【作者】 王剑新；

【导师】 漆松涛；

【作者基本信息】 南方医科大学 ， 神经外科学， 2011， 博士

【摘要】 第一部分：垂体腺瘤对鞍底硬膜影响的病理学研究一、研究背景垂体腺瘤按照生物学行为不同,分为垂体腺瘤和侵袭性垂体腺瘤(invasive pituitary adenoma,IPA)。IPA的概念最早在1940年由Jefferson提出以来至今已有70余年之久,期间其概念、诊断标准及发生率争议颇大,各家报道不一。其最早定义为“生长突破其包膜并侵犯硬脑膜、视神经、骨质等毗邻结构的垂体腺瘤”,Martins等1965年将其定义为突破包膜生长或向邻近结构侵袭的垂体瘤,Scheithauer则将侵袭性垂体腺瘤归于介于垂体瘤和垂体癌之间的过度类型,三者在组织学上不能截然区分,只是在生物学行为上不同。还有人认为：侵袭性垂体腺瘤与非侵袭性垂体腺瘤之间并无严格界限,差异仅在于侵袭性强弱程度的不同。如何有效地诊断侵袭性垂体腺瘤,尚缺乏统一的客观标准,无论是病理学标准、影像学标准还是术中所见标准,争论均颇大。正是由于IPA概念及诊断标准对的多样性,导致了IPA发生率各家报道不一,迄今为止,文献报道侵袭性垂体腺瘤的发生率为6%-85%。IPA概念和诊断标准的繁杂和混乱,影响了手术医生的诊断理念和治疗策略,导致IPA的手术切除率和术后临床症状改善率并不尽人意。研究清楚IPA侵袭征象的实质具有重要的临床意义,为此我们设计了本研究。有关IPA的研究大都集中于临床研究中手术方式改进和临床疗效的总结以及基础研究中的分子生物学方面尤其是基因学和侵袭指标的研究方面,其形态学方面的研究少之又少。不少研究注意到了肿瘤对硬膜的侵犯,但只是着眼于术中术者对硬膜的粗糙感的主观判断及肿瘤对硬膜的侵犯的大体观察,未提到肿瘤与垂体囊之间的关系,且其病理取材方法多自于开颅术中且取材仅限于肿瘤本身。本研究采用适用较广的经鼻碟入路获取垂体腺瘤+膜结构标本,观察IPA患者肿瘤与垂体囊、硬膜等瘤周结构之间的关系,献尚未见报道。具有重要的临床意义。二、研究目的本研究采用从鼻碟入路取“瘤+膜”(一侧是鞍底硬膜,一侧是肿瘤组织)标本,观察肿瘤细胞与垂体囊及硬膜之间的关系,探讨垂体腺瘤的侵袭征象。为进一步研究垂体腺瘤的生长方式提供病理形态学方面的依据。三、研究方法所选取的30例标本均来自南方医院神经外科住院手术治疗的垂体腺瘤患者。其中男性21例,女性9例；年龄20～76岁,平均48.3岁；头痛20例,视力视野障碍21例,月经紊乱或闭经、泌乳8例,尿崩症状5例,肢端肥大4例,向心性肥胖3例,性欲减退3例,嗜睡10例,体检偶然发现肿瘤者1例。术后经病理证实,本组肿瘤病理类型有：PRL型9例,GH型4例,ACTH 2例,混合激素表达型10例,无功能型5例,其中零激素表达型3例。所有患者均经MRI头颅扫描,CT检查包括鼻腔及鼻窦的轴状位和冠状位扫描,主要了解鼻腔内结构、蝶窦气化程度、分隔及对称情况；MRI扫描主要观察了解肿瘤的形态、大小及扩张方向情况。根据Hardy-Wilson分类法和/或Knosp分类法对腺瘤进行侵袭性判断,Hardy-Wilson标准Ⅲ级-Ⅳ级和(或)C～E期的垂体腺瘤以及Knosp分类3-4级以上的垂体腺瘤考虑为侵袭性垂体腺瘤。所选30例患者垂体腺瘤中,符合Hardy-Wilson标准Ⅲ级3例,C期者14例,D期者5例,E期者9例；符合Knosp分类3级者7例,4级者5例。均符合IPA标准。本组所有患者手术方式或者首次手术方式均采用经蝶入路,在神经内镜下操作。显露鞍底硬膜后,细针穿刺确认为非出血性疾病后,用尖刀切取类四方体形的一侧是硬膜另一侧是肿瘤的标本,取出后即置入10%福尔马林液固定备进一步处理。将固定后的标本,常规脱水、石蜡包埋、切片及染色过程。切片时注意膜与瘤的方向性,保证每张切片均有瘤组织和硬膜成分。切片采用Massion’s三重染色法染色后封固。在Olympus-DP70倒置显微镜下观察拍片。详细观察肿瘤组织与垂体囊、硬膜之间的关系并记录描述。垂体囊厚度测量,每例选取5个点,取平均值,以本课题组既往测得的垂体囊正常厚度值作比较。统计方法为两样本t-test,在spss13.0软件上进行。三、研究结果本组所有病例均Ⅰ期手术做到了大部切除,临床症状改善或保持稳定者28例,1例(74岁)因术后出现慢性硬膜下血肿行血肿钻孔引流术,1例术后失访。术后影像学复查受肿瘤压迫的瘤周结构不同程度复位的有15例。本组患者无死亡病例；没有病人发生术后脑脊液漏,脑膜炎或视力恶化。30例中28例取材标本符合实验要求(即一侧是硬膜另一侧是肿瘤的标本),且另送检肿瘤病理检查报告回示均为垂体腺瘤。标本处理染色满意。通过倒置显微镜下仔细阅片观察发现,25例均能见到垂体囊,但厚度不一,平均厚度均小于正常垂体囊厚度。2例垂体囊内发现疑似肿瘤细胞,但垂体囊完整,未见疑似瘤细胞突破垂体囊；所有病例硬膜完整,未见肿瘤细胞浸润；垂体囊与硬膜之间的间隙(囊膜间隙)可辩者有19例,但此间隙显微镜下观察大小不一,其余囊膜间隙有部分难辩。垂体囊厚度(0.1599±0.0700mm)小于正常(t=21.998,P=0.000)。四、研究结论本研究采用经鼻碟入路内镜下操作获取“瘤+膜”标本,从病理学角度探讨了侵袭性垂体腺瘤与鞍底硬膜之间的关系,结合相关文献得出以下结论：1.单纯从鞍底获取“瘤+膜”标本进行IPA侵袭征象的研究是合理和可行的,能够反映IPA对其他方向肿瘤与瘤周结构的实际关系,即侵袭实质；2.IPA瘤周膜性结构仍然存在,这表明传统意义的“侵袭”概念并不准确。垂体囊内可见疑似瘤细胞可能是目前造成侵袭性误判的主要原因；3.垂体腺瘤的侵袭性似乎与肿瘤病理类型、年龄及性别等因素无关；4.IPA病理学诊断和影像学诊断有较大的出入；5.当前IPA概念及界定标准值得质疑、完善和商榷；垂体瘤极有可能是膨胀性生长,而非侵袭破坏性生长。6.有关垂体腺瘤生长方式的影响因素值得进一步深入研究。第二部分：蝶鞍侧壁窗和颈动脉沟形态学特点及其与垂体腺瘤生长方式的关系一、研究背景蝶鞍位于颅底中心,一般认为其境界范围：前界为床突外侧缘与交叉沟的前缘,后界为后床突与鞍背,两侧界为颈动脉沟。由于蝶鞍的结构复杂而独特的解剖特征,曾经是神经外科手术的盲区和禁区。随着该区显微手术的普遍开展,该区域的形态学研究也深受重视。垂体腺瘤是鞍区最常见肿瘤,根据生物学行为的不同分为侵袭性垂体腺瘤和非侵袭性垂体腺瘤。有关侵袭性垂体腺瘤的研究大都集中于临床和基础两大领域：临床研究中主要侧重于手术方式改进和临床疗效的总结；基础研究中主要侧重于分子生物学方面尤其是肿瘤基因学和侵袭指标的研究方面。有关蝶鞍显微解剖学方面的文献及专著已经很多,但经过系统复习有关文献,对于蝶鞍侧壁窗(lateral bone window, LBW)和颈动脉沟(carotid sulcus,CAS)形态学特点及其与垂体腺瘤生长方式的关系进行探讨的研究尚未见报道。本研究一方面收集国人成人干性颅底骨标本,选取蝶鞍骨性结构相对完整的标本进行实体测量,借助相关软件帮助,成功测得蝶鞍侧壁窗的面积大小数据,为蝶鞍解剖学提供了重要数据；还对蝶鞍侧壁窗的形态学特点进行了描述和分类,并结合文献和临床,探讨蝶鞍侧壁窗与垂体腺瘤生长方式尤其是垂体腺瘤向鞍旁(海绵窦)扩展生长之间的关系。另一方面,颈动脉沟是蝶鞍侧壁重要的骨性结构,尽管有关颈动脉沟的解剖学研究已有几项,但尚未见对其从临床应用方面进行分类。本研究结合蝶鞍薄层CT骨性扫描影像学资料,从对垂体腺瘤扩展“嗜好”特别是向鞍旁(海绵窦)扩展的影响的角度对颈动脉沟其作出分型并探讨阐述其与垂体腺瘤生长方式特别是垂体腺瘤向鞍旁(海绵窦)扩展生长之间的关系。本研究具有重要的解剖学意义和临床意义。二、研究目的本研究对蝶鞍侧壁窗(lateral bone window, LBW)和颈动脉沟(carotid sulcus, CAS)形态学特点进行详细观察和描述,为蝶鞍区形态学研究提供了重要数据,为国人体质调查提供解剖学资料和参考；同时从解剖学角度探讨了LBW及CAS与垂体腺瘤生长方式特别是向鞍旁(海绵窦)扩展生长的关系,以期为垂体腺瘤的生长方式的解剖形态学影响因素的相关研究提供依据。三、研究方法1.测量标本收集国内几家医学院校解剖教研室存放的经过常规处理的成人干性颅骨标本,沿颅骨眉弓至枕外隆凸上1cm处,用锯作环形锯开颅盖骨,显露颅底内面观。选取蝶鞍区骨性结构相对完整的颅底骨标本共530例。另收集50例(含100侧)鞍区薄层矢状位扫描冠状位重建的CT图像(主要用于CAS的观察分类)进行观察测量。对于典型的标本和图片进行照相、存档留作资料备用。2.