Anatomy & Histology of Mammary Glands PDF

ANATOMY & HISTOLOGY OF THE BREAST MONTSERRAT EZQUERRA, MD DIANA VERA, MD Modified Dra. Flores Introduction Present in both sexes Rudimentary in male, well developed in female after puberty. Anterior to the pectoral muscles and the thoracic wall 15- 20 lactiferus ducts, which open directly onto the n...

ANATOMY & HISTOLOGY OF THE BREAST MONTSERRAT EZQUERRA, MD DIANA VERA, MD Modified Dra. Flores Introduction Present in both sexes Rudimentary in male, well developed in female after puberty. Anterior to the pectoral muscles and the thoracic wall 15- 20 lactiferus ducts, which open directly onto the nipple The nipple is surrounded by a circular pigmented area of skin (areola) The suspensory ligaments of the breast, are continuous with the dermis of the skin and support the breast. The predominant componente of the breast is fat; while, glandular tissue is more abundant in lactating women BREAST Lies on deep fascia related to the pectoralis major The base, extends from ribs 2 to 6, and trasversely from the sternum to as far laterally as the midaxillary line Cooper's ligaments (suspensory ligaments) are connective tissue in the breast that help maintain structural integrity. ARTERIAL SUPPLY LATERALLY: Axillary artery → superior thoracic, thoracoacromial, lateral thoracic and subscapular arteries MEDIALLY: Branches from the internal thoracic artery (medial mammary artery) VENOUS DRAINAGE Veins drain the breast parallel the arteries and ultimately drain into: – axillary(lateral thoracic) – internal thoracic – intercostal veins (posterior) INNERVATION ANTERIOR AND LATERAL CUTANEOUS BRANCHES OF THE 3rd TO 6 INTERCOSTAL NERVES. – The nipple is innervated by the 4th intercostal nerve Cervical plexus – Lower fibers→ supraclavicular LYMPHATIC DRAINAGE 85% vessels that drain lateraly and superiorly into axillary nodes Remaining drainage is into parasternal nodes Axillary nodes drain into the subclavian trunk Parasternal nodes drain into the bronchomediastinal trunks Histology Learning Objectives Histology of the mammary glands Identify the histological characteristics of the mammary glands during the different stages of life. Puberty Pregnancy (identify differences amongst the 3 trimesters). Post menopause Identify the histological differences of active mammary gland, inactive mammary glands, and atrophic mammary glands. Understand the process of Mammary gland secretion Milk composition Milk ejection reflex – Identify the stages of lactogenesis. Development of Mammary Gland glands. Puberty Hormone stimulation dependent gland. Full development occurs at about 20 years of age. Minor cyclic changes during each menstrual period. Major changes occur during pregnancy and in lactation. Atrophy after age 40 years (the secretory portions as well as some of the ducts and connective tissue elements). Function: Secrete milk, a fluid that contains proteins, lipids, and lactose as well as lymphocytes and monocytes, antibodies, minerals, and fat-soluble vitamins, to provide the proper nourishment for the newborn. Mammary Glands 15 to 20 lobes separated by adipose and collagenous connective tissue. Each lobe is drained by its own lactiferous duct. The nipple. Lactiferous sinus (milk storage) Morphologic changes during the menstrual cycle… Proliferative phase: estrogen stimulates the proliferation of the lactiferous duct components. Secretory phase: progesterone stimulates growth of acini. – Intralobular stroma becomes edematous. Clinically, during the luteal phase, women perceive tenderness and a progressive increase of breast tissue mass. Resting Mammary Glands (non secreting or nonlactating) They are smaller and without developed acini. Lactiferous ducts are lined by a stratified squamous (keratinized) epithelium. The lactiferous sinus are lined by stratified cuboidal epithelium. The smaller ducts leading to the lactiferous duct are lined by a simple columnar epithelium. Stellate myoepithelial cells are nonfunctional. Mammary gland: micrograph of inactive mammary gland. Stain: hematoxylin and eosin. ×102. Development during pregnancy First Trimester Characterized by elongation and branching of the terminal ductules. The lining epithelial and myoepithelial cells proliferate and differentiate from breast progenitor cells found in the epithelium of terminal ductules. Second trimester: Characterized by differentiation of the acini. The development of the glandular tissues isn’t uniform. The cells vary in shape from flattened to low columnar. Plasma cells, lymphocytes, and eosinophils infiltrate the intralobular connective tissue stroma. Third trimester Commences maturation of the