Topic Completed: 1 January 2015

Minor changes: 14 September 2020

Copyright: 2002-2019,, Inc.

PubMed Search: Breast [title] histology [title]

Belinda Lategan, M.D.
Page views in 2019: 18,616
Page views in 2020 to date: 14,942
Cite this page: Lategan B. Histology. website. Accessed November 23rd, 2020.
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
  • Breast is considered an epidermal gland because it develops as diverticula of epidermis into dermis
  • Also considered a modified and highly specialized apocrine gland
  • Mammary gland development begins at week 4, when ectoderm and underlying mesoderm proliferate and differentiate into skin

  • Week 4: paired ectodermal thickenings called mammary ridges or milk lines develop along ventral embryo and extend in curvilinear convex pattern from axilla to medial thigh; ridges will eventually disappear except at 4th intercostal space on anterior thorax, where mammary gland develops
  • Week 5: remnant of mammary ridge ectoderm proliferates and is termed primary mammary bud
  • Week 7: primary mammary bud grows downward into underlying dermis
  • Week 10: primary mammary bud branches into secondary buds
  • Week 12: secondary mammary buds start lobule development
  • Week 20: small lumina develop within mammary buds that coalesce and elongate to form lactiferous ducts
  • Week 20 - 32: differentiation of mesenchyme into fat
    • Stroma originating from reticular dermis form suspensory ligaments of Cooper attaching breast to skin and subdividing breast into lobes
  • Month 5: areola is formed by ectoderm
  • Week 23 - 28: myoepithelial cells arise from basal cells, playing an important role in branching morphogenesis of the mammary gland via synthesis of basement membrane constituents, growth factors and metalloproteinases
  • Near term birth: nipple formed by evagination of mammary pit
  • References: eMedicine: Breast Embryology, UC Davis: Early Development of the Human Breast, J Mammary Gland Biol Neoplasia 2000;5:119
Neonatal breast
  • Identical in males and females at birth
  • Nipple is small pit in center of thickened areola, becomes everted shortly after birth due to proliferation of mesenchyme underlying the areola
  • Breast enlargement (uni or bilateral) is present in up to 70% of neonates due to neonatal prolactin production, caused by falling levels of maternal estrogens; associated with production of "witch's milk" in males and females
  • Continued breast stimulation (squeezing or massaging breasts) may cause hypersecretory state to persist
  • Milk secretion: resembles colostrum; contains water, fat and cellular debris
  • Duct dilation without acini
  • References:Semin Cell Dev Biol 2012;23:567, eMedicine: Breast Embryology
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
Diagrams / tables

Images hosted on other servers - Embryology:

Milk lines

Lifetime mammary gland development

Microscopic (histologic) images

Scroll to see all images:

AFIP images

Neonatal breast ectasia with dilation of mammary ducts

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:

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


Pilosebaceous units

Nipple and lactiferous duct

Lactiferous ducts

Images hosted on other servers - Embryology:

Early branching of the major lactiferous ducts

Doughnut shaped disk

Enlarging breast

Cellular lobules

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
Back to top
Image 01 Image 02