The Normal Breast The Normal Breast
Contents
1.1 Anatomy . . . 2
1.1.1 Nipple-Areolar Complex . . . 2
1.1.2 Structure of the Adult Duct System . . . 2
1.2 Pregnancy and Lactation . . . 2
1.3 Menopause . . . 3
1.4 Immunoprofile . . . 3
1.5 Further Reading . . . 3
Lobules are composed of terminal ducts and acini and their specialized supporting stroma. The terminal ducts are either ex- tralobular or intralobular depending on their location relative to the specialized lobular stroma.
The stroma within the lobules is specialized containing fine collagen fibers, abundant reticulin and numerous small vessels.
It is much more cellular than the interlobular stroma. Due to quantitative and qualitative differences, the intralobular stroma is much more distinctive than the periductal stroma. Intralobu- lar stroma also often displays a mucoid character (positive for alcian blue). One should keep in mind that while the mammary ducts are invested with elastic tissue, the lobules are completely devoid of it.
Except for a small portion of the collecting ducts at the nipple where squamous epithelium lines the duct, the entire duct sys- tem is lined by two cell layers: luminal epithelial cells and basal- ly located myoepithelial cells. Depending on their functions, the luminal epithelial cells can be flattened, low cylindrical, or columnar. Myoepithelial cells are located in close contact with cytoplasm of the epithelial cells and are surrounded by basal lamina (Figs. 1.5 and 1.6). Myoepithelial cells often show ovoid to elongated “bipolar” dense nuclei and small cytoplasms; in the luteal phase of the cycle, however, there is glycogen accumula- tion, which gives a cleared appearance of cytoplasm in sections stained with hematoxylin and eosin.
Normal breast lobules during the early follicular phase of the cycle show poorly defined lumina of acinar structures, luminal epithelial cells with dark, centrally located nuclei, and eosino- philic cytoplasm.
Normal breast lobules in the luteal phase show vacuolization and ballooning of the basally located myoepithelial cells due to an increase in glycogen cytoplasmic content. “Apical snouts” of luminal epithelial cells are present due to the secretory activity.
The lumina are enlarged and contain eosinophilic secretory material. Prominent stromal edema is present [1, 5–8].
1.2 Pregnancy and Lactation
Organoid enlargement and dilation of lobular units occur at the expense of fibrofatty stroma.
The luminal epithelial cells of the enlarged acini show loss of apical aspect of cells through the secretory process, vacuolated cytoplasms, and enlarged round nuclei, often with a “hobnail”
pattern. Prominent nucleoli and increased mitotic activity are common.
There is no intraluminal epithelial proliferation [2–4].
1.1 Anatomy
The “normal” mature female breast ranges from 50 g to greater than 400 g. A typical nonlactating breast weighs between 150 and 250 g, while the lactating breast may exceed 400 g. The size and density of the breast are influenced by the individual’s body habitus. The average breast measures 10–12 cm in diameter, and its average thickness centrally is 5–8 cm. The adult breast lies be- tween the 2nd and 6th ribs in the vertical axis and between the sternal edge and the midaxillary line in the horizontal axis. The breast is attached to the dermis by fibrous bands called suspen- sory (Cooper’s) ligaments anteriorly, and the posterior surface is the pectoral fascia. Approximately three-quarters of the breast is on the pectoralis major muscle (superior and medial portions).
The breast tissue is divided into upper outer, upper inner, low- er outer, and lower inner quadrants; the subareolar area; and the axillary tail of the upper outer quadrant. The arterial blood sup- ply is derived from the axillary, intercostal, and internal mam- mary arteries, and venous drainage is into the axillary and inter- nal mammary veins. Lymphatic drainage is to the axillary, sub- clavicular, and internal mammary lymph nodes. While drainage from the upper outer quadrant is predominantly to the axillary lymph nodes, drainage from the inner quadrants is to the inter- nal mammary chain of nodes. The nerves are branches of the thoracic segmentals.
1.1.1 Nipple-Areolar Complex
The nipple is located in the center of the complex surrounded by the areola. Numerous sebaceous glands (the glands of Mont- gomery) and apocrine glands are present within the areolar der- mis. The nipple dermis and subcutaneous tissue contain smooth muscle bundles arranged radially and longitudinally that serve to identify the nipple histologically. The nipple is rich in sensory nerve endings. Stratified squamous epithelium covers the nipple and areola. Clear cells without cytologic atypia may be present in the surface of the epithelium. Lactiferous ducts course through the nipple dermis and open onto the epidermis. On cross-sec- tions of the nipple, 14–24 ducts may be seen. Lobules can be observed in about 15% of nipples [5, 6, 8, 10].
1.1.2 Structure of the Adult Duct System(Fig. 1)
The breast consists of 15–20 segments (lobes). Each segment is drained by a collecting duct. The segments are ill defined and cannot be identified by gross examination.