测量内容主要观察测量内容如下：①测定记录LBW的面积大小、双LBW面积之间相关性、双LBW与蝶鞍深度相关性分析；②观察测量前后床突间的距离(distance between anterior clinoid process and posterior process,APD)和LBW最大宽度(maximum traverse diameter,MTD)相对比值及中床突(middle clinoid process,MCP)高度与LBW最大高度(maximum longitudinal diameter,MLD)相对比值；③观察测量蝶鞍桥(sella turica bridge, STB)和MCP的发生情况及特点；④结合相关数据和形态对LBW进行初步分级和分型；⑤测量LBW底边骨质最高点至鞍底的距离即底边骨质的高度(height of latera bone,LBH);⑥测量颈内动脉沟(carotid sulcus,CAS)长度(间接反映海绵窦段颈内动脉的长度)；⑦量化分级颈内动脉沟(carotid sulcus,CAS)弧形程度(间接反映CAS对颈内动脉的包裹程度)。3.测量方法LBW的测量：主要借助于橡皮泥、游标卡尺、相机及ImageJ软件帮助下操作完成；CAS形态学分类：是沿CAS弧形程度画圆,将所画圆12等份,即每份弧度为30。,然后即可判断出CAS弧形程度,可间接反映CAS对CA的包裹程度(详细操作过程见结果当中描述)。4.统计处理所有数据处理在SPSS13.0统计软件上进行。计量资料之间的均数比较采用t-test;资料之间的相关性采用Pearson相关分析。显著性水准取α=0.05,P<0.05时认为差异有统计学意义。三、研究结果(一)LBW解剖形态学特点1.LBW概念、位置与构成蝶鞍侧壁(骨)窗(lateral bone window,LBW)是位于骨性蝶鞍侧壁的窗型结构,左右各一。其上界为前后床突连线水平,下界为颈动脉沟的内侧缘,前界为视神经柱的后缘,后界为鞍背的前外侧缘。有时窗内有中床突(middle clinoid process, MCP)和蝶鞍桥(sella turica bridge, STB。即床突之间存在骨性联结)出现。当STB出现时,则窗的上界即为STB的下缘；当MCP与前床突形成颈动脉床突孔(Carotico-clinoid foramen henle, CCFH)时,则窗的前界即为CCFH的前缘。2.LBW面积及分级左LBW面积75.99±25.81mm2；右LBW面积76.00±25.53mm2; STD (depth of sella turica.蝶棱与鞍背顶端连线中点至鞍底距离)为11.00±1.82mm;双侧LBW面积相比无统计学差异(配对t-test,t=0.03.p=0.998)；双侧LBW面积有良好的正相关性(pearson相关分析,r=0.638,P=0.000)；双LBW与STD均有弱正相关性(pearson相关分析,左r=0.214,P=0.000；右r=0.180,P=0.000)。根据测得的结果,可将LBW面积大小作如下分级：A级：LBW面积小于60mm2(本组20%的例数符合)；B级：LBW面积在60mm2至90mm2之间(本组60%的例数符合)；C级：LBW面积大于90mm2(本组20%的例数符合)。3 LBW形态观察本研究对LBW形态的观察,主要集中于影响LBW形态的三大因素：APD(前后床突之间的距离,distance between anterior clinoid process and posterior process)的大小、MCP (middle clinoid process,中床突)的形成情况及STB (sella turica bridge,蝶鞍桥)的形成情况。根据综合观察结果,笔者将LBW形态作如下分型：Ⅰ型(开放型)：LBW上口前后距离(即前后床突距离APD)大于LBW最大宽度MTD的一半以上。Ⅱ型(半开放型)：LBW上口前后距离(即前后床突距离APD)大于LBW最大宽度MTD的1/4而小于MTD的一半。Ⅲ型(完整型)：包括相对完整型(Ⅲa型)和绝对完整型(Ⅲb型)。LBW上口前后距离(即前后床突距离APD)小于LBW最大宽度MTD的1/4,可认为是完整型LBW,当APD=Omm,即存在前后型和前中后型蝶鞍桥STB时,即为绝对完整型。Ⅳ型(闩型)：LBW存在自下而上的中床突MCP,想门闩一样。根据MCP的形态和大小,结合keyes对CCFH的分类,该型又可分为几个亚型：Ⅳa型---(相当于keyes完全型CCFH)即前后床突完全骨性连接形成；Ⅳb型---(相当于keyes接触型CCFH)即前床突和中床突间存在骨缝；We型---(相当于keyes不完全型CCFH)即前后床突间并无接触,存在间隔；Ⅳd型---即完整型LBW+完全型CCFH。4.LBW底边骨质高度(height of latera bone, LBH)的观察测量：LBH位于LBW底部,高度不一。LBH之于LBW,就像门槛之于门一样。测量值：左LBH=1.23±0.79mm,右LBH=1.22±0.82mm;双侧LBH相比无统计学意义(配对t-test,t=1.388.p=0.166)。(二)CAS解剖形态学特点1.CAS位置、形状与毗邻颈动脉沟(carotid sulcus, CAS)位于蝶鞍侧壁,左右各一；沟内走行颈内动脉海绵窦段(C4段),沟的形状多数为前后直行,少部分略呈前后“S”状走行；沟的前缘为颈内动脉海绵窦段与颈内动脉膝段移行部,沟的后缘为破裂孔前缘,沟的内侧缘即为垂体窝外侧缘,LBW的下缘,沟外侧缘与颅中窝毗邻；沟的深度目测以沟两端最深,沟中间部最浅,有的中间沟深度几近为零,沟的形状不明显。2.CAS长度(length of CAS, CASL)观察测量：左CASL=19.83±1.87mm,右CASL=20.45±1.84mm;双侧CASL相比有统计学意义(配对t-test,t=-8.032.p=0.000),右侧大于左侧。3.CAS分型：具体测量是在选取的部分正常成人蝶鞍薄层冠状位扫描的CT图像上完成。在CT正中冠状位,根据颈动脉沟横截面弧形程度画圆(为画图的方便,将图片做适当放大,到能够基本看清CAS,有利于测量为标准),将圆等分为12等分,颈动脉沟内侧骨质最高点A、沟外侧骨质最高点B分别与圆心点O连线,观察(?)AOB度数大小,其不仅能反映CAS横截面的深度,也能反映CAS的宽度。依据测量数据将颈动脉沟分型如下：Ⅰ型：颈动脉沟横截面弧形程度(弧度)小于30。(42侧,42%)；Ⅱ型：颈动脉沟横截面弧形程度(弧度)在30°与60°之间(33侧,33%)；Ⅲ型：颈动脉沟横截面弧形程度(弧度)在60°与90°之间(19侧,19%)；Ⅳ型：颈动脉沟横截面弧形程度(弧度)大于90°(6侧,6%)。四、研究结论本研究对国人正常干性颅底骨标本及正常头颅CT薄层扫描图片分别对LBW和CAS进行解剖学形态特点的观察,并探讨分析其对垂体腺瘤生长方式特别是垂体腺瘤向鞍旁(海绵窦)扩展的关系。结合文献回顾结论如下：1.为蝶鞍区形态学研究提供了重要数据,为国人体质调查提供了解剖学参考资料；2.LBW和CAS等蝶鞍解剖形态学因素对垂体腺瘤的生长方式特别是向鞍旁(海绵窦)扩展生长存在着不同程度的影响；其中LBW中,LBW作为垂体腺瘤通往鞍旁(海绵窦)的“咽喉”,其面积大小与形态,应和肿瘤通过难易程度关系密切,面积大者比面积小者更“畅通”；分型中Ⅰ、Ⅱ、Ⅲa、Ⅲb、Ⅳa、Ⅳb、Ⅳc、Ⅳd型对垂体瘤向鞍旁(海绵窦)扩展的阻力依次增大；CAS中,A型、B型、C型、D型对垂体腺瘤包绕颈内动脉的阻力依次增大；APD相对大小的“天窗”作用；STB的“栏杆”作用、MCP的“闩”作用、LBH的“槛”效应及CCFH对ICA的“箍”作用尤其值得在定义海绵窦侵袭性垂体腺瘤时务需考虑的因素,因为本研究表明它们的发生率不容忽视；3.常用的IPA界定标准,特别是海绵窦侵袭性垂体腺瘤的诊断标准均未将LBW和CAS等蝶鞍解剖学影响因素考虑在内；初步提示出这些诊断标准的不严谨性；4.结合文献,蝶鞍解剖形态学因素特点似乎可以解释垂体腺瘤的生长方式；5.IPA诊断标准之间存在争议,各家发生率报道不一,企待统一和完善；6.有关垂体腺瘤生长方式的影响因素值得进一步深入研究。更多还原

