Breast histology

Basic structure

• The breast is a modified apocrine sweat gland of the skin, made of 15–20 lobes, each drained by a lactiferous duct that widens into a lactiferous sinus under the areola and opens on the nipple.
• The functional unit is the terminal duct lobular unit (TDLU): a terminal duct and its cluster of ductules (acini) in loose stroma. Most carcinomas, cysts and fibroadenomas arise here.
• Every duct and acinus has two cell layers: inner luminal epithelial cells (cuboidal to columnar) and outer myoepithelial cells on a basement membrane.
• Myoepithelial cells are contractile epithelial cells (actin, myosin, keratin) that contract under oxytocin to eject milk. Their presence is reassuring in benign lesions; loss of the myoepithelial layer on a biopsy is a sign of invasive carcinoma.
• Intralobular stroma is loose, cellular and hormone responsive; interlobular stroma is dense fibrous tissue with fat.
• Fibrous suspensory ligaments (Cooper) run from the deep fascia to the dermis. Tumour shortening them pulls the skin in (dimpling, retraction).
• Nipple: keratinised stratified squamous epithelium with circular and longitudinal smooth muscle that erects it. Areola: pigmented, with areolar (Montgomery) glands, sebaceous glands that enlarge in early pregnancy as Montgomery tubercles.

Skin signs explained by structure

• Peau d'orange is a lymphatic sign; dimpling is a ligament sign. Exams offer both as options.

The three states compared

• In the resting breast the stroma dominates; in pregnancy and lactation the epithelium dominates and the stroma is squeezed to thin septa.

Resting breast and the cycle

• In the luteal phase, oestrogen and progesterone cause lobular proliferation and intralobular stromal oedema, explaining premenstrual fullness and tenderness that settle with menstruation.
• After the menopause lobules atrophy and fat replaces glandular tissue, so mammograms become less dense.
• The male breast has ducts but no lobules, because lobule formation needs progesterone and oestrogen together.

Hormones of growth and milk

• Ducts belong to oestrogen; lobules and alveoli belong to progesterone. Prolactin makes the milk; oxytocin moves it.
• During pregnancy high oestrogen and progesterone block the milk-producing action of prolactin at the alveolar cell, so there is little secretion apart from colostrum even though prolactin is high. A woman with high prolactin in pregnancy who does not lactate is being held back by oestrogen and progesterone.
• After delivery of the placenta, oestrogen and progesterone fall and copious milk begins in about 2–4 days. Retained placental tissue can delay it.
• Suckling stimulates prolactin (milk production) and oxytocin (let-down).
• Prolactin suppresses GnRH pulses, so FSH and LH stay low and primordial follicles fail to mature: this is lactational amenorrhoea. Dopamine falls (it is the prolactin-inhibiting factor), and prolactin rises.

Lactating breast: how milk is secreted

• Proteins and lactose: casein is made on rough ER and taken to the Golgi. Lactose is synthesised inside the Golgi by lactose synthase (galactosyltransferase plus alpha-lactalbumin). Lactose is osmotically active, draws water into the vesicles, and leaves with the protein when the vesicles fuse with the apical membrane: merocrine secretion. Lactose does not diffuse out of the cell on its own.
• Milk fat: lipid droplets made in the smooth ER coalesce, bulge from the apex and leave wrapped in plasma membrane with a little cytoplasm: apocrine secretion. The membrane coat (milk fat globule membrane) keeps droplets dispersed.
• The lactating breast runs a very active pentose phosphate (HMP) shunt to provide NADPH for fatty acid synthesis.
• Secretory IgA: made by plasma cells in the stroma as dimers joined by a J chain, carried across the epithelium by the polymeric Ig receptor, whose cleaved part becomes the secretory component. It gives the baby passive mucosal immunity.
• Colostrum (first days): yellow, rich in IgA, protein and leucocytes, lower in fat and lactose than mature milk.

Involution and disease links

• After weaning, milk stasis and falling prolactin cause alveolar cells to die by apoptosis and be cleared by macrophages without inflammation; the breast returns to the resting state.
• Acute lactational mastitis and abscess: milk stasis plus Staphylococcus aureus entering through a cracked nipple.
• Periductal mastitis: in non-lactating smokers, squamous metaplasia of lactiferous ducts with keratin plugs leads to subareolar abscess and fistula.
• Fibroadenoma: commonest benign tumour under 35; proliferating intralobular stroma compresses ducts into slit-like spaces, and both epithelial layers are preserved.
• Galactorrhoea outside pregnancy points to hyperprolactinaemia (prolactinoma, dopamine antagonists, hypothyroidism).

Remember Pregnancy builds the factory (hyperplasia), delivery switches it on (fall of oestrogen and progesterone), suckling keeps it running (prolactin and oxytocin).

Exam trap Milk fat leaves by apocrine secretion but protein and lactose by merocrine; the breast uses both modes at once.

Exam trap The pregnant breast grows by hyperplasia, the pregnant uterus by hypertrophy.

How FCPS asks about this

• Development of breast lobules and alveoli: progesterone; oestrogen develops the ducts.
• Mode of secretion of casein and lactose: merocrine (exocytosis of Golgi vesicles); milk fat is apocrine.
• High prolactin in pregnancy but no milk: oestrogen and progesterone block prolactin's action until the placenta is delivered.
• Peau d'orange is due to: blocked dermal lymphatics; dimpling is due to shortened suspensory ligaments.
• Effect of lactation on the ovary: prolactin suppresses GnRH, so primordial follicles fail to mature.
• Cells that eject milk: myoepithelial cells responding to oxytocin.