蝶鞍膜性结构与垂体腺瘤生长方式的显微解剖学研究
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摘要
一、研究背景
垂体腺瘤为腺垂体细胞起源的良性肿瘤,是第三位的颅内常见肿瘤,位于胶质瘤、脑膜瘤之后,约占所有颅内肿瘤的10-15%。除泌乳素腺瘤外,垂体腺瘤的治疗仍然首选手术治疗。术后复发是临床上的棘手问题,严重影响了患者的生活质量。影响垂体腺瘤术后复发的因素较多,包括肿瘤的大小、生长速度、手术切除程度以及辅助治疗措施等,其中肿瘤向周围结构,特别是海绵窦内扩展生长是复发的主要原因。侵袭性垂体腺瘤的概念最早由Jefferson于1940年提出,定义为“生长突破肿瘤包膜并侵犯硬脑膜、视神经、骨质等毗邻结构的垂体腺瘤”。侵袭性垂体腺瘤是介于良性垂体肿瘤和垂体腺癌之间的肿瘤,三者在组织学上不能明显区分,但是在生物学行为上有较大的不同；垂体腺瘤呈膨胀性生长,为周围结构形成的假包膜包裹,侵袭性垂体腺瘤呈局部侵袭性生长,侵犯鞍膈、骨质、临近血管等结构,但是不具有颅内转移的特性。目前诊断的主要依据有病理学检查、影像学诊断、分子生物学检查以及手术所见,各种诊断方法都提供了不同的信息,但是也充满了不同的观点,难以形成统一的标准。
侵袭性垂体腺瘤的定义、诊断标准一直存在争论,影响了诊治理念和策略。近年来,鞍区结构的解剖学特点对于垂体腺瘤生长方式的影响引起了研究者的关注。鞍区位于头颅正中,局部解剖结构复杂。垂体位于垂体窝内,其前方、后方和下方均为骨性结构,上方和侧方为硬膜结构,这些结构构成了垂体腺瘤向周围扩展的屏障。鞍区骨性结构研究方面,王剑新等描述了蝶鞍和颈动脉沟的形态学特点,并提出蝶鞍侧壁骨窗的大小可对垂体瘤向鞍旁扩展有着不同程度的影响。韦拳堂等关于垂体窝上口形态学特点与垂体腺瘤生长的关系显示垂体腺瘤基本垂直于垂体窝上口生长,垂体窝上口倾斜角决定垂体腺瘤往鞍上生长的方向。海绵窦内侧壁研究方面,有学者认为颈内动脉海绵窦段和垂体之间仅有一层疏松的纤维组织,而这个薄弱之处是垂体腺瘤侵入海绵窦的组织学基础,并不一定是因为肿瘤具有侵袭性所致。部分研究者认为海绵窦内侧壁的存在小的组织学缺陷形成的窗口,其是肿瘤鞍旁扩展的原因。近年来有作者通过组织学和解剖学研究发现海绵窦内侧壁是完整的,认为垂体腺瘤向海面窦扩展,往往只是将海绵窦内侧壁向外推挤了,其间的膜性结构仍然存在,所谓垂体腺瘤向海绵窦内侵袭性生长可能是垂体腺瘤向鞍旁扩展造成海绵窦内侧壁的适形性扩展而形成的影像学假象。
鞍区解剖结构的不同特点对于垂体腺瘤生长方式的影响作用为侵袭性垂体腺瘤的多元化思考提供了新的道路,与其它诊断方法进行综合考虑,可以为临床选择治疗方式、制定治疗方案提供有力的支持。鞍膈和海绵窦内侧壁构成了垂体窝的顶和外侧壁,是垂体腺瘤生长时需要首先突破的屏障,甚至有作者认为垂体腺瘤周围的膜性结构对肿瘤的限制作用要强于骨性结构。本研究将对垂体周围膜性结构,鞍膈、海绵窦内侧壁,及其毗邻结构的进行观察,并结合文献与临床,探讨其形态特点对垂体腺瘤生长方式的影响。
二、研究目的
1、对鞍膈及周围结构视交叉、垂体柄的形态学特点进行详细的观察和描述,为蝶鞍区解剖学的系统化、完善化提供补充；探讨鞍膈对垂体腺瘤生长方式的影响；
2、应用组织学和解剖学方法观察蝶鞍区膜性结构的特点,明确鞍膈、海绵窦内侧壁的膜性构成,并观察海绵窦内侧壁与海绵窦段颈内动脉的位置特点,探讨其与垂体腺瘤生长方式的关系；
三、研究方法
1、视交叉、鞍膈孔、垂体柄的显微解剖学研究
取经动脉灌注的成人尸头标本15例,锯除颅盖,分块切除鞍区以上部分的脑组织,保持视神经、视束等结构完整；观察测量视神经颅内段的长度、视交叉角度、视交叉与鞍膈孔的位置关系；与视神经孔处离断视神经,向后方翻起视神经、视交叉,辨认垂体柄与漏斗连接处并断开,观察垂体柄与鞍结节、鞍背的位置关系,以及垂体柄通过鞍膈孔的位置；观察鞍膈的形态特点,测量鞍膈、鞍膈孔直径；
2、鞍膈及海绵窦内侧壁的组织学及显微解剖学研究
取6-8个月死婴6例,分离出大块颅底(鞍区、双侧海绵窦、部分中颅窝底和岩尖),依此脱钙、脱水、石蜡包埋等处理后作做矢状位、冠状位或轴位的组织学连续切片,分别进行Masson染色和天狼猩红-苦味酸染色,在显微镜下观察海绵窦区各层膜性结构的移行关系；另取经灌注的成人尸头标本10例(20侧),在手术显微镜下进行解剖,逐层切开蝶鞍区各层膜性结构,观察其走行和分布,并注意观察海绵窦段颈内动脉与海绵窦内侧壁的关系；鞍膈及海绵窦内侧壁厚度测量结果比较时采用oneway ANOVA进行分析,若P<0.05则进行进一步多重比较(SNK法)。当P<0.05时认为差异有统计学意义,所有检验均采用双侧检验。文中统计分析均采用SPSS13.0统计软件处理。
四、研究结果
1、视神经颅内段为视神经孔至视交叉的部分。左侧颅内段视神经长度为(12.36±1.71)mm,右侧颅内段长度为(12.20±1.86)mm。视交叉由两侧视神经纤维汇聚而成,向后上方与终板、前联合及下丘脑下部相连接。两侧视神经形成夹角为(62.29±12.17)°,范围(49.20～87.20)°。以鸡冠为中线,视交叉中点66.7%(10例)位于中线上,20%(3例)位于偏向蝶鞍左侧,13.3%(2例)位于偏向右侧。从上方看,鞍膈孔完全被视神经覆盖73.4%(11例),未被完全覆盖26.6%(4例)；鞍膈孔与视交叉的相对位置可分为3种类型,偏向左侧26.7%(4例),居于中线上66.7%(10例),偏向右侧6.6%(1例)。
逐步切除视神经和视交叉,可见蝶鞍两侧的前、后岩床皱襞、蝶棱、鞍背形成一个四边形的区域。鞍膈附着于前方的鞍结节和后方的鞍背之间,构成垂体窝的顶,中央为鞍膈孔,有垂体柄及垂体上动脉通过。鞍膈前后延续为附着于视交叉沟和鞍背的颅底硬膜结构,向两侧延伸构成海绵窦的顶。海绵窦顶与鞍膈无明确的分界。床突间韧带将海绵窦顶分为两个三角即前内侧的颈动脉三角和后外侧的动眼神经三角。鞍膈纤维呈同心圆状环绕鞍膈孔。鞍膈呈下凹型80%(12例),平坦型13.3%(2例),上凸型6.7%(1例)。鞍膈孔为圆形或者椭圆型,内径变异较大,前后径为(6.59±2.45)mm,(2.20～12.10)mm；左右径为(7.32±2.60)mm,(3.10～13.40)mm。根据鞍膈孔的不同,将鞍膈分为3型：紧密型,孔径<5mm,鞍膈较为紧密围绕垂体柄,占13.3%(2例)；常见型：孔径5-10mm,鞍膈孔扩大较为明显,与垂体柄之间有一定间距,占73.4%(11例)；扩大型：孔径>1Omm,鞍膈孔较大,垂体窝周边仅可见少量的硬膜结构,占13.3%(2例)。将鞍结节至鞍背的距离等分为三个部分,则垂体柄与鞍结节、鞍背的位置关系可分为三种类型：前置型,垂体柄位于前三分之一,靠近鞍结节,占6.7%(1例)；居中型,垂体柄居于中间位置,占40%(6例)；后置型,垂体柄位于后三分之一,鞍背的前方,占53.3%(8例)。
2、所有的胎儿颅底标本组织染色均观察到颅底的硬膜在鞍结节和鞍背部位脑膜层和骨膜层分开,脑膜层附于垂体表面,并向下反折包被垂体,双层硬膜在垂体上面形成鞍膈；垂体窝底部位硬膜骨膜层和脑膜层结构再次融合；在有些部位,尤其是脑膜层再次与骨膜层融合的部位,如鞍结节、鞍背和鞍底的部分,两层硬膜可分离从而形成海绵间前窦、海绵间后窦和海绵间下窦。鞍膈从周边即开始发出纤维,膈孔处纤维向下融合于鞍膈周围发出的纤维,共同构成垂体的硬膜囊。垂体囊为连续的硬膜囊袋,其上壁由鞍膈硬膜加强,前壁、后壁和下壁均与骨膜层粘连,外侧壁与海绵窦相邻。垂体被两层膜性结构包裹,内层膜为垂体固有膜,和垂体表面紧贴,并发出纤维束进入腺体中；外层为垂体硬膜囊,两层之间尚有潜在空间。腺垂体向神经垂体过渡中,垂体囊和固有膜逐渐移行接近,在神经垂体表面二者紧贴。海绵窦内的纤维小梁结构将其分为大小不等的许多腔隙,这些小梁结构附着于海绵窦内走行的血管、神经,并贴附于海绵窦顶、内侧壁、外侧壁；海绵窦内侧壁可见由包裹垂体的硬膜囊的外侧壁和附着于其上的纤维层共同构成,其将海绵窦与垂体分隔开来。
