Biochem Biophys Res Commun 55: 1180, 1973, Porter JC: Hormonal regulation of breast development and activity. The increase in hypothalamic-pituitary activity resulting in an increase in gonadal estrogen production is first seen as increasing size of the breast bud or thelarche. During the course of puberty the mammary gland enlarges and changes shape, undergoing the classic changes described by Tanner from simple nipple protuberance to the mature, nonlactational, dome-shaped mammary gland with a centrally located areolar mamma. pregnancy. During seven years of this study, 6% of all patients with breast cancer had PAC. Diagram of the non-lactating breast showing the arrangement of the ducts and lobules. Nontumorous (orchitis, atrophy) and tumorous (choriocarcinoma) lesions of the testicles may result in gynecomastia. 5. The mammary prominence and the nipple secretions result from the actions of fetal prolactin and maternal and placental estrogen on the responsive mammary tissue in utero. One bud forms for each nipple; in the human being, two mammary buds form in the thoracic region. The breast can no longer be considered a passive endocrine target organ. A small quantity of nipple secretions also may be detectable on a physiologic basis during the last few days of the cycle and first few days of the new cycle. Benign lesions, such as sclerosing adenomas, radial scar, and fat necrosis, can mimic these findings. On the periphery of the areolae are located the small duct openings of the sebaceous glands of Montgomery. The patient must be currently non-lactating and non-pregnant. Fueled by the results of the Women’s Health Initiative (WHI), arguably the most controversial area is the potential effect of hormone replacement therapy (HRT) on breast cancer risk. However, despite the acceptance of this modality, the precise screening interval remains somewhat controversial. NORMAL BREAST. Just as adipose tissue seems to be critical for normal embryologic differentiation of the mammary gland, it also plays an integral role in further development at the time of puberty. By age 18 years, or sooner in some individuals, mammary development is complete, and augmentation mammoplasty on the affected side should be considered if significant asymmetry persists. If a mass is palpable, it should be biopsied. New York: Academic Press, 1961, Neumann F, von Berswordt-Wallrabe R, Elger W et al: Aspects of androgen-dependent events as studied by anti-androgens. Branching of the primary sprouts, giving rise to secondary sprouts, begins at approximately the same time as canalization in the primary sprouts. Surgical therapy done prematurely usually results in recurrence of the hypertrophy. Milk line in fetus. Understanding of the pathologic conditions of the breast and the selection of appropriate therapy will be enhanced greatly as the biochemistry and physiology of the mammary gland are clarified. Mastitis refers to inflammation of the breast tissue that may or may not be accompanied by infection. Breast tissue that is not stimulated to lactate consists of resting apocrine cells arranged in nests and small ductules which are lined by cuboidal epithelium. A review of the causes of gynecomastia is, therefore, appropriate. Vol 1. The results of the two study arms, published in JAMA in 2002 and 2004 respectively, demonstrated a small increase in breast cancer incidence in women taking combined conjugated equine estrogens with medroxyprogesterone (RR 1.24, 95% CI 1.03-1.66), whereas hysterectomized women who received conjugated equine estrogens alone had a slight reduction in their overall risk (0.77, 95% CI 0.59-1.01).25, 26 It should be noted, however, that there were limitations to the study design and no increase in breast cancer fatalities was reported by the WHI. Histologically, this condition is defined by dense fibrosis in the stroma, epithelial proliferation with apocrine metaplasia, cyst formation, and alveolar atrophy.27 These changes are best explained by a relative or absolute estrogen dominance over progesterone. Unexplained galactorrhea can be evaluated by measurement of the fasting prolactin concentration and the thyroid-stimulating hormone concentration to rule out an endocrinopathy. This magnified image of a mammary gland during pregnancy, shows the large lipid filled acini/alveoli. Because of the breasts' ability to modulate peripheral endocrine signals, levels of estrogen within ductal secretions may dominate even with seemingly normal ovarian sex steroid production.28 Fibrocystic changes are common; at least one third of women have breast cysts and epithelial hyperplasia found at autopsy. This developmental abnormality results in a retracted but nonfixed nipple. Mastitis does not necessarily occur during lactation, is not always accompanied by microbial infection, and may not resolve with antibiotics. Carcinoma of the adrenal cortex, certain pituitary adenomas, hyperthyroidism, liver disease, and starvation has been associated with the development of gynecomastia. In some other species (e.g. A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring.Mammals get their name from the Latin word mamma, "breast".The mammary glands are arranged in organs such as the breasts in primates (for example, humans and chimpanzees), the udder in ruminants (for example, cows, goats, and deer), and the dugs of other animals (for example, dogs and … Antibiotic therapy for a diffuse infection and occasionally surgical drainage for organized infection are the treatment choices. This modality is also very helpful in ruling out significant