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{=0A= document.writeln('

3D"Click

');=0A= }=0A= =0A= function get_text_link(url, linktext)=0A= {=0A= document.writeln('' + = linktext + '');=0A= }=0A= =0A= function get_htmlftext_link(a, b) {=0A= document.writeln("" + = b + ", ");=0A= }=0A= =0A= ------=_NextPart_000_0000_01CA3DFD.535610D0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://download.interscience.wiley.com/freeflow/js/personalisation.js /*=0A= * Project : Interscience Redesign=0A= * File : personalisation.js=0A= * Creation Date : 25th March 2003=0A= * Author : Jonathan Sugar=0A= *=0A= * Various functions to deliver personalisation functionality.=0A= */=0A= =0A= // Pre-declare userName so it's available when we need to test if the = page=0A= // assembler ran OK=0A= var userName =3D null;=0A= var shcrtCookie =3D null;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= // Factory Methods=0A= =0A= // Simple wraper object to encapsulate the data for a co-branding item.=0A= function coBrandingItem(image, imageAltText, href)=0A= {=0A= //alert("Making new coBrandingItem:\nImage: " + image + = "\nimageAltText" + imageAltText + "\nhref: " + href);=0A= this.image =3D image;=0A= this.imageAltText =3D imageAltText;=0A= this.href =3D href;=0A= }=0A= =0A= /*=0A= * Insert the 'Customer co-branding' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert customer co branding. Loop through 'customerCoBranding' array=0A= * inserting XHTML where needed.=0A= *=0A= * NOTE: the array contains ONLY the resource location (the location of a = gif=0A= * on the file system), the required XHTML is then added where needed. = This way=0A= * we maintain the seperation between presentation and content.=0A= */=0A= function insertCustomerCoBranding(maxBranding)=0A= {=0A= if( customerCoBranding[0].image !=3D "none")=0A= {=0A= document.writeln('

');=0A= document.writeln('

');=0A= document.writeln('

' + imageAltText + '
' + imageAltText + = '
More Providers

');=0A= document.writeln('

');=0A= document.writeln('

3D""

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the 'My Area' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= *=0A= * My profile link absolute as this file isnt only run from w3 anymore.=0A= */=0A= function insertMyArea(userdata)=0A= {=0A= // just in case the page assembler isn't running.=0A= =0A= =0A= if (userName !=3D null)=0A= {=0A= document.writeln("

" + = userName.substring(0,33) + "..., access your
" + userName + = ", access your

My Profile"); =0A= } =0A= document.writeln(getLoginOutLink());=0A= //CR 3652 getAthenStatus() as added=0A= document.writeln(getAthenStatus());=0A= document.writeln("

");=0A= } else {=0A= if(typeof(environment)!=3D'undefined' && = environment=3D=3D'PRODUCTION') {=0A= document.writeln("

Log Out");=0A= document.writeln("

"); =0A= }=0A= }=0A= if (menuloadedflag){=0A= wisMenu();=0A= }=0A= }=0A= =0A= /*=0A= * Insert the Customer Admin 'Login/Logout' link=0A= * -----------------------------=0A= *=0A= * Author: Bobby Jack, December 2004.=0A= *=0A= */=0A= function insertAdminLink(page)=0A= {=0A= val =3D getCookie("AID");=0A= =0A= if (val && val !=3D "-1")=0A= {=0A= document.writeln('

Logout');=0A= }=0A= else=0A= {=0A= document.writeln('

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the username section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert the username.=0A= */=0A= function insertUserName()=0A= {=0A= document.write(userName);=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the login/logout cgi=0A= * ---------------------------------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= * Had to change the links absolute as this file isnt only run from w3 = anymore.=0A= */=0A= function getLoginOutLink()=0A= {=0A= if(userName !=3D "")=0A= {=0A= return "

";=0A= }else=0A= {=0A= return "

";=0A= }=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the shopping cart content page=0A= * ---------------------------------------------------=0A= *=0A= * Author: Zhiming & Warrell June 2007=0A= */=0A= function getShCrtLink(logged)=0A= {=0A= if(logged =3D=3D true )=0A= return "

";=0A= else=0A= return "

";=0A= }=0A= =0A= function toggleShCrtLink()=0A= {=0A= shcrtCookie =3D readCookie("SHCRT");=0A= if(shcrtCookie !=3D null)=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "block";=0A= }=0A= }=0A= else=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "none";=0A= }=0A= }=0A= }=0A= =0A= =0A= =0A= function readCookie(name)=0A= {=0A= var nameEQ =3D name + "=3D";=0A= var ca =3D document.cookie.split(';');=0A= for(var i=3D0; iYou are logged in = to Athens';=0A= }=0A= else=0A= {=0A= return "

";=0A= }=0A= =0A= } ------=_NextPart_000_0000_01CA3DFD.535610D0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://download.interscience.wiley.com/freeflow/js/site.js /************************************************************************= ***************************=0A= FILE: site.js=0A= AUTHOR: Jonathan Sugar, Chris Neatby-Smith and Digital Pulp. July = 2003.=0A= =0A= DESCRIPTION: Javascript relating to site wide functionality across =0A= InterScience.=0A= =0A= INCLUDES FUNCTIONS=0A= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= Search Functions=0A= ----------------=0A= =0A= selectAndSubmit() - for deciding where to submit a query based on the = state of the form.=0A= processallContentSearch() - for validating form input for an all = content search.=0A= processTitleSearch() - for validating form input for a Title search.=0A= checkCitationSearch() - for validating the citation search form.=0A= selectAll() - check all the checkboxes in a form.=0A= do_popup() - stasa Acronym Finder window popup function.=0A= =0A= =0A= Other Functions=0A= ---------------=0A= =0A= fixInlineLists() - fix netscape 4.x bug where