成人尸头解剖显示鞍区硬膜结构的移行与胎儿颅底标本组织学观察相符合。垂体周围膜性结构厚度测量结果四组之间有统计学差异(F=53.412,P=0.000),显示鞍膈周边的厚度显著大于膈孔边缘及海绵窦内侧壁,差异有统计学意义(P<0.05)；海绵窦内侧壁下1/3厚度显著小于其上1/3,差异有统计学意义(P<0.05)。并且注意到尽管海绵窦内侧壁下1/3处较上1/3处薄弱,但是结构完整,未见有穿孔及缺损。观测的10头20侧标本中,40%(8侧)可见垂体前叶越过颈内动脉内侧缘连线向海绵窦内扩展,其中有15%(3侧)见到颈内动脉向垂体窝内移位,部分垂体前叶覆于其上,另外15%(3侧)显示垂体向一侧偏移,与一侧的海绵窦段颈内动脉接触,腺垂体前叶突出于海绵窦内,而远离一侧颈内动脉,另外在10%(1例,2侧)标本中见到垂体前叶向两边突出于海绵窦内,呈舌样越过颈内动脉海绵窦段。
五、结论
1、鞍膈孔大部分被视交叉完全被覆盖,少数未被完全覆盖；鞍膈孔大部分位于视交叉的中线上,少部分可向两侧稍偏移；视交叉与鞍膈孔的位置关系可能与垂体腺瘤生长过程中所致的视觉障碍出现的早晚及程度和表现形式有关,即从位于视交叉中线部位膈孔突出的腺瘤多引起双颞侧偏盲,而从视交叉侧方部位膈孔突出的肿瘤常引起左侧或者右侧视野缺损；
2、依据鞍膈孔直径的大小可将鞍膈分为,紧密型、常见型和扩大型；鞍膈孔径大小的变异较大,可对垂体腺瘤的生长方式产生影响,鞍膈孔径大的腺瘤向上生长阻力较小,容易向鞍上扩展,而鞍膈孔径小的由于向上方生长受阻,容易进入到海绵窦、甚至筛窦、蝶窦内；
3、垂体柄与鞍结节、鞍背的位置关系分为3种类型：前置型、居中型和后置型,其中大部分为居中型和后置型,仅少数为前置型；对此解剖关系的认识可以帮助在垂体腺瘤手术中辨认和保护垂体柄和神经垂体；
4、鞍膈是覆盖于蝶鞍上面的硬膜结构,由脑膜层在垂体上部处返折形成的双层结构；海绵窦内侧壁由两层膜性结构组成,即外侧部的垂体硬膜囊和附着于其上的纤维层；海绵窦内侧壁为完整的膜性结构,无局部缺损；
5、垂体前叶正常情况下可以与海绵窦段颈内动脉直接接触,部分甚至可突入海绵窦段颈内动脉上方。在此种解剖关系下,垂体腺瘤在生长过程中可以较为容易的跨过海绵窦段颈内动脉,并进而突入到海绵窦腔,但与海绵窦内结构仍然相隔固有膜、海绵窦内侧壁等膜性结构,并不一定是因为肿瘤侵袭性生长所致；
6、侵袭性垂体腺瘤的诊断和治疗策略的制定,应该结合内分泌学、病理学、影像检查、术中所见等的结果综合考量,并要注意到个体鞍区解剖特点对垂体腺瘤生长方式可能产生的影响。
Background
Pituitary adenomas are benign tumors arising in adenohypophysial cell and approximately represent10-15%intracranial neoplasms, rank third following gliomas and meningiomas. Surgery remains the primary therapy of choice except for prolactinomas. Tumor recurrence after operation is the hardest problem of therapy for pituitary adenomas and seriously threaten to patients' quality of life. There are many factors affecting tumor recurrence, include the size of the tumors, growth rate,the extent of resection,adjuvant therapy, etc. Among those factors, pituitary adenoma extention into surrounding structures, especially into cavernous sinus, are the principal cause which leading to tumor recurrence. Invasive pituitary adenoma was proposed by Jefferson in1940, which was defined as "the pituitary adenoma grows to break its envelope and to invade the adjacent structure such as the dura, the optic nerve, bone and so on". Scheithauer classified invasive pituitary adenomas as the interim type from benign pituitary adenomas to pituitary cancers. These three diseases can not be distinguished in pathology, but show differences in the biological behaviors, pituitary adenomas developed in expansive growth modes and covered by "pseudocapsule" which formed by compression the surrounding structure, invasive pituitary adenomas bring out aggressive growth pattern and invde the diaphragm sellae, bone, vascular vessel, but do not present characteristic of intracranial metastasis which pituitary cancers show. The concept and diagnostic criteria of invasive pituitary adenomas have considerable controversies that lead to the difficulty in diagnosis and treatment. Pathological examination, imaging technology, molecular biology test and operative observation were applied in the diagnosis of invasive pituitary adenomas, these methods provide different medical information, but could not produce a unified diagnostic criteria.
