breast pathology

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TITLE="Related Links"><U><B>Related Links</B></U></A></div> <div> <B> <img src="HTMLobj-309/aniGif.gif" border="0" align="bottom" width="42" height="64">   <img src="HTMLobj-310/aniGif.gif" border="0" align="bottom" width="143" height="35">  </B></div> <div> <B><IMG SRC="1340e130.jpg" border=0 width="270" height="275" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></div> </td> <td valign="top" height=380 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <I>breast pathology</I></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="611" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FF00FF HEIGHT= 20 WIDTH="298"><div> <B>Breast</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> Cancer Type</B></FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FF00FF WIDTH="298"><div> <B>Comments</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Ductal Carcinoma In-Situ</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="298"><div> Mild malignant potential</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Lobular Carcinoma In-Situ</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="298"><div> Mild malignant potential</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Infiltrating Ductal Carcinoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF><NOBR><div> The most common <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer by far</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Infiltrating Lobular Carcinoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF><NOBR><div> 5 to 10 percent of all <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Inflammatory <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Breast</FONT> Cancer</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="298"><div> Very serious, uncommon</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Medullary <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Breast</FONT> Cancer</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="298"><div> Uncommon</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFFFF HEIGHT= 19 WIDTH="298"><div> Cystosarcoma Phylloides</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFFFF WIDTH="298"><div> Very Rare</div> </tD> </tR> </TABLE></div> <bR> <bR> <DIV ALIGN="LEFT"></DIV> <div> The TNM staging classification for <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Breast</FONT> Cancer can be illustrated as follows:</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="617" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 39 ><NOBR><div> <B>Stage of Tumor</B></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> <B>Size of the Cancer</B></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="184"><div> <B>Cancer in Lymph Nodes?</B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="124"><div> <B>Metastasis</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="136"><div> I</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="148"><div> < 2 cm</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="184"><div> None</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="124"><div> None</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 35 WIDTH="136"><div> II</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="148"><div> 2 - 5 cm</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="184"><div> No, <FONT SIZE="1" COLOR="#000000" FACE="Arial" >or yes on same side of </FONT><FONT SIZE="1" COLOR="#800000" FACE="Arial" >breast</FONT></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="124"><div> None</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="136"><div> III</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="148"><div> > 5 cm</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> yes<FONT SIZE="1" COLOR="#000000" FACE="Arial" >, on same side of </FONT><FONT SIZE="1" COLOR="#800000" FACE="Arial" >breast</FONT></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="124"><div> None</div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="136"><div> IV</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="148"><div> doesn't matter</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="184"><div> doesn't matter</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="124"><div> Yes</div> </tD> </tR> </TABLE></div> <bR> <bR> <div> Types of Procedures To Evaluate a Lump or Calcifications </div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="537" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 23 WIDTH="145"><div> Type</div> </tD> <tD VALIGN=TOP BGCOLOR=#C0C0C0 WIDTH="377"><div> Description </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 134 WIDTH="145"><div> <B>Fine Needle Aspiration </B></div> <div> <B>(FNA) </B></div> </tD> <tD VALIGN=TOP WIDTH="377"><div> A very small needle, attached to a syringe, is inserted into the area and suction applied to remove cells. May or may not have local anesthesia given. No scar left. May return to normal activities. Cells sent for cyto<FONT SIZE="3" COLOR="#800000" FACE="arial" >pathology</FONT> studies. Performed in a physician’s office or clinic. May need to be followed by an incisional or excisional biopsy. </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 96 WIDTH="145"><div> <B>Core Needle Biopsy </B></div> </tD> <tD VALIGN=TOP WIDTH="377"><div> A larger needle with a special cutting edge removes a core of tissues from the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT>. Local anesthesia is used. Performed in a physician’s office or clinic. Sample tissue is sent to <FONT SIZE="3" COLOR="#800000" FACE="arial" >pathology</FONT> lab. Usually no scar. May resume normal activities. </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 210 WIDTH="145"><div> <B>Needle Localization </B></div> </tD> <tD VALIGN=TOP WIDTH="377"><div> Performed on areas difficult to locate by feeling or found on mammography. Area is identified by mammography. Fine wire is inserted so the tip will rest in the identified area. A second mammogram confirms placement of the correct position. Localization wire is taped to the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT> and patient is transferred to surgery for the surgeon to remove the identified area. Local anesthesia is given. The tissue removed is sent to <FONT SIZE="3" COLOR="#800000" FACE="arial" >pathology</FONT>. A small scar is left on the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT>. Activities may be limited for several days until area heals. </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 210 WIDTH="145"><div> <B>Stereotactic Biopsy </B></div> </tD> <tD VALIGN=TOP WIDTH="377"><div> Performed on areas difficult to feel or ones located only on mammography. Patient may sit or lie on a table where the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT> falls through an opening. The <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT> is compressed and <FONT SIZE="3" COLOR="#800000" FACE="arial" >pictures</FONT> taken to identify the area. A computer calculates the position of the biopsy needle. Local anesthesia is given. A small incision may be made on the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT> where the needle will enter. The needle is inserted and removes the suspicious tissues. Biopsy specimen is sent to <FONT SIZE="3" COLOR="#800000" FACE="arial" >pathology</FONT>. No scar is left on the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT>. Normal activities can be resumed. </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 115 ><NOBR><div> <B>Incisional Biopsy </B></div> </NOBR></tD> <tD VALIGN=TOP WIDTH="377"><div> A surgeon removes a portion of the lump in a surgical suite. Local or general anesthesia will be used. A short time is required in the recovery room after the surgery. A scar is left on the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT>. The specimen is sent to the pathologist. Activities will be restricted until stitches are removed. </div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0C0C0 HEIGHT= 115 ><NOBR><div> <B>Excisional Biopsy </B></div> </NOBR></tD> <tD VALIGN=TOP WIDTH="377"><div> A surgeon removes the entire lump in a surgical suite. Local or general anesthesia is used. A short time is required in recovery. Stitches close the incision. Activities are restricted until stitches are removed. A scar is left on the <FONT SIZE="3" COLOR="#800000" FACE="arial" >breast</FONT>. The biopsy specimen is sent to <FONT SIZE="3" COLOR="#800000" FACE="arial" >pathology</FONT>. </div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <div> Types of Benign <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Breast</FONT> Disorders[details atre below and on the chart]</div> <div>  <A NAME="fibro"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Fibrocystic <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Breast</FONT>s</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibrocystic <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s is a condition that affects nearly 50% of American women.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The symptoms are lumpy, painful <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s. Women experience these symptoms to varying degrees and each women will have variable symptoms during her lifetime. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There has been concern about whether any of the fibrocystic changes are premalignant or increase your risk of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There are some specific changes which <I>do indicate</I> an increased risk for cancer development, but most of the changes are not associated with a significant risk. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pathologists also use the term fibrocystic changes to describe several microscopic findings found on <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> biopsy specimens.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These include: </div> <div> <U>Cysts </U></div> <div> <U>Sclerosing Adenosis</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U>Hyperplasia </U></div> <bR> <div> <B>CYSTS</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cysts are spherical fluid filled masses. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They may not cause any symptoms or they may present as painful lumps. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some cysts can be detected on physical examinations, whereas other cysts may only be seen on mammography or ultrasound.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Approximately 7% of women will develop a cyst at some time during her life.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Most commonly it is between the ages of 35-50. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If a cyst is palpable, it can easily be differentiated from a solid mass by <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>inserting a needle</U></FONT> and aspirating fluid.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The fluid may vary from yellow to green to brown. Occasionally the fluid may be bloody. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If a cyst is found, it can be <B>aspirated</B> (drained) using a needle and syringe. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">After cyst aspiration, the patient should be seen again by her physician in three weeks to check for refilling. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cysts do not increase the chances of developing <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer, however, there are a few situations where a cyst may be associated with a cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Therefore, removal of the cyst may be indicated when the cyst does not completely disappear with aspiration, or if the cyst refills after two aspirations.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Finally, if there is a solid component to the cyst seen on ultrasound, then a <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>biopsy </U></FONT>may be indicated. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alternatively a <B>sonogram</B> can be useful in distinguishing whether a lump is solid or cystic. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is about a 10% chance that a cyst will refill with fluid and about a 50% chance that a cyst will develop somewhere else in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s</div> <bR> <div> <B>SCLEROSING ADENOSIS</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sclerosing Adenosis is another common change seen microscopically. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This refers to a proliferation or growth of <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>lobular </U></FONT>tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is usually found as a result of an abnormal mammogram but can also be discovered as a lump or thickening in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Biopsy </U></FONT>is appropriate treatment to establish the diagnosis and rule out cancer. </div> <bR> <div> <B>ATYPICAL </B> <A NAME="hyperplasia"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>HYPERPLASIA</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hyperplasia means that there is an increased number of cells lining either in the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>ducts</U></FONT> or the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>lobules.</U></FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Where you normally have two (2) cells, you would find three or four. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A microscopic view of a duct cross section will show irregular areas of heaped up cells (more than two layers deep). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical means that the cells are slightly abnormal in appearance, but not to the extent that you would consider it cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This entity carries an elevated risk of developing <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The degree of risk depends on the severity of the changes seen but can range from 1.5 to 10 times that of the general population. </div> <div>  <A NAME="fibroaden"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>FIBROADENOMAS</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibroadenomas are benign <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> growths which usually occur in young women.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are a very common cause of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> masses in the 15 to 25 age group.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Fibroadenomas account for 15% of all palpable <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> masses in women 30-40 years of age. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clinically, these growths are smooth, firm and easily movable masses. It is generally accepted practice that suspected fibroadenomas should be removed in women over the age of 25.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These growths are not associated with an increased risk of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer. </div> <bR> <div>  <A NAME="duct"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>DUCT PAPILLOMAS</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Duct Papillomas are small growths that occur in a major duct just under the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>areola.</U></FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </U><FONT SIZE="3" COLOR="#000000" FACE="Arial" >They can produce a clear yellow or bloody nipple discharge.</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are most frequently seen in women between the ages of 30-50 and the treatment is excision of the duct to make sure cancer is not the underlying cause. </div> <div> <B>FAT NECROSIS</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This entity is considered to be a result of injury or trauma to the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It may present as a <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> lump and can mimic the appearance of a cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatment is often biopsy. </div> <bR> <div> <B><U>Breast</U></B><FONT SIZE="3" COLOR="#000080" FACE="Arial" ><B><U> Cancer</U></B></FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> <B><U>Noninvasive</U></B></div> <bR> <div> The term invasive refers to the biologic activity of the cancer cell. If the cancerous cells are confined to the duct or the lobule on microscopic evaluation, then a noninvasive cancer is diagnosed (carcinoma in situ). There are two different types of carcinoma in situ. </div> <bR> <bR> <div>  <A NAME="lcis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>LCIS</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">LCIS is usually found incidentally on microscopic review of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> biopsies done for other reasons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> LCIS itself is not a cancer, but does indicate a higher risk of developing <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer at some time during the affected women's life. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">That risk of cancer applies to either <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>. So, we consider it a marker that indicates increased risk. </div> <bR> <bR> <div>  <A NAME="dcis"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>DCIS</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">DCIS arises from the ducts of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> and is contained within the duct.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Before the widespread use of screening mammography, DCIS represented only 1-2% of all <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Now with more women going for routine mammography and with more sophisticated technical equipment, DCIS accounts for 25-30% of all <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">DCIS can be found either as a lump in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> on physical examination or on mammography.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> More commonly nowadays, it is represented on mammography by microcalcifications. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">DCIS may have two different behavior patterns. Some start as a single focus in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> and with time can spread along the ducts. In about 30-40% of cases, DCIS is considered to be a multicentric disease.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">That means that DCIS can be found in other quadrants of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> and may spread from multiple sites. </div> <bR> <div> <B><U>Invasive</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If the cancer cells have broken through the basement membrane or the outermost layer of the duct or lobule and has invaded the surrounding tissue, then the diagnosis is that of invasive or infiltrating carcinoma. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There are many types of invasive <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers, but two account for most <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers:</div> <div> <B>Infiltrating </B> <A NAME="ductal"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>ductal</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infiltrating ductal carcinoma accounts for more than 70% of all <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It arises from the ducts in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> and may be found by a woman on <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>self examination</U></FONT> as a hard lump or it may be seen on <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>mammography</U></FONT> as a mass OR a grouping of calcifications.</div> <bR> <div>  <A NAME="lobular"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><B>Infiltrating lobular</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Infiltrating lobular carcinoma accounts for about 10% of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It can be found either on mammography or physical exam. </div> <bR> <div> <B>Paget's disease</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paget's disease is an unusual presentation of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer. It is found in approximately 2% of patients. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Characteristically it presents either as a moist eczema type of lesion of the nipple or a dry, crusty area similar to psoriasis. It is almost always associated with an underlying mass or malignant calcification. </div> <bR> <bR> <bR> <bR> <div> <B> <A NAME="mastalgia"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Mastalgia</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mastalgia means <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> pain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast<FONT SIZE="3" COLOR="#000000" FACE="Arial" > pain is extremely common, and for many women who attend hospital clinics, this is their main and only symptom. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It should not be forgotten that mastalgia is a symptom, and therefore is not a specific disease in its own right. Instead,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> it usually indicates the presence of some underlying process or disease within the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>, which in most cases is benign.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In general terms, mastalgia can be one of two types - cyclical and non-cyclical - depending on the relationship to the menstrual cycle<FONT SIZE="3" COLOR="#000000" FACE="Verdana" >.</FONT><FONT SIZE="3" COLOR="#000000" FACE="verdana" > </FONT></div> <bR> <bR> <bR> <div> <B>Cyclical mastalgia</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cyclical mastalgia is the most common type. Virtually all women will experience a degree of pain or discomfort in their <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s at some time of their lives - this is normal and most often occurs in the week prior to menstruation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In some women however, the pain can become quite severe, and in certain cases can result in problems with work, recreation and even marital relationships. When this occurs, cyclical mastalgia can be considered abnormal, and such patients usually seek advice and help from their doctor.