tags with images = display both an image and=0A= the default bullet. =0A= =0A= = *************************************************************************= **************************/=0A= =0A= var http =3D false;=0A= if(navigator.appName =3D=3D "Microsoft Internet Explorer") {=0A= http =3D new ActiveXObject("Microsoft.XMLHTTP");=0A= } else {=0A= http =3D new XMLHttpRequest();=0A= } =0A= =0A= // Global Variables=0A= var debug =3D false;=0A= var first =3D true;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= /*=0A= * Used to switch search mode between APS and TitleFinder on quicksearch = boxes=0A= * = -------------------------------------------------------------------------= --=0A= *=0A= * 1. Decides which search is required based on the value of the radio = buttons=0A= * in 'document.formSelector.whichForm'.=0A= *=0A= * 2. Calls individual functions to process the forms and submit them.=0A= *=0A= */=0A= function selectAndSubmit()=0A= {=0A= var formSelection;=0A= =0A= // find out which form we need to process.=0A= var selector =3D document.formSelector.whichForm;=0A= for (var i =3D 0; i < selector.length; i++){=0A= if (selector[i].checked){=0A= formSelection =3D selector[i].value;=0A= }=0A= }=0A= =0A= // Call the relevent function to process the required form.=0A= if(formSelection =3D=3D "allContentSearch"){=0A= processallContentSearch(document.allContentSearchForm, = document.formSelector)=0A= }=0A= else if(formSelection =3D=3D "searchTitles"){=0A= processTitleSearch(document.searchTitles, document.formSelector)=0A= }=0A= else{=0A= return false;=0A= }=0A= =0A= //@@@DM It was anoying me this error =0A= return false;=0A= }=0A= =0A= /*=0A= *Process the ADS search form=0A= *=0A= */=0A= function trim(str)=0A= {=0A= return str.replace(/(^\s*)|(\s*$)/g,"");=0A= }=0A= =0A= function ADSquery(t) {=0A= var keyword =3D trim(t.getElementsByTagName("input")[0].value);=0A= if (keyword!=3D"") {=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= t.target=3D"popup";=0A= t.qsearch.value=3Dkeyword;=0A= return true;=0A= = //processADSSearch(document.ADSSearchForm,document.ADSQueryForm,keyword);=0A= } else {=0A= alert("Please input a keyword for ADS searching before clicking go");=0A= return false;=0A= }=0A= }=0A= /*=0A= function processADSSearch(hiddenForm ,queryForm , str) {=0A= var terms =3D str;=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= formToSubmit.qsearch.value =3D terms;=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= formToSubmit.action =3D = "http://adsabs.harvard.edu/cgi-bin/nph-basic_connect"=0A= formToSubmit.target =3D "popup";=0A= formToSubmit.submit();=0A= }=0A= */=0A= =0A= /*=0A= * Process the allContentSearch form=0A= * ---------------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= function processallContentSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.WISsearch1.value =3D formToProcess.terms.value;=0A= formToSubmit.submit(); =0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= /*=0A= * Process the Title Search form=0A= * -----------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= =0A= function processTitleSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.query.value =3D formToProcess.terms.value;=0A= formToSubmit.submit();=0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= function doCitationSearch()=0A= {=0A= var form =3D document.citsearchform;=0A= if(checkCitationSearch())=0A= {=0A= form.action =3D "/search/allsearch";=0A= form.submit();=0A= }=0A= }=0A= =0A= // Preprocesses the arguments sent to CitationSearch and checks validity = of user inputs.=0A= function checkCitationSearch()=0A= {=0A= var supplementFound =3D 0; //increment if found;=0A= var hyphenFound =3D 0; //increment if found;=0A= var fm =3D document.citsearchform;=0A= var errmsg =3D "Please use the valid digits '0' to '9'";=0A= // remove all spaces=0A= fm.volume.value =3D fm.volume.value.replace(/ /g, "");=0A= fm.issue.value =3D fm.issue.value.replace(/ /g, "");=0A= fm.pages.value =3D fm.pages.value.replace(/ /g, "");=0A= =0A= if (fm.issn.value.length > 0 && fm.volume.value.length > 0 && = fm.pages.value.length > 0)=0A= {=0A= // check page range=0A= var pageRange =3D fm.pages.value;=0A= var volume =3D fm.volume.value;=0A= var issue =3D fm.issue.value;=0A= var continueFlag =3D 0;=0A= //check the volume=0A= // if (isNaN(volume))=0A= // {=0A= // // volume failed checking=0A= // alert("Volume is invalid. "+errmsg+".");=0A= // return false;=0A= // }=0A= //check the issue=0A= if ((issue.length !=3D 0) && isNaN(issue))=0A= {=0A= // issue failed checking=0A= alert("Issue is invalid. "+errmsg+" or leave blank.");=0A= return false;=0A= }=0A= //check the page range=0A= if (isNaN(pageRange))=0A= {=0A= var isValid =3D false;=0A= // check for hyphen=0A= var hyphenIndex =3D pageRange.indexOf("-");=0A= if ((hyphenIndex !=3D -1) && (hyphenIndex =3D=3D = pageRange.lastIndexOf("-")))=0A= {=0A= // we have only one hyphen, so extract each number=0A= var firstNum =3D pageRange.substring(0, hyphenIndex);=0A= var secondNum =3D pageRange.substring(hyphenIndex + 1);=0A= // check for S=0A= var firstS =3D firstNum.indexOf("S");=0A= var secondS =3D secondNum.indexOf("S");=0A= if (firstS =3D=3D secondS)=0A= {=0A= if ((firstS =3D=3D -1) && isNum(firstNum) && isNum(secondNum) && = (firstNum.length > 0) && (secondNum.length > 0))=0A= isValid =3D true; // both inputs are digits=0A= else if (firstS =3D=3D 0)=0A= {=0A= var firstNumNoS =3D firstNum.substring(1);=0A= var secondNumNoS =3D secondNum.substring(1);=0A= if (isNum(firstNumNoS) && isNum(secondNumNoS) && = (firstNumNoS.length > 0) && (secondNumNoS.length > 0))=0A= isValid =3D true; // both inputs are Sdigits=0A= }=0A= =0A= }=0A= }=0A= if (isValid)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= alert("The page range is invalid. "+errmsg+" and a hyphen '-' if = required.");=0A= return false;=0A= }=0A= }=0A= return true;=0A= }=0A= else=0A= {=0A= alert("Volume and pages are required fields. Please make sure data has = been entered for both fields.");=0A= return false;=0A= }=0A= }=0A= =0A= // returns true if a is an Integer.=0A= function isNum(a)=0A= { return !(isNaN(a)); }=0A= =0A= function fixInlineLists() {=0A= if (!document.getElementById) return;=0A= var allLIs =3D document.getElementsByTagName('li');=0A= var bulletNode =3D document.createElement('img');=0A= bulletNode.src = =3D"http://download.interscience.wiley.com/images/icon.bullet.gif";=0A= =0A= for (var i=3D0; iAbstract | References';=0A= }=0A= //alert("URL: " + loc + "\nStart Index: " + startIndex + "\nEnd Index: = " + endIndex + "\nPage: " + page + "\nLink Text: " + links);=0A= return links;=0A= }=0A= =0A= =0A= function selectAll(fm)=0A= {=0A= //var fm =3D document.viewSelectedForm;=0A= =0A= for (var i =3D 0; i < fm.elements.length; i++)=0A= {=0A= if (fm.elements[i].type =3D=3D 'checkbox' /*&& fm.elements[i].name = =3D=3D 'ID'*/)=0A= {=0A= fm.elements[i].checked =3D true;=0A= }=0A= }=0A= }=0A= =0A= =0A= function do_popup(file)=0A= {=0A= var w =3D window.open(file, 'popWin', = 'width=3D350,height=3D500,scrollbars=3Dyes');=0A= =0A= }=0A= =0A= =0A= function mailTool(itemID, useurl, skin)=0A= {=0A= //var url =3D "/cgi-bin/mailform?item=3D"+itemID;=0A= var url =3D "/cgi-bin/mailform?item=3D" + itemID + "&skin=3D" + skin;=0A= var parameters =3D = 'status=3Dno,scrollbars=3Dno,resizable=3Dyes,width=3D400,height=3D475';=0A= =0A= if (useurl !=3D "")=0A= {=0A= url +=3D "&useurl=3D"+useurl;=0A= }=0A= =0A= if ((isNaN(parseInt(itemID))=3D=3Dtrue)||(arguments.length >=3D 4 && = arguments[3] =3D=3D 'cluster'))=0A= {=0A= url +=3D '&type=3Dcluster';=0A= }=0A= =0A= //check whether the last 2 arguments is used for urllink.=0A= // urllink is needed to open up mail form for mrw pages on tomcat = port=0A= if (arguments.length>=3D5 && = arguments[arguments.length-2]=3D=3D'urllink' && = arguments[arguments.length-1]!=3D'')=0A= {=0A= url =3D arguments[arguments.length-1] + url;=0A= }=0A= =0A= if (arguments.length>=3D5 && arguments[3]=3D=3D'currentlink' && = arguments[4]!=3D'')=0A= {=0A= url =3D url + '¤tLink=3D' + arguments[4];=0A= =0A= //processing specific cases=0A= if (arguments[4]=3D=3D'jcatalogjsphdr')=0A= {=0A= //get the issn and pass it the next stage for processing=0A= var currloc =3D location.href;=0A= var issnloc =3D currloc.indexOf("&issn=3D");=0A= if (issnloc !=3D -1)=0A= {=0A= url =3D url + '¤tISSN=3D' + = currloc.substring(issnloc+6);=0A= }=0A= }=0A= // issn is needed for cocoon rendered mrw to form the final url.=0A= else if ( (arguments[4]=3D=3D'cocoonmrwhome') || = (arguments[4]=3D=3D'cocoonmrwarticle') )=0A= {=0A= if (arguments.length>=3D7 && arguments[5]=3D=3D'issn' && = arguments[6]!=3D'')=0A= {=0A= url =3D url + '¤tISSN=3D' + arguments[6];=0A= }=0A= //getting the parameters of the currently shown mrw from the = url=0A= //the method used here is a little crude, it extracts the = values from the current url of the page the user is in =0A= //to pass it to the background program to reconstruct the = requred url=0A= if (arguments[4]=3D=3D'cocoonmrwhome')=0A= {=0A= var currloc =3D location.href;=0A= var mrwParamArr =3D currloc.split("/");=0A= if (mrwParamArr.length >=3D 7)=0A= {=0A= url =3D url + '&mrwPath=3D' + mrwParamArr[5];=0A= var mrwFileParam =3D mrwParamArr[6];=0A= var seploc =3D mrwFileParam.indexOf("#");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwSection=3D' + = mrwFileParam.substring(seploc+1);=0A= mrwFileParam =3D = mrwFileParam.substring(0,seploc);=0A= }=0A= seploc =3D mrwFileParam.indexOf("?");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwUrlParam=3D' + = mrwFileParam.substring(seploc+1);=0A= url =3D url + '&mrwDocType=3D' + = mrwFileParam.substring(0,seploc);=0A= }=0A= else=0A= {=0A= url =3D url + '&mrwDocType=3D' + mrwFileParam;=0A= }=0A= }=0A= =0A= }=0A= else if (arguments[4]=3D=3D'cocoonmrwarticle')=0A= {=0A= var currloc =3D location.href;=0A= var mrwParamArr =3D currloc.split("/");=0A= if (mrwParamArr.length >=3D 7)=0A= {=0A= url =3D url + '&mrwPath=3D' + mrwParamArr[5];=0A= url =3D url + '&mrwAid=3D' + mrwParamArr[7];=0A= url =3D url + '&mrwVersion=3D' + mrwParamArr[8];=0A= var mrwFileParam =3D mrwParamArr[9];=0A= var seploc =3D mrwFileParam.indexOf("#");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwSection=3D' + = mrwFileParam.substring(seploc+1);=0A= url =3D url + '&mrwDocType=3D' + = mrwFileParam.substring(0,seploc);=0A= }=0A= else=0A= {=0A= url =3D url + '&mrwDocType=3D' + mrwFileParam;=0A= }=0A= }=0A= }=0A= }=0A= }=0A= =0A= //checking if a html file exists in the url=0A= var tmpfname =3D location.href;=0A= var loc =3D tmpfname.indexOf("?");=0A= if (loc !=3D -1)=0A= {=0A= tmpfname =3D tmpfname.substring(0,loc);=0A= }=0A= loc =3D tmpfname.indexOf(".html");=0A= if (loc !=3D -1)=0A= {=0A= loc =3D tmpfname.lastIndexOf("/");=0A= if (loc !=3D -1)=0A= {=0A= tmpfname =3D tmpfname.substring(loc+1);=0A= url =3D url + '¤tFile=3D' + tmpfname;=0A= }=0A= }=0A= =0A= if (arguments.length>=3D7 && arguments[5]=3D=3D'currentyear' && = arguments[6]!=3D'')=0A= {=0A= url =3D url + '¤tYear=3D' + arguments[6];=0A= }=0A= =0A= eval("wileyMailTool =3D = window.open('"+url+"','MailTool','"+parameters+"')");=0A= =0A= // If object exists ensure has focus=0A= if (eval("wileyMailTool") && window.focus)=0A= eval("wileyMailTool").focus();=0A= }=0A= =0A= =0A= /*=0A= * 1. Find the links we need to alter.=0A= * 2. For each link apply the new styles we need.=0A= */=0A= function fixAbsRefRendering()=0A= { =0A= var table =3D document.getElementById('prerendered');=0A= var anchors =3D table.getElementsByTagName('a');=0A= for (var i =3D 1; i < anchors.length; i++)=0A= {=0A= if(anchors[i].href !=3D"") =0A= { =0A= applyAbsRefStyleCorrection(anchors[i]);=0A= =0A= }=0A= }=0A= }=0A= =0A= function applyAbsRefStyleCorrection(currentLink)=0A= {=0A= currentLink.style["color"] =3D "#369";=0A= currentLink.style["fontWeight"] =3D "normal";=0A= currentLink.style["marginLeft"] =3D "3px";=0A= currentLink.style["marginRight"] =3D "5px";=0A= }=0A= =0A= function populatePage(formName)=0A= {=0A= if (formName.Page.value =3D=3D '')=0A= {=0A= formName.Page.value =3D document.location;=0A= }=0A= }=0A= =0A= function equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= document.writeln(' 3D"blank"

