histology review

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Within the lobules are small acini. Lobules are connected to intralobular ductules and interlobular ducts. Lobules are surrounded by loose connective tissue sensitive to sex hormones</FONT></div> <div> <B><IMG SRC="0e9f84b0.jpg" border=0 width="504" height="331" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B><FONT SIZE="4" COLOR="#000000" FACE="Arial" >An immunoperoxidase stain with antibody to actin demonstrates the myoepithelial cell layer around the breast acinus. The myoepithelial cells are contractile and are very sensitive to oxytocin</FONT></div> <bR> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mature female breast consists of multiple major and minor ducts that connect the glandular, milk-secreting lobular units to the skin at the nipple. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Each of the lobuloalveolar units is surrounded by a dense fibrous stroma with fibroblasts, blood vessels, and a variable amount of adipose tissue. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The basic organization of the immature ductal epithelium (before puberty) consists of a double layer of cuboidal epithelium, with an underlying basal layer surrounded by a basement membrane and a surface or luminal layer. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Under hormonal stimulation beginning at telarche (the onset of breast development at puberty), the cuboidal epithelium of the lobuloalveolar units differentiates and proliferates into three types of cells: specialized myoepithelial cells, which have contractile function; columnar luminal secretory cells, which are rich in ribosomes and thus stain basophilic and serve a secretory function; and cuboidal basal cells bounded by a basement membrane, which are thought to be the precursors of the other two cell types.</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The myoepithelial cells are supported by a basement membrane, which serves as the junction between the epithelial element of the lobuloalveolar units and the surrounding stromal component consisting of fibroblasts, vascular supply, and a variable amount of adipose tissue. </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The myoepithelial cells contain myofibrilis that serve a contractile function, which is to express the breast milk secreted by the luminal columnar epithelial cells.</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The myoepithelial cells are exquisitely sensitive to the hormone oxytocin, which is released postpartum to initiate the milk let-down response.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mature breast is sensitive to the menstrual cycle, just as the endometrium is, and responds to the changing hormonal milieu in a predictable manner. </B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These normal changes are very important to recognize in order to distinguish them from true pathologic changes of the breast. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Five distinct phases of morphologic changes have been described in the normal breast throughout the menstrual cycle .</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The first phase consists of days three through seven of the menstrual cycle, which is referred to as the postmenopausal phase.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In this phase, the epithelium is oriented in acinar units lined by two cell layers with poorly defined glandular lumina. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The acinar epithelial cells are uniform, consisting of polygonal small cells with eosinophilic cytoplasm and a small, centrally placed nucleus. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At this phase, the lobuloalveolar units are relatively tightly compacted.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The second phase, called the follicular phase, occurs from days eight through 14. It is marked by the appearance of the three distinct epithelial cell types (luminal columnar cells with abundant basophilic cytoplasm and a basally located nucleus, myoepithelial cells located beneath the luminal columnar cells, and the intermediate precursor cells believed to give rise to the other two cell types).</B></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The third phase is the luteal phase, which occurs during days 15 through 20. It is marked by the vacuolization and ballooning of the basal cell layer due to an increase in glycogen content within myoepithelial cells.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This phase is also marked by luminal swelling and the presence of prominent apical snouting of the luminal surface of the columnar epithelium. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The lobuloalveolar units are enlarged at this stage, and the surrounding stroma is looser than in the earlier follicular phase.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The fourth phase is the secretory phase from days 21 through 27. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is characterized by apocrine secretion from the columnar luminal epithelial cells into the lumina of the lobuloalveolar units, which are markedly dilated at this stage. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This phase marks the point at which the lobuloalveolar units attain their maximum size, and there is also marked stromal edema.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A peak mitotic rate is noted during this phase as well and must be recognized as such, so as not to be overly suspicious of malignancy due to the higher mitotic rate.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The last phase is known as the menstrual phase and occurs during days 28 through 32. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is estrogen and progesterone withdrawal during this phase, and although the lumina of the glands remain distended with secretions, the apocrine budding noted earlier in the luteal and secretory phases has regressed considerably. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At this point, the luminal cells have a scant basophilic cytoplasm, while the basal cells remain distended with stored glycogen.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">During pregnancy and lactation, changes are accentuated by the increased hormonal levels of estrogen and progesterone due to pregnancy.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There are remarkable increases (hyperplasia) in the growth of the lobuloaveolar units, with a decreased amount of intervening stroma. