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Breast-nonmalignant
Atypical hyperplasia
Flat epithelial atypia of breast
Reviewer: Hind Nassar, M.D. in January 2009 (see Authors page)
Revised: 7 October 2012, last major update April 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.
Definition
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● Replacement of epithelium by up to 5 layers of mildly atypical cells, presumably neoplastic
● Introduced by WHO Working Group on Pathology and Genetics of Tumours of the Breast to encompass columnar cell lesions with low grade/monomorphic cytologic atypia that lacked architectural features of ADH or low grade DCIS
Terminology
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● Also called atypical columnar change (columnar cell change with atypia or columnar cell hyperplasia with atypia), flat ductal intraepithelial neoplasia grade 1A (DIN1A), low grade clinging carcinoma, atypical lobular hyperplasia (by some)
Epidemiology
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● Common diagnosis in radiologic specimens classified as B3 - uncertain malignant potential (Hum Pathol 2010;41:522)
Sites
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●
Etiology
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● May be an early neoplastic breast lesion (Semin Diagn Pathol 2010;27:37)
Clinical features
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● Diagnosis is reproducible with available diagnostic criteria (Mod Pathol 2006;19:172)
● Underdiagnosed; often coexists with lobular neoplasia (Histopathology 2007;50:859)
● Associated with tubular carcinoma (Am J Surg Pathol 2007;31:417)
Prognostic factors
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● Risk for DCIS / invasive carcinoma varies by author from slightly increased warranting follow up (Virchows Arch 2007;451:883), to similar to traditional ADH warranting excision (Hum Pathol 2007;38:35), to warranting excision if > 1 cm (J Radiol 2006;87:1671)
● See also Treatment (below)
Case reports
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Treatment
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● No consensus on whether to excise after biopsy diagnosis:
- Recommended (Breast J 2009 Oct 13 [Epub ahead of print], Am J Clin Pathol 2009;131:802)
- Consider since upgrade risk is not negligible (Ann Clin Lab Sci 2009;39:270)
- Not recommended if pure flat epithelial atypia and 11 gauge biopsy that removes most of small radiologic target (Am J Surg Pathol 2009;33:1078), not recommended for low radiologic risk calcifications (Mod Pathol 2009;22:762)
Gross description (Macroscopy)
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●
Gross images
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Micro description (Histopathology)
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● Replacement of epithelial cells by single or stratified layer of cells with low grade cytologic atypia resembling low grade DCIS, and distention of TDLU; usually more blue than normal TDLU at low power
● Flat growth pattern usually resembles blunt duct adenosis, cells are not regularly oriented perpendicular to basement membrane
● Also cystically dilated ducts with secretions or apocrine features (apical snouts)
● Nuclei are usually round with variably prominent nucleoli
● Often chronic inflammatory infiltrate and calcifications
● Does not fulfill criteria of ADH or low grade DCIS
● Usually no/rare micropapillary formations
● Table (Arch Pathol Lab Med 2009;133:879)
Micro images
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Various images
Comparison with
blunt
duct adenosis
Virtual Slides
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Flat epithelial atypia / ALH Flat epithelial atypia with ADH and calcification
Videos
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Cytology description
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Cytology images
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Positive stains
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● CK19, ER, PR
Negative stains
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● CK5, CK6, 34betaE12
Electron microscopy descriptions
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Electron microscopy images
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Molecular / cytogenetics description
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● Different molecular profile of p16(INK4a) epigenetic modifications from ADH and low grade DCIS (Hum Pathol 2008;39:1637)
● Clonally related to invasive tubular carcinoma (Am J Surg Pathol 2009;33:1646)
Molecular / cytogenetics images
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Differential Diagnosis
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● Blunt duct adenosis / columnar cell lesion: lacks atypia
Additional references
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● Breast Cancer Res 2003;5:263, Arch Pathol Lab Med 2008;132:615, Stanford University
End of Breast-nonmalignant > Atypical hyperplasia > Flat epithelial atypia
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