');=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function old_equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= if(debug)=0A= {=0A= alert("Number of feature boxes: " + numberOfFeatures + "\nPercent per = feature: " + percentPerFeature);=0A= }=0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= if (netscape4 =3D=3D false)=0A= {=0A= document.writeln(' 3D"blank"

'); =0A= }=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function writeFBoxCell()=0A= {=0A= if(first)=0A= {=0A= document.write('');=0A= }else=0A= {=0A= document.write('');=0A= }=0A= numFeatures ++;=0A= }=0A= =0A= =0A= //=0A= // escape apostrophe characters within a string=0A= //=0A= function encode(str)=0A= {=0A= out =3D '';=0A= =0A= for (a =3D 0; a < str.length; a++)=0A= {=0A= c =3D str.charAt(a);=0A= =0A= if (c =3D=3D "'")=0A= {=0A= out +=3D '\\';=0A= }=0A= =0A= out +=3D c;=0A= }=0A= =0A= return out;=0A= }=0A= =0A= =0A= //=0A= //=0A= //=0A= function escapeEntities(str)=0A= {=0A= while (str.indexOf("'") > -1)=0A= {=0A= pos =3D str.indexOf("'");=0A= str =3D str.substr(0, pos) + '\\\'' + str.substr(pos + 6);=0A= }=0A= =0A= return str;=0A= }=0A= =0A= =0A= // new popup function less intrusive just uses the DOM to pickup links = with an exwin class.=0A= // currently implemented for Figure popups on D&T homepage.=0A= =0A= function exLinks()=0A= {=0A= if (document.getElementById)=0A= {=0A= var aObject =3D document.getElementsByTagName("a");=0A= for (var x=3D0; x" + = liels[j].innerHTML + "

You do not have = anything saved in this menu.

";=0A= else=0A= tmpinnerhtml +=3D "

" = + liels[j].innerHTML + "

"; =0A= } =0A= } else {=0A= //setup var to see if more is required=0A= var more =3D (subnodeslength < lilength) ? true : = false; =0A= var flag =3D true;=0A= for (var j=3D0; j" + liels[j].innerHTML + = "";=0A= } else if (j > lilength-3){=0A= if (j =3D=3D lilength-2){=0A= var url =3D liels[j].innerHTML.split('"')[1];=0A= tmpinnerhtml +=3D "

" + liels[j].innerHTML + "

";=0A= } else {=0A= tmpinnerhtml +=3D "

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Brain Pathology

ISSN: 1750-3639 (Online)

ISSN: 1015-6305 (Print)

Volume 18, Issue 3, 2008.

