location to the center of the proliferation, becoming small and nearly pyknotic
    • Eosinophilic, nonabundant cytoplasm with indistinct cell borders
  • Architectural features (Semin Diagn Pathol 2004;21:10)
    • Cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern
    • Fenestrated, solid and occasional micropapillary patterns
    • Irregular slit-like fenestrations are common, especially along periphery
    • Cells run parallel to the edges of secondary spaces and do not exhibit a polarized orientation (this contrasts with the cells of atypical ductal hyperplasia and ductal carcinoma in situ, which have apical-basal polarity and radially orient their apical poles toward the spaces)
  • Variant patterns and features
    • Micropapillary
      • Typically focal in a background of conventional pattern usual ductal hyperplasia
      • Mild duct dilation
      • Short stubby papillae of roughly uniform height
      • Cytologic features of usual ductal hyperplasia
      • Cellular maturation present, with tips of papillae formed by tight knots of mature cells
      • Lack of polarization
    • Immature
      • Uncommon variant
      • Larger immature basal hyperplastic cells predominate or are increased beyond their usual 1 - 2 cell layers and are instead several cell layers thick
      • Cellular maturation is still present
      • Most often encountered in fibroepithelial lesions with cellular stroma
    • Necrosis
      • Florid usual ductal hyperplasia can rarely demonstrate central necrosis
      • Typically occurs within a radial scar / complex sclerosing lesion, nipple adenoma or juvenile papillomatosis
    • Mild nuclear enlargement in radial scars
      • Florid usual ductal hyperplasia within radial scars / complex sclerosing lesions can occasionally have more active appearing nuclei with mild nuclear enlargement
      • Other cytologic and architectural features of usual ductal hyperplasia remain intact
Microscopic (histologic) images

Contributed by Melinda Lerwill, M.D.
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Cytologic features

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Cellular maturation

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Merging with apocrine metaplasia

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Fenestrated spaces

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Lack of cellular polarity

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Micropapillary usual ductal hyperplasia

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Immature usual ductal hyperplasia

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Florid usual ductal hyperplasia in radial scar

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Cytokeratin 5/6

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Estrogen receptor

Cytology description
  • Sample may be moderately to highly cellular
  • Sheets and cohesive clusters of bland ductal cells with regular spacing and associated myoepithelial cells (Am J Clin Pathol 1995;103:438)
  • Lack of significant nuclear overlap / crowding
  • Ductal cell nuclei with finely granular chromatin and inconspicuous small nucleoli
  • Lack of ductal cell discohesion
  • Naked myoepithelial cell nuclei in the background may be present
Cytology images

Contributed by Amy Ly, M.D.
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Fine needle aspiration

Positive stains
Molecular / cytogenetics description

High yield breast pathology cases

Sample pathology report
  • Left breast, needle core biopsy:
    • Usual ductal hyperplasia
Differential diagnosis
Board review style question #1

    What is the risk for subsequent breast cancer associated with the illustrated lesion?

  1. 1.5 - 2 times increased risk
  2. 2 - 3 times decreased risk
  3. 4 - 5 times increased risk
  4. 8 - 11 times increased risk
  5. No change in risk compared to control populations
Board review style answer #1
A. 1.5 - 2 times increased risk

This is usual ductal hyperplasia. Usual ductal hyperplasia is associated with a slight increase in risk (1.5 - 2 times) for subsequent breast cancer. Risk appears to be slightly higher in those patients with a positive family history of breast cancer.

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Reference: Usual ductal hyperplasia
Board review style question #2
    What is the typical high molecular weight cytokeratin / estrogen receptor (HWMCK / ER) immunoprofile for usual ductal hyperplasia of the breast?

  1. HMWCK negative / ER diffusely positive
  2. HMWCK negative / ER negative
  3. HMWCK mosaic positive / ER diffusely positive
  4. HMWCK mosaic positive / ER heterogeneously positive
  5. HMWCK mosaic positive / ER negative
Board review style answer #2
D. HMWCK mosaic positive / ER heterogeneously positive

Usual ductal hyperplasia is positive for HMWCK in a mosaic to occasionally diffuse pattern and demonstrates heterogeneous positivity for ER.

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Reference: Usual ductal hyperplasia
Board review style question #3
    Which of the following is a feature of usual ductal hyperplasia that aids in distinguishing it from low grade ductal carcinoma in situ?

  1. Cellular maturation
  2. Monomorphic hyperchromatic nuclei
  3. Palisading around fibrovascular cores
  4. Polarization around secondary spaces
  5. Red macronucleoli
Board review style answer #3
A. Cellular maturation

Many examples of usual ductal hyperplasia demonstrate cellular maturation, where the cells shrink as they progress from a basal location to the center of the proliferation, becoming small and nearly pyknotic. Cellular maturation is not a feature of low grade ductal carcinoma in situ or atypical ductal hyperplasia.

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Reference: Usual ductal hyperplasia
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