【Abstract】 Part I:Pathologic study on the effect of pituitary adenoma on sella floor’s duraBackgroundAccording to biological behaviour, pituitary adenoma is classfied into pituitary adenoma and invasive pituitary adenoma (IPA). Since invasive pituitary adenoma (IPA) was proposed by Jefferson in 1940, there have been controversies in its concept, diagnostic criteria and incidence rate, with different reports from medical institutions. At first it was defined as "the pituitary adenoma grows to break its envelope and to invade the adjacent structures such as the dura, the optic nerve, bone and so on." Then it was defined as the pituitary tumors that grew to break its envelope or invade the adjacent structures by Martins et al. in 1965.While the invasive pituitary adenoma was classified as the interim type between pituitary tumor and pituitary cancer by Scheithauer, and it was also thought that the pituitary adenoma, pituitary tumor and pituitary cancer could not be completely distinguished in histology, the differences of the three lie only in the biological behaviors. Others thought that there were no strict boundaries between the invasive pituitary adenoma and non-invasive pituitary adenomas, the differences were dependent on the strength of invasion. The uniform objective criteria to effectively diagnose the invasive pituitary adenoma were still lacking, although there were many pathologic criteria, imaging criteria and operative standards, they still have considerable controversies. Just because of the diversity of the IPA concept and diagnostic criteria, the reports on IPA were very different, so far, the incidence rate of IPA was reported as 6%-85% The complex and confusing of the IPA concept and diagnostic criteria have affected the treatments and strategies of surgeons, leading to the unsatisfactory resection rate of IPA and the unsatisfactory improvement of post-operation clinical symptoms. To clearly confirm the properties of IPA invasion signs would have very important clinical significances, so the present study was designed.The researches of IPA were focused on the improvement to the ways of clinical surgery, and the summary of clinical effects, as well as the molecular biology of the basic researches, especially the researches on genetics and invasion indicators, the studies on pathomorphology were fewer. Many studies have noted the invasion of tumor to the dura, but only based on the subjective judgments of the rough sense of the dura felt by the surgeon intraoperatively and on the brief observation on the invasion of tumors to the dura.Not only have the relationship between tumor and the pituitary capsule not been mentioned, but also most of the pathology materials were taken from the craniotomy and only limited to the tumor tissue itself. In this present study, "adenoma+membrane" specimen was got by the transsphenoidal approach used commonly and the relations between adenoma, pituitary cupsule and dura were obsevered, which has not been reported, and is of great clinial significance.ObjectiveIn this study, the "tumor +membrane" (the dura mater of sellar floor on one side, the tumor tissues on another side) specimen was obtained by the transsphenoidal approach, the relationship was observed between tumor cells, the pituitary capsule and dura, and the invasion signs of pituitary adenoma was explored. And this study can provide pathologic basis for further study on the pattern of growth of pituitary adenoma.Materials and MethodsThe 30 pituitary adenoma specimens were from the patients who accepted the inpatient treatment in the neurosurgical department of nanfang hospital of Southern Medical University:21 males and 9 females; age from 20 to 76 years old, average age was 48.3 years, the average disease duration was 2.9 years; 20 cases had headache,21 cases had visual disorder,8 cases had