Atypical Ductal Hyperplasia

Atypical Ductal Hyperplasia

ADH has some, but not all, of the features of DCIS. Although some of the bridges appear rigid image, others have a streaming pattern image. A 2nd cell population also appears to be present image.

Some definitions of ADH include the extent of the lesion. The proliferation may need to involve at least 2 spaces, such as in this case, or be > 2 mm to be sufficient for low-grade DCIS.



  • Atypical ductal hyperplasia (ADH)


  • Ductal intraepithelial neoplasia (DIN) type 1b or 1c, depending on system used


  • Clonal intraductal proliferation with architectural and cytologic features approaching those seen in low-grade ductal carcinoma in situ (LGDCIS)


Molecular Pathology

  • DNA studies show genetic similarity between ADH and LGDCIS

    • Shared alterations include chromosomal gain of 1q and loss of 16q

      • Also seen in low-grade invasive ductal carcinoma (LGIDC)

  • Gene expression profiling data also show similarities shared by low-grade lesions

    • ADH, LGDCIS, and LGIDC have similar gene expression patterns

    • Differences are in quantitative levels of expression

    • No significant qualitative differences in expression patterns

    • Low-grade carcinomas express a unique set of genes rarely seen in high-grade carcinomas

  • ADH likely represents an early stage in a low-grade breast neoplasia pathway

  • However, majority of ADH does not progress to carcinoma

    • Factors responsible for progression from ADH to DCIS and IDC are poorly understood



  • Incidence

    • Present in 15-20% of breast biopsies performed to evaluate mammographic microcalcifications

  • Age

    • Peak: Women in mid 40s


  • Most commonly detected as clustered calcifications on screening mammography


  • Risk reduction

    • Interventions to decrease risk of subsequent breast cancer must address both breasts

    • Surgical approach would require bilateral mastectomies

    • Chemoprevention with tamoxifen reduces risk of ER-positive cancers

    • Majority of women opt for careful surveillance


  • ADH is a marker of increased risk for developing invasive carcinoma and a nonobligate precursor of carcinoma

    • Associated with a 4-5x increased relative risk or a 13-17% lifetime risk of invasive carcinoma

      • Cancer risk approximately equal in both breasts

      • Some (but not all) studies show increased risk for women with positive family history

Core Needle Biopsy

  • ADH on core needle biopsy is an indication for excision

    • DCIS is found in adjacent tissue in ˜ 15-20% of cases

      • Likelihood of DCIS is less for larger bore core needle biopsies

    • Invasive carcinoma is present in < 5%

  • Extent or type of ADH on core does not predict with certainty which patients will or will not have DCIS on excision

  • Factors associated with increased likelihood of malignant diagnosis on surgical excision

    • Marked nuclear atypia

    • Multiple foci of ADH

    • Micropapillary architecture


Mammographic Findings

  • Amorphous calcifications most common finding

    • Clustered distribution

    • Other calcification morphologies (punctate, pleomorphic, fine linear) favor DCIS

  • ADH may be an incidental microscopic finding associated with other benign lesions

    • Papilloma, fibroadenoma, apocrine cysts, radial sclerosing lesion, gynecomastia


Gross Findings

  • ADH does not form grossly apparent lesions


Histologic Features

  • ADH is a proliferation of luminal-type cells

    • May involve terminal ductal lobular units or interlobular ducts

    • Diagnosis is based on both qualitative and quantitative assessment

    • Main differential diagnosis is between ADH and LGDCIS

      • LGDCIS requires cytologic, architectural, and size criteria to be met

      • ADH demonstrates some but not all features of LGDCIS

  • Qualitative assessment in diagnosis of ADH

    • Architectural features

      • Most common are cribriform spaces or arched bridges; spaces often not as uniform as those seen in DCIS

      • Bridges across cribriform spaces may be thin and show streaming of cells

      • Micropapillae may be present, but generally not extensive

      • Often associated with columnar cell change

      • Focal necrosis is rarely present

    • Cytologic features

      • Cells are all luminal in type; lack expression of high molecular weight keratin 5/6

      • Cells appear to stand apart from one another with well-defined borders

      • Usually partially uniform in appearance

      • Cell populations of different morphologies may be present (cuboidal, spindle, columnar)

      • Involved spaces usually contain more than 1 cell population; monomorphic-appearing cells may merge with areas of usual type hyperplasia

      • High-grade nuclei should not be seen in ADH

  • Quantitative assessment in diagnosis of ADH

Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Atypical Ductal Hyperplasia

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