Pages: 307=96316

Top of Page
Abstract
INTRODUCTION
GRADE IV OLIGOASTROCYTOMA VS. "GLIOBLASTOMA WITH = OLIGODENDROGLIAL=20 COMPONENT"=97CLARITY OR CONFUSION
THE PROGNOSTIC SIGNIFICANCE OF MICROVASCULAR PATTERNS IN = GLIOMAS
GLIONEURONAL TUMORS=97A RUNAWAY TUMOR CATEGORY?
PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE = DIFFERENTIATION=97THE NEED=20 FOR PRECISE CRITERIA
HEMANGIOPERICYTOMA AND SOLITARY FIBROUS TUMOR=97THE = NEUROPATHOLOGIC=20 APPROACH
CONCLUSION
References

List of=20 Images

Abstract=20 Only

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block } ------=_NextPart_000_0000_01CA3DFD.535610D0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www3.interscience.wiley.com/freeflow/js/site.js /************************************************************************= ***************************=0A= FILE: site.js=0A= AUTHOR: Jonathan Sugar, Chris Neatby-Smith and Digital Pulp. July = 2003.=0A= =0A= DESCRIPTION: Javascript relating to site wide functionality across =0A= InterScience.=0A= =0A= INCLUDES FUNCTIONS=0A= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= Search Functions=0A= ----------------=0A= =0A= selectAndSubmit() - for deciding where to submit a query based on the = state of the form.=0A= processallContentSearch() - for validating form input for an all = content search.=0A= processTitleSearch() - for validating form input for a Title search.=0A= checkCitationSearch() - for validating the citation search form.=0A= selectAll() - check all the checkboxes in a form.=0A= do_popup() - stasa Acronym Finder window popup function.=0A= =0A= =0A= Other Functions=0A= ---------------=0A= =0A= fixInlineLists() - fix netscape 4.x bug where

tags with images = display both an image and=0A= the default bullet. =0A= =0A= = *************************************************************************= **************************/=0A= =0A= var http =3D false;=0A= if(navigator.appName =3D=3D "Microsoft Internet Explorer") {=0A= http =3D new ActiveXObject("Microsoft.XMLHTTP");=0A= } else {=0A= http =3D new XMLHttpRequest();=0A= } =0A= =0A= // Global Variables=0A= var debug =3D false;=0A= var first =3D true;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= /*=0A= * Used to switch search mode between APS and TitleFinder on quicksearch = boxes=0A= * = -------------------------------------------------------------------------= --=0A= *=0A= * 1. Decides which search is required based on the value of the radio = buttons=0A= * in 'document.formSelector.whichForm'.=0A= *=0A= * 2. Calls individual functions to process the forms and submit them.=0A= *=0A= */=0A= function selectAndSubmit()=0A= {=0A= var formSelection;=0A= =0A= // find out which form we need to process.=0A= var selector =3D document.formSelector.whichForm;=0A= for (var i =3D 0; i < selector.length; i++){=0A= if (selector[i].checked){=0A= formSelection =3D selector[i].value;=0A= }=0A= }=0A= =0A= // Call the relevent function to process the required form.=0A= if(formSelection =3D=3D "allContentSearch"){=0A= processallContentSearch(document.allContentSearchForm, = document.formSelector)=0A= }=0A= else if(formSelection =3D=3D "searchTitles"){=0A= processTitleSearch(document.searchTitles, document.formSelector)=0A= }=0A= else{=0A= return false;=0A= }=0A= =0A= //@@@DM It was anoying me this error =0A= return false;=0A= }=0A= =0A= /*=0A= *Process the ADS search form=0A= *=0A= */=0A= function trim(str)=0A= {=0A= return str.replace(/(^\s*)|(\s*$)/g,"");=0A= }=0A= =0A= function ADSquery(t) {=0A= var keyword =3D trim(t.getElementsByTagName("input")[0].value);=0A= if (keyword!=3D"") {=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= t.target=3D"popup";=0A= t.qsearch.value=3Dkeyword;=0A= return true;=0A= = //processADSSearch(document.ADSSearchForm,document.ADSQueryForm,keyword);=0A= } else {=0A= alert("Please input a keyword for ADS searching before clicking go");=0A= return false;=0A= }=0A= }=0A= /*=0A= function processADSSearch(hiddenForm ,queryForm , str) {=0A= var terms =3D str;=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= formToSubmit.qsearch.value =3D terms;=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= formToSubmit.action =3D = "http://adsabs.harvard.edu/cgi-bin/nph-basic_connect"=0A= formToSubmit.target =3D "popup";=0A= formToSubmit.submit();=0A= }=0A= */=0A= =0A= /*=0A= * Process the allContentSearch form=0A= * ---------------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= function processallContentSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.WISsearch1.value =3D formToProcess.terms.value;=0A= formToSubmit.submit(); =0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= /*=0A= * Process the Title Search form=0A= * -----------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= =0A= function processTitleSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.query.value =3D formToProcess.terms.value;=0A= formToSubmit.submit();=0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= function doCitationSearch()=0A= {=0A= var form =3D document.citsearchform;=0A= if(checkCitationSearch())=0A= {=0A= form.action =3D "/search/allsearch";=0A= form.submit();=0A= }=0A= }=0A= =0A= // Preprocesses the arguments sent to CitationSearch and checks validity = of user inputs.=0A= function checkCitationSearch()=0A= {=0A= var supplementFound =3D 0; //increment if found;=0A= var hyphenFound =3D 0; //increment if found;=0A= var fm =3D document.citsearchform;=0A= var errmsg =3D "Please use the valid digits '0' to '9'";=0A= // remove all spaces=0A= fm.volume.value =3D fm.volume.value.replace(/ /g, "");=0A= fm.issue.value =3D fm.issue.value.replace(/ /g, "");=0A= fm.pages.value =3D fm.pages.value.replace(/ /g, "");=0A= =0A= if (fm.issn.value.length > 0 && fm.volume.value.length > 0 && = fm.pages.value.length > 0)=0A= {=0A= // check page range=0A= var pageRange =3D fm.pages.value;=0A= var volume =3D fm.volume.value;=0A= var issue =3D fm.issue.value;=0A= var continueFlag =3D 0;=0A= //check the volume=0A= // if (isNaN(volume))=0A= // {=0A= // // volume failed checking=0A= // alert("Volume is invalid. "+errmsg+".");=0A= // return false;=0A= // }=0A= //check the issue=0A= if ((issue.length !=3D 0) && isNaN(issue))=0A= {=0A= // issue failed checking=0A= alert("Issue is invalid. "+errmsg+" or leave blank.");=0A= return false;=0A= }=0A= //check the page range=0A= if (isNaN(pageRange))=0A= {=0A= var isValid =3D false;=0A= // check for hyphen=0A= var hyphenIndex =3D pageRange.indexOf("-");=0A= if ((hyphenIndex !=3D -1) && (hyphenIndex =3D=3D = pageRange.lastIndexOf("-")))=0A= {=0A= // we have only one hyphen, so extract each number=0A= var firstNum =3D pageRange.substring(0, hyphenIndex);=0A= var secondNum =3D pageRange.substring(hyphenIndex + 1);=0A= // check for S=0A= var firstS =3D firstNum.indexOf("S");=0A= var secondS =3D secondNum.indexOf("S");=0A= if (firstS =3D=3D secondS)=0A= {=0A= if ((firstS =3D=3D -1) && isNum(firstNum) && isNum(secondNum) && = (firstNum.length > 0) && (secondNum.length > 0))=0A= isValid =3D true; // both inputs are digits=0A= else if (firstS =3D=3D 0)=0A= {=0A= var firstNumNoS =3D firstNum.substring(1);=0A= var secondNumNoS =3D secondNum.substring(1);=0A= if (isNum(firstNumNoS) && isNum(secondNumNoS) && = (firstNumNoS.length > 0) && (secondNumNoS.length > 0))=0A= isValid =3D true; // both inputs are Sdigits=0A= }=0A= =0A= }=0A= }=0A= if (isValid)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= alert("The page range is invalid. 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return hwnd; } =0A= function pagetitle() {return 'Brain Pathology Vol. 18, 3 Pages: = 307-316'; } =0A= function dochead(hwnd, spec) {var title =3D pagetitle(); = hwnd.document.open(); = hwnd.document.write(''+spec+title+''); } =0A= function doctail(hwnd) {hwnd.document.write(''); } =0A= function pagehead(hwnd) {hwnd.document.write('