Effects of sellar regional anatomy on growth pattern of pituiary adenomas have drawn the attentions of researchers in recent years. Sellar region is located near the center of the head and consist of the complex configure. The front, rear and bottom of hypophyseal fossa where pituitary gland sited are bony structure, the top and sides are the dura mater and all these structure could restrict the pituitary adenomas extension. In term of morphological study of sellar bone, Wang jian-xin have presented the anatomic features of sellar turcica and carotid sulcus and stated that lateral bone windows of sella turcica and carotid sulcus can affect to different degrees the growth pattern of pituitary. Wei quan-tang found that most of pituitary adenomas grow perpendicularly to pituitary fossa superior orifice and the slant angle of pituitary fossa superior orifice could determine the growth direction of pituitary adenoma toward suprasellar region. Studies on membrane surrounding the pituitary gland have been made for many years. Some researchers state that the there is no a dural wall existing between cavernous sinus and carotid artery, but a loose, fibrous tissue and the extension of pituitary tumors into the cavernous sinuses is not for aggressive growth, but for the absence of a strong separation. There are also some authors declare that the defects exist on the medial wall of cavernous sinus which leads to the expansion of pituitary adenomas into cavernous sinus. Recently, some researchers found through histological and micro-dissection method that the medial wall of cavernous sinus is a intact dural membrane and deduce that invasive adenomas might be a radiological misunderstanding of the extremely displacement of the medial wall by the tumor's pushing, a membranous interface still exists between the tumor and the cavernous sinus.
Sellar region anatomy application for explanation of pituitary adenoma growth modes provided a new way to investigate the reality of invasive pituitary adenomas and would helpful to diagnosis and treatments. The roof of hypophyseal fossa formed by diaphragm sellae and lateral wall by medial wall of cavernous sinus, which are the major obstacles to pituitary adenomas expansion. There were authors even thought that the cancellous bone of the sella turcica is less of a barrier against extension of tumor than the ligamentous attachments of the dural structures. This study was designed to research the anatomic features of dura mater enclosing the pituitary gland and its relationships with the growth pattern of pituitary adenomas was explored.
Objective
1、Observation and description of morphological features of diaphragm sellae, optic chiasm, pituitary stalk are about to make the anatomy of sellar region more systematic and detailed. The relations between diaphragm sellae and pituitary adenomas extension were explored.
2、Histological and anatomic method were used to define the membrane composition of diaphragm sellae and medial wall of cavernous sinus; the position relationship of medial wall of cavernous sinus relative to cavernous segment of internal carotid artery were paid attention to explore its effect on growth pattern of pituitary adenoma.
Material and method
1. Microanatomy of diaphragm sellae, optic chiasm and pituitary stalk
Fifteen adult cadaveric head, the arteries of which were injected with red latex, were used to perform anatomic study. The cranial vault and brain tissue above sellar region were removed and optic nerve, optic tract were intently reserved. Under the surgical microscopy, the length of intracranial segment of optic nerve, the angle of optic chiasm were measured and position relationships of foramen diaphragm sellae relative to optic chiasms were noted. After optic nerve being cut in the intracranial opening of the optic canal, we backward fliped the optic nerve and optic chiasm, discontinued the pituitary stalk at the junction connected to the infundibulum. The anatomical data and morphological characteristic of pituitary stalk, diaphragm sellae and adjacent structure were measured and demonstrated.
2. Microanatomy of diaphragm sellae and medial wall of cavernous sinus
Heads from6fetal cadavers aged6to8months were studied. All specimens were infused with10%formalin solution into the umbilical to embalm all specimens. Tissue blocks of skull base (include sellar region, cavernous sinus, part of middle cranial fossa and petrous bone) were dealt with decalcification, dehydrating, embedding. Serial histological sections were obtained in sagittal and coronal direction. All these sections were stained with Masson's triple and picrosirius-picric acid staining. Under the light microscopy, the course and distribution of the membranate structures were observed. Ten adult cadaveric head, the arteries of which were injected with red latex and the veins with blue latex, were used to perform anatomic study. Under the surgical microscope, membranous structure of sellar region were dissected step by step, their course and distribution of the membranate structures were described, the position relationships of cavernous segment of internal carotid artery and medial wall of cavernous sinus were remarked especially. Mean of the thickness of diphragma sellae and medial wall of cavernous sinus was compared with oneway ANOVA, and if P<0.05, for further multiple comparison with SNK method. The criterion for statistical significance for all tests was P<0.05, all tests used two-tailed test. All data processing were carried out in SPSS13.0statistical software.
Result
1. The length of intracranial segment of right optic nerve were12.36±1.71mm, and the left were12.20±1.86mm. Both sides of the optic nerve fibers converge to form the optic chiasm, which posteriorly continued with lamina terminalis, anterior commissure and lower part of the hypothalamus. The angle of optic chiasm were62.29±12.17°(range,49.20-87.20°). The midpoint of the optic chiasm passing through crista galli were located on the midline in66.7%(10cases) and to the left and right sides of the sella turcica in20%(3cases) and13.3%(2cases) respectively. The foramen diaphragm sellae (FDS) was completely covered by OC in73.4%(11cases), but it was partly seen superiorly in26.6%(4cases). The position of FDS relative to OC situated in the midline in66.7%(10cases), to the left part in26.7%(4cases) and right part in6.6%(1case).