menstrual disorders or amenorrhea and lactation,5 cases had diabetes insipidus,4 cases had acromegaly,3 cases had central obesity,3 cases had loss of libido,10 cases had lethargy,1 case had tumors who was accidentally discovered in the physical examination; The pathological types:9 cases of PRL type,4 cases of GH type,2 cases of ACTH,10 cases of the mixed hormone expression type,5 cases of non-functional type, of which 3 cases were the zero hormone expression type.All patients available should be conducted the MRI head scans, CT examination, including the scans to the nasal cavity and the axial and coronal positions of paranasal sinuses, to understand the structure of the nasal cavity, the extent of sphenoid gasification and the situation of separation and its symmetry; MRI scan was used to observe the shape, size and the expansion direction of tumors. The invasiveness of adenoma should be judged according to Hardy-Wilson classification and/or Knosp classification, the pituitary adenomas above the Hardy-Wilson standardⅢ-Ⅳlevel and (or) pituitary adenoma of C～E phase and Knosp classification 3-4 level were considered as the IPA. In the pituitary tumors of the selected 30 patients,3 case was consistent with Hardy-Wilson StandardⅢlevel,14 cases were C phase,5 cases were D phase,9 cases were E phase; 7 cases were consistent with Knosp classification 3 level,5 cases were of 4 level. All of them were in line with the IPA standard.The operation methods to all the patients in this group or the operation methods of their first surgery were used transsphenoidal approach by virtu of endoscope. When the dura was seen, the specimen was like-tetragonal body cutted by dagger with dura mater on one side and tumor on another side, and the specimen was put into 10% formalin to be futher deal with.Following the fixing,embedding,dehydrating and slicing,the specimens were stained by H.E.and Massion’s triple. Under the Olympus-DP70 inverted microscope (Germany), the relationship between the tumor tissues and pituitary capsule, dura should be carefully observed and recorded. The thicknesses of pituitary capsule were measured as follows:5 points were selected for each case, taking the average value, compared with the normal thickness of pituitary capsule measured in the past by our research group.Statistical method was t-test, and conducted on the software spss13.0.ResultsThe tumors were almost removed in the I phase surgery. Of the all cases,28 cases have improved the clinical symptoms or remained the stability; 1 case (74 years old) have been conducted the hematoma drainage hole surgical due to postoperative chronic subdural hematoma; 1 case has lost information after operation. The compressed and distorted peritumoral structure was oberved being reposited clearly in 15 cases through the post-operation Imaging review. No patients suffered death, postoperative cerebrospinal fluid leakage, meningitis or visual deterioration.The materials of 28 cases were in line with the experimental requirements among the 30 cases. The staining to the specimen was satisfactory. The slices should be observed carefully by the inverted microscope,The pathological results showed the pituitary capsule with different thickness could be identified in 25 specimens, however, the thickness was 0.16±0.07mm, being statistically less than the thickness of the normal pituitary capsule (t=21.998, p=0.000).The pituitary capsules of 2 cases were suspected to be invaded by tumor cell, but the pituitary capsules were integrated, without being broken by suspect tumor cells. The dural maters of all cases were integrated, without being infiltrated by tumor cells. In 