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Due to the relationship with the menstrual cycle, it is thought that the cause of cyclical mastalgia is hormonal. It has been suggested that an abnormality in the secretion of prolactin is to blame, and certainly drugs that inhibit prolactin secretion can be of benefit in the treatment of this disorder (see below). There are also other suggestions that consumption of too much caffeine, or a deficient intake of essential fatty acids can also result in cyclical mastalgia. For this reason women are often advised to decrease their caffeine intake and are given evening primrose oil, both of which can help (see below). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The usual age of patients with cyclical mastalgia is around 30 - 40 years. In the mildest form, the pain lasts only a few days prior to menstruation. The number of symptomatic days varies however, and in a few women, they can experience pain for virtually the whole month, with relief occurring only at the time of menstruation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cyclical mastalgia normally affects both <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s, but can be unilateral. Many women also feel lots of "nodules" or "lumpiness" in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> when the pain is present, and the upper outer quadrants of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> are most commonly affected.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>triple assessment</U></FONT> is performed on such patients, the following findings are typical. On clinical examination, there is often diffuse tenderness with lumpiness and nodularity. There is no single discrete lump to feel and there are no abnormalities with the nipple. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Mammography</U></FONT> typically shows no abnormality, but the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> tissue can appear glandular and dense. When <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>cytopathology</U></FONT> is taken in the form of an FNA, the result is benign. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Another form of assessment that it used to confirm the cyclical nature of the symptoms is a <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> pain chart. This is given to the patient on attendance at the clinic, and they are asked to score their pain on a daily basis as either severe, mild or no pain at all. The commencement of menstruation is also recorded and after a couple of months it becomes apparent that the symptoms are cyclical in nature. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Once assessment has been performed, and no serious abnormality found, the question of treatment then arises. Most women require no treatment at all - simple reassurance is all that is needed. For these patients, the knowledge that they do not have <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT> is reassuring and they learn to live with the symptoms. Often, cyclical mastalgia will settle over the course of a few months, returning to "normal" pre-menstrual <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> discomfort without any specific treatment.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">For those women whose symptoms are severe however, treatment is required in the form of drugs. The simplest, and perhaps the most commonly used first treatment is evening primrose oil capsules. These are usually taken in a dose of 6-8 capsules per day for at least 2 months. They work by replacing essential fatty acids that may be deficient in the patient's diet. It is thought that mastalgia may be caused by such deficiencies in certain patients. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It should be remembered by patients, that evening primrose is not a pain-killer, and must be taken every day. Normally no effect is noted for the first 2-4 weeks, after which time symptoms will begin to settle if treatment is effective. Approximately 50% of patients will respond to this form of therapy, requiring no further treatment. They usually continue with the medication for a few months and many find that symptoms do not recur once the medication is stopped. The only significant side-effect that is reported is nausea, though this occurs in only 1% of all patients. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If evening primrose oil fails, and symptoms persist, the next drug that is often used is danazol (200 - 400 mg daily). This drugs acts by inhibiting follicle-stimulating hormone and leutenising hormone in the pituitary gland. It is very effective in treating <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> pain, relieving symptoms in around 70% of patients. However, it is associated with significant side-effects that can occur in about 25% of patients on treatment. These side effects include acne, deepening of the voice (that can be permanent), hirsutism (facial hair), increase in weight and amenorrhoea (cessation of the menstrual cycle whilst on treatment). For these reasons, this drug is normally reserved for those women whose pain is severe and who are willing to risk the side-effects for the sake of symptom relief.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Another drug that is used to treat cyclical mastalgia is bromocriptine (2.5mg twice daily). This drug acts to lower the levels of prolactin secretion and is effective in 50% of cases. However, it can cause severe nausea, headaches and dizziness and for this reason many patients are unable to continue with it.</div> <bR> <div> <B>Non-cyclical mastalgia</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Non-cyclical mastalgia, as its name suggests, is pain in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> that is not related to the menstrual cycle. A number of conditions can give rise to non-cyclical mastalgia, each with certain additional <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>symptoms</U></FONT> or clinical signs that aid diagnosis. Amongst these conditions is <FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>breast</U></FONT><U> </U><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>cancer</U></FONT>, and for this reason it is important to investigate these patients before treatment is commenced. </div> <bR> <bR> <div> <B>Sclerosing adenosis</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is an "ANDI" problem (<FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>see above</U></FONT>) that is characterised by over-proliferation of the terminal duct lobules. It can cause impingement to adjacent nerve endings, thereby resulting in <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> pain. It can also present as a painful lump or be detected on routine screening <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>mammography</U></FONT> as a calcified, "stellate" abnormality - an appearance that is not infrequently confused with <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT>. Areas of sclerosing adenosis are often excised surgically during <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>biopsy</U></FONT> or <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>needle-localisation procedures</U></FONT> (when there is no palpable lesion but only mammographic abnormality). A woman with an area of sclerosing adenosis, may also experience "trigger-point" pain on pressing the affected part.</div> <bR> <bR> <bR> <div> <B>Tietz's syndrome</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is an inflammatory condition affecting the costochondral junctions and costal cartilages. The ribs are bony along their entire length. At the back, they join with the bones of the spinal column. At the front however, they join the costal cartilages, that are in turn joined to the sternum (<FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> bone). These joints and costal cartilages can become inflamed and cause pain on the anterior chest wall, just to the side of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> bone. Obviously in women, this can be mistaken for <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> pain, since the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> overlies the affected area. Typically, there is tenderness to palpation, and no specific clinical, radiological or pathological abnormality in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> - after all, it is not a disease of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>. Treatment is by reassurance and sometimes the injection of a small quantity of local anaesthetic and steroid that will help to settle the pain and inflammation. Non-steroidal drugs such as diclofenac or ibuprofen can also be used in such cases.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT><B>cancer</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pain is not typically a symptom of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT>, but it can be. For this reason, as with most <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> symptoms, a proper clinical assessment is required to ensure that <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT> is not present before a benign diagnosis is made. The presence of a lump, an elderly patient or someone with significant risk factors, should alert the clinician to the possibility of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT> being present. At the end of the day however, as with most <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> complaints, the working assumption of "<FONT SIZE="3" COLOR="#800000" FACE="Arial" >cancer</FONT> till proven otherwise", should ensure that no cases are missed.</div> <bR> <bR> <div> <B>Inflammatory </B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B>Breast</B></FONT><B> Cancer</B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="1008" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" BGCOLOR=#000099 > <tR> <tD VALIGN=CENTER HEIGHT= 16 WIDTH="332"><div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Plugged Duct</div> </tD> <tD VALIGN=CENTER WIDTH="313"><div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mastitis</div> </tD> <tD VALIGN=CENTER WIDTH="343"><div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abscess</div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 226 WIDTH="332"><bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Symptoms: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast tender in the area of the plug. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Plug will feel like a small knot. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">May appear as a small white bleb on the surface of the nipple. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The breast should not appear inflamed or reddened. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No Fever: no systemic symptoms. </div> </tD> <tD VALIGN=TOP WIDTH="313"><bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Symptoms: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Red, inflamed area on breast or red streaks on breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fever. Chills. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Body aches. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Headache. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Flu like symptoms: Diarrhea, nausea, vomiting. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">History of recent plugged duct. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">History of recent inadequate breast emptying: Recently returned to work, baby begun sleeping through the night or sudden weaning. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Recent breast injury or sore nipples with breaks in the nipple or areolar tissue. </div> </tD> <tD VALIGN=TOP WIDTH="343"><bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Symptoms: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">History of delayed [ > 24 hours from start of symptoms] or inadequate treatment of mastitis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Area may no longer be painful. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Systemic symptoms may be absent. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Area of the abscess may look discolored or bruised. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The abscessed area has risen to the surface of the breast tissue and is indurated (hard) in the center. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Has a soft, mushy spot in the center right before rupture. </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 66 ><NOBR><div> <B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Apply Home Treatment (listed below)</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="313"><div> <B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Call your doctor or Lactation Consultant for medication and treatment. </B><B>You should be seen by your doctor as soon as possible: in less than 24 hours after the symptoms started.</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">See your doctor now. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is considered a medical emergency.</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 848 WIDTH="332"><bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Home Treatment: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Moist heat to affected breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Manual expression to assist in removing the plug. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nurse or pump every two hours, beginning each feeding with the affected breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Alter position of infant at breast to assist in removing plug. The infant's chin should be near the area of the plug. </div> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Remove any constrictive clothing and/or bra. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Take oral temperature every four hours, report any fever over 101° F to medical provider. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Watch for aches and pains, flu like symptoms. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Watch for increasing redness and pain.</div> </tD> <tD VALIGN=TOP WIDTH="313"><div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">SUGGESTED MEDICATION PROTOCOLS: Dicloxacillin 250 or 500 mg </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If allergic to Dicloxacillin, Penicillin: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Erythromycin 333 mg., </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Medication Schedule: 1 capsule, every 6 hours, for 10 to 14 days. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If allergic to both Dicloxacillin, Penicillin or Erythromycin: can use Keflex 500 mg., 1 capsule, every 6 hours, for 10 days (Delayed response when the medication prescribed is Keflex has been observed in the lactation clinic) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Take the antibiotics on a regular schedule. If the bottle says take 4 times a day that doesn't mean before breakfast, lunch, dinner and at bedtime. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It means taking it every 6 hours around the clock (I tell moms to use a 6-12-6-12 schedule because it is easier to remember) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Home treatment: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Strict bed rest until systemic symptoms (fever, headache, body aches) are absent, usually within 72 hours after starting antibiotics. </div> <div> <I><IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Strict bedrest means</I> you can feed the baby, shower once a day and get up and go to the bathroom as needed. The rest of the time you should be in bed. It has been proven that fatigue leaves mom's body wide open for these infections because fatigue and stress decrease our body's immune response. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nurse or pump the affected side every two hours. Keep the breast as "empty" as possible. This serves two purposes. It gets the level of antibiotic up in the breast itself by increasing blood flow to the area and keeps the milk from stagnating which gives the offending bacteria a wonderful place to grow. If the bacteria grows unchecked the body will wall it off (which is an abscess). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Moist heat to affected breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Removal of bra and constrictive clothing. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Increase fluid intake. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Start taking several million units of live Acidophilus several times a day to prevent the GI problems which include gas, bloating and diarrhea. The Acidophilus will also help prevent <U>thrush.</U> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Report any increase of symptoms to the medical provider immediately. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Return to the medical provider for further evaluation before refilling the prescription. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most cases of mastitis are caused by simple skin staph. However, if mastitis recurs after one or two rounds of antibiotics, ask that the baby's nose and throat be cultured to make sure baby isn't a hidden strep carrier.</div> </tD> <tD VALIGN=TOP WIDTH="343"><bR> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Medical treatment: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Surgical incision and drainage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hospitalization for IV antibiotics as needed. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Continue to nurse the baby or pump on a regular schedule. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cover incision with a clean dressing at each feeding. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800ffff00.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breastmilk is not harmful to the incision as the macrophages in the milk will assist in the destruction of the offending bacteria and aid in the healing process. </div> </tD> </tR> </TABLE></div> <div> Breast<FONT SIZE="4" COLOR="#000000" FACE="Arial" > infections during pregnancy</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast<FONT SIZE="3" COLOR="#000000" FACE="Arial" > infections fall along a spectrum of severity from cellulitis to mastitis to </FONT>breast<FONT SIZE="3" COLOR="#000000" FACE="Arial" > abscess. Infections mainly occur during the first month after delivery and are likely to affect young, inexperienced mothers who do not practice proper hygiene.</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Staphylococcus aureus is the most common organism. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cellulitis responds rapidly to antibiotics and does not require drainage. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Abscesses are localized collections of pus which may respond to antibiotic therapy or may require aspiration or surgical drainage. </div> <DIV ALIGN="LEFT"></DIV> <div> <IMG SRC="1402cd80.gif" border=0 width="300" height="216" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Because milk is an excellent culture medium, the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> must be kept empty. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast<FONT SIZE="3" COLOR="#000000" FACE="Arial" > feeding from the contralateral side may usually be continued; suckling from the affected </FONT>breast<FONT SIZE="3" COLOR="#000000" FACE="Arial" > has been reported to cause pneumonia in the infant and should be avoided.</FONT></div> <bR> <div> Galactoceles</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These simple milk-filled cysts probably form because of ductal obstruction. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The patient complains of a tender mass, usually peripheral in the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>. Needle aspiration is both diagnostic and curative.</div> <bR> <div> Fibroadenomas</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These benign tumors often increase in size during pregnancy, sometimes dramatically. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occasionally the lesion outgrows its blood supply and infarcts. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Both rapid growth and infarction may be associated with pain and a mass difficult to distinguish from cancer. </div> <bR> <div> Mammary hamartomas</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Also benign, these tumors are quite similar to fibroadenomas; sometimes they become quite large causing significant <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> asymmetry. </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Often these uncommon lesions are diagnosed for the first time after pregnancy, when post-lactational involution allows the surrounding <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> parenchyma to shrink. Excision is the treatment of choice when a mass or <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> asymmetry is present.</div> <bR> <div> Other benign tumors unique to the puerperium</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nodular lactational hyperplasia and lactating adenomas are benign focal lesions that may be single or multiple. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical presentation and appearance is similar to fibroadenoma.</div> <bR> <div> Breast<FONT SIZE="4" COLOR="#000000" FACE="Arial" > hypertrophy with pregnancy</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occasionally the normal <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> enlargement accompanying pregnancy becomes massively exaggerated. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT>s often regress postpartum, but recurrence may occur with subsequent pregnancies. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Reduction mammoplasty</U></FONT> is an option. </div> <bR> <div> Nipple discharge</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The physiologic proliferative changes of pregnancy occasionally cause bloody nipple discharge to appear during the second or third trimester. Cytology may be misleading due to the amount of normal proliferative changes present. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Observation and reassurance are appropriate and further studies are generally not advised unless the condition persists more than two months after delivery.</div> <div> Breast<FONT SIZE="4" COLOR="#000000" FACE="Arial" > infarcts</FONT></div> <div> Sometimes normal <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> tissue infarcts during pregnancy. The palpable, often tender, mass that results must be distinguished from cancer. Biopsy may be necessary.