pathology when breast pain or nipple discharge occurs without a palpable abnormality. There is, however, a critical distinction that must be made between premenopausal and postmenopausal use and the risk of breast disease. Although there are reports to the contrary, the preponderance of existing data suggests no significant relationship between premenopausal exogenous hormone ingestion and benign or malignant neoplasia of the breast. These studies, completed by Kleinberg and coworkers,8 indicate that a functioning pituitary gland and estradiol are necessary for breast maturation. Factors associated with an increased risk of developing breast carcinoma, Late first pregnancyNulliparousNo lactationFamily history of breast and other malignancyPrevious breast surgery, Mother and sister with breast carcinomaMother or sister with bilateral breast carcinomaMother or sister with early (<35) onset breast carcinoma. Gynecol Endocrinol 6: 37, 2001. The acini empty into ducts, that are lined by cuboidal, or low columnar The acini empty into ducts, that are lined by cuboidal, or low columnar epithelial cells, and surrounded by myoepithelial cells. The functional alveolar unit is composed of an outer layer of vascular supply and a surrounding matrix of contractile myoepithelial cells. For example, the taller the individual, the higher the breasts will be located on the thoracic cage. to menarche, pregnancy, lactation, and menopause – Target organ for variety of hormones that regulate development and physiologic function – Result in broad range of what is normal breast histology Due to superficial location, breast has social, sexual, and cultural significance – Patients are 1st to diagnose their carcinomas in 2). J Mammal 8: 86, 1927, Kleinberg DL, Newman CB: The pituitary gland in primate mammary development: Evidence that prolactin is not essential. This unique development was in a large part responsible for the rapid proliferation of the class of vertebrates that we now know as mammals. Calcifications are often seen within these masses. Breast Cancer Research 8: 1, 2006, Fenton SE. Histopathology 1997 ; 30 (3): 214 –220. The accumulation of adipose tissue appears to be estrogen dependent. Rarely, galactorrhea has been reported with the use of higher-dose oral contraceptives. Another clinical entity, the pseudoinverted nipple, reflects an embryologic development appropriate to certain species of mammals other than the human being. Within this bud resides the potential for the remainder of mammary development. Intraductal papillomas often manifest with a serosanguineous or bloody breast discharge. We use cookies to ensure you get the best experience from our website.By using the website or clicking OK we will assume you are happy to receive all cookies from us. Background The management of granulomatous mastitis depends on the causative factor, and accurate diagnosis in distinguishing between idiopathic granulomatous mastitis (IGM) and tuberculous mastitis (TBM) is indispensable. A case control study of pregnancy/lactation associated breast carcinoma (PAC) was conducted on 24 test cases with two controls per case, matching age, tumor grade, tumor size and axillary lymph nodes status. Even in the embryonic form these cells contract on exposure to oxytocin, squeezing the alveolus into a tight sphere. Some asymmetry in mature breast size and shape is usual. Comment Here Reference: Breast - Histology An expert resource for medical professionalsProvided FREE as a service to women’s health, The Global Library of Women’s Medicine’s The gynecologist or reproductive endocrinologist is occasionally consulted to evaluate a young boy with gynecomastia because of concern about a possible intersex disorder. Mammography also is important in the evaluation of a palpable breast mass as an adjuvant to fine-needle aspiration. The mammary ridge is present for only a few days during development, after which specific paired areas of prominence begin to develop in the locations characteristic for the species. The non-pregnant and non-lactating female breast is composed primarily of adipose and collagenous tissue, with mammary glands making up a very minor proportion of breast volume. The non-lactational mastitis are more frequent in the postmenopausal and the menopausal period, but MDAIDS (Mammary Ducts Associated Inflammatory Diseases Sequence) are particularly interesting. The most common presentation for breast cancer is a breast lump. Gynecomastia in other clinical settings is characterized histologically by fatty and fibrous tissue proliferation. developing breast. 1). Each of theses lobes is a compound tubular acinar gland. Fibroadenomas arise from breast lobules and are the most common solid benign masses in women younger than age 30 years. In general, therapy is delayed as long as possible until the accelerated phase of mammary development is complete, and then reduction mammoplasty is the treatment of choice. This mammary ridge is seen primarily in the axial-thoracic area in the human being, but it can occur anywhere from the cervical region to the thighs. Histological structure• The breast is formed of compound tubulo- alveolar glands covered by thin skin. Arch Dis Child 60: 1180, 1985, Ilicki A, Lewin RP, Kauli R et al: Premature thelarche: Natural history and sex hormone secretion in 68 girls. The most common symptoms of fibrocystic breast disease include cyclic breast pain (mastodynia), tenderness, and palpable thickening with discrete cysts. IN-SITU CARCINOMAS The increase in FSH stimulates ovarian estradiol production sufficiently to promote breast growth.14 In girls with true isosexual precocity, pulses of gonadotropin with LH dominant can be detected with frequent blood sampling; in girls with premature thelarche, the same techniques identify only pulses of FSH. These florid changes seen can be alarming and can be mistaken for atypia or malignancy. Surgical excision of the papillomas is recommended, because cytology cannot definitively diagnose a benign papilloma. This difference not only confirms the etiology of premature thelarche but provides a method to differentiate the two disorders.15 Studies suggest that up to 14% of girls with presumed premature thelarche progress to true precocious puberty.16 For this reason, patients with the diagnosis of premature thelarche should be monitored closely. 