19 cases, a distinguished gap between the dura and pituitary capsule (envelope gap) can be obviously identified with variant sizes, the rest envelope gaps were hard to identify. It could also be found that besides pituitary cupsule with different thicknesses, envelop gap with different sizes and dura without tumor cells were been seen.Thicknesses of IPA is thinner than normal (t=21.998, P= 0.000).ConclusionsIn this study, the "tumor +membrane" (the dura mater of sellar floor on one side, the tumor tissues on another side) specimen was obtained by the transsphenoidal approach by virtu of endoscope, the relationship was observed pathologicly between tumor cells, Combined with the relevant literatures, conclusions can be drawn as follows:1. In order to study the relationship between tumor and peritumoral dura, it was not only reasonable but feasible obtaining the specimen of "tumor+membrane" from the sellar floor, which can reflect the real relationship (ie. invasive sign) between pituiary adenoma and peritumoral structures in other directions;2. The membranous structures around the IPA tumors still exist in all cases, which indicates the traditional concept of "invasion" is not accurate with big possibility. The suspect tumor cells found in pituitary capsule may be the main reason to misjudge the invasion.3. It seems that the invasivness of pituitary adenoma has nothing to do with types of hormones, age and gender;4. There are obvious discrepancies between pathological diagnosis and imaging diagnosis.5. Currently, some views about the IPA is worth thinking, discussing and improving; there are great possibilities that the pattern of growth of pituitary adenoma is expansivness,not invasivness.6. The influence factors about the pattern of growth of are deserved to be further explored.PartⅡ:Morphological characteristics of later bone window (LBW) and carotid sulcus (CAS) and their relations with the pattern of growth of pituitary adenomaBackgroundSella turcica lies in the center of the skull base, It is generally believed that the scope of the sella turcica is:the former boundary is the lateral border of clinoid process and the front edge of chiasmatic sulcus; the posterior boundary is posterior clinoid process and dorsum sellae; and carotid sulcus lies in both sides of sella turcica. Owing to its complex and unique anatomical features, sella turcica was ever thought to be blind and restricted region of neurosurgery operation. With the micro-surgery being carried out generally, morphological study of the region has aleadly been put into attention,too.Sellar pituitary adenoma is the most common tumor, according to the different biological behavior of pituitary adenomas, it is divided into invasive pituitary adenomas and non-invasive pituitary adenomas. The researches of IPA were focused on the improvement to the ways of clinical surgery, and the summary of clinical effects, as well as the molecular biology of the basic researches, especially the researches on genetics and invasion indicators. There are many literatures and monograph of microscopic anatomy of the sella turcica,however, after a overall review of the literatures concerned, it was found that morphological characteristics of lateral bone window(LBW) and carotid sulcus(CAS) and their relations with the growth pattern of pituitary adenoma haven’t ever been studied.In the present reasearch, on one hand, samples of adult dry skull base of chinese were collected, with the help of associated software, the value of area LBW was measured successfully, which could provide important data for anotomical study of sella turcica. At the same time, morphological