After the optic nerve and optic chiasm having been removed, a quadrilateral area were seen which formed by limbus sphenoidale, dorsum sellae, and anterior, posterior petroclinoid ligament. The diaphragma sellae attachs to the tuberculum sellae and dorsum sellae and forms the roof of the hypophyseal fossa. In the center, the diaphragm has an opening through which the infundibulum and inferior hypophyseal artery courses. The diaphragm sellae extends from the tuberculum sellae anteriorly to the dorsum sellae posteriorly. Laterally, it limits to the roof the cavernous sinus. There is no a clear boundary between diaphragm and the roof. The roof of cavernous sinus were divided by interclinoid ligament into anteromedial carotid triangle and posterolateral oculomotor triangle. Diaphragmatic fibers were concentrically around the foramen. Diaphragm sellae appeared concave in80%(12cases), convex in13.3%(2cases) and flat in6.7%(1case) when view from above. The foramen diaphragm sellae is round or oval and its diameter greatly varied. The average of anteroposterior distance of foramen diaphragm sellae was6.59±2.45mm (range,2.20-12.10mm) and the average lateral-to-lateral distance was7.32±2.60mm (range,3.10-13.40mm). we classified the diaphragm sellae into three types according to the foramen diaphragm sellae diameters variations, closed type, the diaphragmatic opening was less than5mm and the pituitary stalk was tightly surrounded in13.3%(2cases); normal type, the diaphragmatic foramen was5-10mm and the gap exist between stalk and diaphragma in73.4%(11cases); and open type, the diaphragmatic opening was more than10mm and the remnants of the diaphragma were seen around the upper part of the pituitary fossa in13.3%(2cases). The position relationship of pituitary stalk relative to the tuberculum and dorsum sellae can be classified3type, prefix typed, pituitary stalk sited in front of dorsum sellae in53.3%(8cases);middle type, in the middle part in40%(6cases) and postfix type, in the the back of tuberculum sellae in6.7%(1case).
2. In all fetal skull base specimens, dura mater was found to divided into meningeal and periosteal layer over the tuberculum sellae and dorsum sellae. The meningeal layer covers the pituitary gland and folds downward around the foramen. Two meningeal layer formed diaphragm sellae on the top of hypophyseal fossa. Meningeal and periosteal layer mix together again in the bottom of sellar floor. In the meningeal layer and periosteal layers confluence, anterior intercavernous sinus, posterior intercavernous sinus and inferior intercavernous sinus were shaped. The dural fibers sent out from the periphery and the center of diaphragma fused to constitute the pituitary dural sac. The pituitary sac is a continuous dual pouch, its superior wall is strengthened by diaphragm sell, the anterior, posterior and inferior wall adhere to the periosteal layer, lateral wall is a screen which separated the cavernous sinus. The pituitary gland is founded to be packed by two membranous layer, the inner layer is lamina propria which tightly adheres to the gland and and some connective tissue penetrated the gland, the outer layer is the dural sac. A potential space between the2layers was found on the surface of the adenohypophysis. these2layers got closer and closer from the anterior lobe toward the posterior lobe of the gland and finally adhered on the surface of the neurohypophysis. Many fibrous trabeculae divided cavernous sinus into a lot of cavity, which adhere to the wall of cavernous sinus and neurovascular structure coursed in it. The medial wall of the cavernous sinus is a bilayered membrane, composed of the lateral part of the pituitary sac and the fibrous layer, which separated the pituitary gland from the cavernous sinus.
The course and distribution of the membranous structures observed by adult cadaver head dissection are corresponded to the results obtained from histological study in the fetal skull base specimens. Thickness of membranes surrounding pituitary gland were statistically difference between four groups(F=53.412, P=0.000). The periphery of diaphragm sellae was significantly thicker than the center and the medial wall of cavernous sinus(P<0.05); the thickness of the upper third was statistically greater than the lower third(P<0.05).The medial wall of cavernous sinus are intact without perforations and defects although the weakness were founded in lower third than upper third of it. In8of the20cavernous sinus, the sellar part of the medial wall rested against the intracavernous carotid; in15%(3sides) the internal carotid arteries shifted from sulcus and partly squeezed into the hypophyseal fossa, that leaded to be partly coated by medial wall of cavernous sinus; in15%(3sides) the anterior lobe of pituitary gland extended towards one side of the cavernous sinus and closely contact the internal carotid artery, but away from another side; and in10%(2sides in the same specimens) there was a tongue-like lateral protrusion of the gland that extended around the cavernous segment of the intracavernous carotid.
Conclusion
1. Most of the foramen diaphragm sellae are completely covered by optic chiasm, but few are partly seen superiorly. The position of foramen diaphragm sellae relative to optic chiasm situated in the midline account for the majority, to the left and right part manifest minority. This positional relationship could be used to explain the visual symptoms of patients with pituitary tumors. Pituitary adenomas protrude from diaphragmatic foramen located in the midline of optic chiasm result in bitemporal hemianopsia, while in the side of the optic chiasm lead to left or right visual field defect.
2. The diaphragm sellae could be classified into three types according to the diaphragmatic foramen diameters variations, closed type; normal type; and open type. The sizes of diaphragmatic opening could affect the growth direction of pituitary adenomas. If the opening was large, the resistance from the top was less than from others sides and the pituitary tumor was inclined to suprasellarly grow. While if the opening was small, the tumor was barriered by diaphragm sella and easily extended into the cavernous sinus, even broke through the bony structures into ethmoid and sphenoid sinus.
3. The position of pituitary stalk could be categorized as3types:prefixed type, middle type, and postfixed type. Postfix and middle type accounted for the vast majority, only a small number of prefix type. This anatomic knowledge is helpful to identify and protect the pituitary stalk and neurohypophysis in the operations.
4. The diaphragm sellae covers the hypophyseal fossa and formed by2meningeal layer. The dural fibers sent out from the periphery and the center of diaphragma fused to constitute the pituitary dural sac. The medial wall of the cavernous sinus is a bilayered membrane and the2layers of the medial wall are composed of the lateral part of the pituitary sac and the fibrous layer. The medial wall is intact without perforations and defects.
5. The normal anterior lobe of pituitary gland might rest against the cavernous segment of internal carotid artery. In this anatomic conditions, the tumor could easily cross the carotid artery into the cavernous sinus and membranous layers such as lamina propria, the medial wall would exist between the tumor and the cavernous sinus, so that the tumor was not invasive growth.
6. The diagnosis and treatment of invasive pituitary adenomas should based on endocrinology, pathology, imaging, and intraoperative findings, especially the influence of sellar regional anatomy on the growth pattern should be taken into considerations.