3 and 4). Electives Sites is a great name because it tells you exactly what they do. Analyses of ductal secretions have found high concentrations of estradiol and progesterone, much in excess of serum concentrations. • The alveoli develops during early weeks of pregnancy and lactation begins after birth. Circulating androgens can be converted locally to other, more potent androgens or to estrogens, modifying peripheral endocrine signals.17. Pathology of R4 spiculated lesions in the breast screening programme. Enlargement and differentiation of the lobules of the mammary gland. Recent information documents the capability of breast tissue to alter significantly the local hormonal environment. Serum luteinizing hormone (LH) concentration and the LH response to GnRH are normal in these children. Nonhormonal treatments, including use of a supportive brassiere, a decrease in methylxanthines, and vitamin A and E use, have been suggested. Stages of development of the human mammary gland, Another cell type having its origin from the same epithelium as the mammary bud is the myoepithelial cell. Lancet 350: 1047, 1997, Colditz GA, Hankison SE, Hunter DJ et al: The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. JAMA 288: 221, 2002, The Women’s Health Initiative Steering Committee: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. These functional units continue to increase somewhat during each cycle under the growth stimulus of estrogen, progesterone, and prolactin until approximately age 30 years. The lumina become more prominent during the mid point of the menstrual cycle. The area of prominence in the embryo corresponds to the area of future mammary development in the adult. Can you identify ducts, the secretory units and the outer dense connective tissue (that around the ducts is loose)? We have just begun to appreciate the potential long-range sequelae of breast-feeding biologically and behaviorally. The predominance of fibrous tissue and the small size of the lobular units are indicative of a small breast from a non-pregnant/non-lactating woman. Stimulation of the nipple causes it to become erect and everted. Breast tissue is not considered completely mature or ripened until pregnancy and lactation occurs If there is no "immediate" pregnancy, the breast tissue fully matures 2 years post menarche Breasts are normally asymmetric in size; usually L>R Histology Guide © Faculty of Biological Sciences, University of Leeds | Credits. Nevertheless, the small increase in breast cancer should always be considered prior to initiating HRT. Changes in human milk composition during the initiation of lactation. JAMA 291: 1701, 2004, Farber JL (ed): Pathology, p 998. Fig. P63 IMMUNOHISTOCHEMICAL Myoepithelial cells STAIN . The primary mesenchymal cell type composing the matrix in which the mammary gland develops is the fat cell. Radiol Clin North Am 33: 1085, 1985, Founders and Publishers: Paula and David Bloomer In memory of Abigail, Editor-in-Chief: Peter von Dadelszen, FRANZCOG, FRCSC, FRCOG, Professor of Global Women’s Medicine, Kings College, LondonSupported by a distinguished International Editorial Board. Many irregularities and small, cystically dilated glands appear during the latter portions of the cycle, under maximal hormonal stimulation, which are not palpable during the early portions of the new menstrual cycle. From a functional point of view, there are those who would contend that the human mammary gland has outlived its usefulness; however, the discovery of the multiple valuable and unique properties of human milk for humankind and the devastating results of attempting nonlactational nutrition for infants in many of the developing nations of the world would argue strongly against this point. Athelia (failure of nipple development) and amastia (failure of mammary gland development) occur rarely in the human being. Mammography can also be used for needle localization of masses before biopsy or excision.39, Breast cancer care requires a multidisciplinary approach. Interference with this occurrence could lead to altered timing of mammary development or formation of the glandular structures (altered number of primary ducts or blind ducts or unusual presence of nipple/areola), leaving lasting effects on the gland.3. This is particularly problematic in the cases of granulomatous mastitis in which the microbiological studies are negative. The investigators concluded that, in primates, estradiol, growth hormone, and other pituitary hormones are required for normal pubertal breast maturation.8 Prolactin may not be required during the actual period of growth and development, but exposure of the mammary gland to prolactin before estradiol stimulation still is considered essential.9 The mechanism through which prolactin influences breast