Breast-nonmalignant

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Breast-nonmalignant

General

Normal histology of breast

Author: Nat Pernick, M.D. (see Authors page)

Revised: 14 March 2010, last major update March 2010

General

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Major ducts:

● Lined by pseudostratified columnar epithelium (extralobular) or double layer of cuboidal epithelium (intralobular); extralobular ducts are surrounded by well developed layer of elastic tissue

Terminal duct lobular unit (TDLU):

● Ductules (acini) with lobular architecture and intralobular connective tissue

Ductules (lobular ducts):

● Lined by inner layer of columnar or cuboidal epithelium (secretory and absorptive) and outer basal layer of myoepithelium (myofilaments oriented parallel to long axis of duct)

● A continuous basement membrane follows contour of duct and ductules

● Occasional neuroendocrine cells are present

Intralobular connective tissue:

● Loose myxomatous stroma with fibroblasts, lymphocytes, macrophages, vessels

● Hormonally responsive

● No elastic fibers

Interlobular connective tissue:

● Denser, more collagenous than intralobular connective tissue

● Becomes more fatty after age 18 years

Nipple:

● Contains numerous sebaceous glands independent of hair follicles, dense fibrous stroma containing erectile smooth muscle tissue, stratified squamous epithelium resembling skin but with increased melanin pigment, Toker cells (clear cells basally located in the epidermis, identifiable in 10% of normal nipples, but hyperplastic in 27% of these and atypical in 12%, Hum Path 2008;39:1295)

● Stratified squamous epithelium extends into duct lumens for a short distance

● Nipple is unpigmented before menarche, pigmentation increases after first menstrual cycle

Areola:

● Contains sebaceous glands

Menstrual cycle related changes:

● Proliferative phase breast has small lobules with few terminal duct structures, rare mitotic figures, condensed intralobular stroma

● Secretory phase breast has larger lobules, more terminal duct structures, basal epithelial cell proliferation and vacuolization, stromal edema (breast fullness), increased mitotic figures

● Stromal lymphocytes increase at end of secretory phase

● Perimenstrual breast tissue exhibits desquamation, apoptosis, atrophy, shrinkage (AJSP 1986;10:382)

Clear cell change:

● Clear cytoplasm contains glycogen, may represent metaplastic change towards eccrine sweat glands

Pregnancy / lactation:

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Post-menopausal:

● Largely adipose tissue with few residual ducts, acini or vessels

● Atrophy of glandular component is normal with age, may be microcystic (but not considered fibrocystic disease)

● In elderly women, residual estrogenic stimulation maintains vestigial remnants of lobules

● Elastosis (excess elastic fibers) found in 50% of women age 50+ years without breast disease, either diffusely in stroma, around vessels or around ducts

● Marked perivascular elastosis is suggestive of malignancy (Archives 1991;115:1241)

Males:

● Testosterone causes involution of male mammary gland, except in testicular feminization syndrome (no testosterone receptors)

Micro images

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Subgross

Normal lobules

Two layers

Terminal duct lobular unit

Various images

AFIP Fig 9-10: Clear cell change

Myoepithelial hyperplasia with clear, round AFIP Fig 333: myoid metaplasia derived

myoepithelial cells displacing glandular from myoepithelial cells (HHF+);

epithelial cells squamous metaplasia arising in duct

Menstrual cycle changes

Stage 1: days 0-5, eosinophilic luminal secretions

Stage 2: days 6-15, vacuoles in myoepithelial cells, can distinguish ductal and myoepithelial cells

Stage 3: days 16-24, prominent myoepithelial vacuoles

Stage 4: days 25-28, extensive stromal edema

Aging related changes

Post-treatment: normal acini

Epithelial cells have ER+ nuclei Epithelial cells have PR+ nuclei

E-cadherin

Myoepithelial stains

Smooth muscle actin Calponin

p63+

CD10, smooth muscle actin, S100

Type IV collagenase (upper left)

Nipple

With pilosebaceous units Nipple and lactiferous duct

Lactiferous ducts

Drawings

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Virtual Slides

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Infant breast

Normal breast

Videos

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normal breast

Cytology description

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Cytology images

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Normal breast

Positive stains

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Basement membrane:

● Laminin, type IV collagen, reticulin

Epithelium/luminal cells:

● CK 8/18, CK 19, CK7, EMA (apical region of active secretory cells), E-cadherin

● Milk fat globule membrane antigen, lactalbumin

Myoepithelial cells:

● Smooth muscle actin, CK5/6, CK14, CK17, S100

● p63 (nuclear staining, AJSP 2001;25:1054), CD10 (Mod Path 2002;15:397)

● E-cadherin and P-cadherin (J Pathol 1993;169:245)

● Calponin, smooth muscle myosin heavy chain, maspin, type IV collagen

Toker cells:

● ER, PR, CK7, EMA (Pathology 2009;41:640)

Negative stains

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Myoepithelial cells:

● EMA, ER, PR, p53, HER2 (AJCP 2003;120:161)

Toker cells:

● CD138, p53, p63, HER2, Ki-67 (or low)

Electron microscopy descriptions

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Electron microscopy images

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Acini Glandular and myoepithelial cells

Molecular / cytogenetics description

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● Global gene expression abnormalities exist in normal epithelium of breast cancer patients (Int J Cancer 2008;122:1557)

Molecular / cytogenetics images

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Differential Diagnosis

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● Atypical Toker cells may resemble Paget’s disease, but Toker cells are usually ER+, PR+, CD138-, p53-, HER2-, Paget’s cells are opposite (Hum Path 2008;39:1295)

Additional references

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End of Breast-nonmalignant > General > Normal histology

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