Breast - nonmalignant
Atypical hyperplasia
Atypical ductal hyperplasia (ADH)

Author: Jaya Ruth Asirvatham, MBBS, M.D. (see Authors page)
Editor: Julie M. Jorns, M.D.

Revised: 14 August 2017, last major update October 2014

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Atypical ductal hyperplasia [title] breast

Cite this page: Asirvatham, J.R., Jorns J.M. Atypical ductal hyperplasia (ADH). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastadh.html. Accessed September 22nd, 2017.
Definition / general
  • Neoplastic intraductal lesion with architectural and cytological features suggestive but not diagnostic of low grade DCIS
Terminology
  • Also called DIN 1B, atypical intraductal hyperplasia (AIDH), mammary intraepithelial neoplasia (MIN)
Epidemiology
Etiology
  • ADH and coexisting cancers may arise independently in field of increased cancer risk, as genetic changes (at 1q and 16q) are not identical (J Pathol 2006;209:307)
Clinical features
  • There are no clinical features associated with ADH
Radiology description
  • No definite diagnostic features
  • On mammography, lesions may be identified as masses, asymmetric densities, microcalcifications and architectural distortions
  • On ultrasound, lesions appear as hypoechoic masses with irregular shape, microlobulated margins, abrupt interface
  • Underestimation rate of ADH is high (56% by mammograph / USG and 32% by MRI) (AJR Am J Roentgenol 2014;202:1389, AJR Am J Roentgenol 2014;203:682)
Prognostic features (for carcinoma)
  • Relative risk of carcinoma is 4 - 5x; lower risk if 0 - 2 foci at core biopsy (see below)
  • Early studies suggested a 10x relative risk if positive family history of breast cancer but newer studies find no such increase (Cancer Prev Res (Phila) 2014;7:211)
  • Estimated 10 year cancer risk is 17 - 26% (Breast Cancer Res Treat 2012;136:627)
  • There is a 2:1 ratio of ipsilateral to contralateral breast cancer, with higher ipsilateral risk within the first five years (Cancer Prev Res (Phila) 2014;7:211)
  • Risk for breast cancer is higher for younger women and those with multiple foci of ADH
  • Mean time from atypia to carcinoma diagnosis is 10.3 years
  • 25% develop DCIS, 75% develop invasive carcinoma
  • 76% of carcinomas are ductal, 8.5% are lobular; 75% are node negative
  • 2/3 are moderate or high grade
Treatment
Microscopic (histologic) description
  • Usually less than 2 - 3 mm, may be multicentric
  • Must rule out DCIS (Breast Cancer Res 2003;5:254)
  • Micropapillae, tufts, bridges, solid and cribriform patterns of evenly distributed, monomorphic cells with rounded or ovoid nuclei
  • Either closely mixed with epithelial ductal hyperplasia (without atypia) or only partially involving the terminal duct lobular unit
  • Perineural invasion is rare and usually associated with sclerosing adenosis or radial scar (Hum Pathol 2001;32:785)
  • Variable microcalcifications
  • Recommended to include size of lesion in surgical pathology report
  • Either (1), (2) or (3) AND no high grade cytology (Stanford University: Atypical Ductal Hyperplasia):
    1. Ducts are completely filled and exhibit sharp punched out spaces or micropapillae but lack uniform cytologic features due to partial population of columnar cells or focal streaming of cells
    2. Ducts filled by uniform population of cells with cytologic features of low grade DCIS but lack architectural features due to only partial filling of ducts or no uniformly sharp punched out spaces, microacini or characteristic micropapillae AND have excluded solid low grade DCIS
    3. Cytologic and architectural features of DCIS but lesion is too small (fewer than two duct spaces involved or less than 2 - 3 mm in aggregate dimension)*
  • * Differentiation of ADH and low grade DCIS based on size cutoffs is controversial due to lack of expert agreement
Microscopic (histologic) images

Images hosted on PathOut server:

AFIP images:
    

Cells don't stream and are haphazardly
arranged in cellular bridges with
mitotic activity (arrows) but
secondary lumina are irregular

    

Cells have uniform size and shape,
small foci of necrosis and calficiation
but secondary lumina are irregular
and more numerous at periphery


Uniform cells but irregular secondary lumina

Papillary proliferation of multilayered epithelium involving only part of duct

Rounded secon-dary lumens and heterogenous cell population

 

Ducts are lined by
crowded, hyperplastic,
tall columnar cells
forming small papillae


Contributed by Dr. Mark R. Wick

Contributed by Dr. Marilin Rosa, University of Florida - ADH involving areas of sclerosing adenosis in complex sclerosing lesion



Images hosted on other servers:

Irregular glandular spaces

Enlarged, irregular, hyperchromatic nuclei

Solid filling of a duct

Atypical cells quite homogeneous

Micropapillary and cribriform pattern

Nuclei are crowded and hyperchromatic


Similar architecture seen in DCIS

Nuclei are crowded and overlapping

Proliferating epithelium are rigid and "punched out"

Nuclei are haphazardly arranged

Cribriform type

Micropapillary type


Cribriform type, high power

Cells are irregularly arranged

Cell margins are indistinct

Usual ductal hyperplasia (CK903+) versus ADH (CK903-)

Various images of ADH at core biopsy

ADH and subsequent invasive carcinoma

Virtual slides

Images hosted on other servers:

ALH and ADH involving a fibroadenoma

ADH, papillary lesions

Cytology description
  • Three dimensional cells with uniform nuclei and occasional mild atypia
Cytology images

Images hosted on other servers:

Ductal lavage

Positive stains
Negative stains
Differential diagnosis
  • Columnar cell lesion: prominent apical cytoplasmic snouts and intraluminal secretions
  • Flat epithelial atypia: replacement of epithelial cells by single or stratified layer of cells with low grade cytologic atypia resembling low grade DCIS but does not fulfill criteria of ADH or low grade DCIS
  • Low grade DCIS: larger lesion involving entire terminal duct lobular unit, uniform cells, no secondary lumina
  • Usual ductal hyperplasia: mix of cell types (luminal, basal, myoepithelial) that express different cytokeratins (note that because ADH is clonal, CK expression is restricted to one type, usually luminal)