Collecting ducts connect the nipple with lactiferous sinus.
Segmental (lactiferous) and subsegmental (major) ducts connect lactiferous sinus with terminal duct-lobular units (TDLUs).
Chapter 1 3 The Normal Breast
1.3 Menopause
Postmenopausal breast involution is generally characterized by regression of the parenchymal TDLUs revealing marked reduc- tion of glandular tissue with an increase in fat deposition and relative predominance of fibroconnective tissue. At the end stage of menopausal involution of the breast, only small islands of lobules (TDLUs) embedded in dense, hyalinized fibrous tissue remain [4, 7].
1.4 Immunoprofile
The luminal epithelial cells are typically immunoreactive for low molecular weight (LMW) cytokeratin (CK) such as CK8, CK18, and CK19. These cells also show a heterogeneous reaction for high molecular weight (HMW)-CK such as CK34BE12 (K-903) and CK5/6. In contrast, the vast majority of myoepithelial cells are negative (or only focally and weakly positive) for LMW-CKs.
The myoepithelial cells may show a heterogeneous immunoreac- tion for HMW-CKs such as CK5/6 or CK34BE12.
Myoepithelial cells can be decorated with a variety of antibod- ies against actin (smooth muscle actin or muscle-specific actin);
smooth muscle myosin, heavy chain; calponin; S100 protein; p63;
CD10; 14-3-3 sigma; and so on (Figs. 1.7 and 1.8).
Estrogen receptors (ER), progesterone receptors (PR), and an- drogen receptors (AR) are sporadically positive in luminal ep- ithelial cells (some areas are, however, completely negative for ER, PR, and AR). ER, PR, and AR are almost always negative in myoepithelial cells [9, 11].
1.5 Further Reading
1. Azzopardi JG. Problems in breast pathology. WB Saunders, Philadel- phia, 1979, pp. 8–22.
2. Barwick K, Kashgarian M, Rosen PP. Clear cell change within duct and lobular epithelium of the human breast. Pathol Annu 1982;17 (Pt 2):319–328.
3. Battersby S, Anderson TJ. Proliferative and secretory activity in the pregnant and lactating human breast. Virchows Arch (A) 1988;413:189–196.
4. Fanager H, Ree HJ. Cyclic changes of human mammary gland ep- ithelium in relation to the menstrual cycle – an ultrastructural study. Cancer 1974;34:574–585.
5. Faverly D, Holland R, Burgers L. An original stereomicroscopic analysis of the mammary glandular tree. Virchows Arch (A) 1992;421:115–119.
6. Giacometti L, Montagna W. The nipple and the areola of the human female breast. Anat Rec 1962;144:191–197.
7. Huston SW, Cowen PN, Bird CC. Morphologic studies of age-related changes in normal human breast and their significance in the evo- lution of mammary cancer. J Clin Pathol 1985;38:281–287.
8. Moffat DF, Going JJ. Three dimensional anatomy of complete duct systems in human breast: pathological and developmental implica- tions. J Clin Pathol 1996;49:48–52.
9. Moinfar F, Okcu M, Tsybrovsky O, et al. Androgen receptors fre- quently are expressed in breast carcinomas. Potential relevance to new therapeutic strategies. Cancer 2003;98:703–711.
10. Stirling JW, Chandler JA. The fine structure of ducts and subareolar ducts in the resting gland of the female breast. Virchows Arch (A) 1977;373:119–132.
11. Tavassoli FA. Pathology of the breast. Appleton & Lange, Stamford, CT, 1999, pp. 1–20.
1 Figs. 1.5 and1.6: The acini (ductules) are lined by luminal epithelial and basally located myoepithelial cells. The myoepithelial cells often show elongated or bipolar nuclei.The acini are surrounded by a con- tinuous layer of basal lamina.
Fig. 1.7: Immunohistochemistry for smooth mus- cle actin showing cytoplasmic positivity in the myoepithelial cells.
Fig. 1.8: The myoepithelial cells typically display nuclear positivity for p63.
Fig. 1: Normal breast.
Figs. 1.1 and 1.2: Low magnification of normal breast shows several lobules composed of terminal ducts and acini (ductules) within a specialized sup- porting stroma.
Fig. 1.3: A terminal duct-lobular unit (TDLU) with regular acinar structures and a small segment of extralobular (terminal) duct. The vast majority of benign and malignant proliferations of the breast develop in the TDLUs.
Fig. 1.4: A lobule showing acini and specialized stromal cells. The stroma is more cellular than the interlobular stroma. The intralobular stroma con- tains fine collagen fibers and abundant reticulin but characteristically lacks elastic fibers (not shown).
Chapter 1 5 The Normal Breast
