Breast-nonmalignant - Epithelial ductal hyperplasia

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Breast-nonmalignant

Fibrocystic disease

Epithelial ductal hyperplasia of breast

Reviewer: Hind Nassar, M.D. in January 2009 (see Authors page)

Revised: 6 October 2012, last major update March 2010

Definition

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● Benign ductal proliferative lesion that typically has secondary lumens and streaming of central proliferating cells

Terminology

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● Also called usual ductal hyperplasia, intraductal hyperplasia, hyperplasia of usual type, papillomatosis (but this term may be confused with papilloma or florid papillomatosis of nipple), epitheliosis

Epidemiology

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● Common form of fibrocystic disease

Sites

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Etiology

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● May be due to increase in mitotic rate of epithelial cells compared to apoptotic rate, causing an increased number of epithelial cells within preexisting glandular components (Hum Path 1998;29:1539, Breast Cancer Res 2001;3:276)

● Appears to derive from a CK5+ committed stem cell lesion with the same differentiation potential as normal breast, in contrast to ADH/DCIS, which displays a differentiated glandular immunophenotype (CK8/18/19+, CK5-, J Pathol 2002;198:458)

● May be influenced by EZH2 upregulation and colocalization with beta-catenin (Am J Pathol 2009;175:1246)

Clinical features

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● Overall may have slightly increased risk for invasive carcinoma with relative risk of 1.5-2.0 (Archives 1998;122:1053); high ERalpha/ERbeta ratio lesions are more likely to progress to breast cancer (Am J Surg Pathol 2005;29:1593)

Prognostic factors

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Case reports

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Treatment

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● No treatment needed

Clinical images

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Gross description (Macroscopy)

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Gross images

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Micro description (Histopathology)

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● Streaming (parallel arrangement) of central cells with indistinct cell borders, irregularly shaped and sized secondary lumens, often peripheral; tufts of cells project into lumina

● Peripheral elongated clefts (not round, not central), irregularly shaped bridges connect opposite portions of wall with nuclei parallel to long axis of the bridge (not Roman bridges)

● Cells have acidophilic and granular cytoplasm, oval normochromatic nuclei with slight overlap, small or indistinct nucleoli

● Myoepithelial cells and foamy macrophages are present

● Individual cells are well supported by their stroma

● Variable apocrine metaplasia, variable intraluminal or stromal calcifications, variable intranuclear round eosinophilic bodies (helioid inclusions); occasional fibrosis, elastosis or chronic inflammation; rarely necrosis

● Perineural invasion is rare, usually associated with sclerosing adenosis or radial scar (Hum Path 2001;32:785, Archives 2000;124:465)

● No/minimal mitotic figures; no psammoma bodies, no atypia, no prominent nucleoli

● Mild hyperplasia: 2-4 epithelial layers; no increased risk for invasive carcinoma

● Moderate hyperplasia: 4 or more epithelial layers; 1.5 to 2x increased risk for invasive carcinoma, higher if age 50+ years

● Florid hyperplasia: epithelium almost completely fills duct but with fenestrations (irregular lumina at periphery) and papillomatosis; 1.5 to 2x increased risk for invasive carcinoma

● Gynecomastia-like hyperplasia: micropapillary, resembles gynecomastia of male breast

● Thyroid-like hyperplasia: resembles tall cell variant of papillary thyroid carcinoma (see also Tall cell-like tumors in Breast-malignant chapter)

Micro images

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Distention of duct by cellular proliferation Oval/spindled epithelial cells and elongated

with irregular and slit-like spaces myoepithelial cells with dense chromatin

Spindled epithelial cells are parallel to long Micropapillary ductal hyperplasia with

axis of intraductal cellular bridges; cell bridges parallel arrangement of most cells

merge to form secondary lumina; myoepithelial and uniform nuclei

cells are present along borders of duct

Secondary lumina have irregular shapes Apocrine metaplasia forming secondary

lumina with foam cells

Secondary lumina adjacent to basement Perineural invasion

membrane are more rounded than smaller

central lumina and cell population is

heterogeneous

Mild hyperplasia

Florid hyperplasia

Various images

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

Virtual Slides

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Epithelial hyperplasia

Videos

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Epithelial hyperplasia

Cytology description

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● May rarely be hyperchromatic with increased N/C ratio and loss of 2 cell layers; however, be cautious if radiologic imaging and physical exam are not definitive for malignancy (Breast Cancer 2007;14:388)

Cytology images

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With apocrine metaplasia #1; #2; #3

Positive stains

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● 34betaE12 keratin (strong, Am J Surg Pathol 1990;14:939), CK 5/6 (Hum Path 2006;37:787), E-cadherin

● S100 (weak), ER

Negative stains

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Electron microscopy descriptions

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Electron microscopy images

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Molecular / cytogenetics description

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Molecular / cytogenetics images

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Differential Diagnosis

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Additional references

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End of Breast-nonmalignant > Fibrocystic disease > Epithelial ductal hyperplasia

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