垂体腺瘤为腺垂体细胞起源的良性肿瘤,是第三位的颅内常见肿瘤,位于胶质瘤、脑膜瘤之后,约占所有颅内肿瘤的10-15%。除泌乳素腺瘤外,垂体腺瘤的治疗仍然首选手术治疗。术后复发是临床上的棘手问题,严重影响了患者的生活质量。影响垂体腺瘤术后复发的因素较多,包括肿瘤的大小、生长速度、手术切除程度以及辅助治疗措施等,其中肿瘤向周围结构,特别是海绵窦内扩展生长是复发的主要原因。侵袭性垂体腺瘤的概念最早由Jefferson于1940年提出,定义为“生长突破肿瘤包膜并侵犯硬脑膜、视神经、骨质等毗邻结构的垂体腺瘤”。侵袭性垂体腺瘤是介于良性垂体肿瘤和垂体腺癌之间的肿瘤,三者在组织学上不能明显区分,但是在生物学行为上有较大的不同；垂体腺瘤呈膨胀性生长,为周围结构形成的假包膜包裹,侵袭性垂体腺瘤呈局部侵袭性生长,侵犯鞍膈、骨质、临近血管等结构,但是不具有颅内转移的特性。目前诊断的主要依据有病理学检查、影像学诊断、分子生物学检查以及手术所见,各种诊断方法都提供了不同的信息,但是也充满了不同的观点,难以形成统一的标准。
侵袭性垂体腺瘤的定义、诊断标准一直存在争论,影响了诊治理念和策略。近年来,鞍区结构的解剖学特点对于垂体腺瘤生长方式的影响引起了研究者的关注。鞍区位于头颅正中,局部解剖结构复杂。垂体位于垂体窝内,其前方、后方和下方均为骨性结构,上方和侧方为硬膜结构,这些结构构成了垂体腺瘤向周围扩展的屏障。鞍区骨性结构研究方面,王剑新等描述了蝶鞍和颈动脉沟的形态学特点,并提出蝶鞍侧壁骨窗的大小可对垂体瘤向鞍旁扩展有着不同程度的影响。韦拳堂等关于垂体窝上口形态学特点与垂体腺瘤生长的关系显示垂体腺瘤基本垂直于垂体窝上口生长,垂体窝上口倾斜角决定垂体腺瘤往鞍上生长的方向。海绵窦内侧壁研究方面,有学者认为颈内动脉海绵窦段和垂体之间仅有一层疏松的纤维组织,而这个薄弱之处是垂体腺瘤侵入海绵窦的组织学基础,并不一定是因为肿瘤具有侵袭性所致。部分研究者认为海绵窦内侧壁的存在小的组织学缺陷形成的窗口,其是肿瘤鞍旁扩展的原因。近年来有作者通过组织学和解剖学研究发现海绵窦内侧壁是完整的,认为垂体腺瘤向海面窦扩展,往往只是将海绵窦内侧壁向外推挤了,其间的膜性结构仍然存在,所谓垂体腺瘤向海绵窦内侵袭性生长可能是垂体腺瘤向鞍旁扩展造成海绵窦内侧壁的适形性扩展而形成的影像学假象。
鞍区解剖结构的不同特点对于垂体腺瘤生长方式的影响作用为侵袭性垂体腺瘤的多元化思考提供了新的道路,与其它诊断方法进行综合考虑,可以为临床选择治疗方式、制定治疗方案提供有力的支持。鞍膈和海绵窦内侧壁构成了垂体窝的顶和外侧壁,是垂体腺瘤生长时需要首先突破的屏障,甚至有作者认为垂体腺瘤周围的膜性结构对肿瘤的限制作用要强于骨性结构。本研究将对垂体周围膜性结构,鞍膈、海绵窦内侧壁,及其毗邻结构的进行观察,并结合文献与临床,探讨其形态特点对垂体腺瘤生长方式的影响。
二、研究目的
1、对鞍膈及周围结构视交叉、垂体柄的形态学特点进行详细的观察和描述,为蝶鞍区解剖学的系统化、完善化提供补充；探讨鞍膈对垂体腺瘤生长方式的影响；
2、应用组织学和解剖学方法观察蝶鞍区膜性结构的特点,明确鞍膈、海绵窦内侧壁的膜性构成,并观察海绵窦内侧壁与海绵窦段颈内动脉的位置特点,探讨其与垂体腺瘤生长方式的关系；
三、研究方法
1、视交叉、鞍膈孔、垂体柄的显微解剖学研究
取经动脉灌注的成人尸头标本15例,锯除颅盖,分块切除鞍区以上部分的脑组织,保持视神经、视束等结构完整；观察测量视神经颅内段的长度、视交叉角度、视交叉与鞍膈孔的位置关系；与视神经孔处离断视神经,向后方翻起视神经、视交叉,辨认垂体柄与漏斗连接处并断开,观察垂体柄与鞍结节、鞍背的位置关系,以及垂体柄通过鞍膈孔的位置；观察鞍膈的形态特点,测量鞍膈、鞍膈孔直径；
2、鞍膈及海绵窦内侧壁的组织学及显微解剖学研究
取6-8个月死婴6例,分离出大块颅底(鞍区、双侧海绵窦、部分中颅窝底和岩尖),依此脱钙、脱水、石蜡包埋等处理后作做矢状位、冠状位或轴位的组织学连续切片,分别进行Masson染色和天狼猩红-苦味酸染色,在显微镜下观察海绵窦区各层膜性结构的移行关系；另取经灌注的成人尸头标本10例(20侧),在手术显微镜下进行解剖,逐层切开蝶鞍区各层膜性结构,观察其走行和分布,并注意观察海绵窦段颈内动脉与海绵窦内侧壁的关系；鞍膈及海绵窦内侧壁厚度测量结果比较时采用oneway ANOVA进行分析,若P<0.05则进行进一步多重比较(SNK法)。当P<0.05时认为差异有统计学意义,所有检验均采用双侧检验。文中统计分析均采用SPSS13.0统计软件处理。
四、研究结果
1、视神经颅内段为视神经孔至视交叉的部分。左侧颅内段视神经长度为(12.36±1.71)mm,右侧颅内段长度为(12.20±1.86)mm。视交叉由两侧视神经纤维汇聚而成,向后上方与终板、前联合及下丘脑下部相连接。两侧视神经形成夹角为(62.29±12.17)°,范围(49.20～87.20)°。以鸡冠为中线,视交叉中点66.7%(10例)位于中线上,20%(3例)位于偏向蝶鞍左侧,13.3%(2例)位于偏向右侧。从上方看,鞍膈孔完全被视神经覆盖73.4%(11例),未被完全覆盖26.6%(4例)；鞍膈孔与视交叉的相对位置可分为3种类型,偏向左侧26.7%(4例),居于中线上66.7%(10例),偏向右侧6.6%(1例)。
逐步切除视神经和视交叉,可见蝶鞍两侧的前、后岩床皱襞、蝶棱、鞍背形成一个四边形的区域。鞍膈附着于前方的鞍结节和后方的鞍背之间,构成垂体窝的顶,中央为鞍膈孔,有垂体柄及垂体上动脉通过。鞍膈前后延续为附着于视交叉沟和鞍背的颅底硬膜结构,向两侧延伸构成海绵窦的顶。海绵窦顶与鞍膈无明确的分界。床突间韧带将海绵窦顶分为两个三角即前内侧的颈动脉三角和后外侧的动眼神经三角。鞍膈纤维呈同心圆状环绕鞍膈孔。鞍膈呈下凹型80%(12例),平坦型13.3%(2例),上凸型6.7%(1例)。鞍膈孔为圆形或者椭圆型,内径变异较大,前后径为(6.59±2.45)mm,(2.20～12.10)mm；左右径为(7.32±2.60)mm,(3.10～13.40)mm。根据鞍膈孔的不同,将鞍膈分为3型：紧密型,孔径<5mm,鞍膈较为紧密围绕垂体柄,占13.3%(2例)；常见型：孔径5-10mm,鞍膈孔扩大较为明显,与垂体柄之间有一定间距,占73.4%(11例)；扩大型：孔径>1Omm,鞍膈孔较大,垂体窝周边仅可见少量的硬膜结构,占13.3%(2例)。将鞍结节至鞍背的距离等分为三个部分,则垂体柄与鞍结节、鞍背的位置关系可分为三种类型：前置型,垂体柄位于前三分之一,靠近鞍结节,占6.7%(1例)；居中型,垂体柄居于中间位置,占40%(6例)；后置型,垂体柄位于后三分之一,鞍背的前方,占53.3%(8例)。
2、所有的胎儿颅底标本组织染色均观察到颅底的硬膜在鞍结节和鞍背部位脑膜层和骨膜层分开,脑膜层附于垂体表面,并向下反折包被垂体,双层硬膜在垂体上面形成鞍膈；垂体窝底部位硬膜骨膜层和脑膜层结构再次融合；在有些部位,尤其是脑膜层再次与骨膜层融合的部位,如鞍结节、鞍背和鞍底的部分,两层硬膜可分离从而形成海绵间前窦、海绵间后窦和海绵间下窦。鞍膈从周边即开始发出纤维,膈孔处纤维向下融合于鞍膈周围发出的纤维,共同构成垂体的硬膜囊。垂体囊为连续的硬膜囊袋,其上壁由鞍膈硬膜加强,前壁、后壁和下壁均与骨膜层粘连,外侧壁与海绵窦相邻。垂体被两层膜性结构包裹,内层膜为垂体固有膜,和垂体表面紧贴,并发出纤维束进入腺体中；外层为垂体硬膜囊,两层之间尚有潜在空间。腺垂体向神经垂体过渡中,垂体囊和固有膜逐渐移行接近,在神经垂体表面二者紧贴。海绵窦内的纤维小梁结构将其分为大小不等的许多腔隙,这些小梁结构附着于海绵窦内走行的血管、神经,并贴附于海绵窦顶、内侧壁、外侧壁；海绵窦内侧壁可见由包裹垂体的硬膜囊的外侧壁和附着于其上的纤维层共同构成,其将海绵窦与垂体分隔开来。