growth may involve the induction of estrogen receptors by prolactin in breast tissue.10, During development, different tissues within the breast are responsive to different endocrine stimuli. A multidisciplinary approach to the management of breast cancer, Part 1: Prevention and Diagnosis. Mammary gland• These are a pair of compound tubulo-alveolar glands to nourish new- borns• The histological structure varies according to sex ,age & physiologic status In patients older than 50 years of age, carcinoma of the mammary gland is the leading cause of discharge of these types. If the animals are hypophysectomized before estradiol treatment, the breast does not mature. A similar controversy exists regarding the relationship between endogenous levels of sex steroids and the origin and pathology of fibrocystic breast disease (benign mastopathy). Conversely, exposure of the male to the antiandrogen, cyproterone acetate, results in formation of a complete mammary gland.4, 5 Exposure of the developing male embryo to testosterone apparently desensitizes the mammary bud to the eventual stimulation of rising estrogen levels. Recent Prog Horm Res 25: 337, 1970, Hamer DB: Gynaecomastia. Lactiferous ducts open into the nipple. The team of breast experts includes primary care physicians, geneticists, breast radiologists, breast pathologists, surgical breast specialists, and radiation and medical oncology specialists. This tragic mistake still occurs far too often. The mammary gland is like a modified During this time, the mammary gland increases in size, and the production of breast milk is initiated. The breasts reach maximum volume just before the onset of menses due to increased intracellular and intercellular water, maximal glandular and ductal development, and the accumulation of secretory materials within the alveolar structures. Eur J Pediatr 145: 190, 1986, Pasguino AM, Pacrelle I, Passeri F et al: Progression of premature thelarche to central precocious puberty. BREAST HISTOLOGY AND PATHOLOGY Dr. Deborah Marks-Jones, MD Anatomic & Clinical Pathology Cytopathology ... component of non-lactating breast Collagen Adipose tissue FIBROTIC STROMA FATTY STROMA . Breast self-examination (BSE) for detection of masses is somewhat controversial. By 84 days of development, epithelial outgrowths of the mammary buds can be seen invading the surrounding mesenchyme. In the marsupial the beginnings of nipple formation can be observed. The secretory epithelium of the alveolus itself is composed of clear basal B or chief cells, which act as stem cells for both the myoepithelial cells and the secretory luminal A or foam cells. Palpation of the axillary area is also important to include with the breast examination. This separation and failure of nipple development occurs as the result of proteolytic enzyme action initiated by testosterone. In younger women, most breast masses are benign, with only 4% representing cancer.34 Risk prediction models can be used to estimate the risk of developing breast cancer and predict the likelihood of carrying a BRCA1 or BRCA2 gene mutation. Compare this to Slide 59 , showing lactational change. Not surprisingly, it is in these same locations that carcinoma of the breast most commonly occurs. The WHI, a long-term, prospective, randomized, placebo-controlled trial initiated by the National Institutes of Health, evaluated the risk of postmenopausal hormone replacement therapy. non-lactating female breast is composed primarily of adipose and collagenous tissue, with Larger breasts contain more adipose tissue. If symptoms demand early surgical reduction, ovarian suppression with leuprolide acetate or danazol for 1–2 years after the procedure should be seriously considered. Frouge C , Tristant H , Guinbretiere JM , et al. Adipose tissue known to be metabolically active may also provide local growth-promoting factors necessary for the full differentiation of the potential mammary-producing epithelial cells. If breast growth begins after the age of two years, the condition usually persists until puberty, when other sexual characteristics appear at the normal age. The long and complex evolutionary development of the mammary gland from a simple sweat gland can be seen within the mammalian family. Excessive growth of primarily fat and connective tissue causes both psychosocial maladjustment and physical symptoms of pain, and shoulder and back strain. Mother and sister with breast carcinoma Mother or sister with bilateral breast carcinoma Mother or sister with early (<35) onset breast carcinoma. In the younger age group, benign cytology findings, a normal breast examination, and normal mammography are usually sufficient to evaluate these forms of nipple discharge. A substantial fatty pad is necessary for the extensive invasion by the mammary ducts during development of these structures during puberty and pregnancy. An introduction to the histology of the breast as presented by the University of Rochester Pathology IT Program. Each breast is made up of 15-25 secretory lobes, embedded in adipose tissue. Keratin plug in a non-lactating nipple. The nature of the discharge is of great help in determining the appropriate evaluation and treatment. And so any time you have societies, this means a cell. Aromatase and other enzymes necessary for the production and metabolism of steroids are present in the adipose tissue and glandular epithelium of the mammary gland. For most of these compounds there is little correlation between the concentration in serum and that within the ducts.18 The ability of the breast to modulate endocrine