</div> <bR> <div> Breast<FONT SIZE="4" COLOR="#000000" FACE="Arial" > cancer</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Approximately 1-2% of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancers in women are diagnosed during pregnancy. It is likely that this number will increase as the tendency to defer childbirth results in more pregnancies in older women.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A baseline <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> exam at the time of the first obstetrical visit is crucial.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Evaluation of mass lesions becomes much more difficult as pregnancy progresses. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mammography is of limited benefit because of the increased <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> mass, density, and vascularity. Ultrasound may help to distinguish cystic from solid lesions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Delay in diagnosis is common due to the difficulty in feeling masses and a reluctance to biopsy. Stage for stage, survival is identical to the general <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer population. However, over 75% of pregnant women diagnosed with <FONT SIZE="3" COLOR="#800000" FACE="Arial" >breast</FONT> cancer have nodal metastases, far more than the general population.</div> <bR> <bR> <div> Breast<FONT SIZE="4" COLOR="#000000" FACE="Arial" > biopsy during pregnancy and lactation</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Biopsy can be performed safely using a cutting needle or open biopsy technique with suitable precautions to avoid hemorrhage (due to increased vascularity), hematoma formation, and milk fistula (during lactation).</div> <bR> <bR> <bR> <div> ============================================================================================================================</div> <div> Breast</div> <bR> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">big axillary nodes & normal breasts</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">breast dose in mammography</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">circumscribed breast lesions</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">coarse breast architecture</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">halo sign</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">large breast lesions</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">large, dense breast lesions</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paget disease of breast</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stellate breast lesions</U></div> <bR> <div> <B><U>big axillary nodes & normal breasts</U></B></div> <bR> <div> consider: </div> <div> lymphoma </div> <div> leukemia </div> <div> rheumatoid arthritis </div> <bR> <div> breast dose in mammography</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">180 mrad / view -- mid-breast dose </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">guideline: < 1 rad for 2-view exam </div> <bR> <div> circumscribed breast lesions</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lucent </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lipoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">oil cyst (following hematoma or biopsy) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">galactocele (a/w lactation) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mixed density </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fibro-adeno-lipoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">galactocele </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">intramammary lymph node </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hematoma </div> <bR> <div> coarse breast architecture</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">inflammatory carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">other lymphatic spread of tumor </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">edema </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CHF </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">uremia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">drug-induced </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">radiation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mastitis </div> <bR> <div> <B><U>halo sign</U></B></div> <bR> <div> narrow, radiolucent ring surrounding breast lesion </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">indicates benign tumor </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rare exceptions: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">intracystic carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">papillary carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">carcinoma arising in fibroadenoma </div> <bR> <div> <B><U>large breast lesions</U></B></div> <bR> <div> breast masses > 5 cm </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lucent: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lipoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mixed lucent/opaque: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fibro-adeno-lipoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">low-density opaque: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">giant fibroadenoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cyst </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cystosarcoma phylloides </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mucinous carcinoma </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">high-density opaque</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > (large + dense) </FONT></div> <bR> <div> <B><U>large, dense breast lesions</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sarcoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cystosarcoma phylloides </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cyst </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">abscess </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lymph nodes (lymphoma, leukemia, mets</div> <bR> <div> <B><U>Paget disease of breast</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">form of ductal carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">associated with eczematous changes of the nipple </div> <bR> <bR> <div> <B><U>stellate breast lesions</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">infiltrating ductal Ca </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">radial scar </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">traumatic fat necrosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hyalinized fibroadenoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">postoperative scar/hematoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">summation (use comp/mag views) </div> <bR> <bR> <bR> <div> <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=CENTER HEIGHT= 95 WIDTH="622"><div> <B>BENIGN BREAST LESIONS</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>OR</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>NON-NEOPLASTIC CHANGES AND NEOPLASMS</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 597 ><NOBR><div> <B>I. </B><B><U>Fibrocystic change</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B>A. Cyst</B> </div> <div> <B>B. Ductal hyperplasia with and without atypia</B> </div> <div> <B>C. Adenosis</B> </div> <div> <B>D. Fibrosis</B> </div> <div> <B>II. </B><B><U>Mammary ductal ectasia</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>III. </B><B><U>Benign papillary neoplasm and changes</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B>A. Papilloma</B> </div> <div> <B>B. Radial scar</B> </div> <div> <B>III. </B><B><U>Fibroepithelial tumors</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B>A. Fibroadenoma</B> </div> <div> <B>B. Phyllodes tumor</B> </div> <div> <B>IV. </B><B><U>Benign and malignant epithelial and nonepithelial tumors</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B>A. Hamartoma</B> </div> <div> <B>B. Vascular tumors</B> </div> <div> <B>C. Granular cell tumor</B> </div> <div> <B>D. Stromal tumors</B> </div> <div> <B>V. </B><B><U>Nipple diseases</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B>A. Paget's disease</B> </div> <div> <B>B. Chronic dermatitis</B> </div> <div> <B>C. Nipple adenoma (papilloma, papillomatosis)</B> </div> <div> <B>VI. </B><B><U>Others changes</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <DIV ALIGN="LEFT"></DIV> <div> <B> Fat necrosis</B> </div> </NOBR></tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <bR> <div> <B><U>Benign lesions</U></B></div> <bR> <div> <B><U>1. Nipple discharge</U></B></div> <bR> <div> Present in 75% of women. </div> <div> Discharge associated with: </div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">duct ectasia (green); </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">benign intraductal papilloma and cancer (serous or bloody). </B></I></div> <div> Likelihood of cancer: </div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">serous discharge (6%), </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bloody discharge (13-20%).</B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Evaluate suspicious discharge with ductogram and excision. </B></I></div> <div> <I><B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cytology rarely helpful.</B></I></div> <bR> <bR> <div> <B><U>2. Fibrocystic change </U></B></div> <bR> <div> Present in up to 75% of women.</div> <div>  No longer considered an accurate diagnostic term.</div> <div> <B><U><IMG SRC="0cca51d0.jpg" border=0 width="421" height="285" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B><FONT SIZE="4" COLOR="#000000" FACE="Arial" ><B>Fibrocystic change. The ducts are lined by apocrine metaplastic cells with focal papillary proliferation</B></FONT></div> <div> <B><U><IMG SRC="0ceb0440.gif" border=0 width="432" height="324" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B><B>Apocrine Metaplasia of Breast (Med Pow) ONE TYPE OF FIBROCYSTIC CHANGE</B></div> <div> <B>•</B> This medium power view of several ducts shows the features of apocrine metaplasia. </div> <div> <B>•</B> The lining cells have abundant eosinophilic cytoplasm on the lumenal edge of the cell. </div> <div> <B>•</B> The nuclei are uniform and round. </div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibrocystic "disease" or change is one of the most common benign conditions that affects more than 50 percent of women having palpably irregular breasts, cyclic pain, and tenderness. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is related to regular and, sometimes irregular, menstrual cycles with hormonal fluctuations. The target organ, mammary tissue, in response to the imbalanced estrogen and progesterone stimulation over time, undergoes a wide variety of morphologic changes under the old term of fibrocystic change.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Essentially, at the time of increased estrogenic stimulation epithelial cells proliferate in the ducts (ductal hyperplasia) and lobules (adenosis). </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With decreased estrogen levels, the epithelium involutes, the ducts become cystic, and the lobules and stroma increase fibrous tissue (sclerosing adenosis and stromal fibrosis, respectively). </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, fibrocystic change occurs in the following three major elements through the mediation of estrogen and progesterone receptors: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. ducts: ductal hyperplasia and cyst formation </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. lobules: adenosis (lobular hyperplasia) and sclerosing adenosis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3. stroma: fibrosis </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A lack of uniform criteria for the term of "fibrocystic change" for many years created controversies as to the relationship to breast cancer. The original study by Dupont and Page (1985) has demonstrated the importance of precisely classifying and specifying epithelial proliferations into those with and without atypia. Based on the review of more than 10,500 consecutive benign breast biopsies for benign diseases from 3,300 women who were followed for a median period of 17 years, the relative risk of specific changes is summarized as follows: </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">About 10% of women have clinically evident disease </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">•</B><B> May be associated with tenderness and irregular nodularity which varies during the menstrual cycle </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">•</B><B> Microcalcifications may be demonstrable on mammogram </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">•</B><B> May be associated with epithelial hyperplasia or sclerosing adenosis although these entities should be reported separately </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">•</B><B> Cysts, fibrosis, and apocrine metaplasia do not elevate risk for breast carcinoma </B></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="445" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#800000 HEIGHT= 44 ><NOBR><div> <B>Proliferative Lesions and their Relative Risks </B></div> <div> <B>for Developing Invasive Breast Cancer*</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 51 ><NOBR><div> <B>Nonproliferative changes: 70% of cases</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>Relative Risk = 1.0</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 75 ><NOBR><div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Adenosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cysts and apocrine change </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ductal ectasia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mild epithelial hyperplasia of usual type </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 73 WIDTH="435"><div> <B>Proliferative disease without atypia: 26% of cases</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>Relative Risk = 1.5-2.0</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 56 ><NOBR><div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hyperplasia of usual type, moderate or florid </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Papilloma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Sclerosing adenosis </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 51 ><NOBR><div> <B>Proliferative disease with atypia: 4% of cases</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B>Relative Risk = 4-5</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="435"><div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical ductal hyperplasia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical lobular hyperplasia </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 76 WIDTH="435"><div> *Modified from Table 1 by DL Page and WD Dupont: Premalignant conditions and markers of elevated risk in the breast and their management. Surg Clin N Amer 1990;70:831-851.</div> </tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> <I><B>How to translate the relative risk factors to prevalence rates?</B></I> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">During a 15-year follow-up period, 20% of women who have atypical hyperplasia and a family history of breast cancer developed breast cancer, as compared to 8% for those with atypical hyperplasia and without family history.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The comparable rates are 2% for women without non-proliferative change and 4% with proliferative change without atypia. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the subsequent studies by Dupont and Page (1986 and 1989), the highest risk for the development of invasive breast carcinoma occurs during the first 10 years after biopsy and the risk decreases thereafter. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This implies that the most critical follow-up should be the initial 10 years following diagnosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The importance of atypical hyperplasia as a biologic marker for increased risk of developing invasive breast cancer has been confirmed in a multicenter study involving more than 280,000 women (Dupont et al, 1993). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">For these reasons, the morphologic criteria and definition as proposed by Dupont and Page are adopted in this presentation. Needless to say, these changes should be recognized and reported in the pathology reports. </div> <bR> <div> <U>A. Cysts</U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cysts are fluid-filled spaces that originate from the terminal ductal lobular unit or from an obstructed ectatic duct. They are frequently multiple and bilateral and may vary in size from microscopic to a few centimeters. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cysts are the most common breast masses in women aged 40 to 50 years (Bassett et al). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cysts are usually multiple and measure in size from 2 mm to greater than one cm.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are lined attenuated, atrophic ductal cell or apocrine metaplastic cells  </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The apocrine cells have abundant eosinophilic, granular cytoplasm and cytoplasmic protrusions into the luminal border, so called apocrine snouts  </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The nuclei often prominent nucleoli. It is common to find papillary projections </div> <bR> <bR> <bR> <bR> <div>  </div> <div> <B>Epithelial Hyperplasia With and Without Atypia</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Epithelial hyperplasia is divided into ductal and lobular types under the low power microscopic observation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In general, lobules include acini and terminal ductules, whereas ducts comprise of interlobular ducts and beyond.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It should be emphasized that, due to the substantial individual variations under the influence of hormones, the separation between lobules and ducts is subjective and sometimes arbitrary.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The "usual" ductal hyperplasia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The morphologic hallmarks of ductal hyperplasia is increased cellularity and altered architectures, most commonly with </div> <bR> <bR> <div> 1.<FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> papillary formation  </B></FONT></div> <div> <B>2. sieve-like, cribriform, back to back pattern </B></div> <div> <B>3. solid filling of ductal lumens </B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These ductal hyperplasias have also been referred to by various authors as epitheliosis and papillomatosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In ductal hyperplasia, both epithelial and myoepithelial cells proliferate giving the impression of a heterogeneous population of cells . </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is a mild irregularity in nuclear size and shape. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Based on the architecture, ductal hyperplasia is graded as mild, and moderate (or florid). In the latter, solid pattern predominates.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the presence of architectural and nuclear atypicality, the ductal hyperplasia is designated as atypical ductal or lobular hyperplasia. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These atypical hyperplasias are defined as having some but not all the morphologic features of carcinoma in situ. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In atypical ductal hyperplasia, the proliferating atypical cells have enlarged, irregular, hyperchromatic nuclei, and small nucleoli. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are mixed with the normal secretory or myoepithelial cells without reaching to a homogeneous population of atypical cells expected of a ductal carcinoma in situ </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is common for ductal and atypical ductal hyperplasias to undergo focal stromal fibrosis, elastosis, and hyalinization producing stellate shaped, indurated lesions, the so called radial scar. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This lesion will be discussed in a later section along with papilloma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical lobular hyperplasia is characterized by partial expansion of the lobules and the atypical cells are loosely cohesive.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Their nuclei are slightly larger than the normal cells, slightly irregular in shape and variable in size. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The chromatin particles are fine chromatin particles and the nucleoli are small. In the background, myoepithelial cells, although reduced in number, can still be identified. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In lobular carcinoma in situ, the lobules are expanded and solidly filled by atypical cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The myoepithelial cells are absent, except a few in the periphery of the lobules.</div> <bR> <div> <B>C. Adenosis</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Adenosis refers to a spectrum of changes within the lobules beginning from the hyperplasia to the subsequent fibrosis and calcifications. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The term adenosis tumor is used by some authors, when the adenosis presents as a mass.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the early stage of adenosis, the lobules are enlarged with an increased number of acini .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Later, myoepithelial proliferation and stromal fibrosis cause distortion of the individual acini, the so called sclerosing adenosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Within the acini, laminated, purple, psammoma bodies often occur .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A compressed, cord-like arrangement sometimes simulate invasive carcinomas. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although the lobular borders become irregular, the lobules remain intact .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> With further stromal fibrosis and atrophy, the acini become few in number and the lobules become small </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is important to appreciate the lobular pattern under low power magnification. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">On high power, the preservation of the basement membrane and normal two cell layer of the acini is indication of benignancy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglandular adenosis is typically seen in postmenopausal women. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Clusters of round glandular profiles occur in the adipose tissue .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This feature and a single layer of lining cells sometimes lead to an erroneous diagnosis of tubular carcinoma .</div> <bR> <div> <B>D. Fibrosis (Fibrous Mastopathy)</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibrosis or fibrous mastopathy is an increase of fibrous connective tissue, which is usually hypo- to acellular. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The lobules in particular are reduced in number and in size </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Focal fibrosis may present as a palpable mass or as an impalpable mammographic abnormality. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A variant of fibrosis occurs in some women with a long history of insulin-dependent diabetes mellitus, referred to as diabetic fibrous breast disease</div> <bR> <bR> <div> <B><U>3. Cysts</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Common during reproductive years. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Probably develop due to estrogen.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Evaluate palpable mass by FNA. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">If clear fluid obtained without residual mass, then repeat exam in 1 month. If bloody fluid obtained, or if mass persists, submit cytology specimen, order mammogram, and perform biopsy.</div> <bR> <div> <B><U>4. Fibroadenoma</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most common benign tumor of breast.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Peak incidence age 20-30. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Usually firm, well circumscribed, and solitary. FNA often diagnostic. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Phylloides tumors can mimic fibroadenoma.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lobular CIS reported in these tumors occasionally. Biopsy appropriate.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibroadenoma is the most common benign breast tumors seen in women under the age of 35 years. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The peak age of incidence is in the third decade. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most fibroadenomas are 2-3 cm in size, but may reach to 6-7 cm, the so called giant fibroadenomas. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are well-circumscribed, but not encapsulated.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cut surfaces have a lobulated, grey-white myxoid, semitransparent to dense fibrous appearance. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cleft-like spaces corresponding to branching ducts may be evident .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> About 10-20% of fibroadenomas are multiple and bilateral  and may increase in size during pregnancy and undergo infarct following childbirth. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fibroadenomas consist of epithelial and fibrous components.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Branching and budding ducts are surrounded by fibrous tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The pericanalicular fibroadenoma maintains round and oval dilated ductal spaces .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Whereas in the intracanalicular type, the ductal lumens are compressed by polypoid fibrous stroma creating slit-like irregular spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The ducts are lined by two layers of cells: epithelial and myoepithelial cells. Under the influence of hormones, the ducts become hyperplastic with papillary formation and more than two layers of cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The fibrous stroma varies from myxoid and hypocellular to fibrous and moderately cellular. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rare mitotic figures may occur, but nuclear atypia is absent or minimal, allowing separation from phyllodes tumor. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Involution is common with increasing age of the lesion. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stroma becomes less cellular, more fibrotic and hyalinized .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Coarse calcifications. In old fibroadenomas, the ductal epithelium becomes so atrophic as to disappear completely. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rarely, fibroadenomas enlarge in postmenopausal women, with or without hormone replacement therapy.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Several variants of fibroadenomas have been described. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The giant fibroadenoma is simply a fibroadenoma that has reached a large size.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Microscopically these are the same as other fibroadenoma, the cellularity can be high. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tubular adenomas contain predominantly tubular elements and minimal amount of fibrous stroma and sometimes are found during pregnancy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lactational change may produce a localized mass having enlarged lobules and ducts with vacuolated cytoplasm and secretory product in the lumens. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Very rarely ductal or lobular carcinoma in situ occurs within fibroadenomas  (Pick and Iossifides). Invasive carcinoma has also been report to arise in a fibroadenoma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When in situ or invasive carcinoma involves the fibroadenoma, about 50% of women also have disease outside of fibroadenoma .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thus, it is important to evaluate the surrounding tissue of fibroadenoma to determine the extent of disease for optimal treatment.</div> <bR> <div> <B><U>Phyllodes Tumor (Cystosarcoma Phyllodes)</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The malignant counterpart of fibroadenoma is cystosarcoma phyllodes or the newer term of phyllodes tumor, in which the epithelial elements are benign, but the stromal tissue is malignant. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It results from malignant degeneration of fibroadenoma, estimated to occur in 1% of patients, who have fibroadenoma for many years. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">At presentation, most women are between 40 and 50 years with a typical presentation of a rapidly growing mass. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The phyllodes tumor has a lobulated, leaf-like appearance and varies in size from 1 cm to greater than 15 cm  Microscopically, the branching, hyperplastic ducts are surrounded by a stroma, which is mostly fibrous and much more cellular than fibroadenoma . In addition, nuclear atypia and increased mitotic activity occur.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stromal components may contain liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, angiosarcoma, chondrosarcoma and osteosarcoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> For this reason, it is important to adequately sample the neoplasm to determine whether ductal elements are present. In the absence of epithelial cells, the neoplasm is classified as primary stromal sarcoma of the breast, which is generally more aggressive than phyllodes tumor. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical behavior of phyllodes tumor is unpredictable.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The majority of phyllodes tumors are local problems and do not metastasize. Less than 20% of phyllodes tumors metastasize by vascular spread, most commonly to the lung, pleura, and bone. (Hart, 1978; Pietrusz, 1978). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, lymph node dissection is not indicated. Local recurrence is likely, if incompletely excised. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Therefore, a wide local excision is required. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some recent studies have attempted to separate cystosarcoma phyllodes into benign and malignant groups. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The benign group is characterized by smooth, non-infiltrative borders and the fibrous elements have minimal nuclear atypia and low mitotic activity. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This is in contrast to infiltrative borders , presence of nuclear atypia and increased mitotic activity usually greater than five mitotic figures per 10 high power fields in the malignant group (Hart et al; Pietrusz and Barnes).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It should be mentioned that not all metastatic phyllodes tumors meet the above criteria. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thus, it is more appropriate to classify the phyllodes tumors into low and high grades and to treat these tumors with wide clear margins. </div> <bR> <bR> <div> <B><U>5. Papilloma, intraductal</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Associated with bloody discharge.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Palpable subareolar lesions in 30%.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Evaluate with ductogram and excision.</div> <bR> <bR> <bR> <bR> <div> <B><U>MAMMARY DUCT ECTASIA</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Duct ectasia is a nonspecific dilatation of the major subareolar ducts with occasional involvement of the smaller ducts, unrelated to fibrocystic change. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microscopically, the dilated ducts contain foamy macrophages mixed with lipid material, cholesterol clefts and eosinophilic debris.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The material within the ducts often calcifies. Infiltration of lymphocytes, plasma cells, and histiocytes occurs in the periductal tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With time, fibrosis increases in amount .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thus terms, such as plasma cell mastitis, obliterative mastitis and comedomastitis, were used. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The etiology of the condition is unknown.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The theory of an initial inflammatory process leading to destruction of the elastic network and secondary ductal ectasia and periductal fibrosis is favored. </div> <bR> <div> <B><U>III.</U></B><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><B><U> </U></B></FONT><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B><U>BENIGN PAPILLARY NEOPLASM AND CHANGES</U></B></FONT></div> <bR> <div> <B><U>A. Intraductal papilloma</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Intraductal papilloma usually occurs within a major duct in the subareolar region. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When a similar papilloma occurs in the nipple, the term nipple adenoma or papillomatosis is used </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical presentation is bloody, or serous nipple discharge. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The excised lesion is usually small, less than 1-2 cm in siz.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, some papillomas are larger than 4 cm, especially those associated with hemorrhage and cystic change. Sometimes the papillomas are multiple involving a group of ducts. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Multiple peripheral papillomas are associated with an increased risk for local recurrence and subsequent development of breast carcinoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microscopically, the papillomas form papillary fronds supported by fibrous cores and covered with hyperplastic epithelium .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, solid areas are common, either focal or predominant.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The proliferative epithelium is made up of epithelial and myoepithelial cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Secondary changes occur often in the form of hemorrhage, infarct, fibrosis and hyalinization, most likely resulting from torsion of the fibrous stalks and ischemic injury.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The damaged epithelium and hyalinized stroma may also deposit calcium. In core biopsies, potential diagnostic problems include entrapped ducts in the hyaline stroma interpreted as invasive carcinoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Nuclear atypia in papillary lesions needs careful evaluation to rule out atypical hyperplasia and ductal carcinoma in situ. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Juvenile papillomatosis refers to a marked ductal hyperplasia in adolescents and young women.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B><U>The involved ducts are cystically dilated with a Swiss cheese pattern.</U></B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical ductal hyperplasia and carcinoma may occur </div> <bR> <div> <B><U>B. Radial Scar</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Radial scar is a benign lesion known by a variety of names in the literature, including infiltrating epitheliosis, nonencapsulated sclerosing lesion, indurative mastopathy, scleroelastic lesion, sclerosing papillary proliferation, benign sclerosing ductal hyperplasia, and radial sclerosing lesion. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most radial scars are spiculated masses or areas of architectural distortion, often with multiple long spicules and central areas of lucency. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Radial scar occurs in the background of benign ductal hyperplasia, intraductal papilloma and/or sclerosing adenosis, in which fibrous stromal undergoes fibrosis and elastosis .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> As a result, the ducts and ductules become distorted and arranged in a radiating pattern  </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The ducts entrapped in the scar superficially resemble invasive carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These benign ducts retain the usual epithelial and myoepithelial cells without significant nuclear atpyia. </div> <bR> <div> <B>BENIGN AND MALIGNANT EPITHELIAL AND NONEPITHELIAL TUMORS</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B>A. Hamartoma</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hamartoma of breast is a circumscribed benign nodule composed of variable amounts of fat, glandular tissue, and fibrous connective tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hamartoma is usually, asymptomatic, but may become palpable with increasing size and fibrous tissue giving firm consistency. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The majority occur in women over age 35 years.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Histologically, hamartoma consists of varying amounts of adipose tissue, fibrous stroma, and glandular tissue, some of which may be cystic. Capsule may be complete or partial </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> An unusual finding in the fibrous stroma is the presence of capillary-like spaces, referred to as pseudoangioma ). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hamartoma of breast has distinct mammographic features with circumscription and fat and soft-tissue density surrounded by a thin radiopaque capsule or pseudocapsule .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Pathologist unaware of the mammographic findings may not use the term hamartoma, but rather fibroadenolipoma and lipofibroadenoma to indicate lesional components. </div> <bR> <div> <B><U>B. Vascular Tumors</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Benign hemangiomas in the form of capillary, cavernous and venous types rarely occur in the breast parenchyma. These are benign, localized growth without infiltration </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The lining endothelial cells may appear active, but nuclear atypia is absent. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Thrombus formation is common. Rarely the endothelial cells may appear atypical with nuclear enlargement and hyperchromasia. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These atypical hemangiomas are small, usually less than 2 cm and well circumscribed without local infiltration. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Angiosarcoma is usually greater than 2 cm in size and locally infiltrative with ill-defined borders.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Histologically, the angiosarcomas are divided into well and poorly differentiated categories. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In well-differentiated angiosarcoma, the endothelial cells form freely anastomosing, irregular vascular channels, which are lined by flat endothelial cells having enlarged hyperchromatic nuclei and occasional mitotic figures . Sometimes villous papillary formation occurs. Ill-defined borders and local infiltration are essential features. In biopsies, these characters may be absent making correct diagnosis difficult. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the poorly differentiated angiosarcoma the malignant nature is apparent with anaplastic endothelial cells forming complex vascular channels or solid sheets.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The latter case often suggests a poorly differentiated carcinoma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A correct diagnosis requires immunohistochemical stain for Factor VIII or endothelial cell markers.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Angiosarcoma of the breast has a tendency to affect young women with a mean age of 34 years.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The typical presentation is a mass with bluish discoloration of the overlying skin. (Rosen et al, 1988). Angiosarcoma is a highly aggressive tumor and the total mastectomy is the preferred treatment. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The survival is closely related to the histologic grade. The five-year disease free survivor rate is 76% for low grade, well differentiated tumors and 70% for intermediate grade and 15% for high grade, poorly differentiated neoplasms (Rosen et al, 1988).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Postmastectomy angiosarcoma (lymphangiosarcoma) occurs in association with lymphedematous upper extremity following radical mastectomy. About two thirds of the patients have also received radiation to the axilla and the chest wall. </div> <div> The prognosis is dismal.</div> <bR> <div> <B><U>C. Granular Cell Tumor</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Granular cell tumor is a benign tumor initially thought to be muscle origin by Abrikossoff in 1926 with the label of granular cell myoblastoma. Its origin from Schwann cells is well-established by electron microscopy and immunohistochemistry. About 6% of all granular cell tumors involve the breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mean age at diagnosis is 40 years. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Granular cell tumors on clinical breast examination simulate carcinoma with fixation to the skin and rock hard on palpation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The excised tumor strongly suggests carcinoma with its firm consistency, gritty cut surface, and ill-defined borders . </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most distinct histologic feature is the abundant granular eosinophilic cytoplasm. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tumor cells are arranged in bundles, cords and nests in a dense fibrous stroma . </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The nuclei are sometimes hyperchromatic, irregular, and contain prominent nucleoli</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Because of these findings, granular cell tumor may be misdiagnosed as apocrine carcinoma, especially on frozen sections.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, mitotic figures are absent or rare. </div> <div> A complete local excision results in cure. </div> <bR> <div> <B><U>D. Stromal Tumors</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lipomas are circumscribed fat-containing lesions which may occur anywhere within the breast.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> When palpable, they are usually soft and freely movable. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Liposarcomas are extremely rare lesions that can arise de novo or as malignant components within phyllodes tumor. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The myxoid stroma contains immature lipoblasts with signet-ring appearance</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. Rare examples of :</div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fibrosarcoma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">malignant fibrous histiocytoma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">leiomyosarcoma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rhabdomyosarcoma</B>, </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">postradiation sarcoma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chondrosarcoma ,</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> osteosarcoma, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> hemangiopericytoma h</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" >ave been reported to occur in breast (Tavassoli, 1992).</FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The prognosis is dependent on the degree of differentiation and the local extent of the disease.</div> <bR> <div> <B><U>V. N</U></B><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B><U>IPPLE </U></B></FONT><B><U>D</U></B><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B><U>ISEASES</U></B></FONT></div> <bR> <div> Women with eczematous, erosive, pruritic changes of the nipple should be biopsied promptly to distinguish among chronic dermatitis, Paget's disease of the nipple, and nipple adenoma (papilloma, papillomatosis). </div> <bR> <bR> <bR> <div> <B><U>A. Paget's Disease</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paget's disease results from an intraductal spread of malignant cells to involve the nipple. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">About 1-2% of breast cancer patients present with Paget's disease. 