characteristics of LBW were first described and classified, and combined with the clinical literature, its relations with the growth pattern of pituitary adenoma was explored, particularly when pituitary adenoma grows into the parasellar area (cavernous sinus). On the other hand, CAS is important sellar bone structure existing in both lateral sides of sella turcica, although there were severa anatomical study, its classification of the clinical application was not still reported. In this article, CAS was diveded into four types, combined with imaging data of sellar CT scan, in the first time, from the view of the its relations with the expandsive "hobby" of pituitary adenoma particularly when pituitary adenoma grows into the parasellar area (cavernous sinus); Futhermore, its relations with the growth pattern of pituitary adenoma was explored. This study will be greatly statistical antomically and clinically.ObjectiveIn this study, detailed observation and description of the morphological characteristics of LBW and CAS are about to provide morphological study of sella trucica with important data and chinese physical investigations with anatomical data and references; Futhermore, relations were explored between LBW, CAS and the pattern of the growth of pituitary adenoma, in order to provides anatomic bases for the "hobby" of parasellar extension of pituitary adenoma.Materials and Methods1.Specimen for measurementAdult dry skulls were collected from department of anatomy of a few home medical schools, delt with conventionally and sawed open from superciliary arch to 1cm above the occipital skull carina, in order to expose the view of the inner surface of the skull base.530 cases were selected with relatively complete bony structures. Besides,50 cases (including 100 side) saddle thin sagittal reconstruction of coronal CT scan images (mainly for observation CAS classification) were observed and measured. Typical samples and pictures were photoed, reserved for archive to get ready for follow-up use.2. Contents of measurementContents of measurement in this study are as follows:①The value of LBW area was measured, the correlation between both LBW areas and the correlation between LBW and depth of sella turcica were analyzed;②APD (distance between anterior clinoid process and posterior process), MTD (maximum traverse diameter) and MLD (maximum longitudinal diameter) were observed and measured;③Occurrence characteristics of STB (sella turica bridge) and MCP (middle clinoid process) were observed and measured;④LBW was classified and typed according to relevant data and shapes;⑤LBH (height of latera bone) was measured, ie. between the highest point of LBW bottom to sellar floor;⑥Length of CAS was measured(which can indirectly reflect the length of cavernous segment of internal carotid artery);⑦CAS arc level got quantitativly classified (which can indirectly reflect the CAS package degree of internal carotid artery).3. Methods of measurement Measurement of LBW was accomplished with the main aid of plasticine, caliper, camera and software ImageJ; morphological classification of CAS:along CAS arc, a circle was drawn and divided into 12 equal parts, namely each arc is 30 degree, by which, degree of CAS arc can be determined, reflect ing tdegree of CAS on the CA package (detailed descriptions can be seen in the results).4. Statistical processAll data processing were carried out in SPSS 13.0 statistical software. Mean of measurement data was compared with t-test; data correlations were analyzed using Pearson orrelationwith analysis. The criterion for statistical significance for all tests was P<0.05.Results(I) Morphological