成人尸头解剖显示鞍区硬膜结构的移行与胎儿颅底标本组织学观察相符合。垂体周围膜性结构厚度测量结果四组之间有统计学差异(F=53.412,P=0.000),显示鞍膈周边的厚度显著大于膈孔边缘及海绵窦内侧壁,差异有统计学意义(P<0.05)；海绵窦内侧壁下1/3厚度显著小于其上1/3,差异有统计学意义(P<0.05)。并且注意到尽管海绵窦内侧壁下1/3处较上1/3处薄弱,但是结构完整,未见有穿孔及缺损。观测的10头20侧标本中,40%(8侧)可见垂体前叶越过颈内动脉内侧缘连线向海绵窦内扩展,其中有15%(3侧)见到颈内动脉向垂体窝内移位,部分垂体前叶覆于其上,另外15%(3侧)显示垂体向一侧偏移,与一侧的海绵窦段颈内动脉接触,腺垂体前叶突出于海绵窦内,而远离一侧颈内动脉,另外在10%(1例,2侧)标本中见到垂体前叶向两边突出于海绵窦内,呈舌样越过颈内动脉海绵窦段。
五、结论
1、鞍膈孔大部分被视交叉完全被覆盖,少数未被完全覆盖；鞍膈孔大部分位于视交叉的中线上,少部分可向两侧稍偏移；视交叉与鞍膈孔的位置关系可能与垂体腺瘤生长过程中所致的视觉障碍出现的早晚及程度和表现形式有关,即从位于视交叉中线部位膈孔突出的腺瘤多引起双颞侧偏盲,而从视交叉侧方部位膈孔突出的肿瘤常引起左侧或者右侧视野缺损；
2、依据鞍膈孔直径的大小可将鞍膈分为,紧密型、常见型和扩大型；鞍膈孔径大小的变异较大,可对垂体腺瘤的生长方式产生影响,鞍膈孔径大的腺瘤向上生长阻力较小,容易向鞍上扩展,而鞍膈孔径小的由于向上方生长受阻,容易进入到海绵窦、甚至筛窦、蝶窦内；
3、垂体柄与鞍结节、鞍背的位置关系分为3种类型：前置型、居中型和后置型,其中大部分为居中型和后置型,仅少数为前置型；对此解剖关系的认识可以帮助在垂体腺瘤手术中辨认和保护垂体柄和神经垂体；
4、鞍膈是覆盖于蝶鞍上面的硬膜结构,由脑膜层在垂体上部处返折形成的双层结构；海绵窦内侧壁由两层膜性结构组成,即外侧部的垂体硬膜囊和附着于其上的纤维层；海绵窦内侧壁为完整的膜性结构,无局部缺损；
5、垂体前叶正常情况下可以与海绵窦段颈内动脉直接接触,部分甚至可突入海绵窦段颈内动脉上方。在此种解剖关系下,垂体腺瘤在生长过程中可以较为容易的跨过海绵窦段颈内动脉,并进而突入到海绵窦腔,但与海绵窦内结构仍然相隔固有膜、海绵窦内侧壁等膜性结构,并不一定是因为肿瘤侵袭性生长所致；
6、侵袭性垂体腺瘤的诊断和治疗策略的制定,应该结合内分泌学、病理学、影像检查、术中所见等的结果综合考量,并要注意到个体鞍区解剖特点对垂体腺瘤生长方式可能产生的影响。
Background
Pituitary adenomas are benign tumors arising in adenohypophysial cell and approximately represent10-15%intracranial neoplasms, rank third following gliomas and meningiomas. Surgery remains the primary therapy of choice except for prolactinomas. Tumor recurrence after operation is the hardest problem of therapy for pituitary adenomas and seriously threaten to patients' quality of life. There are many factors affecting tumor recurrence, include the size of the tumors, growth rate,the extent of resection,adjuvant therapy, etc. Among those factors, pituitary adenoma extention into surrounding structures, especially into cavernous sinus, are the principal cause which leading to tumor recurrence. Invasive pituitary adenoma was proposed by Jefferson in1940, which was defined as "the pituitary adenoma grows to break its envelope and to invade the adjacent structure such as the dura, the optic nerve, bone and so on". Scheithauer classified invasive pituitary adenomas as the interim type from benign pituitary adenomas to pituitary cancers. These three diseases can not be distinguished in pathology, but show differences in the biological behaviors, pituitary adenomas developed in expansive growth modes and covered by "pseudocapsule" which formed by compression the surrounding structure, invasive pituitary adenomas bring out aggressive growth pattern and invde the diaphragm sellae, bone, vascular vessel, but do not present characteristic of intracranial metastasis which pituitary cancers show. The concept and diagnostic criteria of invasive pituitary adenomas have considerable controversies that lead to the difficulty in diagnosis and treatment. Pathological examination, imaging technology, molecular biology test and operative observation were applied in the diagnosis of invasive pituitary adenomas, these methods provide different medical information, but could not produce a unified diagnostic criteria.