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Online ISSN: = 1096-9896 Print ISSN: 0022-3417
The Journal of = Pathology
Volume 214, Issue 3, 2008. Pages: 328-336

Copyright =C2=A9 2007 Pathological Society of Great = Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Brain Pathology

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Volume 18, Issue 3, Pages 307-316

Published Online: 2 Jun 2008

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CONTROVERSIES IN NEUROPATHOLOGY

The 2007 WHO Classification of Tumors = of the=20 Nervous System: Controversies in Surgical = Neuropathology

Bernd=20 W. Scheithauer, MD ¹ = ; Greg N. Fuller, MD=20 ² ; Scott R. VandenBerg,=20 MD ³ =

¹ Department of = Laboratory Medicine and Pathology, Mayo Clinic, Rochester, = Minn.=20
= ² Department of = Pathology, University of Texas, MD Anderson Cancer Center, = Houston,=20 Tex.
=20 ³ Department of=20 Anatomic Pathology and Neuropathology, University of California, = San=20 Francisco, Calif.

Correspondence to Bernd = W. Scheithauer,=20 MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, = 200=20 First Street, SW, Rochester, MN 55905 (E-mail: scheithauer.bernd@mayo.edu= )=20

Copyright Journal compilation =A9 2008 = International Society of Neuropathology

KEYWORDS

brain tumors =95 classification =95 = controversial issues =95=20 pathology =95 World Health Organization

ABSTRACT

3DAbstract=20

Controversy surrounds the recent 2007 WHO = Classification of=20 Tumours of the Nervous System. A number of nosologic issues remain = to be=20 resolved, some a reflection of conceptual disagreement, others the = result=20 of inadequate data to permit their definitive resolution. Among = these and=20 discussed herein are (i) the nosologic place of highly anaplastic=20 oligoastrocytic tumors, (ii) the forms and significance of = microvascular=20 changes in high-grade gliomas, (iii) the makeup of the = glioneuronal tumors=20 category, (iv) the subclassification of pineal parenchymal tumors = of=20 intermediate type, and (v) the classification of principle forms = of=20 mesenchymal neoplasms, specifically hemangiopericytoma and = solitary=20 fibrous tumor. These issues and others are the substance of this = and an=20 upcoming companion article.

Received 10 April 2008; accepted 11 April=20 2008.

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1750-3639.2008.00179.x About=20 DOI

=20

=20

=20

INTRODUCTION

The last four decades have seen the formulation of = four=20 editions of the World Health Organization Classification of = Tumours of the=20 Central Nervous System (25,=20 24, 33, 76), three in rapid succession over the past 14 years = alone.=20 Each brought with it revisions reflecting changes of concept, some = fundamental, as well as minor or subtle alterations. Not all = changes met=20 with overall, unanimous approval by members of the working group. = Although=20 each edition represented a marked improvement over prior efforts, = knotty=20 problems remained. This and a companion article will address = controversies=20 surrounding the 2007 WHO classification, leaving readers to draw = their own=20 conclusions.

=20

=20

GRADE IV OLIGOASTROCYTOMA VS. = "GLIOBLASTOMA=20 WITH OLIGODENDROGLIAL COMPONENT"=97CLARITY OR CONFUSION

This important issue of dissension has its basis = in=20 persistence of the antiquated term "glioblastoma" in an era in = which all=20 of diagnostic surgical pathology has focused upon cellular = differentiation=20 rather than morphologic epiphenomena. In gliomas, the latter = include=20 "microvascular proliferation" (see below) and necrosis. Neither=20 contributes to a cell-based diagnosis, serving only to establish = tumor=20 grade. Harkening back to Cushing and the concept of the = "glioblast" also=20 serves no purpose in present day tumor nosology. Instead, it is a = reminder=20 of the days when it was considered appropriate to combine very = high-grade=20 astrocytomas, oligodendrogliomas and ependymomas featuring = vascular=20 proliferation and necrosis into a "glioblastoma" category (76).=20 A relevant quote from the 1979 WHO "blue book" states: "Some = typical=20 glioblastomas show no evidence of a more differentiated tumor, = whereas=20 others are predominantly glioblastomas with focal areas of = recognizable=20 astrocytoma, less commonly oligodendroglioma or, exceptionally,=20 ependymoma. Any of these gliomas may in fact = terminate as a=20 glioblastoma." That concept was abandoned years ago when = the 1993=20 version of the WHO blue book clearly stated that glioblastomas are = poorly=20 differentiated astrocytic tumors corresponding to grade IV (25).=20 This served to remove some of the misconception and confusion = surrounding=20 glioblastoma. It could only have been bettered by introducing the=20 alternative term "grade IV astrocytoma," thus bringing the = classification=20 into line with the practice of establishing cell-based diagnoses. = Indeed,=20 only tumor classifications predicated upon cellular = differentiation should=20 carry the day.

Thus, it is not surprisingly that the most = contentious=20 issues to arise at the 2007 Heidelberg conference was a nosologic = shift to=20 include tumors featuring both oligodendroglial and astrocytic = components=20 in addition to necrosis (Figure 1),=20 in substance grade IV oligoastrocytoma, into the glioblastoma = category=20 under the pattern designation "glioblastoma with oligodendroglial=20 component". High-grade oligoastrocytic tumors with a variable, = often minor=20 oligodendroglial component (oligoastrocytomas) have long been = recognized,=20 and are familiar to pathologists and neurosurgeons/oncologists = alike (3,=20 40). In contrast, the term "glioblastoma with oligodendroglial = component" has a much shorter track record. The designation has = been used=20 in the research setting (15,=20 31, 45). In clinical studies it has been applied to occasional = cases=20 of "glioblastoma with long term survival"(7,=20 35), in one large series of "glioblastomas" in which an=20 oligodendroglial element was seen in 20% of cases (20),=20 and in another wherein 4% of tumors consisted in part (up to 30%) = of=20 oligodendrocytes (72).=20 The term "oligodendroglial component" has even been appended to = WHO grade=20 III or anaplastic astrocytoma (8),=20 somehow totally circumventing use of the time-honored = oligoastrocytoma=20 category. (31,=20 72). Thus, it is not surprising that some members of the 2007 = working=20 group considered formal adoption of the term "glioblastoma with=20 oligodendroglial component" to be not only a conceptual error, but = an=20 invitation to diagnostic and therapeutic confusion, particularly = as 15=9620%=20 of such tumors show chromosome 1p and 19q co-deletion, a feature = of=20 oligodendroglial neoplasia (41).=20 Introduction of this cumbersome designation is hard to understand, = as even=20 its proponents consider it synonymous with grade IV=20 oligoastrocytoma.