acini. The epithelial glandular cells become cuboidal with nuclei positioned at the basal cell surface. The actual proliferation of the interlobular stromal cells declines, and subsequent enlargement of the breast occurs through hypertrophy of the secretory cells and accumulation of secretory product in the acini. Lactating (Active) Mammary Glands Estrogen and Progesterone. (during pregnancy) As pregnancy progresses, the breasts enlarge as a result of hypertrophy of the glandular parenchyma and engorgement with colostrum , a protein-rich fluid, in preparation for the newborn. Prolactin Activates the secretion of milk, which replaces the colostrum. Acini: cuboidal cells partially surrounded by a meshwork of myoepithelial cells. Changes of breast tissue during lactation. (A) Terminal duct-lobular unit in non-pregnancy (H&E, ×200). (B) Dilated lobular acini with vacuoles and secretions can be seen during lactation (H&E, ×200). The secretory cells possess abundant RER and mitochondria, several Golgi complexes, many lipid droplets, and numerous vesicles containing caseins (milk proteins) and lactose. Higher magnification active mammary gland. myoepithelial cell (mEp) and plasma cells (arrows700x. ACINAR CELL Electron micrograph of an acinar cell from the lactating mammary gland of the rat. Note the large lipid droplets (L), abundant rough endoplasmic reticulum (ER), and the Golgi apparatus (G). F, Folds of the basal plasmalemma; m, mitochondria; MV, microvilli; Sg, secretory granules (×9000). From Clermont Y, Xia I, Rambourg A, et al. Structure of the Golgi apparatus in stimulated and nonstimulated acinar cells of mammary glands of the rat. Anat Rec. 1993;237:308–317. Reprinted with permission from Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc. The pathways identified for milk synthesis and secretion in the mammary alveolus, include four major transcellular pathways and one paracellular pathway : 1. Exocytosis of milk protein and lactose in Golgi-derived secretory vesicles 2. Milk fat secretion via the milk-fat globule 3. Secretion of ions and water across the apical membrane 4. Pinocytosis–exocytosis of immunoglobulins 5. Paracellular pathway for plasma components and leukocytes Pathways for milk synthesis and secretion into mammary alveolus. I , Exocytosis of milk protein and lactose in Golgi-derived secretory vesicles. II , Milk-fat secretion via milk-fat globule. III , Secretion of ions and water across apical membrane. IV , Pinocytosis–exocytosis of immunoglobulins. V , Paracellular pathway for plasma components and leukocytes. MFG , Milk-fat globule; RER ; rough endoplasmic reticulum; SV , secretory vesicle. (Modified from Neville MC. The physiological basis of milk secretion. Part I. Basic physiology. Ann NY Acad Sci. 1990;586:1.) Plasma cells Function: production of Immunoglobulin A (IgA) dimers. Plasma cells in glands produce stabilized dimers of IgA known as SECRETORY IgA that are then taken up and transported into the lumen of the gland by the acinar cells. Secretions of acinar cells The secretions of the acinar cells are of two kinds: Lipids Proteins. Merocrine secretion: Merocrine glands secrete products as they are synthesized. Proteins are synthesized in the rough endoplasmic reticulum then packaged into small vesicles, transported to the golgi apparatus, and then released by exocytosis, and the secretory cell remains intanct after secretion. Apocrine secretion: Lipids Arises as free lipid droplets in the cytoplasm. The lipid coalesces to form large droplets that pass to the apical region of the cell and project into the lumen of the acinus. The lipid droplets are pinched off and become part of the secretory product. Areola and Nipple It contains sweat glands and sebaceous glands at its margin, as well as areolar glands (of Montgomery). They produce a lubricating and protective secretion that changes the skin’s pH and discourages microbial growth. The nipple, a protuberance covered by stratified squamous keratinized epithelium containing the terminal openings of the lactiferous ducts. At Puberty: The pigmentation of the nipple increases, and it will become more prominent. In the adult: (during pregnancy)The epidermis of the nipple and areola is highly pigmented and somewhat wrinkled and has long dermal papillae invading into its deep surface. NIPPLE A section of the nipple. D , A cross-section of the nipple. There is a corrugated layer of stratified squamous keratinized epithelium over the nipple surface; 20 or more lactiferous ducts (L) open on to the surface; sebaceous glands (S) are deep to the epidermis. D, With permission from Dr JB Kerr, Monash University, from Kerr JB 1999 Atlas of Functional Histology. London: Mosby. Digital model of nipple duct anatomys (From Going JJ, Moffat DF. Escaping from flatland: clinical and biological aspects of human mammary duct anatomy in three dimensions. J Pathol. 