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These changes are complex in themselves and persist into the postpartum period for as long as the woman continues to nurse; lactation is typically stopped around four to six months postpartum.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At menopause, involution of the breast is characterized by regression of the lobuloalveolar units and a relative increase in the proportion of adipose and connective tissue between the remaining lobuloalveolar units.</B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="2" CELLSPACING="1" WIDTH="766" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=TOP BGCOLOR=#FFFBF0 HEIGHT= 284 WIDTH="754"><div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The normal breast is made up of lobules and ducts .</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Both are lined by two layers of cells: inner secretory epithelial cells and outer myoepithelial cells</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Epithelial cells have columnar or cuboidal shape and their amount of cytoplasm depends on the hormonal influence. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Under active hormonal stimulation, the cells maintain tall shape and abundant cytoplasm. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cuboidal configuration and decreased cytoplasm characterize inactive hormonal influence. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Myoepithelial cells are located beneath the epithelial cells and have smaller, darker nuclei, which are elongated when cut longitudinal and triangular in cross sections. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In longitudinal sections, myoepithelial cells have fibrillar eosinophilic cytoplasm, due to the presence of smooth muscle contractile protein, which provides contractility to squeeze the duct and to push the secretory product towards the nipple. Myoepithelial cells can be identified by immunohistochemical stains for S-100 protein and smooth muscle actin . </B></div> <bR> <bR> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <bR> <div> <B><U>Lymphatic Drainage of the Breast</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lymphatic drainage of the breast is clinically important because of its role in spreading malignant processes. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Approximately 75% of breast drainage is to the axillary lymph nodes (armpit region), which act as filters between breast and venous circulation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The majority of the breast is drained lymphatically by a network of lymphatic vessels: the perilobular and subareolar plexuses.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The perilobular plexus drains into the subareolar plexus, which is located beneath the <FONT SIZE="3" COLOR="#0000FF" FACE="Century Schoolbook" ><B><U>areola</U></B></FONT>, and into two larger collecting trunks (the lateral and the medial). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These lymphatic vessels extend around the edge of the <FONT SIZE="3" COLOR="#0000FF" FACE="Century Schoolbook" ><B><U>pectoralis</U></B></FONT> muscle and penetrate the dense, fibrous axillary fascia, to enter the base of the axilla.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The medial aspect (towards the body’s midline) of the breast gland is drained by lymphatic collecting vessels. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They follow blood vessels through the pectoralis major muscle, and into the parasternal (also known as internal thoracic) lymph nodes behind the internal intercostal muscles (muscles extending between the ribs).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The skin of the breast drains into various axillary, deep cervical (lower neck region), deltopectoral, and parasternal lymph nodes, except the areola and nipple, which drain deep to join the collecting trunks of the main breast gland.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Because most lymphatic drainage of the breast is directed toward the axilla, a detailed description of the axillary lymph nodes is provided.</div> <bR> <bR> <div> <B><U>Axillary Lymph Nodes</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The lymph nodes of the axilla drain the lymphatic vessels from the arms, the majority of the breast, and the abdominal skin above the umbilicus.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These lymph nodes, which lie primarily under the arm on the lateral (peripheral) aspect of the chest wall, are divided into five groups, based on their location. A detailed description of the axillary lymph nodes follows:</div> <bR> <div> <B>1. Lateral nodes are the lowest (most distal) on the arm and drain the arm almost exclusively. They lie behind the axillary vein and usually consist of one to seven nodes.</B></div> <bR> <div> <B>2. Pectoral nodes are at the lower border of the pectoralis muscle, along the lateral thoracic veins (the upper, outer edge of the breast).</B></div> <div> <B> They drain the majority of the breast and usually consist of one to seven nodes.</B></div> <bR> <div> <B>3. Posterior nodes, also called subscapular nodes, are located along the lateral edge of the scapula (shoulder blade), along the subscapular vein. </B></div> <div> <B>They drain the posterior (back) portion of the shoulder region and usually consist of one to seven nodes.</B></div> <bR> <div> <B>4. Central nodes are the largest group, usually consisting of 10 to 14 nodes. </B></div> <div> <B>They are at the base of the axilla </B><B>(</B><B>deepest portion of the armpit) and are usually the most easily felt or palpated. </B></div> <div> <B>They receive lymphatic drainage from the lateral, pectoral, and posterior lymph nodes.</B></div> <bR> <div> <B>5. Apical nodes are on the medial aspect (towards the midline) of the pectoralis muscle and axillary vein, behind the clavipectoral fascia. </B></div> <div> <B>This group is also very large, consisting of 10 to 14 nodes, and receives lymphatic drainage from all the other groups.</B></div> <div> <B> Occasionally, it also receives direct drainage from the breast.</B></div> <div> <B>From the apical nodes, the lymphatic flow continues into large subclavian trunks, or into a common lymphatic duct, and ultimately into the chest to empty into the venous circulation.</B></div> <div> <B> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="626" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=BOTTOM HEIGHT= 20 WIDTH="622"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="622" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <bR> </td> </tr></table></body>