characteristics of LBW1. Concept, location and composition of LBWLBW is like a window, located in lateral bony structure of sella turcica, including left LBW and right one. The upper bound is the connection level of anterior clinoid process and posterior clinoid process, the lower bound is the inner edge of carotid sulcus, the front bound is posterior border of the optic nerve column, and the posterior bound is the lateral border of dorsum sellae. Sometimes there are MCP and STB inside LBW, when STB appears, which is the connection between elinoid processes, the upper bound of LBW is the lower of STB; when the MCP and anterior clinoid process form carotico-clinoid foramen henle (CCFH), the front bound of LBW is the front border of CCFH.2. Area and classification o f LBWLeft area value of LBW is 75.99±25.81mm2, and right area value is 76.00±25.53 mm2. STD (depth of sella turica) is 11.00±1.82mm, ie, distance from midpoint of the line from sphenoidal limbus to the highest point of dorsum sellae to the sellar floor; there are no statistical difference between bilateral areas of LBW (paired t-test, t=0.03.p=0.998); there is a good positive correlation between bilateral areas of LBW (pearson correlation analysis, r=0.638) and a weak positive correlation between bilateral area of LBW and STD (pearson correlation analysis, the left r=0.214, the right r=0.180);Based on the measured results as above, LBW size can be graded as follows: Grade A is LBW area of less than 60 mm2 (20% patients in this group); Grade B is LBW area between 60 mm2 to 90 mm2 (60% patients in this group); Grade C is LBW area larger than 90 mm (20% patients in this group).3. Morphology of LBWIn this study, in order to observe morphology of LBW, three factors were mainly considered as follws:APD (distance between anterior clinoid process and posterior process), MCP (middle clinoid process)and formation of STB (sella turica bridge).According to overall observation results, LBW can be typed as follows:TypeⅠ(open type):APD larger than half MTD;TypeⅡ(half-open type):APD larger than one fourth MTD,smaller than half MTD;TypeⅢ(complete type):APD smaller than one fourth MTD, including typeⅢa(relatively intact type) and typeⅢb(absolutly intact type);Ⅲb means that APD equal to zero or that STB appears;TypeⅢ(obexlike type):inside LBW, MCP appears, like a obex of a door. According to shape and size of MCP and combined with classification of CCFH by keyes, this type can be typed again as follows:Ⅳa(equivalent to complete type CCFH);Ⅳb(equivalent to contact type CCFH);Ⅳc(equivalent to incomplete type CCFH) IVd(ie, complete type LBW plus complete type CCFH).4.Measurment of LBHLBH (height of latera bone) with different values lies in the bottom edge of LBW just like a latch of a door. The values:Left LBH is 1.23±0.79mm, right LBH is 1.22±0.82mm; there is no statistical difference beteen bilateral LBH (paired t-test, t=1.388.p= 0.166).(Ⅱ) Morphological characteristics of CAS1. Location, shapes and adjacent structures of CASCarotid sulcus (CAS) lies in the lateral wall, one on each side and carotid cavernous segment (C4) of ICA lies inside it; Most shapes of CAS is straight, and few shapes is like "S"; The front edge of CAS is the migration department between cavernous segment and knee segent of ICA, and the later edge is the front edge of foramen lacerum; the inner edge is the lateral border of the pituitary fossa, ie. the lower edge of LBW, and its lateral margin is adjacent to middle cranial fossa; both ends of CAS is the deepest, and the middle segent of CAS is the most shallow, even sometimes it is flat,sulcus’s shape is not obvious.2. Measurment