Normal Breast and Physiological Changes

and Aysegul A. Sahin2



(1)
Division of Pathology, Singapore General Hospital, Singapore, Singapore

(2)
The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

 



Keywords
Normal histologyPregnancyMenopauseCalcifications


The breast is a modified sweat gland located in the superficial fascia of the anterior chest wall. The mature female breast has a distinctive protuberant, mound-shaped, or conical form and covers the area from the second or third rib to the sixth or seventh rib (Fig. 1.1). The nipple projects from the anterior surface and consists mainly of dense fibrous tissue covered by hyperpigmented skin and contains bundles of smooth muscle fibres. The skin immediately surrounding the nipple, called the areola, is also more pigmented than the rest of the breast skin. The areola contains sebaceous glands and numerous sensory nerve endings but lacks pilosebaceous units and hair (Figs. 1.2 and 1.3).

The breast is made up of glandular and ductal elements embedded within fibrofatty tissue with a ratio of glandular to fibrofatty tissue that varies among individuals (Fig. 1.4) [1]. In addition, with the onset of menopause and decreased oestrogen levels, the relative amount of fatty tissue increases as the glandular tissue diminishes. The breast ductal system consists of 15–20 branching ducts, which radiate from the nipple to continue to the functional units of the breast, the terminal ductal lobular units (TDLUs) (Fig. 1.5). The TDLUs consist of the intralobular ducts and round saccules called ductules, which differentiate into the secretory units or acini during pregnancy and lactation. The terms ductules and acini are often used interchangeably. Individual TDLUs vary greatly in size and typically enlarge to become functional during lactation (Fig. 1.6). The TDLUs are embedded in specialised, hormonally responsive connective tissue stroma called intralobular stroma (Fig. 1.7) [28]. The largest amount of breast parenchyma is located in the upper outer quadrant, where the majority of cancers develop. An axillary tail of breast tissue often extends into the axilla. Before puberty, female and male breasts have the same appearance. The structure of the breast is under the influence of hormones, growth, and differentiation factors. When puberty begins in females, mammary ducts branch out, terminal duct buds are formed, and the stromal component (mainly adipose tissue) of the breast proliferates. Both stroma and epithelium undergo changes during the menstrual cycle, pregnancy, lactation, and menopause. During male puberty, breast development is limited to rudimentary large duct development without breast enlargement.

The mammary epithelium is ectodermally derived. Small segments of lactiferous duct orifices at the nipple are lined by squamous epithelium, while the rest of the breast ductal system is lined by two cell layers, inner luminal cells and outer myoepithelial cells, surrounded by the basement membrane (Fig. 1.8). Extension of squamous epithelium beyond lactiferous duct orifices represents squamous metaplasia. The luminal cells are usually low columnar to cuboidal, and myoepthelial cells are located between luminal cells and the basement membrane. The myoepithelial cells are often ovoid to spindle shaped and have scant cytoplasm. The mammary ducts and lobules are embedded in fibrofatty stroma. Interlobular stroma contains adipose tissue, fibroblasts and elastic fibres. Scant inflammatory cells, including lymphocytes, plasma cells, mast cells, and histiocytes, are commonly seen. Rarely, stromal cells show prominent myoid differentiation (Fig. 1.9). The intralobular stroma is usually loose and more cellular than the interlobular stroma, and unlike the interlobular stroma, it usually does not have adipose tissue. Intralobular stroma is hormone sensitive and shows cyclic histologic changes.

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Fig. 1.1
Normal adult female breast. Photograph of a normal female prior to undergoing prophylactic mastectomy


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Fig. 1.2
Normal adult female breast. Gross features. (a) Skin-sparing total mastectomy specimen showing full extension of breast tissue with the nipple located in the normal central position. (b) Higher magnification of the nipple-areolar complex. (c) Cut section through the nipple shows dense subareolar fibrous connective tissue. (d) Higher magnification of (c) showing subareolar fibrous tissue radiating into the fatty breast parenchyma


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Fig. 1.3
Normal adult female breast. Gross features. Cut sections of breast mastectomy specimen. The ratio of fat to fibrous tissue is variable and correlates with mammographic density


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Fig. 1.4
Normal adult female breast. Histologic features. (a–d) H&E sections showing varying ratios of fat to fibrous tissue in stroma and various amounts of glandular elements from different cases


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Fig. 1.5
Normal adult female breast. Histologic features. (a–d) H&E sections of the nipple-areolar complex showing nipple or lactiferous ducts extending from the skin surface into the breast parenchyma. The lactiferous ducts show a branching shape and are lined by bilayered epithelium (luminal epithelial and outer myoepithelial cells). There may be stromal folds protruding into the ductal lumens which should not be mistaken for a papillary lesion. Smooth muscle bundles are seen among the lactiferous ducts. (e, f) Terminal ductal lobular unit, which is the functional unit of breast parenchyma, consists of a feeding duct with branching acini embedded in connective tissue


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Fig. 1.6
Normal adult female breast with physiological changes. Histologic features. (a) Expanded terminal ductal lobular unit of a lactating breast comprises an increased number of acini with luminal secretions. (b) Atrophic terminal ductal lobular unit of a postmenopausal female


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Fig. 1.7
Normal adult female breast. Histologic features. Intralobular stroma shows a loose myxoid appearance, with less collagenisation compared to interlobular fibrous tissue


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Fig. 1.8
Normal adult female breast. Histologic and immunohistochemical features. (a) A lobule composed of multiple acini. The luminal epithelial cells are surrounded by myoepithelial cells, some of which have clear cytoplasm. (b) Immunohistochemical staining for p63 highlights myoepithelial cell nuclei


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Fig. 1.9
Normal adult female. (a, b) Stroma shows myoid cells in addition to fibroblasts. (c) Spindle cells with myoid differentiation show immunoreactivity for smooth muscle myosin


Physiological Changes



Menstrual Cyclic Changes


Both stromal and glandular components of the breast undergo histologic changes during the menstrual cycle. However, these changes are not distinct and specific, unlike changes observed in endometrial epithelium during the menstrual cycle [68]. In general, during the proliferative phase (days 3–7), the stroma is dense and hypovascular. Crowded and poorly oriented ductal epithelial cells line the acini, and mitoses are easily found, while myoepithelial cells are inconspicuous. Acinar lumens are closed and no secretion is found. In the follicular phase (days 8–14), epithelial cells become columnar, mitotic activity decreases, acinar lumens form but no secretion is evident, and myoepithelial cells become easily identifiable at the periphery of acini. During the secretory phase (days 15–27), myoepithelial cells become more prominent with their clear cytoplasm, lumens are open and contain variable amounts of secretions, and the stroma becomes loose and oedematous. The late secretory and early menstrual phase (days 28–2) is characterised by regression of lobules with the stroma becoming compact and may contain inflammatory cells (Fig. 1.10) [911].
Aug 26, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Normal Breast and Physiological Changes

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