Breast - nonmalignant
Normal histology of breast

Author: Belinda Lategan, M.D. (see Authors page)

Revised: 24 July 2017, last major update January 2015

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

PubMed Search: Breast [title] histology [title]

Cite this page: Normal histology of breast. website. Accessed March 19th, 2018.
Definition / general
  • Composed of epithelial and stromal components
  • The ductolobular system is composed of a dual layer of epithelia resting on a basement membrane ("basal lamina") and enveloped by stroma
  • A variety of benign metaplastic changes may be seen in the luminal and myoepithelial cells
  • See also normal anatomy of breast
Luminal (epithelial) cells
  • Columnar: cuboidal epithelium, may be pseudostratified (extralobular); innermost layer of bilayered ductolobular system
  • Myoepithelium: outermost layer resting on a basement membrane
Basement membrane
  • Only partially covered by contractile meshwork; i.e. incomplete on cross section
  • Surrounds mammary ducts, ductules and acini
  • Contains type IV collagen and laminin
  • Separates the ductal system from the surrounding stroma
    • Transgression of the basement membrane and myoepithelial layer by tumor cells defines invasive carcinoma in the setting of DCIS
    • Some types of invasive carcinoma may demonstrate basement membrane material by special stains
  • Stroma can be divided into
    • Interlobular stroma
      • Surrounds large ducts and terminal duct lobular units (TDLUs)
      • Denser, more collagenous than intralobular connective tissue
      • Becomes more fatty after puberty; increase in volume of this compartment is responsible for majority of breast volume
      • Increased density of this compartment may make mammographic detection of breast lesions more difficult
    • Intralobular stroma
      • Surrounds acini within terminal duct lobular units
      • Stroma is loose and contains fibroblasts, scattered lymphocytes and plasma cells, macrophages and vessels
      • May appear myxoid
      • Hormonally responsive
      • No elastic fibers
  • Multinucleated stromal giant cells
    • Worrisome at first glance but no known clinical significance
  • Intramammary lymph nodes
    • May appear as densities on mammography
    • Most often incidentally detected in surgical specimens
    • Treated as axillary nodes for TNM staging purposes in setting of malignancy
Nipple - areolar complex
  • Nipple and areolar skin is variably pigmented
    • Essentially unpigmented before menarche, pigmentation increases around puberty
  • Contains numerous sebaceous glands
    • Independent of hair follicles except at the periphery of the areola
    • Montgomery tubercles are sebaceous glands which share an ostium with a lactiferous duct
      • More prominent during pregnancy and lactation
    • Apocrine glands may also be present
  • Contains dense fibrous stroma containing bundles of smooth muscle tissue
  • Contains Toker cells, which are clear cells basally located in epidermis
    • Identifiable in 10% of normal nipples
    • Of these, Toker cell hyperplasia occurs in 27%, with atypia in up to 12% (Hum Pathol 2008;39:1295)
  • Stratified squamous epithelium extends into duct lumens for a short distance
Clear cell change / metaplasia
  • Epithelial cells become enlarged with well defined cell membranes and hyperchromatic, condensed nuclei often displaced into center of cell
    • Ultrastructural studies demonstrate the cytoplasm is distended by lipid and protein granules
  • Often affects the majority of cells in a given lobule
  • Uncertain significance and etiology
    • Unrelated to exogenous hormones, menopause, pregnancy, lactation or malignancy
    • May be seen in normal breast tissue or incidentally in the epithelium or myoepithelium of other breast lesions
    • Potential pitfall of mistaking benign clear cell change for involvement of lobules by clear cell variants of in situ carcinoma
    • Very rarely represents metastatic clear cell carcinoma from other sites
  • Clear cell change may also be seen in otherwise unremarkable myoepithelial cells
Menstrual cycle related changes
  • Clinically manifested by changes in breast size and texture, varies between individuals
  • Proliferative phase (follicular) breast
    • Small lobules with few terminal duct structures, rare mitotic figures and condensed intralobular stroma
    • Acinar lumina small and inapparent early on, open and better defined during late follicular phase
    • Since breast tissue typically is less nodular at days 8 - 14, this may be the optimal time for clinical breast exam and possibly mammography (J Natl Cancer Inst 1998;90:906)
  • Secretory phase (luteal) breast
    • Larger lobules, more terminal duct structures, basal epithelial cell proliferation and vacuolization, stromal edema (breast fullness) and increased mitotic figures
    • Stromal lymphocytes increase at end of secretory phase
  • Perimenstrual breast
Pregnancy / lactation
  • Reduction of estrogen and progesterone causes progressive involution and atrophy of TDLUs, reduction in size and complexity of acini and loss of specialized interlobular stroma
  • In elderly women, residual estrogenic stimulation maintains vestigial remnants of lobules
  • Hormone replacement therapy (HRT) attenuates these changes and may even stimulate proliferative changes
  • TDLUs are small, epithelium has less cytoplasm and basement membrane material may appear more prominent and hyalinized
  • As specialized breast stroma also involutes, small atrophic lobules may be seen fully surrounded by fat
  • Ducts may become ectatic with cystic appearance (not fibrocystic change)
  • Pre-existing fibroadenomas may decrease in size with stromal calcification
  • Vascular calcifications become more prominent, especially in those with coronary artery disease and diabetes
  • Elastosis (excess elastic fibers) is found in 50% of women age 50+ years without breast disease, either diffusely in stroma, around vessels or around ducts
  • Marked perivascular elastosis may be suggestive of malignancy (Arch Pathol Lab Med 1991;115:1241)
  • Testosterone causes involution of male mammary gland, except in testicular feminization syndrome (no testosterone receptors)
  • Breast is primarily composed of ductal structures within collagenized stroma, with no / rare lobular elements compared to female breast
Transsexual breast
  • Female to male conversion results from prolonged androgen administration, starting prior to mastectomy
    • Calcifications are more frequent in androgen suppressed breast compared to other reduction mammoplasty specimens
    • Prominent collagenized stroma and atrophy of ductolobular structures
  • Male to female conversion involves prolonged estrogen therapy and chemical castration with progestational agents which block androgen receptors
Microscopic (histologic) images

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Images hosted on PathOut server:

Clear cell change (AFIP, fig 9 - 10)

Myoepithelial hyperplasia with clear
round myoepithelial cells displacing
glandular epithelial cells

Myoid metaplasia derived from
HHF+ myoepithelial cells; squamous
metaplasia arising in duct

Images hosted on other servers:

Normal lobules

Two layers

Clear cell change, by Dr. Semir Vranic, University of Sarajevo

Treatment related atypia

Menstrual cycle changes

Epithelial cells have ER+ nuclei

Epithelial cells have PR+ nuclei


Smooth muscle actin (SMA)


CD10, SMA, S100


Type IV collagenase (upper left)

FOSB protein


Pilosebaceous units

Nipple and lactiferous duct

Lactiferous ducts

Positive stains
Negative stains
Electron microscopy images

Images hosted on other servers:


Glandular and myoepithelial cells

Molecular / cytogenetics description

Shotgun histology inactive breast
Differential diagnosis