=20

= Figure 1. WHO=20 grade IV "Glioblastoma with oligodendroglial features" = (A,B) differs from WHO grade III = oligoastrocytoma=20 simply by the presence of necrosis in the latter.=20

[Normal View=20 ]

Interestingly, justification for this terminologic = shift is=20 sought in a recent study showing that high oligoastrocytoma = featuring=20 anaplasia and necrosis, a tumor already referred to by some as = grade IV=20 oligoastrocytoma, to have a less favorable prognosis than either = WHO grade=20 III astrocytoma or oligoastrocytoma, but one more favorable than = WHO grade=20 IV astrocytoma (glioblastoma) (3,=20 41). What better case could be made for endorsing the term = "WHO grade=20 IV oligoastrocytoma?"

Despite strong objection, both during and after = the=20 Heidelberg Meeting, the term "glioblastoma with oligodendroglial=20 component" persists (26,=20 71). Its imprecision will be the nidus of confusion, not only = to=20 pathologists but to surgeons and oncologists alike. The prognostic = difference between oligoastrocytoma of grades III and IV based = upon the=20 absence or presence of necrosis, is well known (3).=20 It is precisely for that reason that oligodendroglial tumor = treatment=20 protocols relying upon these distinctions, particularly those = predicated=20 upon a clear distinction between very high-grade oligoastrocytoma = and=20 glioblastoma, as we know it, cannot accommodate this designation. = From the=20 therapeutic viewpoint, this is the crux of the matter. As a = result,=20 "glioblastoma with oligodendroglial component" may not be = universally=20 adopted. Indeed, what may occur is informal use of the term "grade = IV=20 oligoastrocytoma" in an effort to maintain nosologic continuity = with the=20 grade III lesion. Lastly, employing the term "glioblastoma with=20 oligodendroglial component" may have a negative effect upon = patients and=20 treating physicians alike, inducing despair and therapeutic = nihilism.=20 Indeed, it may discourage vigorous pursuit of ancillary studies = such as=20 FISH for 1p/19q co-deletion, now a common practice in dealing with = oligoastrocytomas. Even experienced clinicians may be negatively = affected=20 by the designation "glioblastoma", no matter how favorably = qualified.

The present departure from a strict definition of=20 glioblastoma as an astrocytic neoplasm and the inherent difficulty = in=20 confidently identifying a minor oligodendroglial component may = play havoc=20 with the evolving definition of the tumor and our emerging = knowledge of=20 so-called primary and secondary types. The latter, originating by=20 progressive anaplasia from astrocytomas of WHO grades II or III, = may well=20 be viewed as truly astrocytic in nature, whereas primary = glioblastoma with=20 their small, undifferentiated-appearing cells may correspond to = tumor=20 originating in or composed in part of neuroepithelial stem cells = capable=20 of glioneuronal differentiation. Such stem cells have been = demonstrated in=20 human brain ("neuronal stem cells") (21,=20 56) and in brain tumors ("brain tumor stem cells") (12,=20 56). This would explain the occurrence of glioblastomas with = true=20 epithelial differentiation (62)=20 as well as examples with PNET components (51),=20 an issue further discussed below.

=20

=20

THE PROGNOSTIC SIGNIFICANCE OF = MICROVASCULAR=20 PATTERNS IN GLIOMAS

Whether subtle or conspicuous, increased = vascularity is a=20 well-known feature of gliomas. It varies, not only in degree, but = in type.=20 As a reflection of the metabolic state of a tumor and its = production of a=20 particular combination of factors that regulate vasculo- and = angiogenesis,=20 it may simply consist of increased prominence of otherwise=20 normal-appearing vessels, or a conspicuous increase in vascular = density.=20 Examples of the former include the accentuated geometric cortical=20 vasculature that characterizes oligodendroglioma (58),=20 and subtle increase in white matter vasculature that accompanies = low- to=20 intermediate-grade astrocytomas of the diffuse or infiltrative = type. In=20 addition to such "physiologic hypervascularity", high-grade = gliomas often=20 feature conspicuous vascular proliferation, either in the form of=20 glomeruloid vessels or as so-called "endothelial proliferation" = (Figure 2).=20 Such neovascularity exhibits MIB-1 labeling indices five times = higher (10%=20 vs. 2%) than that of the above-noted, less conspicuous vasculature = (73).

=20

= Figure 2. Vascular = alterations in=20 gliomas include both complex capillary tangles termed = "glomeruloid=20 vasculature" (A), and larger, often = single=20 lumen, multi-layered vessels termed "endothelial = proliferation"=20 (B=96D). Both vascular patterns = feature=20 proliferation of primarily pericytic or smooth muscle = cells.=20

[Normal View=20 ]

First introduced by Daumas-Duport et al in 1988, the term "endothelial = proliferation"=20 denotes apparent multi-layering of endothelium, typically in=20 single-lumened vessels of small to intermediate dimension (5)=20 (Figure 2).=20 In this sizable, 287 case, systematically studied series of = ordinarily=20 infiltrative astrocytic tumors, this vascular change was largely = limited=20 to glioblastomas (WHO grade IV astrocytoma). Multivariate analysis = found=20 both it and necrosis to be strongly associated with survival, the = P-value being less than 0.0001 for both. When = subsequent=20 immunohistochemical studies, particularly of glomeruloid vessels, = showed=20 that pericytes and smooth muscle cells rather than endothelial = cells=20 contribute most to the complex vascularity of gliomas (14,=20 44, 74) (Figure 2),=20 an alternative, all-encompassing designation was introduced. The = term=20 "microvascular proliferation" was coined to de-emphasize the = contribution=20 of endothelium (74).=20 Unfortunately, its inherent imprecision as an umbrella term = obscured the=20 distinction between the innocuous alteration (glomeruloid vascular = proliferation) and the one of demonstrated prognostic importance=20 ("endothelial proliferation"). The 2007 WHO classification does = nothing to=20 clarity the issue. The 2007 WHO chapter, Glioblastoma, mentions = both in=20 the same breath (26).=20 The issue of what comprises "microvascular proliferation" is = similarly=20 obscured in the chapters Anaplastic Astrocytoma (28)=20 and Anaplastic Oligoastrocytoma (71).

No doubt, the term "microvascular proliferation" = will=20 persist. It should not, however, be employed as an unqualified = umbrella=20 term for hypervascularity of all types. If used to denote either=20 glomeruloid vasculature or what Daumas-Duport et al once termed "endothelial = proliferation"(5),=20 admittedly a misnomer, it should be stated as such.

Lastly, the significance of vascular thrombosis in = gliomas=20 varies, as do the types of necrosis observed. On occasion, = degenerative=20 vascular changes, as seen in pilocytic astrocytoma (65)=20 and ependymoma (37),=20 are accompanied by infarction, that is, broad zones of necrosis=20 unaccompanied by peri-necrotic palisading of tumor cells. In that = setting,=20 infarct-like necrosis, unlike palisading necrosis, is of no = prognostic=20 significance. In contrast, any form of necrosis accompanying = anaplastic=20 features in diffuse or infiltrative astrocytic tumors indicate a = very=20 negative prognosis (5).=20 One recent study has shown that vascular thrombosis in diffuse = astrocytic=20 tumors is largely limited to high-grade tumors and, for practical=20 purposes, equates with WHO grade IV or "glioblastoma"(67).=20 Therefore, the prognostic relevance of both necrosis and vascular=20 thrombosis depends entirely upon a tumor's histologic type. They = do not=20 represent universally ominous findings.