50-60% of women have a palpable mass. Of these 90% have underlying infiltrating ductal carcinoma (Rosen and Oberman, 1993). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">10-28% have no clinical lesion.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The diagnosis is made by finding large cells with pale, vacuolated cytoplasm, round to oval large nuclei, prominent nucleoli migrating through the epidermis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A highest concentration of Paget's cells occurs in the basal and parabasal cell layers</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The overlying is sometimes hyperkeratotic, and chronic inflammation is commonly seen in the dermis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paget's cells are positive with mucicarmine stain, and express CEA, epithelial membrane antigen, milk fat globule by immunohistochemistry.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">95% or more have underlying in situ or invasive ductal carcinoma in the breast or nipple </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Rarely carcinoma occurs in the lactiferous ducts just beneath the skin. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paget's disease is not associate with lobular carcinoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The underlying DCIS is usually comedo or solid type, and the invasive carcinoma poorly differentiated. In mastectomy specimens, 78% of carcinomas have spread beyond the subareolar area.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prognosis depends on the behavior and extent of the underlying carcinoma.</div> <bR> <div> <B><U>B. Nipple adenoma or papillomatosis</U></B><B> </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is a ductal hyperplasia of the lactiferous ducts, sometimes protruding onto the nipple surface to manifest as a granular or ulcerated lesion. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Typical patients are 40-50 years of age.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Histologic appearance is usually a mixture of intraductal papilloma, adenosis, and tubular glands, which are lined by epithelial and myoepithelial cells without nuclear atypia.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Rare mitotic figures may be seen.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This benign tumor coexists with breast carcinoma in 16% of patients.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nipple adenoma should be distinguished from subareolar sclerosing papillomatosis which occurs deeper in the breast tissue.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Histologic appearance of both lesions is similar.</div> <bR> <div> <B><U>C. Chronic Dermatitis</U></B></div> <div> It is characterized by hyperkeratosis, spongiosis, hyperplasia of the epidermis and chronic inflammation of the underlying dermis</div> <bR> <div> <B><U>VI. O</U></B><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B><U>THER </U></B></FONT><B><U>C</U></B><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B><U>HANGES</U></B></FONT></div> <bR> <div> <B><U>Fat Necrosis</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fat necrosis may mimic carcinoma with a mass, pain, or skin retraction. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It is associated with trauma, surgical intervention, and radiotherapy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cause is unknown in some cases.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The excised lesion has a slightly firm consistency in the periphery and golden brown color, soft, sometimes liquified, material in the center. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Histologically fat necrosis is characterized by irregular empty spaces, which are lined by foamy histiocytes foamy histiocytes .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The fatty acid released by necrotic cells is removed by alcohol during tissue processing resulting in empty spaces. With time multinucleated giant cells, lymphoplasmacytic infiltration, and fibrosis occur .</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Calcification eventually deposits in fibrous tissue over a period of several months.</div> <bR> <bR> <bR> <div> <B><U>Premalignant lesions (May be either precursors or marker lesions.)</U></B></div> <div> <B><U>1. Ductal carcinoma in situ</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Average age 55y. Represents 10-20% of new breast cancers. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Often multifocal: up to 60% have residual DCIS after biopsy, 12% associated with cancer in contralateral breast , and 21-30% associated with cancer in ipsilateral breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lifetime breast cancer risk increased 10x. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Treatment controversial. Options include excision +/- radiation, or mastectomy.</div> <div> <B><U>2. Lobular carcinoma in situ</U></B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Average age 45y. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Usually an incidental finding (not detected on clinical or mammogram exam) in premenopausal women. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Multifocal: 60-90% have residual LCIS after biopsy, 30-50% associated with LCIS in contralateral breast , and 25% associated with cancer in either breast (usually ductal). Treatment controversial. Options include bilateral mastectomy, or excision with close followup.</div> <bR> <div> <B><U>DCIS - Ductal Carcinoma In Situ</U></B></div> <div> Malignant cells proliferate within the pre-existing ductal structures and basement membranes  to replace benign lining cells located within the ducts proximally and the lobules distally .</div> <div>  The risk for progression to invasive carcinoma and for local recurrence is closely related to the pathology of DCIS. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b7011800000000.gif" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Gross Pathology of DCIS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">By gross examination, most lesions of DCIS do not present with a distinct appearance. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The background breast tissue may be fatty or fibrous, and slightly firm on palpation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Only extensive comedo type of DCIS depicts visible abnormality raising the possibility of malignancy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The involved area has a granular character. By squeezing the area, necrotic material exudes from the ducts Because of the lack of obvious abnormality in most DCIS lesions, all excisional specimens should be handled properly right from the outset. </div> <bR> <bR> <bR> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b7011800000000.gif" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Classification of DCIS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> Classification of DCIS is based on the microscopic characters of </div> <div> 1. architecture (growth pattern) </div> <div> 2. nuclear features </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="792" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 30 ><NOBR><div> <B>Classification of DCIS by the Predominant Architecture</B></div> </NOBR></tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="30" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="698"><div> <B>1. Papillary/micropapillary type</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 HEIGHT= 114 WIDTH="77"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="114" ALIGN="bottom" WIDTH="77" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="618"><div> - Multiple isolated papillary projections, most of which lack fibrovascular stalks </div> <div> - Papillae become fused to form Roman bridges and arches giving the impression of rigidity </div> <div> - Most tumor cells have low nuclear grade </div> <div> - The tumor can be quite extensive </div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="114" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="698"><div> <B>2. Cribriform type</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 83 WIDTH="80"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="83" ALIGN="bottom" WIDTH="80" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="615"><div> - Tumor cells are arranged in a sieve-like pattern, multiple small round glands growing in a larger gland or duct. These glands are confluent without fibrous walls. Sometimes the glands grow in a back to back fashion with only one layer of fibroblasts between them </div> <div> - Most tumor cells have low nuclear grade </div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="83" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="698"><div> <B>3. Solid type</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 70 WIDTH="1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="70" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=3 WIDTH="694"><div> - Tumor cells fill the ducts and ductules as solid sheets</div> <div> - Nuclear grade is predominantly intermediate or high grade </div> <div> - Necrosis is usually focal </div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="70" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="698"><div> <B>4. Comedo type</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> </tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 95 WIDTH="1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="95" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=3><NOBR><div> - Solid growth pattern</div> <div> - Central necrosis of the involved ducts is a prominent feature</div> <div> - Calcification occurs within the necrosis </div> <div> - High nuclear grade in most tumors, less commonly intermediate nuclear grade </div> </NOBR></tD> <tD VALIGN=TOP WIDTH="73"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="95" ALIGN="bottom" WIDTH="73" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> It should be noted that several different grow patterns may occur within the same lesion, for example in papillary and cribriform types cribriform glands often occur. The classification is based on the most prevalent pattern. Necrosis, a prominent feature in comedo type, also occurs in other types focally. </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="644" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=CENTER COLSPAN=5 HEIGHT= 30 ><NOBR><div> <B>Classification of DCIS by Nuclear Features</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 23 WIDTH="598"><div> <B>1. Low grade </B></div> </tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="25"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="25" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 121 WIDTH="7"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="7" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="588"><div> -<FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> Nuclear size 1-1.5 times the size of red blood cells </B></FONT></div> <div> <B>- Uniform in size and shape </B></div> <div> <B>- Finely granular chromatin even distributed </B></div> <div> <B>- Nucleoli small, indistinct, few in number </B></div> <div> <B>- Mitotic activity low </B></div> </tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="25"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="25" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="620"><div> <B>2. Intermediate grade</B></div> </tD> <tD VALIGN=CENTER WIDTH="3"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="3" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 121 WIDTH="7"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="7" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=3 WIDTH="610"><div> - <FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B>Nuclear size up to 2 times the size of red blood cells </B></FONT></div> <div> <B>- Mild to moderate variation in nuclear size and shape </B></div> <div> <B>- Coarsely granular chromatin, evenly distributed </B></div> <div> <B>- Nucleoli small to medium in size </B></div> <div> <B>- Mitotic activity between the low and high grades </B></div> </tD> <tD VALIGN=CENTER WIDTH="3"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="3" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 HEIGHT= 23 WIDTH="565"><div> <B>3. High grade </B></div> </tD> <tD VALIGN=CENTER COLSPAN=3 WIDTH="58"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="58" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 121 WIDTH="7"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="7" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER><NOBR><div> -<FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> Nuclear size more than 2 times of red blood cells </B></FONT></div> <div> <B>- Marked variation in nuclear size and shape </B></div> <div> <B>- Coarsely granular chromatin unevenly distributed </B></div> <div> <B>- Nucleoli large and multiple </B></div> <div> <B>- Mitotic activity high </B></div> </NOBR></tD> <tD VALIGN=CENTER COLSPAN=3 WIDTH="58"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="121" ALIGN="bottom" WIDTH="58" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> Some authors prefer two grade system. </div> <div> For example, Van Nuys system combines low and intermediate grades into non-high category and the remaining as high grade.</div> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="642" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 20 WIDTH="626"><div> <B>SUMMARY OF NUCLEAR GRADE</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="227"><div> <B>CRITERIA</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> LOW GRADE</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="163"><div> INTERMEDIATE GRADE</div> </tD> <tD VALIGN=CENTER><NOBR><div> HIGH GRADE</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>NUCLEAR SIZE (xRBC)</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="110"><div> 1-1.5</div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> 1.0-2.0</div> </tD> <tD VALIGN=CENTER WIDTH="117"><div> >2.0</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>VARIATION IN SIZE & SHAPE</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="110"><div> MILD</div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> MODERATE</div> </tD> <tD VALIGN=CENTER WIDTH="117"><div> MARKED</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="227"><div> <B>CHROMATIN</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> FINE, EVEN</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="163"><div> COARSE,EVEN</div> </tD> <tD VALIGN=CENTER><NOBR><div> COARSE,UNEVEN</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="227"><div> <B>NUCLEOLI</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> SMALL, RARE </div> <div> 0-1/NUCLEUS</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="163"><div> SMALL, SOME </div> <div> 1-2/NUCLEUS</div> </tD> <tD VALIGN=CENTER><NOBR><div> LARGE, MANY </div> <div> >2/NUCLEUS</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="227"><div> <B>MITOTIC ACTIVITY</B></div> </tD> <tD VALIGN=CENTER WIDTH="110"><div> LOW</div> </tD> <tD VALIGN=CENTER WIDTH="163"><div> INTERMEDIATE</div> </tD> <tD VALIGN=CENTER WIDTH="117"><div> HIGH</div> </tD> </tR> </TABLE></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b7011800000000.gif" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Prognosis of DCIS (by pathological analysis)</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> 1. Nuclear grade is more important than architecture (growth) pattern </div> <div> 2. Status of surgical margin </div> <div> 3. Lesion size </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="635" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 HEIGHT= 23 WIDTH="623"><div> <B>Van Nuys Prognostic Classification</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="265"><div> Group 1</div> </tD> <tD VALIGN=CENTER><NOBR><div> Non-high nuclear grade without necrosis</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="265"><div> Group 2</div> </tD> <tD VALIGN=CENTER><NOBR><div> Non-high nuclear grade with necrosis</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="265"><div> Group 3</div> </tD> <tD VALIGN=CENTER><NOBR><div> High nuclear grade with or without necrosis</div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=2 HEIGHT= 38 WIDTH="623"><div> <B>Note:</B> As indicated earlier, the non-high nuclear grade includes low and intemediate scores</div> </tD> </tR> </TABLE></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="641" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="625"><div> <B>Van Nuys Prognostic Index Scoring Index</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="187"><div> Parameter</div> </tD> <tD VALIGN=CENTER WIDTH="105"><div> 1 Point</div> </tD> <tD VALIGN=CENTER WIDTH="129"><div> 2 Points</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> 3 Points</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Van Nuys Classification</div> </tD> <tD VALIGN=CENTER WIDTH="105"><div> Group 1</div> </tD> <tD VALIGN=CENTER WIDTH="129"><div> Group 2</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> Group 3</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Clear Margin</div> </tD> <tD VALIGN=CENTER WIDTH="105"><div> > or = 10 mm</div> </tD> <tD VALIGN=CENTER WIDTH="129"><div> 1-9 mm</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> <1 mm</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Lesion Size</div> </tD> <tD VALIGN=CENTER WIDTH="105"><div> < or = 15 mm</div> </tD> <tD VALIGN=CENTER WIDTH="129"><div> 16-40 mm</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> > 41 mm</div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="625"><div> <B>Final Score</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Group 1</div> </tD> <tD VALIGN=CENTER><NOBR><div> 3 - 4 points</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="129"><div> 3.8% Recurrence</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> 93% 8 year disease free</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Group 2</div> </tD> <tD VALIGN=CENTER><NOBR><div> 5 - 7 points </div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="129"><div> 11.1% Recurrence</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> 84% 8 year disease free</div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="187"><div> Group 3</div> </tD> <tD VALIGN=CENTER><NOBR><div> 8 - 9 points</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="129"><div> 26.5% Recurrence</div> </tD> <tD VALIGN=CENTER WIDTH="195"><div> 61 % 8 year disease free</div> </tD> </tR> </TABLE></div> <bR> <div> <B>INVASIVE BREAST CARCINOMA </B></div> <bR> <div> Infiltrating (invasive) breast carcinoma differs from intraductal carcinoma (ductal carcinoma in situ) by the presence of stromal invasion, through which tumor cells spread not only locally but also regionally and distantly via vascular lymphatic space. </div> <div> Invasive carcinoma are divided into two major types: ductal and lobular. The majority (75%) of infiltrating ductal carcinomas fall into the not otherwise specified category. The remaining 20% are special variants, which have distinct morphology and prognosis. The remaining 5% are infiltrating lobular carcinomas, including classic type and variants.</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="540" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="524"><div> <B>Infiltrating Ductal Carcinoma</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="524"><div> <B>Not otherwise specified type (75%)</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="524"><div> <B>Special variants (20%)</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>tubular</B></div> </tD> <tD VALIGN=CENTER ROWSPAN=8 WIDTH="189"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="189" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>mucinous</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>papillary</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>medullary</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>metaplastic carcinomas</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>metaplastic carcinomas</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>inflammatory</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER COLSPAN=2 WIDTH="281"><div> <B>others</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=4 HEIGHT= 23 WIDTH="524"><div> <B>Infiltrating Lobular Carcinoma (5%)</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="139"><div> <B>Classic</B></div> </tD> <tD VALIGN=CENTER ROWSPAN=4 COLSPAN=2 WIDTH="331"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="331" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="139"><div> <B>Signet-ring</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="139"><div> <B>Solid</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="48"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="48" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="139"><div> <B>Pleomorphic</B></div> </tD> </tR> </TABLE></div> <bR> <div> <B>II. GROSS PATHOLOGY</B></div> <bR> <div> <B>A. Tumor Size</B></div> <div> Tumor size is closely related to lymph node metastasis and prognosis (Palmer et al; Rosen et al, 1989).</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="574" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="292"><div> <B>TUMOR SIZE</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>LYMPH NODE METASTASIS</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="292"><div> <B>Tumors 1 cm or less</B></div> </tD> <tD VALIGN=CENTER WIDTH="267"><div> <B>14-26%</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="292"><div> <B>Tumors 1.1 to 2.0 cm</B></div> </tD> <tD VALIGN=CENTER WIDTH="267"><div> <B>33%</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="292"><div> <B>Tumors 10 cm or greater</B></div> </tD> <tD VALIGN=CENTER WIDTH="267"><div> <B>78% </B></div> </tD> </tR> </TABLE></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="11" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="7"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="7" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="635" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 ><NOBR><div> <B>TUMOR SIZE IN T1 TUMORS</B></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> <B>20-YEAR RECURRENCE FREE SURVIVAL</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="259"><div> <B>Tumor 1 cm or less</B></div> </tD> <tD VALIGN=CENTER WIDTH="361"><div> <B>86 %</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="259"><div> <B>Tumor 1.1 to 2.0 cm</B></div> </tD> <tD VALIGN=CENTER WIDTH="361"><div> <B>69%</B></div> </tD> </tR> </TABLE></div> <bR> <div> <B>B. Tumor Borders</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">About one third of infiltrating carcinomas have pushing, smooth borders, and, when small, they may be misconstrued as benign lesions .