signals by conversion or concentration of circulating hormones explains the poor correlation between peripheral levels of hormones and pathologic conditions thought to be endocrine dependent. Watery, serous, serosanguineous, and bloody nipple discharges should be considered symptoms of underlying carcinoma of the mammary gland until proved otherwise. NORMAL HISTOLOGY OF BREAST • Non-lactating phase • Embedded in the surrounding connective tissue there are inactive tubular portions of breast tissue is recognized. the horse), no nipple formation occurs in the male due to a separation of the mammary bud from its connection with the surface epithelium early in development. This case talks about: A 20 year-old female with a breast mass. Endocrine-Disrupting compounds and mammary gland development: Early exposure and later life consequences. The human nipple usually develops as a proliferative-type protruding nipple; certain other mammals have an ingrown-type nipple that protrudes only in late pregnancy or with the stimulation of nursing. Great variability occurs in the size, shape, and location of the mature mammary gland due to constitutional factors, differences in amount and location of fat distribution, connective tissue development, thoracic cage shape, and overall body height. The first visible sign of mammary formation in the human embryo is a thickening of cells within the malpighian layer of the epithelium along the ventrolateral surface at approximately 35 days of development. Focal lactational change; Pseudolactational change Focal lactating effect Diagnostic Criteria. Nipple discharge, found by the patient or by the physician during a physical examination, is one of the more common abnormalities encountered in the breast. The deposition of adequate adipose tissue under the influence of ovarian estrogen is necessary to form the loose matrix in which the extensive glandular and ductal proliferation of puberty occurs. Breast Pathology - Images. The mammary gland is composed of milk-transporting lactiferous ducts, which expand and branch extensively during pregnancy in response to estrogen, growth hormone, cortisol, and prolactin. Cytologic analysis of the discharge should be obtained whenever possible. This earliest sign of secondary sexual maturation at the onset of puberty can normally occur anywhere from age 8 to 14 years. Each breast is made up of 15-25 secretory lobes, embedded in adipose tissue. These cells are evident in the human being by 140 days of development, and a number of them surround each alveolus. After 50 years of age, annual mammograms are recommended.37, For patients at higher risk, screening MRI is recommended for women with an approximately 20–25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin’s disease.38. Hyperestrogenism frequently exists during the perimenopausal years or with chronic oligoanovulation, as seen in clinical settings where an increased incidence of fibrocystic breast changes has been observed. NORMAL LOBULES. A characteristic green nipple discharge is occasionally the presenting complaint. There is no known hormonal therapy for partial or complete unilateral amastia. There is an idiopathic form of gynecomastia that differs from the other forms in that it produces full ductal and glandular development. LACTATING BREAST. Many studies, including the Cancer and Hormone Study, have demonstrated no association between breast cancer and the use of oral contraceptives.19 However, there are limited studies suggesting a small increase in breast cancer among young women with a positive family history. It may be that the mammary growth seen after oophorectomy in the presence of high doses of prolactin occurs because of local estrogen production by the adipose tissue from nonestrogenic precursors. Mammography is usually not possible in the acute phase due to pain, but may be indicated post treatment in non-lactating women to rule out underlying malignancy. Still, most health organizations and practitioners recommend monthly examinations. The discharge is frequently associated with a burning and itching sensation of the nipple. These glands contain no terminal hairs but do contain lanugo hairs. The important point is that it is impossible to determine the final degree of asymmetry until development has been completed. Most research has been done with higher-dose oral contraceptives, which are in limited use in the United States today. Tissue transplantation studies demonstrate that mesenchymal cues control the branching pattern of the epithelium, regardless of epithelial origin.2 The mesenchymal tissue also gives rise to vascular elements, which along with the neural tissue derived from the neural ectoderm complete the structures necessary for the future functioning mammary gland. As these sprouts continue to develop and invade the mesenchyme, increased pressure under the surface epithelium gives rise to a protuberance of the surface that will further differentiate into a discrete nipple or teat. Whether this is occurring because of an increase in the exposure of individuals to substances stimulating mammary glandular epithelium, or whether an increasing awareness on the part of physicians of the importance of galactorrhea in relation to possible pituitary adenomas has resulted in more careful breast examination, is unknown at the present time. PLAY. The normally developed mammary gland of a newborn infant usually contains prominent glandular tissue under the nipple from which a milky discharge can be expressed.
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