=20

=20

GLIONEURONAL TUMORS=97A RUNAWAY = TUMOR=20 CATEGORY?

Before embarking upon a discussion of specific = glioneuronal=20 tumors, a few words regarding the category and the diagnostic = criteria of=20 glioneuronal differentiation are in order. The term "divergent=20 differentiation" denotes a substantial shift in differentiation of = a tumor=20 toward one or more other distinct cell types. The process, key to = normal=20 development and elegantly expressed in the central nervous system = (CNS),=20 has its most obvious neoplastic manifestation in teratomas.

The increasing recognition of divergent, = particularly=20 neuronal differentiation in common gliomas has its basis in the = routine=20 application of immunohistochemistry. Although the method enjoys = great=20 popularity, when push comes to shove, electron microscopy can play = as much=20 if not more of a role in exploring differentiation by providing = precise=20 morphologic data. This, of course, begs the question, "What is the = 'gold=20 standard' in the identification of neuronal differentiation?" In = many=20 instances, routine histochemistry is inadequate, disclosing only = obvious,=20 mature neurons. Immunohistochemistry is also plagued by vagaries. = Glaring=20 examples include neuron-specific enolase and S-100 protein, both = of which=20 are known to be unreliable markers of neuronal and glial = differentiation,=20 respectively. It is precisely for this reason that batteries of = markers=20 are employed to maximize diagnostic specificity. In contrast,=20 ultrastructural parameters are relatively free of the = nonspecificities so=20 much a part of routine immunohistochemistry. Despite waning = expertise in=20 the general and neuropathology communities, electron microscopy = and its=20 variant technologies, such as immunoelectron microscopy, remain = powerful=20 tools. Although perhaps not applicable in routine practice, its = role in=20 determining and confirming tumor differentiation and thus shaping=20 nosologic concepts remains essential.

Discomforting as it may be to see time-honored=20 classification schemes threatened, the notion that parenchymal = tumors of=20 the CNS are either glial or neuronal in nature has long been = abandoned.=20 The finding of divergent glioneuronal differentiation in some CNS = tumors=20 meets with little surprise. For example, in embryonal tumors of = the CNS,=20 such as medulloepithelioma, medulloblastoma and primitive = neuroectodermal=20 tumor, the occurrence of divergent glial and/or neuronal = differentiation=20 is almost "physiologic". Such tumors may also feature mesenchymal=20 components, elements even more deserving of the designation = "divergent"(36).=20 In tumors featuring mature cellular elements, the two lines of=20 differentiation may be histologically obvious (ganglioglioma and = the more=20 recently described extraventricular neurocytoma, papillary = glioneuronal=20 tumor, and rosette-forming glioneuronal tumor) (1,=20 2, 29, 30). Divergent glioneuronal differentiation in tumors=20 associated with phakomatoses, diseases known to be associated with = such=20 dysgenetic lesions as subependymal giant cell astrocytoma of the = tuberous=20 sclerosis complex, comes as little surprise (19).=20 The same is true of "quasi-hamartomatous" lesions such as = ganglioglioma (55)=20 and dysembryoplastic neuroepithelial tumors (6),=20 both of which are often associated with cortical dysplasia.

Unlike the finding of mature neurons in = conventional=20 ganglion cell tumors such as ganglioglioma, the cytologic features = of=20 neuronal cells in newcomers to the glioneuronal category are quite = varied.=20 For example, less obviously neuronal cells termed "ganglioid = cells" are a=20 key feature of "infantile desmoplastic ganglioglioma", a rare = pediatric=20 variant of ganglion cell tumor (69).=20 Whereas the spectrum of neuronal cells in papillary glioneuronal = tumor is=20 remarkably broad, ranging from neurocytes through ganglioid to = mature=20 ganglion cells (29),=20 in rosette-forming glioneuronal tumor the diagnostic Homer = Wright-like=20 rosettes consist entirely of neurocytes (29).=20 Lastly, the oligodendrocyte-like cells of dysembryoplastic = neuroepithelial=20 tumor only reluctantly express neuronal features (18).=20

Also of note in the context of this section are=20 phenotypically astrocytic tumors in which neuronal differentiation = tends=20 to be solely an immunophenotypic and/or ultrastructural feature. = For=20 example, recognizable ganglion cells are infrequent in = subependymal giant=20 cell astrocytoma (19,=20 22, 32). The same is true in conventional pleomorphic=20 xanthoastrocytoma (13,=20 17, 53) wherein ganglion cells are rarely a significant = component (10,=20 17, 50, 75).

More surprising is the immunohistochemical finding = of=20 divergent neuronal differentiation in tumors long considered = patently=20 glial in nature. Relatively recent reports document its occurrence = in the=20 full spectrum of gliomas, including anaplastic astrocytoma (23,=20 54, 68), oligodendroglioma (34,=20 52) and ependymoma (61).=20 Such differentiation often takes the form of neurocyte islands (Figure 3).=20 The emergence of mesenchymal elements, fibrous, chondroid, osseous = and=20 even myogenic, in gliosarcomas (27),=20 occurs more frequently in high-grade astrocytomas (63)=20 than in oligodendroglioma (60)=20 or ependymoma (59,=20 61). Differentiation toward true epithelium of squamous, = glandular or=20 neuroendocrine type is very rare and occurs most often in WHO = grade IV=20 astrocytoma (glioblastoma) (9,=20 43).

=20

= Figure 3. Neuronal = differentiation=20 on a WHO grade II astrocytoma is here seen as neurocyte = islands=20 (A). The latter are synaptophysin = positive=20 (B).

[Normal=20 View ]

Of particular interest in this vein is a recent = publication=20 reporting diffuse astrocytomas, especially high-grade, giant=20 cell-containing examples in which phenotypically astrocytic cells=20 immunolabel for one or more neuronal markers (70)=20 (Figure 4).=20 Dubbed "malignant glioneuronal tumor", the suggestion was made = that it=20 differs in behavior from its conventional counterparts, featuring = a=20 greater tendency to craniospinal and systemic metastasis but, = nonetheless,=20 a more favorable prognosis. The study as well as the concept has = its=20 problems. The spectrum of glioneuronal neoplasms, although = considerably=20 expanded in recent years, consists almost entirely of benign = lesions,=20 their designation as specific entities being predicated more upon=20 distinctive morphology than upon differences in biologic behavior. = Whereas=20 the addition of glioneuronal tumor with neuropil islands (68)=20 to the glioneuronal tumor category, a move initially given = consideration=20 at the 2007 Heidelberg meeting, would have represented a = significant=20 departure, inclusion of the "malignant glioneuronal tumors" = described by=20 Varlet et al(70)=20 would change the landscape of the category entirely. One further = criticism=20 with respect to these tumors is that the study relied upon = neurofilament=20 protein immunoreactivity as the baseline diagnostic criterion (70).=20 Accordingly, otherwise classic glioblastomas with neurofilament = positivity=20 would be reclassified as "malignant glioneuronal tumor." Although = confocal=20 microscopy did show dual GFAP and neurofilament protein double = labeling in=20 a small number of cases, no ultrastructural correlation was = provided.=20 Relying solely upon immunochemistry, particularly focusing upon a = single=20 stain that yields highly variable results from one laboratory to = another,=20 is an insufficient basis upon which to establish a nosologic = entity. Thus,=20 for good reason, "malignant glioneuronal tumor" is not, at = present, an=20 entity in the WHO Classification of Tumours of the Nervous System. = Only=20 systematic translational studies predicated upon immunobatteries = and=20 ultrastructural correlation on the one hand and = therapeutic/outcome data=20 on the other could establish a clinically meaningful nosologic = place for=20 such tumors.