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The remaining two-thirds have infiltrative, poorly circumscribed, irregular borders .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Tumor cells extend into the adjacent breast and fibroadipose tissue in a radiating pattern creating stellate, white streaks seen on gross examination and mammographic images </div> <bR> <div> <B>C. Tumor Characters</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most tumors have gray-white to tan color and firm consistency.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The latter results from fibroblastic proliferation (desmoplastic reaction), elastosis, and hyalinization of the stroma. Involvement of fascial tissue by fibrous reaction causes skin retraction.</div> <bR> <div> <B>D. Tumor Necrosis and Hemorrhage </B></div> <div> These are common in large tumors .</div> <bR> <div> <B>E. Skin Retraction, Ulcer and Infiltration by Tumor</B></div> <bR> <div> <B>MICROSCOPIC PATHOLOGY</B></div> <bR> <div> <B>A. Histologic Grade</B></div> <div> Microscopic architecture (growth patterns) in the majority of infiltrating carcinomas are variable and often mixed, although a particular pattern may predominate.</div> <div>  The architecture reflects the degree of differentiation. Tubules, cribriform glands, irregular glands, papillae and acinioccur in well-differentiated tumors. </div> <div> Cords are common in intermediate grade of tumors  </div> <div> Solid nests and sheets predominate in poorly-differentiated neoplasms</div> <bR> <bR> <div> <B>The nuclear grade is determined by:</B> </div> <div> <B>1. Uniformity or irregularity of nuclear size and shape</B> </div> <div> <B>2. Chromatin particle size (finely or coarsely granular) and distribution (even or uneven)</B> </div> <div> <B>3. Nucleoli (size and frequency)</B> </div> <div> <B>4. Mitotic activity.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <bR> <div> In general, there is a good correlation between the architecture and the nuclear features. </div> <div> Those well-differentiated tumors have predominantly glands and uniform tumor cells with small nuclei, fine chromatin, inconspicuous nucleoli and low mitotic activity.</div> <div>  Whereas poorly differentiated tumors have mostly nests and sheets present with large, irregular nuclei, coarse chromatin, prominent nucleoli and high mitotic activity.</div> <div>  Moderately differentiated neoplasms are intermediate between the two groups.</div> <div> Because of the heterogeneity within the same tumor, it would be advantageous to adopt a uniform, reproducible system that correlates with prognosis. </div> <div> The Bloom/Richardson (Elston Modified) grading method is one such system. It combines the architecture and nuclear scores into a final histologic grade. This System is recommended for all invasive carcinomas </div> <bR> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="638" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 23 ><NOBR><div> <B>BLOOM/RICHARDSON (ELSTON MOD.) GRADING METHOD</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="358"><div> <B>Tubular Formation</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>Score</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Majority of tumor (>75%)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 1</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Moderate Degree (10-75%)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 2</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Little or none (<10%)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 3</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="358"><div> <B>Nuclear Pleomorphism</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>Score</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Uniform Cells (size is not criterion)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 1</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Moderate Increase in Variability</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 2</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 ><NOBR><div> Marked Variation (Often large nucleoli)</div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="130"><div> 3</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 44 WIDTH="358"><div> <B>Mitotic Counts (per 10 high power fields)</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>Score</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="44" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Low (0-5 mitotic figures)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 1</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> Moderate (6-10 mitotic figures)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 2</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="358"><div> High (>11 mitotic figures)</div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> 3</div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="358"><div> <B>FINAL GRADE</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>Score</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="358"><div> <B>Grade I, Well differentiated</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>3-5 points</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 ><NOBR><div> <B>Grade II, Moderately differentiated</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>6-7 points</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 ><NOBR><div> <B>Grade III, Poorly differentiated</B></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="130"><div> <B>8-9 points</B></div> </tD> <tD VALIGN=CENTER WIDTH="130"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="23" ALIGN="bottom" WIDTH="130" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <div> <B>B. Stromal Changes</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These include desmoplastic reaction with proliferation of newly formed fibroblasts in an edematous, myxomatous or highly collagenized matrix. In the background, elastosis also occurs</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The number of lymphocytes, plasma cells and histiocytes is variable. </div> <bR> <div> <B>C. Vascular Lymphatic Space Invasion </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This feature should be carefully evaluated and reported. Shrinkage artefact due to fixation produces an empty space between the tumor nest and fibrous stroma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This space is often mis-interpreted as vascular lymphatic space . A true vascular lymphatic space clearly lined by clearly recognizible endothelial cells </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. This invasion is most readily seen in the periphery of the tumor and beyond. Less commonly, the tumor cells invade the blood vessels and perineural spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Studies have demonstrated that the presence of vascular lymphatic space invasion increases tumor recurrence. The study of Rosen et al further reveals that invasion of the lymphatics, capillaries and blood vessels  in tumors up to 2 cm in size with or without lymph node metastases increases death rate, when compared to comparable tumors without such a finding .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Perineural space invasion does not have prognostic significance by itself.</div> <bR> <div> <B>D. Infiltrating Ductal Carcinoma with Extensive Intraductal Component (EIC)</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Within the infiltrating ductal carcinoma, the intraductal carcinoma may be extensive or completely absent. It is important to assess the amount of intraductal carcinoma. Extensive intraductal component (EIC) positive tumors include the following conditions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Predominantly invasive carcinoma containing DCIS in more than 25% of tumor </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. Predominantly DCIS with focal invasion, and DCIS extends beyond the borders of invasive carcinoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When treated by conservative surgery and radiotherapy, these EIC positive tumors are more likely to recur than EIC negative tumors. Based on data from Joint Center for Radiation Therapy, 28% of recurrent infiltrating ductal carcinomas are EIC positive.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Five-year actuarial local recurrence rate is 6% and 24% for EIC negative and positive tumors, respectively. </div> <bR> <bR> <bR> <div> <B>SPECIAL VARIANTS OF INFILTRATING DUCTAL CARCINOMA</B></div> <bR> <div> <B>A. Tubular Carcinoma</B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tubular carcinoma represents an extremely well differentiated form of infiltrating ductal carcinoma usually less than 2 cm in dimension.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Most if not all tumor cells form regular or sometimes angulated tubular glands surrounded by desmoplastic stroma and elastosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Infiltration into fat, when present, is indicative of invasive carcinoma .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These glands are lined by a single layer of cells with mild nuclear atypia .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Apocrine differentiation is commonly observed. In two-thirds of the cases, non-comedo, ductal carcinoma <U>in situ </U>is present </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some authors require the "pure" tubular carcinoma to have at least 75% of tubular glands (Rosen and Oberman), others demand 100% tubular glands (Tavassoli). </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When the tubular component is less than 75% of the tumor, the tumor should be classified as mixed form of tubular carcinoma or conventional infiltrating ductal carcinoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pure tubular carcinomas have an excellent prognosis, due to low rates of lymph node metastasis and recurrence following complete excision. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mixed form of tubular carcinoma is prognostically similar to infiltrating ductal carcinoma of comparable degree of differentiation and tumor size .</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Tubular carcinoma may be confused with sclerosing adenosis.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Sclerosing adenosis maintains a lobular architecture and the glands, although distorted by fibrosis, are lined by double cell layers consisting of both epithelial and myoepithelial cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In contrast, tubular carcinoma infiltrates locally without lobular pattern and the glands are lined by a single layer of tumor cells.</div> <bR> <div> <B>B. Mucinous Carcinoma</B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These tumors have lobulated borders, soft consistency and gelatinous cut surfaces, and may be confused with benign tumors, such as fibroadenoma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Mucinous carcinoma is characterized by abundant extracellular mucin in which tumor cells form papillary clusters, glands and occasionally sheets </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Individual cells have low grade nuclear atypia. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some cells have signet ring appearance.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The entire tumor or at least 75% of the tumor should contain mucinous area. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Those invasive ductal carcinomas having less than 75% of mucinous component are best classified as mixed carcinoma, because of their less favorable outcome when compared to pure mucinous carcinoma. </div> <bR> <div> <B>C. Papillary Carcinoma</B></div> <bR> <bR> <div> It typically occurs in the central portion of the breast as a round, 2-3 cm nodule with cystic change and hemorrhage. </div> <div> It closely resembles papillary and cribriform ductal carcinoma in situ </div> <div> Complex papillary projections and cribriform glands consist almost entirely of epithelial cells without myoepithelial cells. </div> <div> Fibrovascular stalks are less prominent than benign intraductal papilloma. The borders are irregular and infiltrative </div> <div> Tumor cells have low nuclear grade, inconspicuous nucleoli, and low mitotic activity. </div> <div> Prognosis is excellent with low frequency of lymph node metastasis and tumor recurrence, if completely excised</div> <bR> <bR> <div> <B>D. Medullary Carcinoma</B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Medullary carcinoma can be quite large, soft on palpation, hemorrhagic and necrotic.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Microscopically, medullary carcinoma should meet all of the following criteria: </div> <bR> <div> <B>1) smooth, non-infiltrative borders </B></div> <bR> <div> <B> 2) prominent lymphoplasmocytic infiltration present diffusely within the tumor and involving at least 75% of the tumor periphery, </B></div> <bR> <div> <B>3) tumor cells are arranged in large solid nests and sheets with poorly defined cell borders, the so-called syncytial pattern ,</B></div> <bR> <div> <B> 4) Individual cells have large pleomorphic nuclei, prominent nucleoli, and high mitotic activity, </B></div> <bR> <div> <B>5) Fibrous stroma should be limited in amount. A small portion of the tumor may undergo squamous metaplasia or contains papillary, glandular elements. </B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Those tumors, having some but not all of the above mentioned features, are classified as "atypical" medullary carcinoma  or the usual variant of infiltrating ductal carcinoma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Using the above strict criteria, medullary carcinomas have better outcome than atypical medullary carcinoma or the conventional infiltrating ductal carcinoma, stage by stage .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The survival rates for women with medullary carcinoma is 94%, as compared to 64% for those with atypical medullary carcinoma </div> <bR> <div> <B>E. Metaplastic Carcinoma </B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It tends to be bulky and the tumor consists of poorly differentiated tumor cells undergoing squamous, spindle cell, and sarcomatoid metaplasias.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the latter,<B><U> cartilaginous, osteoblastic and rhabdomyoblastic elements occur</U></B>. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The areas of poorly differentiated ductal carcinoma may be limited.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Without immunohistochemical stains,<B> spindle cell and sarcomatoid components are difficult to distinguish from fibrosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and metastatic tumors</B>.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> By immunohistochemistry, expression of cytokeratin and other epithelial tumor antigens can be demonstrated to support the diagnosis of metaplastic carcinoma .</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The overall prognosis is worse than conventional infiltrating ductal carcinoma.</div> <bR> <div> <B>F. Inflammatory Carcinoma </B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The clinical manifestation of diffuse thickening and edema involving at least one third of the mammary skin is essential for this diagnosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The affected area is warm, erythematous with orange peel appearance. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microscopically, inflammatory carcinomas are usually poorly differentiated with malignant cells filling the dermal lymphatic spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The surrounding dermis is edematous and infiltrated by lymphocytes .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Recurrent carcinoma associated with inflammatory skin changes is referred to as secondary inflammatory carcinoma, in which case, nodules of malignant cells involve both the dermis and the lymphatic spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When these dermal changes are evident histologically, but not associated with typical clinical findings, the lesion is referred to as occult inflammatory carcinoma. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most studies have demonstrated poor outcome for patients with primary, secondary or occult inflammatory carcinoma. </div> <bR> <div> <B>G. Adenoid Cystic Carcinoma of the Breast </B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It has the same histologic appearance as that occurred in the salivary gland.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Basaloid cells forming sieve-like cribriform spaces which contain mucinous material. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A second feature is the deposit of basement membrane substance resulting in hyaline membranes and hyaline cylinders. Less commonly the tumor cells form tubules and solid sheets. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The prognosis of women with adenoid cystic carcinoma is excellent following complete local excision. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Axillary nodal metastasis rarely, if ever, occurs (Rosen 1989).</div> <bR> <div> <B>H. Microinvasive Carcinoma</B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The histologic criteria for the early, minimal invasive carcinoma of the breast have not been well defined. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some authors have limited this entity to early stromal invasion arising from the ducts and lobules involved by intraductal carcinoma with tongue-like processes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. According to Tavassoli, the depth of invasion should be less than 1 mm measuring from the basement membrane and the diameter of the invasive foci to be less than 2 mm .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The optimal management of these cases remains controversial.</div> <bR> <bR> <bR> <div> <B>LOBULAR CARCINOMA IN SITU & INFILTRATING LOBULAR CARCINOMA</B></div> <bR> <div> <B>A. Lobular carcinoma in situ (LCIS) </B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">LCIS was originally described in 1941 by Foote and Stewart. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most of these changes are found incidentally in specimens excised for benign or malignant diseases, because LCIS is not detectable by clinical and mammographic examinations.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They may be multifocal, multicentric, or bilateral. LCIS is believed by most to be a high risk marker, rather than a true malignancy. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">As compared to general population, a woman with LCIS increases the relative risk of developing invasive carcinoma by eight to eleven times. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The risk of developing invasive carcinoma is 20 to 25 percent at 15 to 20 years following biopsy (Haagensen, Rosen et al 1978). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The invasive carcinoma may be ductal or lobular in type and may occur at any location in either breast. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The involved lobules and terminal ductules become distended and filled with homogeneous population of atypical cells which have relatively uniform round to oval, hyperchromatic nuclei, inconspicuous or small nucleoli, and low mitotic activity.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The cytoplasm is scant to moderate in amount.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Sometimes intracytoplasmic lumens are evident and contain mucinous material in the cytoplasm, a feature useful for diagnosis .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The background myoepithelial cells have largely disappeared. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The neoplastic cells proliferate and spread to the adjacent ducts in a pagetoid fashion between the epithelial and myoepithelial cells </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">LCIS can be distinguished from ductal carcinoma in situ extending into lobules by having small to medium nuclear size, mild to moderate degree of nuclear irregularity, small nucleoli, and limited amount of cytoplasm. It should be mentioned that in excised specimens for LCIS, about 30% also have coexisting DCIS. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The risk for local recurrence of LCIS is directly related to the number of foci involved in the excised tissue.</div> <bR> <div> <B>B. Infiltrating Lobular Carcinoma</B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The gross appearance of infiltrating lobular carcinomas is similar to invasive ductal carcinoma presenting as an ill-defined, indurated, firm mass .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, because of a high propensity for multifocality and diffuse infiltration of the adjacent fibroadipose tissue, some neoplasms do not produce a discrete mass. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The excised breast tissue may appear entirely normal, except for slight firmness on palpation </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the tumor, in situ and infiltration lobular carcinoma sometimes coexist </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> About 85% of infiltrating lobular carcinomas are of the classic type and the remaining 15% special variants.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the classic type, the tumor cells spread between the collagen bundles in a single line, the so-called Indian file pattern </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. As the tumor cells spread around the periductal fibrous tissue concentrically, a targetoid pattern results Individual cells have small to medium sized, uniformly round to oval nuclei, scant cytoplasm, inconspicuous nucleoli and low mitotic activity. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cytoplasm may contain intracytoplasmic lumen or accumulation of mucinous substance with a signet ring appearance </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Sometimes the tumor cells appear so benign as to simulate mature lymphocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Several variants of infiltrating lobular carcinoma have been recognized. </div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the solid type</U></B>, the tumor cells appear in diffuse sheets with little intervening stroma to simulate malignant lymphoma or leukemic infiltration </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. In the alveolar variant</U></B>, loosely cohesive tumor cells form discrete aggregates and are surrounded by fibrous stroma. