Mammary Gland

Overview

  • The mammary gland is a distinctive organ of mammals, typically located on the upper anterior thorax.
  • It is a modified sweat gland that plays a role in milk production and secretion.
  • The mammary gland’s functional units begin developing at puberty and reach full maturation during pregnancy, preparing the gland for lactation.
  • Milk secretion involves both merocrine and apocrine mechanisms:
    • The protein component is produced by merocrine secretion.
    • The lipid component is produced by an apocrine mechanism.
    • Morphological changes occur during the menstrual cycle, pregnancy, lactation, and menopause, depending on estrogen and progesterone stimulation.

    Mammary Parenchyma

    • The mammary gland is organized into 12–20 lobes, each lobe is arranged radially and drains into the nipple through a distinct lactiferous duct.
    • Each mammary lobe contains numerous Terminal duct–lobular unit (TDLU), and each TDLU drains into an interlobular duct (ILD).
    • Each TDLU is composed of multiple lobules drained each by a short extralobular terminal duct (ELTD).
    • Each lobule contains numerous acini (Ductules) that drain each into an intralobular terminal duct (ILTD).
    • Each lobe has 3 components:
    • 1. Branched Tubulo-Alveolar Glands and Ducts:
      • a.  Acini and intralobular terminal ducts :
      • Acini are arranged in an alveolar pattern and group together to form lobules.
      • b.  Extralobular terminal ducts : These are larger ducts that are continuous with the lobules, which constitute the TDLU.
      • c.  Lactiferous ducts (Collecting ducts) : Large ducts that drain each lobe and may show a short dilation near the nipple (classically termed the lactiferous sinus).
      • 2. Intralobular Connective Tissue:
      • Surrounds acini within the TDLU.
      • Loose connective tissue containing fibroblasts and inflammatory cells.
      • 3. Adipose Tissue:
      • Composed of mature adipocytes.
      • The amount of adipose tissue is variable.
      • Mammary lobes are separated by dense fibrous septa that constitute the interlobular connective tissue:
      • It surrounds lactiferous ducts and TDLU.
      • Denser and more collagenous than intralobular connective tissue.

      The mammary gland consists of three components in varying proportions: glandular tissue, connective tissue, and adipose tissue.

      Trichrome stain highlights the abundance of fibrous tissue compared to the glandular component in a resting mammary gland.

      Lobules are composed of an alveolar arrangement of acini, surrounded by a delicate stroma.

      Intralobular stroma is a loose connective tissue surrounding the acini and intralobular termlinal ducts.
      Interlobular stroma is denser, collagen-rich tissue that separates and supports the lobules and ducts.

      Intralobular stroma is hormonally responsive, and consists of loose connective tissue containing inflammatory cells and fibroblasts.

      The interlobular stroma contains a variable amount of adipose tissue and a rich vascular network.

      • The mammary gland epithelium consists of a bilayered lining throughout the entire ductal and lobular system:
      • Internal layer (luminal or epithelial cells) : Cuboidal to columnar secretory cells with a central nucleus and eosinophilic cytoplasm.
      • Cuboidal epithelial cells line the acini and the small ducts, namely the intralobular terminal ducts, and extralobular terminal ducts.
      • Columnar epithelial cells are found mainly in interlobular ducts and lactiferous ducts.
      • Distal to the lactiferous sinus, ductal columnar epithelium becomes keratinized stratified squamous for 1-2mm from the nipple surface.
      • External layer (myoepithelial cells) : Composed of stellate-shaped myoepithelial cells with a single nucleus. The cytoplasm often appears clear due to glycogen accumulation, which varies with the cycle, and it contains abundant filaments that enable contraction and basement-membrane production.
      • Epithelial and myoepithelial cells arise from a bipotent progenitor cell.
      • The basement membrane surrounds and separates the ductal and lobular system from the stroma.
      • It contains type IV collagen and laminin.

      Epithelial cells are cuboidal to columnar, with eosinophilic cytoplasm and central nuclei. Myoepithelial cells are flattened with clear cytoplasm and elongated nuclei.

      Large distal lactiferous ducts are lined by columnar epithelial cells, which are taller than those lining the acini, along with underlying myoepithelial cells.

      Nipple-Areolar Complex

      Nipple:

      • A skin projection consisting of admixed dense fibrous tissue and smooth muscle bundles, covered by variably hyperpigmented and hyperkeratotic skin:
      • The thick keratin layer provides protection against trauma during nursing.
      • Smooth muscle in the nipple-areolar complex enables nipple erection, facilitating milk expression.
      • Large ducts open through 10–15 orifices at the nipple surface.
      • The squamous epithelium may contain clear cells (Toker cells), which are of presumed mammary ductal origin and are benign.

      Areola:

      • A pigmented skin area surrounding the nipple.
      • Contains Montgomery’s sebaceous glands.
      • Specialized areolar glands (modified sebaceous glands) that produce the surface elevations (Montgomery tubercles) and lubricate the areolar epidermis.
      • They become more prominent during pregnancy and lactation.

            The nipple is a skin projection composed of dense fibrous tissue and smooth muscle bundles.
            Multiple lactiferous ducts extend toward the surface.

            The nipple contains multiple smooth muscle bundles in a fibrous stroma, some bundles are sectioned longitudinally, while others are transversally sectioned.

            Trichrome stain highlights the fibrous architecture of the nipple and the unstained muscle fibers.

            Cross-section of the nipple’s lactiferous duct showing an undulating lumen surrounded by smooth muscle bundles and collagenous stroma.

            The skin of the nipple consists of keratinizing squamous epithelium with associated adnexal structures (sebaceous glands).

            The nipple-areolar complex exhibits basal layer hyperpigmentation of the epidermis.

            Physiologic Changes of the Mammary Gland

            • Menstrual Cycle:
            • Epithelial cells become taller due to the effects of estrogen during ovulation.
            • Pregnancy:
            • During the secretory phase, the glands proliferate and the ductal lumina become prominent.
            • Acini enlarge, and the epithelial cells undergo hypertrophy.
            • The number and size of ducts increase.
            • The amount of connective and adipose tissue decreases.
            • Lactation:
            • The epithelial component becomes more prominent compared to the stromal component.
            • The lumina of acini may contain heterogeneous secretions and cell debris.
            • Epithelial cells contain large fat droplets.
            • Menopause Effects:
            • Mammary glands gradually undergo involution.
            • Acini atrophy and are resorbed.
            • Epithelial cells undergo apoptosis and are phagocytosed by macrophages in the stroma.
            • Ducts also regress, although some persist and may occasionally form cysts.
            • Connective and adipose tissue atrophy.

            During pregnancy, the acini enlarge, while the amount of connective and adipose tissue decreases.

            During pregnancy, epithelial cells undergo hypertrophy, and the ducts increase in size and number.

            During lactation, the glandular component becomes more prominent compared to the stromal component.

            During lactation, epithelial cells often contain large fat droplets, giving some cells a clear appearance.