of CASCASL (length of CAS):left CASL is 19.83±1.87mm, right CASL is 20.45±1.84mm; there is statistical difference beteen bilateral CASL(paired t-test, t=-8.032. p=0.000),and right CASL is longer than left CASL.3. Typing of CASSpecific measurement was accomplished in the thin sagittal reconstruction of coronal CT scan images of normal adults. In the mid-coronal CT scan, circle was drawn according to the degree arc of CAS (for the convenience of drawing, CT picture can be enlarged to be easy see clear CAS, and to be measured). Then the circle was divided into 12 equal portions, Line between point A (inner highest point of CAS), point B(outer highest point of CAS) and point O (center point of the circle) was linked respectively, and then angle AOB formed; the degree of angle AOB was obsevered, which not only reflect the depth of CAS, but also the width of CAS.Based on measurement,CAS was typed as follows:TypeⅠ:arc degree of CAS is less than 30°(42 side,42%);TypeⅡ:arc degree of CAS is between 30°and 60°(33 side,33%);TypeⅢ:arc degree of CAS is at between 60°and 90°(19 sides,19%);TypeⅣ:arc degree of CAS is greater than 90°(6 sides,6%).ConclusionsIn this study, detailed observation and description of the morphological characteristics of LBW and CAS were carried in dry skull base of normal adults and the thin sagittal reconstruction of coronal CT scan images of normal adults; their relations with the growth pattern of pituitary adenomas(especially pituitary adenoma growing parasellarly into cavernous sinus) were explored and analyzed. Combined with literature review, the following conclusions can be drawn:1. This study provided morphological study of sella trucica with important data and chinese physical investigations with anatomical data and reference;2. Anatomic factors of LBW,CAS and etc. of sella turcica can affect to different degrees the growth pattern of pituitary adenoma, especially, especially pituitary adenoma growing parasellarly into cavernous sinus. With regard to LBW,,as a "throat" of between pituitary adenoma and parasellar structures (cavernous sinus),its areas and shapes have close relationship with tumors expanding through LBW, big area can benefit tumors expanding parasellarly more "smoothly " than small area; and cancer by level of difficulty should be closely related area is greater than the small area were "; Resistance from typeⅠ,Ⅱ,Ⅲa,Ⅲb,Ⅳa,Ⅳb,Ⅳc,Ⅳd of LBW should become biger and biger to pituitary adenoma growing parasellarly into cavernous sinus; With regard to CAS, from type A to type D, resistance should become gradully to baffle tumor to encase ICA; APD’s "Skylight" function, STB’s "fence" effect, MCP’s "latch" role, LBH’s "threshold" effect and CCFH’"hoop" effect on ICA’s is worth considering when cavernous sinus invasion of pituitary adenomas is defined, because the studies show that the incidence can not be ignored;3. None of definition standards of IPA used commonly, particularly for the diagnosis criteria of cavernous sinus invasion of pituitary adenomas, takes into account anatomical impact factors of sella turcica such as LBW, CAS and etc., which preliminarily indicates these diagnostic criteria are in short of conscientiousness.4.Combined with literatures, it seems that sella anatomic factors appear to be used to explain the features of growth patterns of pituitary adenoma;5. Disputes among the diagnostic criteria of IPA and discrepancies of IPA incidence from various reports exist,which suggests that diagnostic criteria be uniformed and improved as soon as possible;6. it is worth futher study on the factors that can affect growth pattern of pituitary adenomas.更多还原