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The pleomorphic variant</U></B> is made up of cells with medium to large, irregular, hyperchromatic nuclei and eosinophilic cytoplasm simulating rhabdomyoblasts </div> <bR> <div> .</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When compared stage by stage, stage I infiltrating lobular carcinoma patients have a higher disease-free survival than those with infiltrating ductal carcinoma (p = 0.02) (DiCostanzo et al). No difference is detected for stage II patients with infiltrating lobular or ductal carcinomas. Patients with classic infiltrating lobular carcinoma have a better prognosis than those with variants of lobular carcinoma (DiCostanzo et al).</div> <bR> <bR> <div> <I><B><U>Incidence of Breast Cancer</U></B></I></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Breast cancer is very rare before age 20 and is rarely diagnosed in women younger than age 25. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Past that age, the incidence rises steadily to reach a peak around the age of menopause. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The rate of increase is lessened after menopause, but older women are still at increasing risk over time.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">About 1 in 8 women in the United States and Canada will develop breast cancer. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This incidence is similar for many European countries.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, breast cancer is much less common in Asia.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The incidence rate for breast cancer rose 24% in the U.S. between 1973 and 1991, while mortality from breast cancer did not increase.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, more localized cancers were diagnosed over time. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These statistics indicate that screening for breast cancer, including mammography, probably played a role in detecting more cancers at an earlier stage.</div> <bR> <bR> <div> <B><U>Risk Factors for Breast Cancer</U></B></div> <div> Although a specific cause for breast cancer has not been identified, there are risk factors that increase the likelihood that a woman will develop a breast cancer. These risks include:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Maternal relative with breast cancer. Women whose mother or sister or aunt had breast cancer, particularly at a younger age, have a greater risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">BRCA1 and BRCA2 genes. The incidence of the BRCA1 gene on chromosome 17 may be 1 in 800 women. The BRCA2 gene on chromosome 13 is less frequent but associated with early onset breast carcinomas. The presence of these genes may explain some of the familial cases, and may be the etiology for about 1% of breast cancers overall.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Longer reproductive span. Women who have an earlier menarche and/or a later menopause, increasing the length of reproductive years, are at greater risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Obesity. Women who are overweight are at increased risk. In addition, increased dietary fat intake is a risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nulliparity. Women who have never borne children are at greater risk, while women who have been pregnant are at a lower risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Later age at first pregnancy. Women who had their first child over age 30 are at greater risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Atypical epithelial hyperplasia. Although fibrocystic changes that produce benign breast "lumps" are not premalignant, the presence of atypical changes in ductular epithelium does increase the risk.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Previous breast cancer. Women who have had breast cancer in the opposite breast are at increased risk for cancer in the remaining breast.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Previous endometrial carcinoma. Women who have had adenocarcinoma of the endometrium are at increased risk for breast cancer.</div> <div> Aside from the genetic predisposition, the common factor in many of these risks is increased endogenous estrogen exposure over a long time.</div> <bR> <bR> <div> <B><U>Classification of Breast Cancer</U></B></div> <div> Breast cancers can be classifed histologically based upon the types and patterns of cells that compose them. Carcinomas can be invasive (extending into the surrounding stroma) or non-invasive (confined just to the ducts or lobules). </div> <div> The tables below identify the major histologic types of invasive and non-invasive breast cancers, of all breast cancer types, and overall relative 5-year survival (% of patients with that histologic type surviving for 5 years following diagnosis).</div> <div>  The "NOS" categories contain carcinomas not easily classified into other histologic types or carcinomas for which minimal tissue was available for diagnosis.</div> <DIV ALIGN="LEFT"></DIV> <div> Invasive Carcinomas of the Breast</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="476" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 WIDTH="456"><div> <B>Histologic Type </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Infiltrating Ductal Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Infiltrating Lobular Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Infiltrating Ductal & Lobular Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Medullary Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Mucinous (colloid) Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Comedocarcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Paget's Disease </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Papillary Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Tubular Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Adenocarcinoma, NOS </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="456"><div> Carcinoma, NOS </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <bR> <div> Non-invasive Carcinomas of the Breast</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="324" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 WIDTH="304"><div> <B>Histologic Type </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="20" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="304"><div> Intraductal Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 ><NOBR><div> Lobular Carcinoma in situ (LCIS) </div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="304"><div> Intraductal & LCIS </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="304"><div> Papillary Carcinoma </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="304"><div> Comedocarcinoma</div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="0"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="0" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <div> <B><U>Immunoperoxidase Techniques</U></B></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Estrogen receptor positivity</U></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Progesterone receptor positivity </U></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cathepsin D</U></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> positivity HER2 (C-erb B2) positivity </U></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The hormone receptor status of the breast cancer cells can be useful information for treatment and prognosis. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The neoplastic cells can express a variety of receptors. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The presence of these receptors can provide a means for controlling cell growth through chemotherapeutic agents.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In general, cancers in which the cells express estrogen receptor (ER) in their nuclei will have a better prognosis. This is because such positive neoplastic cells are better differentiated, and they can respond to hormonal manipulation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The drug tamoxifen is often utilized for this purpose. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Almost three-fourths of breast cancers expressing ER will respond to this therapy, whereas less than 5% not expressing ER will respond.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The significance of progesterone receptor (PR) positivity in a breast carcinoma is less well understood. In general, cancers that are ER positive will also be PR positive.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, carcinomas that are PR positive, but not ER positive, may have a worse prognosis.</div> <div> <I><B><U><IMG BORDER="0" SRC="Symb075c00b700f06600ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There are other markers that can be identified in breast carcinomas. One important marker for breast cancer is C-erb B2 (HER2-neu), and it is identified by staining around the cytoplasmic membrane of the cells. There is a correlation between HER2 (C-erb B2) positivity and high nuclear grade and aneuploidy, and a specific drug (trastuzumab) is available as a therapeutic option with HER2 positive carcinomas. </U></B></I></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Another marker is cathepsin D, an acidic lysosomal protease that can be found in the cytoplasm of breast carcinoma cells, and it is also found in the stroma between the cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There is a correlation between cathepsin D positivity and presence of metastases (particularly lymph nodes). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Non-ductal carcinomas (a minority of breast cancers) are more likely to stain with Cathepsin D.</div> <bR> <bR> <div> <B><U>Flow Cytometry</U></B></div> <div> The amount of DNA contained in the nuclei of breast carcinoma cells will provide an indication of their malignant potential. </div> <div> Flow cytometry is a means for measuring the amount of DNA. Normal cells, or those of a benign neoplasm, tend to have a single homogenous population of cells with a "euploid" DNA content. However, malignant cells are less differentiated and have abnormal expression of DNA content. </div> <div> This is measurable as the degree of "aneuploidy" by flow cytometry. The prognosis is worse for carcinomas with a greater degree of cellular aneuploidy.</div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">to resume kc</U></B></div> <bR> <div> <B><U> <A NAME="malig"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Malignant lesions</U></B></div> <div> <B><U>1. Ductal carcinoma</U></B></div> <div> <U>i. Infiltrating ductal carcinoma</U></div> <div> 80% of breast cancers (53% pure, 28% mixed ductal patterns). Arise in myoepithelial cells around duct. Marked desmoplastic response can cause skin dimple or nipple retraction. In inflammatory carcinoma, a poor-prognosis subtype, dermal lymphatics contain tumor.</div> <div> <U>ii. Comedocarcinoma</U></div> <div> 5% of breast cancers. Predominantly intraductal tumor.</div> <div> <U>iii. Medullary carcinoma</U></div> <div> 6% of breast cancers. Arise in ductal epithelium. Tumors bulky, soft, often necrotic. Less likely to spread than infiltrating ductal tumors. Prognosis good (85-90% 5y survival).</div> <div> <U>iv. Papillary carcinoma</U></div> <div> < 1% of breast cancers. Commonly involves multiple ducts.</div> <div> <U>v. Colloid carcinoma</U></div> <div> < 1% of breast cancers. Bulky, gelatinous, mucin-containing tumors with relatively good prognosis.</div> <bR> <bR> <div> <B><U>2. Lobular carcinoma</U></B></div> <div> 5% of breast cancers. Arise in acinar cells and terminal ducts. Usually multicentric.</div> <div> <B><U>3. Paget's disease</U></B></div> <div> 2% of breast cancers. Arises from mammary ducts. Clinical appearance of eczematoid nipple.</div> <div> <B><U>4. Sarcoma</U></B></div> <div> < 1% of breast cancers. Cystosarcoma phylloides has benign and malignant types, and is most common sarcoma of breast. Metastases rare. Treatment usually simple mastectomy.</div> <bR> <bR> <div> <B><U><IMG SRC="0661c400.gif" border=0 width="540" height="320" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></div> <bR> <bR> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="627" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#00FFFF HEIGHT= 39 WIDTH="621"><div> <B>American Joint Committee on Cancer TNM</B></div> <div> <B>Clinical Breast Cancer Staging System, 1988 </B></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#00FFFF HEIGHT= 336 WIDTH="48"><div> Tx</div> <div> T0</div> <div> Tis</div> <bR> <div> T1</div> <div> a</div> <div> b</div> <div> c</div> <div> T2</div> <bR> <div> T3</div> <div> T4</div> <bR> <bR> <div> a</div> <div> b</div> <div> c</div> <div> d </div> </tD> <tD VALIGN=TOP BGCOLOR=#00FFFF><NOBR><div> Primary tumor not assessable</div> <div> No evidence of primary tumor</div> <div> Carcinoma in situ. Includes Paget's disease if no </div> <div> underlying tumor present</div> <div> Tumor = 2cm. May include invasion of pectoral fascia or muscle</div> <div> Tumor = 0.5cm</div> <div> Tumor > 0.5cm, and = 1cm</div> <div> Tumor > 1cm, and = 2cm</div> <div> Tumor > 2cm, and = 5cm. May include invasion of pectoral fascia</div> <div> or muscle</div> <div> Tumor >5cm. May include invasion of pectoral fascia or muscle</div> <div> Extension to chest wall (ribs, intercostal muscles, serratus anterior), </div> <div> skin edema, skin ulceration, satellite skin nodules, </div> <div> inflammatory carcinoma</div> <div> Extension to chest wall</div> <div> Edema (including peau d'orange), ulceration, or ipsilateral satellite nodules</div> <div> Both T4a and T4b</div> <div> Inflammatory carcinoma </div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#00FFFF HEIGHT= 112 WIDTH="48"><div> Nx</div> <div> N0</div> <div> N1</div> <div> N2</div> <bR> <div> N3</div> </tD> <tD VALIGN=TOP BGCOLOR=#00FFFF><NOBR><div> Regional lymph nodes not assessable</div> <div> No regional lymph node involvement</div> <div> Metastases to movable ipsilateral axillary nodes</div> <div> Metastases to ipsilateral axillary nodes fixed to one another or </div> <div> adjacent structures</div> <div> Metastases to ipsilateral internal mammary nodes </div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#00FFFF HEIGHT= 75 WIDTH="48"><div> Mx</div> <div> M0</div> <div> M1</div> </tD> <tD VALIGN=TOP BGCOLOR=#00FFFF WIDTH="572"><div> Distant metastases cannot be assessed</div> <div> No distant metastases</div> <div> Distant metastases present, including</div> <div> ipsilateral supraclavicular nodes</div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="472" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER COLSPAN=2 BGCOLOR=#00FFFF HEIGHT= 20 WIDTH="466"><div> <B>AJCC Clinical Stage grouping </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#00FFFF HEIGHT= 19 WIDTH="185"><div> Stage</div> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="280"><div> TNM</div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#00FFFF HEIGHT= 150 WIDTH="185"><div> 0</div> <div> I</div> <div> I I A</div> <div> I I B</div> <div> I I I A</div> <div> I I I B</div> <div> I V</div> <bR> </tD> <tD VALIGN=CENTER BGCOLOR=#00FFFF WIDTH="280"><div> TisN0M0</div> <div> T1N0M0</div> <div> T0,1N1M0; T2N0M0</div> <div> T2N1M0; T3N0M0</div> <div> T0,1,2N2M0; T3N1,2M0</div> <div> T4N(any)M0; T(any)N3M0</div> <div> T(any)N(any)M1</div> <bR> </tD> </tR> </TABLE></div> <div> <B>Note:</B> </div> <div> Regional lymph nodes include axillary and ipsilateral internal mammary nodes. </div> <div> The axillary nodes are divided into 3 groups: Level I nodes are lateral to pectoralis minor muscle, </div> <div> Level II nodes are between lateral and medial border of pectoralis minor (Rotter's nodes), and Level III nodes are medial to pectoralis minor including subclavicular, infraclavicular and apical nodes. Metastases to other nodes, including supraclavicular, cervical, and contralateral internal mammary nodes are considered distant (M1).</div> <div> Diagnostic Procedures</div> <div> One of the best methods for detection of breast abnormalities is self-examination. In women of reproductive age, this is best carried out just after menstruation as a new menstrual cycle is beginning. Thorough self-examination on a regular basis will bring attention to any changes that may occur, as a woman can become familiar with the normal appearance of her breasts on palpation. Breast examination is part of a routine physical examination performed by a physician or other health care worker. However, a breast cancer may have been present for 5 to 10 years before reaching a size (about 1 cm) that is detectable by palpation.</div> <bR> <bR> <div> <B><U>The location of breast cancers is as follows:</U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b701400000ff00.gif" HEIGHT="21" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Upper outer quadrant: 50% </U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b701400000ff00.gif" HEIGHT="21" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Central area: 20% </U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b701400000ff00.gif" HEIGHT="21" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lower outer quadrant: 10% </U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b701400000ff00.gif" HEIGHT="21" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Upper inner quadrant: 10% </U></B></div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b701400000ff00.gif" HEIGHT="21" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lower inner quadrant: 10% </U></B></div> <bR> <bR> <div> <B><U>read more on the following in the breast exploration</U></B></div> <div> The most sensitive and specific method to detect breast cancer is mammography. This procedure is performed by compressing each breast between metal plates and producing an image of the breast on a radiographic film. The film is then examined by a radiologist for any abnormalities. Current mammographic methods employ very small amounts of radiation, which cumulatively are not enough to be a hazard even with yearly mammographic examinations. If a palpable "lump" is present, then diagnostic mammography can aid in defining and localizing it. However, mammography can detect masses that are not palpable, because carcinomas generally have a density greater than the surrounding breast tissue. The presence of breast implants makes it difficult to see lesions in the breast mammographically.</div> <div> Mammography is optimally performed when the woman has no cyclic breast tenderness or other conditions that would increase breast density. There is no consensus as to recommendations for use of routine mammographic screening; the patient and her physician can decide what is needed based upon individual circumstances. A screening mammogram for asymptomatic women includes standard views of both breasts. The major purpose of a screening mammogram is to separate normal from abnormal findings and to identify patients who need further evaluation. The films can be compared to previous films, if available. If the patient has an abnormal screening mammogram or signs and symptoms of a breast abnormality, then a diagnostic mammogram is performed.</div> <div> Following detection of an abnormality by palpation and/or by mammography, a tissue sample can be obtained. For small lumps that are not clearly cancers, a procedure called "fine needle aspiration" or FNA is performed. The physician performing an FNA will guide a thin needle, under local anesthetic, into the breast to the location of the abnormality. Then, cells are aspirated into the needle with several passes through the abnormal area. The cells are placed on glass slides, stained to highlight the cells, and then examined by a cytopathologist. The cytopathologist tries to determine if malignant cells are present. In general, false positive diagnoses (a lesion is called cancer, but in reality is not) are rare. However, with this technique, false negative diagnoses (in which a cancer may be missed) are possible some of the time, because of sampling error or the small number of cells examined or the nature of the lesion.</div> <div> Breast biopsy is performed to remove a lesion and make a definitive diagnosis, if a malignancy has not been demonstrated by FNA but is still suspected, or if a lump is likely to be malignant. Such a biopsy can be done under local or general anesthesia. The biopsy can also be directed radiographically by placing a needle and/or colored dye into the area that is abnormal. The biopsy can be examined by frozen section by the pathologist for a quick, preliminary diagnosis. More commonly, the biopsy is processed routinely, and a diagnosis is made. If a malignancy is found, the biopsy can be further studied via immunoperoxidase staining to determine receptor status.