Atypical ductal hyperplasia

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Author: Mikael Häggström [note 1]

Gross examination

As per:

or mastectomy.

Microscopic evaluation

Histological appearance of atypical ductal hyperplasia (ADH) and immunohistochemical phenotype:[1]
- A - One focus (< 2 mm) of two architecturally disarranged cross sections of tubuli showing a monotonous intraductal proliferation with secondary intraluminal architecture.
- B - One area of an ADH with associated intraluminal calcifications.
- C - Higher magnification of ADH shows low-grade nuclear atypia and monotonous cell proliferation along with secondary intraluminal architecture.
- D - Strong and uniform expression of estrogen receptors (ER). ER immunohistochemistry.
- E - Lack of basal cytokeratins (CK5/6). CK5/6 immunohistochemistry.

Atypical ductal hyperplasia shows epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.[2]

Differential diagnoses

Ductal carcinoma in situ

There is no single definite cutoff that separates atypical ductal hyperplasia from ductal carcinoma in situ, but the following are important distinctive features of atypical ductal hyperplasia, with suggested cutoffs:[3]

  • Size less than 2 mm.
  • Not involving more than one duct.
  • The atypical epithelial proliferation is admixed with a second population of proliferative cells without atypia.
  • The proliferation completely involves the terminal ductal lobular unit(s), to a limited extent.

Also, ADH tends to have rounded lacunae between cells, in contrast to more crescent-shaped (compressed) lucunae in DCIS.

Usual ductal hyperplasia (UDH)

In contrast to usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) displays:[4]

  • Increased amounts of pale eosinophilic to amphophilic cytoplasm with conspicuous cell borders
  • Atypical architectural patterns, including cribriform spaces, Roman arches, trabecular bars and micropapillae

If uncertain, immunohistochemistry can be performed:[4]

Usual ductal hyperplasia (UDH) Atypical ductal hyperplasia (ADH)
High molecular weight keratins Mosaic to occasionally diffuse Negative
Estrogen receptor Heterogenous staining Diffusely positive


  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

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  1. Rageth, Christoph J.; Rubenov, Ravit; Bronz, Cristian; Dietrich, Daniel; Tausch, Christoph; Rodewald, Ann-Katrin; Varga, Zsuzsanna (2018). "Atypical ductal hyperplasia and the risk of underestimation: tissue sampling method, multifocality, and associated calcification significantly influence the diagnostic upgrade rate based on subsequent surgical specimens ". Breast Cancer 26 (4): 452–458. doi:10.1007/s12282-018-00943-2. ISSN 1340-6868.  This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (
  2. David J. Myers; Andrew L. Walls.. Atypical Breast Hyperplasia. StatPearls, National Center for Biotechnology Information. Last Update: February 15, 2019.
  3. Tozbikian, Gary; Brogi, Edi; Vallejo, Christina E.; Giri, Dilip; Murray, Melissa; Catalano, Jeffrey; Olcese, Cristina; Van Zee, Kimberly J.; et al. (2016). "Atypical Ductal Hyperplasia Bordering on Ductal Carcinoma In Situ ". International Journal of Surgical Pathology 25 (2): 100–107. doi:10.1177/1066896916662154. ISSN 1066-8969. 
  4. 4.0 4.1 Sofia Lérias, M.D., Melinda Lerwill, M.D.. Usual ductal hyperplasia. Pathology Outlines. Last author update: 11 February 2021. Last staff update: 25 April 2022

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