Effects of sellar regional anatomy on growth pattern of pituiary adenomas have drawn the attentions of researchers in recent years. Sellar region is located near the center of the head and consist of the complex configure. The front, rear and bottom of hypophyseal fossa where pituitary gland sited are bony structure, the top and sides are the dura mater and all these structure could restrict the pituitary adenomas extension. In term of morphological study of sellar bone, Wang jian-xin have presented the anatomic features of sellar turcica and carotid sulcus and stated that lateral bone windows of sella turcica and carotid sulcus can affect to different degrees the growth pattern of pituitary. Wei quan-tang found that most of pituitary adenomas grow perpendicularly to pituitary fossa superior orifice and the slant angle of pituitary fossa superior orifice could determine the growth direction of pituitary adenoma toward suprasellar region. Studies on membrane surrounding the pituitary gland have been made for many years. Some researchers state that the there is no a dural wall existing between cavernous sinus and carotid artery, but a loose, fibrous tissue and the extension of pituitary tumors into the cavernous sinuses is not for aggressive growth, but for the absence of a strong separation. There are also some authors declare that the defects exist on the medial wall of cavernous sinus which leads to the expansion of pituitary adenomas into cavernous sinus. Recently, some researchers found through histological and micro-dissection method that the medial wall of cavernous sinus is a intact dural membrane and deduce that invasive adenomas might be a radiological misunderstanding of the extremely displacement of the medial wall by the tumor's pushing, a membranous interface still exists between the tumor and the cavernous sinus.
Sellar region anatomy application for explanation of pituitary adenoma growth modes provided a new way to investigate the reality of invasive pituitary adenomas and would helpful to diagnosis and treatments. The roof of hypophyseal fossa formed by diaphragm sellae and lateral wall by medial wall of cavernous sinus, which are the major obstacles to pituitary adenomas expansion. There were authors even thought that the cancellous bone of the sella turcica is less of a barrier against extension of tumor than the ligamentous attachments of the dural structures. This study was designed to research the anatomic features of dura mater enclosing the pituitary gland and its relationships with the growth pattern of pituitary adenomas was explored.
Objective
1、Observation and description of morphological features of diaphragm sellae, optic chiasm, pituitary stalk are about to make the anatomy of sellar region more systematic and detailed. The relations between diaphragm sellae and pituitary adenomas extension were explored.
2、Histological and anatomic method were used to define the membrane composition of diaphragm sellae and medial wall of cavernous sinus; the position relationship of medial wall of cavernous sinus relative to cavernous segment of internal carotid artery were paid attention to explore its effect on growth pattern of pituitary adenoma.
Material and method
1. Microanatomy of diaphragm sellae, optic chiasm and pituitary stalk
Fifteen adult cadaveric head, the arteries of which were injected with red latex, were used to perform anatomic study. The cranial vault and brain tissue above sellar region were removed and optic nerve, optic tract were intently reserved. Under the surgical microscopy, the length of intracranial segment of optic nerve, the angle of optic chiasm were measured and position relationships of foramen diaphragm sellae relative to optic chiasms were noted. After optic nerve being cut in the intracranial opening of the optic canal, we backward fliped the optic nerve and optic chiasm, discontinued the pituitary stalk at the junction connected to the infundibulum. The anatomical data and morphological characteristic of pituitary stalk, diaphragm sellae and adjacent structure were measured and demonstrated.
2. Microanatomy of diaphragm sellae and medial wall of cavernous sinus
Heads from6fetal cadavers aged6to8months were studied. All specimens were infused with10%formalin solution into the umbilical to embalm all specimens. Tissue blocks of skull base (include sellar region, cavernous sinus, part of middle cranial fossa and petrous bone) were dealt with decalcification, dehydrating, embedding. Serial histological sections were obtained in sagittal and coronal direction. All these sections were stained with Masson's triple and picrosirius-picric acid staining. Under the light microscopy, the course and distribution of the membranate structures were observed. Ten adult cadaveric head, the arteries of which were injected with red latex and the veins with blue latex, were used to perform anatomic study. Under the surgical microscope, membranous structure of sellar region were dissected step by step, their course and distribution of the membranate structures were described, the position relationships of cavernous segment of internal carotid artery and medial wall of cavernous sinus were remarked especially. Mean of the thickness of diphragma sellae and medial wall of cavernous sinus was compared with oneway ANOVA, and if P<0.05, for further multiple comparison with SNK method. The criterion for statistical significance for all tests was P<0.05, all tests used two-tailed test. All data processing were carried out in SPSS13.0statistical software.
Result
1. The length of intracranial segment of right optic nerve were12.36±1.71mm, and the left were12.20±1.86mm. Both sides of the optic nerve fibers converge to form the optic chiasm, which posteriorly continued with lamina terminalis, anterior commissure and lower part of the hypothalamus. The angle of optic chiasm were62.29±12.17°(range,49.20-87.20°). The midpoint of the optic chiasm passing through crista galli were located on the midline in66.7%(10cases) and to the left and right sides of the sella turcica in20%(3cases) and13.3%(2cases) respectively. The foramen diaphragm sellae (FDS) was completely covered by OC in73.4%(11cases), but it was partly seen superiorly in26.6%(4cases). The position of FDS relative to OC situated in the midline in66.7%(10cases), to the left part in26.7%(4cases) and right part in6.6%(1case).