=20

= Figure 4. So-called = "malignant=20 glioneuronal tumor" in which pleomorphic cells in an = otherwise=20 typical glioblastoma (A) show GFAP = (B), neurofilament protein (C),=20 and synaptophysin immunoreactivity (D).=20

[Normal View=20 ]

It could be argued that the category of = glioneuronal tumors=20 is not the rightful place for malignant, phenotypically glial = tumors with=20 neuronal differentiation, be it gangliocytic or neurocytic. This = would=20 preserve the inherently favorable prognosis presently associated = this=20 category.

=20

=20

PINEAL PARENCHYMAL TUMOR OF = INTERMEDIATE=20 DIFFERENTIATION=97THE NEED FOR PRECISE CRITERIA

The term "pineal parenchymal tumor of intermediate = differentiation" was adopted by the 2000 WHO (46)=20 pursuant to a study (66),=20 suggesting that such lesions are associated with a prognosis = intermediate=20 between that of pineocytoma and pineoblastoma. Diffuse in = histologic=20 pattern (Figure 5),=20 featuring occasional Homer Wright type rather than pineocytomatous = rosettes and lacking the primitive, small cell appearance and = necrosis of=20 pineoblastoma, this lesion with its variable, but often low-level=20 proliferative activity, is associated with a lesser likelihood of=20 craniospinal metastasis than the latter. Nonetheless, its = morphologic=20 spectrum is considerable, varying somewhat in cellularity, nuclear = cytoplasmic ratio, cytologic atypia and mitotic activity (Figure 5).=20 Thus, the designation "intermediate differentiation" begged for=20 refinement. As experience had increased, it became obvious that = the term=20 included both prognostically favorable and unfavorable lesions. = The=20 question=97"Where to draw the line?" It was clear that a large,=20 multi-institutional effort was required in order to establish = criteria for=20 low and higher grade variants of differing prognoses. The large=20 cooperative study of Fevre-Montague et al(11)=20 confirmed their existence, but it was felt by the 2007 WHO working = group=20 that the criteria proffered fell short of arriving at a = statistically=20 meaningful morphologic breakpoint. This was not surprising, as=20 proliferative activity may vary, even in pineocytomas. = Furthermore, degree=20 of cellular differentiation, a criterion focused upon by prior = histologic=20 (66)=20 and ultrastructural (42)=20 studies, also reckons into classification and prognostication. The = approach at stratification employed by Jouvet et al relied mainly upon two criteria, = proliferative=20 activity (mitoses) and immunoreactivity for neurofilament protein, = the=20 latter being sparse in higher grade examples (Figure 5).=20 The working group decided that even larger studies based upon = additional=20 parameters and more complete, extended follow-up were needed. = Nonetheless,=20 the strength of Jouvet's study is that it confirmed the existence = of an=20 intermediate differentiation category comprising a sufficiently = broad=20 pathobiologic spectrum as to require its division into at least = two=20 prognostic subcategories.

=20

= Figure 5. Pineal=20 parenchymal tumor of intermediate differentiation variation=20 illustrated in low- (A) and = high-grade (B) form. Note differences in nuclear atypia = and=20 proliferative activity. Note necrosis in the high-grade = variant=20 (B).

[Normal=20 View ]

=20

=20

HEMANGIOPERICYTOMA AND SOLITARY = FIBROUS=20 TUMOR=97THE NEUROPATHOLOGIC APPROACH

Once termed "angioblastic meningioma" in the = mistaken belief=20 it was meningothelial in nature, what is now hemangiopericytoma is = an=20 easily recognized, prognostically important mesenchymal neoplasm. = The=20 newer designation was adopted when ultrastructural (64),=20 immunohistochemical (49,=20 57) and genetic studies (16)=20 showed no link to conventional meningioma, benign or malignant.=20 Unfortunately, clearcut pericytic features were also lacking. = Unlike the=20 trend in soft tissue pathology, to abandon hemangiopericytoma as a = diagnostic entity and to reassign it piecemeal to other tumor = categories=20 based on morphologic, immunohistochemical and genetic grounds, the = neuropathology community has opted to retain the designation. This = is=20 justified. Unlike systemic hemangiopericytoma, most of which are = benign,=20 those affecting the CNS are considered malignant by definition, = existing=20 in low- and high-grade form (38)=20 with predictably aggressive clinical behavior, including high = rates of=20 recurrence and late metastases.

In the majority of instances, the distinction of=20 hemangiopericytoma from solitary fibrous tumor, a lesion described = as=20 occurring in the CNS (4)=20 and rather recently added to the WHO Classification of Tumours of = the=20 Nervous System (48),=20 poses no problem (Figure 6).=20 As a rule, the latter are benign, their behavior resembling that = of WHO=20 grade I meningioma. Histologic malignancy in solitary fibrous = tumors, an=20 infrequent event, is more often focal than widespread (39,=20 47). Nonetheless, the resemblance of malignant solitary = fibrous tumor=20 to hemangiopericytoma may be striking (Figure 6).=20 Their uniform, strong immunoreactivity for C34 and total lack of = EMA=20 staining, as well as ultrastructural features which more closely = resemble=20 those of fibroblasts, aid in the distinction from both = hemangiopericytoma=20 and meningioma. Further justifying retention of hemangiopericytoma = in the=20 WHO classification is the sheer volume of old and modern = therapeutic=20 literature regarding "angioblastic meningioma" and = hemangiopericytoma.=20 Experience with solitary fibrous tumor of the CNS is also = accumulating.=20 Arbitrarily abandoning the term hemangiopericytoma or combining = the=20 lesions would engender more than nosologic confusion. All things=20 considered, there are both diagnostic and therapeutic reasons for=20 retaining the distinction. Both the 2000 and 2007 WHO committees = opted to=20 do so.

=20

= Figure 6. Malignant=20 hemangiopericytoma (A) as well as = solitary=20 fibrous tumor (B) may show = considerable=20 morphologic overlap. Note transition from typical cytology = of=20 solitary fibrous tumor to more cellular, = hemangiopericytoma-like=20 tissue (B).

[Normal=20 View ]

=20

=20

CONCLUSION

The 2007 WHO Classification of Tumours of the CNS = is,=20 rightfully, the international standard of tumor classification. It = masterfully summarizes our knowledge of the subject. Necessarily, = as what=20 has become an illustrated, "state of the art" book, it deals = little with=20 divergence of opinion on a number of important issues. Hopefully = this and=20 an upcoming companion commentary on what remains knotty issues = will both=20 prompt consideration and focus efforts upon their resolution.

A philosophical comment is in order. The human = need to=20 classify or impose conceptual order exemplified by Linnaeus = (1707=961778)=20 continues in all spheres of knowledge. In pathology, the process = has very=20 human implications. In the spirit of the WHO, it must maintain=20 practicality and, above all, worldwide utility, regardless of = available=20 methodology. This underscores the need to maintain a balance = between those=20 basic necessities on the one hand and concept as well as = technologic=20 advances on the other.

=20

=20

=20

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