2004;203:538.) Smooth muscle: In two arrangements, circularly and longitudinally. The contraction of these muscle fibers is responsible for erection of the nipple. Most of the sebaceous glands located around the lactiferous ducts open onto the surface or sides of the nipple. Light micrograph of a human nipple shows a small part of the areola (Are). A lactiferous duct (D) is seen on its way to the surface. Note that the nipple is covered by skin, with a thin epidermis (E) and a thicker dermis (De) housing sebaceous glands (SeG). The dense collagenous connective tissue core (CT) is interwoven with elastic fibers and smooth muscle bundles (SM). (×14) Neural Stimulus (prolactin release) A neural stimulus at the nipple resulting from suckling determines: 1. The ejection of milk by the release of oxytocin. Oxytocin causes contraction of myoepithelial cells surrounding the alveoli. 2. The temporary arrest of ovulation. Mammary Gland Secretions 1st -3rd day after birth: Colostrum is secreted 4th day: Production of Milk Oxytocin Contraction of the myoepithelial cells (surrounding the alveoli) Expression of the milk from the alveoli to the ductus Colostrum: protein-rich thick fluid (vitamin A, sodium, and chloride, lymphocytes monocytes, minerals, lactalbumin, and antibodies (immunoglobulin A) MILK EJECTION REFLEX Milk Composition Water (87%) Lipids (4%) Lactose (7%) Proteins (2%) (casein, lactalbumin). Lipids include cholesterol, triglycerides, short-chain fatty acids, and long-chain polyunsaturated fatty acids. Immunoglobulins: Immunoglobulin A (IgA). It provides passive acquired defense for several weeks before the baby can produce its own secretory IgA in the small intestine. Stages of Lactogenesis Lactogenesis stage I. Full alveolar development and maturation of the breast must await the hormones of pregnancy, progesterone, prolactin, and human placental lactogen (hPL). Lactogenesis stage II Occurs as the progesterone levels fall after delivery of the placenta, during the subsequent 7 days. During the first 2 to 4 days after delivery, incremental secretion of colostrum occurs (50 to 400 mL/day). Lactogenesis stage III: 3 to 7 days postpartum, lactation enters an indefinite period of milk production formerly called galactopoiesis. The duration of this stage is dependent on the continued production of breast milk and the efficient transfer of breast milk to the infant. Milk Ejection Reflex. Changes in rates of secretion of estrogens, progesterone, and prolactin for 8 weeks before parturition and 36 weeks thereafter. Note especially the decrease of prolactin secretion back to basal levels within a few weeks after parturition, but also the intermittent periods of marked prolactin secretion (for about 1 hour at a time) during and after periods of nursing. Lactogenesis stage IV Is involution and cessation of breastfeeding. Breastfeeding is reduced to less than six episodes in 24 hours, and the produced milk volume is less than 400 mL in 24 hours. Prolactin levels fall in proportion to the frequency of nipple stimulation, which ultimately leads to a total cessation of milk production. Production of lactation inhibitory factor from the alveolar epithelium appear to initiate apoptosis of the secretory epithelial cells and proteolytic degradation of the basement membrane. ATROPHIC MAMMARY GLANDS After pregnancy and breast-feeding , mammary glands atrophy and lobules degenerate. After menopause slowly (involution) ✓Only larger ducts remain. ✓Any remaining alveoli atrophy and are resorbed. ✓Epithelial cells undergo apoptosis and are phagocytosed by macrophages in the stroma. ✓Ducts also regress, but a few may remain; some ducts may proliferate and transform into cysts. Alveoli shrink until they are no longer distinguishable, but some persist. Atrophic mammary gland from an elderly postmenopausal woman. H&E. Bibliography: Gray's Anatomy, Chapter 53, 931-952.e2, Susan Standring MBE, PhD, DSc, FKC, Hon FAS, Hon FRCS Leslie P. Gartner PhD. Female Reproductive System. Textbook of Histology. 2017. 4TH Edition. Elsevier. William K. Ovalle, PhD. Female Reproductive System. Netter’s essential histology. Second edition. Elsevier. Di Fiore’s Atlas of histology with functional correlations. Victor P. Eroschenko 12th ediition. John E. Hall PhD. Pregnancy and Lactation. Guyton and Hall Textbook of Medical Physiology. Chapter 83 Anatomy of the Breast. Ruth A. Lawrence. Breastfeeding, 2, 3857