After the optic nerve and optic chiasm having been removed, a quadrilateral area were seen which formed by limbus sphenoidale, dorsum sellae, and anterior, posterior petroclinoid ligament. The diaphragma sellae attachs to the tuberculum sellae and dorsum sellae and forms the roof of the hypophyseal fossa. In the center, the diaphragm has an opening through which the infundibulum and inferior hypophyseal artery courses. The diaphragm sellae extends from the tuberculum sellae anteriorly to the dorsum sellae posteriorly. Laterally, it limits to the roof the cavernous sinus. There is no a clear boundary between diaphragm and the roof. The roof of cavernous sinus were divided by interclinoid ligament into anteromedial carotid triangle and posterolateral oculomotor triangle. Diaphragmatic fibers were concentrically around the foramen. Diaphragm sellae appeared concave in80%(12cases), convex in13.3%(2cases) and flat in6.7%(1case) when view from above. The foramen diaphragm sellae is round or oval and its diameter greatly varied. The average of anteroposterior distance of foramen diaphragm sellae was6.59±2.45mm (range,2.20-12.10mm) and the average lateral-to-lateral distance was7.32±2.60mm (range,3.10-13.40mm). we classified the diaphragm sellae into three types according to the foramen diaphragm sellae diameters variations, closed type, the diaphragmatic opening was less than5mm and the pituitary stalk was tightly surrounded in13.3%(2cases); normal type, the diaphragmatic foramen was5-10mm and the gap exist between stalk and diaphragma in73.4%(11cases); and open type, the diaphragmatic opening was more than10mm and the remnants of the diaphragma were seen around the upper part of the pituitary fossa in13.3%(2cases). The position relationship of pituitary stalk relative to the tuberculum and dorsum sellae can be classified3type, prefix typed, pituitary stalk sited in front of dorsum sellae in53.3%(8cases);middle type, in the middle part in40%(6cases) and postfix type, in the the back of tuberculum sellae in6.7%(1case).
2. In all fetal skull base specimens, dura mater was found to divided into meningeal and periosteal layer over the tuberculum sellae and dorsum sellae. The meningeal layer covers the pituitary gland and folds downward around the foramen. Two meningeal layer formed diaphragm sellae on the top of hypophyseal fossa. Meningeal and periosteal layer mix together again in the bottom of sellar floor. In the meningeal layer and periosteal layers confluence, anterior intercavernous sinus, posterior intercavernous sinus and inferior intercavernous sinus were shaped. The dural fibers sent out from the periphery and the center of diaphragma fused to constitute the pituitary dural sac. The pituitary sac is a continuous dual pouch, its superior wall is strengthened by diaphragm sell, the anterior, posterior and inferior wall adhere to the periosteal layer, lateral wall is a screen which separated the cavernous sinus. The pituitary gland is founded to be packed by two membranous layer, the inner layer is lamina propria which tightly adheres to the gland and and some connective tissue penetrated the gland, the outer layer is the dural sac. A potential space between the2layers was found on the surface of the adenohypophysis. these2layers got closer and closer from the anterior lobe toward the posterior lobe of the gland and finally adhered on the surface of the neurohypophysis. Many fibrous trabeculae divided cavernous sinus into a lot of cavity, which adhere to the wall of cavernous sinus and neurovascular structure coursed in it. The medial wall of the cavernous sinus is a bilayered membrane, composed of the lateral part of the pituitary sac and the fibrous layer, which separated the pituitary gland from the cavernous sinus.
The course and distribution of the membranous structures observed by adult cadaver head dissection are corresponded to the results obtained from histological study in the fetal skull base specimens. Thickness of membranes surrounding pituitary gland were statistically difference between four groups(F=53.412, P=0.000). The periphery of diaphragm sellae was significantly thicker than the center and the medial wall of cavernous sinus(P<0.05); the thickness of the upper third was statistically greater than the lower third(P<0.05).The medial wall of cavernous sinus are intact without perforations and defects although the weakness were founded in lower third than upper third of it. In8of the20cavernous sinus, the sellar part of the medial wall rested against the intracavernous carotid; in15%(3sides) the internal carotid arteries shifted from sulcus and partly squeezed into the hypophyseal fossa, that leaded to be partly coated by medial wall of cavernous sinus; in15%(3sides) the anterior lobe of pituitary gland extended towards one side of the cavernous sinus and closely contact the internal carotid artery, but away from another side; and in10%(2sides in the same specimens) there was a tongue-like lateral protrusion of the gland that extended around the cavernous segment of the intracavernous carotid.
Conclusion
1. Most of the foramen diaphragm sellae are completely covered by optic chiasm, but few are partly seen superiorly. The position of foramen diaphragm sellae relative to optic chiasm situated in the midline account for the majority, to the left and right part manifest minority. This positional relationship could be used to explain the visual symptoms of patients with pituitary tumors. Pituitary adenomas protrude from diaphragmatic foramen located in the midline of optic chiasm result in bitemporal hemianopsia, while in the side of the optic chiasm lead to left or right visual field defect.
2. The diaphragm sellae could be classified into three types according to the diaphragmatic foramen diameters variations, closed type; normal type; and open type. The sizes of diaphragmatic opening could affect the growth direction of pituitary adenomas. If the opening was large, the resistance from the top was less than from others sides and the pituitary tumor was inclined to suprasellarly grow. While if the opening was small, the tumor was barriered by diaphragm sella and easily extended into the cavernous sinus, even broke through the bony structures into ethmoid and sphenoid sinus.
3. The position of pituitary stalk could be categorized as3types:prefixed type, middle type, and postfixed type. Postfix and middle type accounted for the vast majority, only a small number of prefix type. This anatomic knowledge is helpful to identify and protect the pituitary stalk and neurohypophysis in the operations.
4. The diaphragm sellae covers the hypophyseal fossa and formed by2meningeal layer. The dural fibers sent out from the periphery and the center of diaphragma fused to constitute the pituitary dural sac. The medial wall of the cavernous sinus is a bilayered membrane and the2layers of the medial wall are composed of the lateral part of the pituitary sac and the fibrous layer. The medial wall is intact without perforations and defects.
5. The normal anterior lobe of pituitary gland might rest against the cavernous segment of internal carotid artery. In this anatomic conditions, the tumor could easily cross the carotid artery into the cavernous sinus and membranous layers such as lamina propria, the medial wall would exist between the tumor and the cavernous sinus, so that the tumor was not invasive growth.
6. The diagnosis and treatment of invasive pituitary adenomas should based on endocrinology, pathology, imaging, and intraoperative findings, especially the influence of sellar regional anatomy on the growth pattern should be taken into considerations.
引文
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