</div> <div> Grading and Staging</div> <div> A completely uniform system of grading for breast cancers is not possible because of the wide variety of histologic cell types. The cell types themselves, along with the invasiveness of the cancer, help to predict the biologic behavior of the cancer. A grading system (a modified Scarff-Bloom-Richardson system) outlined below utilizes histologic characteristics of the breast carcinoma. </div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="635" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 ><NOBR><div> <B>Tubule Formation (% of carcinoma composed of tubular structures)</B> </div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> <B>Score </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> >75% </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 1 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> 10-75% </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 2 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> less than 10% </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 3 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 WIDTH="567"><div> <B>Nuclear Pleomorphism</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> <B>Score </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> Small, uniform cells </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 1 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> Moderate increase in size and variation </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 2 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> Marked variation </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 3 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 WIDTH="567"><div> <B>Mitotic Count (per 10 high power fields)</B> </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00><NOBR><div> <B>Score </B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> Up to 7 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 1 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> 8 to 14 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 2 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="567"><div> 15 or more </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="53"><div> 3 </div> </tD> </tR> </TABLE></div> <DIV ALIGN="LEFT"></DIV> <div> The grade is calculated by adding the above scores. The grade correlates with survival as follows:</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="641" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 20 WIDTH="69"><div> <B>Grade </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="81"><div> <B>Score </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> <B>5-year Survival (%) </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> <B>7-year Survival (%) </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="69"><div> 1 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="81"><div> 3 to 5 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 95 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 90 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="69"><div> 2 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="81"><div> 6 or 7 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 75 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 65 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 19 WIDTH="69"><div> 3 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="81"><div> 8 or 9 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 50 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="233"><div> 45 </div> </tD> </tR> </TABLE></div> <bR> <bR> <div> Carcinomas have a propensity to spread via lymphatics. Breast cancers, when they metastasize, often go first to the axillary lymph nodes where most lymphatics from the breast drain. Spread of carcinoma to the dermal lymphatics produces a so-called "inflammatory carcinoma" which is a descriptive term, not a histologic type. This term arose from the grossly red to orange and firm, indurated appearance of such a lesion. More distant metastases are also possible. Supraclavicular lymph nodes can be involved. Other organs can be sites of metastases, and such sites as lung, bone, and liver are more common.</div> <div> The least aggressive cancers--ones that rarely metastasize outside of the breast--histologically are: non-invasive intraductal and lobular carcinoma in situ. Carcinomas which can potentially metastasize but less commonly do so are: colloid carcinoma, medullary carcinoma (when a lymphoid stroma is present), and papillary carcinoma. All other cancers have a greater potential to metastasize than those listed above.</div> <div> The stage of a breast cancer is based upon its size and degree of spread. The staging system goes from stage I to stage IV as follows:</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="641" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 58 ><NOBR><div> <B>Stage </B></div> </NOBR></tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="476"><div> <B>Definition </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> <B>5-year Survival (%) </B></div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> <B>7-year Survival (%) </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 38 WIDTH="22"><div> I </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="476"><div> Tumor 2 cm or less in greatest diameter and without evidence of regional (nodal) or distant spread </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 96 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 92 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 76 WIDTH="22"><div> II </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="476"><div> Tumor more than 2 cm but not more than 5 cm in greatest dimension, with regional lymph node involvement but without distant metastases, OR > a tumor of more than 5 cm in diameter without regional (nodal) and distant spread </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 81 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 71 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 57 WIDTH="22"><div> III </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="476"><div> Tumors of any size with possible skin involvement, pectoral and chest wall fixation, and axillary or internal mammary nodal involvement, fixed, but without distant metastases </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 52 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 39 </div> </tD> </tR> <tR> <tD VALIGN=CENTER BGCOLOR=#FFFF00 HEIGHT= 38 WIDTH="22"><div> IV </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="476"><div> Tumor of any size with or without regional spread but with evidence of distant metastases </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 18 </div> </tD> <tD VALIGN=CENTER BGCOLOR=#FFFF00 WIDTH="59"><div> 11 </div> </tD> </tR> </TABLE></div> <bR> <div> <B>ADDITIONAL PROGNOSTIC MARKERS BY IMMUNOCHEMISTRY & FLOW CYTOMETRY</B></div> <bR> <div> <B>A. Estrogen Receptor (ER) Protein and Progesterone Receptor (PR) Protein</B></div> <div> ER positivity is favorable prognostic indicator, PR positivity alone is a weak favorable prognostic indicator. Patients with ER positive metastatic tumor receiving endocrine therapy had 60% overall clinical response, and 20% reduction in recurrence/mortality (Early Breast Cancer Trialists' Collaborative Group). When ER and PR are combined, the frequency and response rates are summarized as follows (McGuire et al):</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="288" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="284"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="284" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="447" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="103"><div> <B>STATUS</B></div> </tD> <tD VALIGN=CENTER><NOBR><div> <B>FREQUENCY</B></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> <B>RESPONSE RATE</B></div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="103"><div> <B>ER+/PR+</B></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <B>58%</B></div> </tD> <tD VALIGN=CENTER WIDTH="192"><div> <B>77%</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="103"><div> <B>ER+/PR-</B></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <B>23%</B></div> </tD> <tD VALIGN=CENTER WIDTH="192"><div> <B>27%</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="103"><div> <B>ER-/PR+</B></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <B>4%</B></div> </tD> <tD VALIGN=CENTER WIDTH="192"><div> <B>46%</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 23 WIDTH="103"><div> <B>ER-/PR-</B></div> </tD> <tD VALIGN=CENTER WIDTH="132"><div> <B>15%</B></div> </tD> <tD VALIGN=CENTER WIDTH="192"><div> <B>15%</B></div> </tD> </tR> </TABLE></div> <div> ER/PR status has been based on biochemical ligand assay, which requires fresh tissue frozen immediately following excision. ER/PR status can be obtained on formalin embedded tissue sections by immunohistochemical stains using monoclonal antibodies.</div> <div> There is 80-90% agreement between biochemical ligand assay and immunohistochemical stains for ER/PR. The result of the latter is reported by the percent of positive tumor cells </div> <div> Immunohistochemical stains for ER/PR have several advantages: precise localization, accurate quantification by visual estimates or by digital imaging technique, possible to perform on routinely processed tissue and archival paraffin block from earlier surgery, workable on cells in effusion or smears obtained by fine needle aspiration. However, laboratory agreement on the type of antibody to use and scoring method is needed.</div> <bR> <div> <B>B. HER-2/neu Oncogen</B></div> <div> HER-2/neu is an oncogen and its protein product is located on the cell surface. It may influence growth factor receptor and promote cellular differentiation, adhesion and motility. It is detected by immunohistochemical stain on tissue section. Amplified or over-expression is seen in 20-30% of breast cancers </div> <div> HER-2/neu over-expression is a predictive marker for resistance to adjuvant therapy (cytoxan/methotrexate and tamoxifen).</div> <div> HER-2/neu is over-expressed in high grade DCIS only, therefore cannot be used to distinguish low grade DCIS from atypical ductal hyperplasia </div> <bR> <div> <B>C. P-53</B></div> <div> Tumor suppressor gene and its protein product is a nuclear transcription factor related to cell cycle regulation and apoptosis. Detected by immunohistochemical stain on tissue section.</div> <div> Abnormal p53 phenotype in tumor is associated with poor clinical outcome among node negative patients</div> <bR> <div> <B>D. Flow DNA Cytometry</B></div> <div> By flow cytometry, the DNA ploidy patterns and ploidy levels of the stem cells and their cell cycle kinetics can be determined. Isolated tumor cells are obtained from the solid tumor by mechanical dispersion or enzyme dissection. Most laboratories currently use tumor tissue embedded in paraffin block.</div> <div> The tumor cells are stained with dye specific for DNA, suspended in fluid and passed through the laser beam. The DNA content is plotted in a histogram. Benign tissue in the same specimen is processed similarly to serve as diploid control. The Go/G1 peak represent cells in the resting phase. As cells begin to synthesize DNA, the DNA content is increased (S-phase). At the completion of DNA duplication, G2 and M (mitotic) cells produced a second peak with double amount of DNA. </div> <div> The ploidy level of stem cells is compared with benign diploid cells in the form of DNA index. To allow for instrument error of 5%, the diploid tumors have DNA index of 0.95 to 1.05  tetraploid tumors 1.90 to 2.1, and aneuploid tumors outside of diploid and tetraploid ranges </div> <div> Flow DNA cytometric analysis provides an objective measure of DNA/chromosome abnormality and rate of cellular proliferation in a more consistent manner than subjective evaluation of histologic features. </div> <div> In the study of stage I-III breast cancers by Kallioniema et al, the 6-year survival rates for patients with diploid tumor is 80%, tetraploid tumors 60%, hyperdiploid aneuploid tumors (DNA index 1.05-1.8) about 55%, and hypertetrapolid aneuploid tumors 40%. When DNA index and S-phase fraction are combined, the best survival is found among patients with diploid tumors and S-phase fraction of less than 7%. The lowest survival are those with aneuploid tumors with S-phase fraction of greater than 12%. The remaining tumors have intermediate prognosis. </div> <bR> <div> Clinical Features</div> <div> The clinical presentation of DCIS is varied. Prior to the widespread use of screening mammography, most patients presented with nipple discharge, Paget’s disease, or a palpable mass. A more recent review of patients participating in screening mammography found that nearly 60% of DCIS cases were discovered solely by mammography.<FONT SIZE="1" COLOR="#000000" FACE="Arial" >11</FONT></div> <div> Currently, most cases of DCIS consist of small lesions detected by mammography. In fact, while DCIS comprises approximately 5% of symptomatic breast cancers, it represents 15% to 20% of those detected at radiologic screening.<FONT SIZE="1" COLOR="#000000" FACE="Arial" >12,13</FONT> A change over time in a mammographic finding is associated with malignancy approximately 18% of the time; of these, most are <I>in situ</I> lesions. A mass that is greater than 1 cm on a mammogram represents a malignancy in approximately 25% of cases. However, most of these are invasive lesions.<FONT SIZE="1" COLOR="#000000" FACE="Arial" >14</FONT> The palpable forms of DCIS are associated with multicentricity, occult invasion, and an overall poorer prognosis.<FONT SIZE="1" COLOR="#000000" FACE="Arial" >15</FONT> The finding on a mammogram that commonly leads to biopsy is a focus of microcalcifications, which is seen in as many as 95% of cases of DCIS. Calcium deposits in DCIS are dystrophic calcifications secondary to necrotic tumor cells. The number of clustered microcalcifications and their presentation, such as branching or linear distribution, are associated with the likelihood of finding malignancy (Figs 4-6). Studies that have attempted to link pathologic and radiologic findings have largely been unsuccessful. Overall findings agree that screening-detected DCIS is less extensive, has smaller calcification cluster size, and has less retroareolar and upper inner quadrant involvement than symptomatic DCIS.<FONT SIZE="1" COLOR="#000000" FACE="Arial" >13</FONT> The issue of recognizing cancers with extensive intraductal involvement has been improved with mammography. The extent of calcium deposits is readily discernible on today’s mammograms and aids in evaluating treatment options.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="475" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="141"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="141" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="153"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="153" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="171"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="171" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 30 WIDTH="467"><div> Fig 4A-C. — Mammogram (craniocaudal and magnification views) demonstrating numerous scattered clusters of microcalcifications.</div> </tD> </tR> </TABLE></div> <bR> <div> <IMG SRC="0c18ff30.jpg" border=0 width="143" height="243" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="0c29bd70.jpg" border=0 width="155" height="215" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="0c3adf40.jpg" border=0 width="173" height="244" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="494" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="166"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="166" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="160"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="160" HSPACE="0" VSPACE="0"></tD> <tD VALIGN=CENTER WIDTH="158"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="158" HSPACE="0" VSPACE="0"></tD> </tR> <tR> <tD VALIGN=CENTER COLSPAN=3 HEIGHT= 30 WIDTH="486"><div> Fig 5A-C. — Mammogram (mediolateral oblique, mediolateral, and craniocaudal views) exhibiting extensive branching microcalcifications.</div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="322" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 447 WIDTH="155"><div> <IMG SRC="0c6a0d00.jpg" border=0 width="160" height="208" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="0c4a6e50.jpg" border=0 width="166" height="229" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=CENTER><NOBR><div> <IMG SRC="0c59dd20.jpg" border=0 width="157" height="210" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP COLSPAN=2 HEIGHT= 30 WIDTH="316"><div> Fig 6A-B. — Mammogram (craniocaudal and mediolateral views) showing a linear pattern of microcalcifications.</div> </tD> </tR> </TABLE></div> <bR> <div> <I><B><U><IMG SRC="0c79dfd0.jpg" border=0 width="157" height="253" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="0c8a2fc0.jpg" border=0 width="162" height="252" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></I></div> <bR> <bR> <bR> <bR> <div> <I><B><U>ASSAY FOR LAB EXPLORATION OF BREAST CANCER</U></B></I></div> <div> <B>ESTROGEN RECEPTOR</B> </div> <div> <B>)</B> is a nuclear regulatory protein which specifically binds estradiol as well as other estrogenic hormones, and, through interactions with the “estrogen response elements” of particular genes, activates the transcription of these specific, estrogen-responsive genes. ER content is important in the clinical management of women with breast cancer because the presence of ER in breast cancer cells is correlated with longer disease-free survival, longer overall survival and responsiveness to tamoxifen (anti-estrogen) therapy</div> <div> This method has the advantage of permitting a cell-by-cell assessment of ER content and permitting analysis of paraffin-embedded as well as frozen tissue specimens. </div> <bR> <div>  <img src="HTMLobj-244/aniGif.gif" border="0" align="bottom" width="300" height="239">  </div> <bR> <div> <B>PROGESTERONE RECEPTOR</B> </div> <bR> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B>Her-2/neu GENE</B> </div> <div> The human epidermal growth factor receptor type 2 (HER-2) gene is also known as the neu oncogene (neu roblastoma) or </div> <div> c-erb B-2 oncogene. This gene is found on the long arm of chromosome 17 and codes for a membrane receptor protein (see HER-2/neu oncoprotein, below). Some breast cancers have an increased number of copies of this gene, referred to as gene amplification SKBR3 chromosome spread. Amplification of the HER-2/neu gene in breast cancer, ovarian cancer, endometrial cancer and salivary gland cancer is associated with more aggressive disease as demonstrated by a shorter disease-free survival and a shorter overall survival. Our laboratory uses fluorescence in situ hybridization (FISH) to evaluate HER-2/neu gene amplification in clinical tissue specimens, either paraffin-embedded or frozen</div> <div>  <img src="HTMLobj-245/aniGif.gif" border="0" align="bottom" width="150" height="150">  </div> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B>Her-2/neu ONCOPROTEIN</B> </div> <bR> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B>EPIDERMAL GROWTH FACTOR RECEPTOR</B> </div> <bR> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B>p53 TUMOR SUPPRESSOR</B> </div> <bR> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">The<B> p53 tumor suppressor protein</B> is a nuclear protein which is involved in regulating entry to S-phase of the cell cycle and apoptotic cell death. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Mutations in the p53 gene are correlated with increased expression (overexpression)</U></FONT> of the p53 protein in a variety of cancers. Overexpression of p53 protein in breast cancer cells is correlated with shorter disease-free survival and shorter overall survival of the women with breast cancer</div> <bR> <bR> <div> <B>Ki-67 NUCLEAR ANTIGEN</B> </div> <bR> <div> <IMG SRC="0ec18180.gif" border=0 width="24" height="24" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B>DNA PLOIDY</B></div> <div> <B>Male Breast Cancer</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT></div> <div> <B>Male breast cancer is rare</B>, accounting for less than one percent of all diagnosed breast cancers. The diagnosis usually occurs in older men. The average age is approximately 63 years. In females, breast cancer occurs on average in the mid-fifties. The presenting characteristics and treatments given for male breast cancer are very similar to that of female breast cancer. </div> <div> <B>The causes</B> for the majority of male breast cancer, like female breast cancer, are not readily identifiable. No one knows what really causes the majority either. Discovery of the BRCA1 and BRCA2 genes identified the cause of a small portion of the breast cancers. These mutated genes greatly increase the risk for breast cancer. The BRCA2 gene has been implicated in male breast cancer and is often recognized as a potential cause if there is a family history of a number of females or males with breast, ovarian, prostate or colon cancer. </div> <div> Research has identified <B>possible risk factors</B> for male breast cancer other than a mutated gene. These risk factors are listed below.</div> <div> <B>Incidence increases in men who have:</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Jewish heritage </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">African-American heritage </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">History of mumps orchitis after age 20 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Klinefelter’s syndrome </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Conditions of increased or excessive estrogen levels </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Conditions causing decreased testosterone levels </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Occupational jobs that cause high environmental exposure to heat (steel mills, etc.) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Exposure to electromagnetic fields for extended periods of time </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Exposure to ionizing radiation </div> <div> <B>Diagnosis </B>of male breast cancer is like that of the female. Most male breast cancers present as a lump on one side, under the areola, that is hard and anchored in surrounding tissues when examined with the hand. Nipple discharge is an occasional presenting symptom. Breast discharge on one side of a male is cause for a diagnostic work-up. Infiltrating ductal carcinoma, as in female breast cancer, composes the vast majority of male breast cancer (87%). </div> <div> <B>Mammograms</B> are very helpful in identifying the presenting symptom as a malignancy. However, on a thin male it may be difficult to obtain. Ultrasound is a helpful tool. Needle biopsies, FNA or core, are used to obtain a histological diagnosis. </div> <div> <B>Mastectomy is usually the surgery of choice.</B> A modified radical is most often used, unless there is chest wall involvement of the muscle, which requires a radical mastectomy with removal of the pectoralis muscles.</div> <div> <B>Radiation therapy</B> is often used because of the close proximity of the tumor to the chest wall. Chemotherapy is used for large tumors and/or positive lymph nodes. More men present with later stage disease than women because of the lack of screening programs.</div> <div> <B>Chemotherapy protocol drugs</B> are identical to female breast cancer drugs. Cytoxan, Methotrexate, and 5FU are usually used in combination as first round chemotherapy. Tamoxifen is added if the tumor tested positive for estrogen or progesterone receptors. For many years, orchiectomy (removal of the testes) was used to reduce hormones in the man’s body. Now, men are more often treated with various anti-hormonal drugs. Buserelin, used in combination with a steroidal anti-androgen called cyproterone acetate, has proven to have equal response rates for controlling the disease. Orchiectomy is now a third-line option because of the effectiveness of anti-hormonal drugs.</div> <div> Dealing with the <B>side-effects of chemotherapy</B> is the same as in females. The use of tamoxifen causes hot flashes and reduces the sex drive.</div> <div> <B>The challenge in male breast cancer, like female breast cancer, is early detection. The earlier the stage of the disease, the better the prognosis.</B></div> <bR> </td> </tr></table></body>