儿童遗传性多发性骨软骨瘤软骨帽的超微结构观察
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摘要
儿童遗传性多发性骨软骨瘤(Hereditary Multiple Exostoses, HME)是一种涉及人体骨骼系统,影响正常软骨化骨过程的遗传性骨骼疾病。本病是小儿骨科中最常见的良性骨肿瘤,发病率较低约为1/5万,男性发病率高于女性,男女比例约为3：1。儿童HME的瘤体由软骨组织的帽状结构和几乎与骨骼骨面垂直突出的骨组织构成,大多数分布在关节周围,即长骨的干骺端,肋骨、肩胛骨、骨盆等处有少量分布。肿瘤的特点是生长于瘤体的顶部有一形似帽子的软骨层即软骨帽,通过其深层的软骨化骨作用,使瘤体持续生长,肿瘤增长较大时可引起局部疼痛或者导致骨骼畸形,近关节的可引起活动障碍,或可压迫邻近的血管神经而引起相应的症状,若肿瘤突然长大或生长迅速,应考虑有恶变的可能。很多学者从遗传致病基因定位、发病机制、临床表现及分型、影像学等方面对HME进行过深入的研究,软骨帽过度生长已被认为是HME恶变的主要原因之一。
目的
本课题通过扫描电镜和透射电镜观察儿童遗传性多发性骨软骨瘤软骨帽的超微结构,以提高对儿童HME的超微病理认识,探寻该病的发病机制,为儿童HME超微病理诊断提供可靠依据。阐述儿童HME复发原因,为手术治疗提供一定的指导。
方法
1.研究对象
实验组：病例选择我院小儿骨科病区2010年10月-2012年6月收治的32例HME患儿。对照组：病例选择我院小儿骨科病区相同时期收治的多指患儿32例,因手术切除的多指骨骺软骨。对照组与实验组在年龄、性别、标本处理方法等相配对；明确无家族遗传病史；术前检查无代谢系统及它处骨骼疾病。以上病例均经医院伦理委员会审批和家属签署知情同意书。
2.研究方法
将所取新鲜的瘤体软骨帽或多指正常软骨用生理盐水冲洗后,放入10%福尔马林溶液中,制作光学显微镜切片,应用光镜观察。
去除所取HME软骨帽及多指正常软骨标本表面附着物并用磷酸盐缓冲液或生理盐水将标本清洗后,立即置于25g/L的戊二醛固定液中4℃恒温固定2h以上。根据实验的需要,按要求制作成扫描电镜及透射电镜标本,应用扫描电镜及透射电镜观察研究。
结果
1.多指正常软骨和儿童HME瘤体软骨帽的光镜观察
多指正常软骨HE染色后光镜观察：镜下见软骨膜以及软骨组织,近软骨膜处有呈散在分布,体积较小,呈扁平状的软骨细胞；组织深部可见分裂增生,体积增大,呈同源群分布的软骨细胞,软骨陷窝明显,软骨基质均质状分布,呈紫蓝色。
儿童HME瘤体软骨帽光镜观察：软骨帽表面可见粉红色纤维性骨膜；软骨细胞都在隐窝内,常垂直于基底骨排列成柱状,在基底部它们形成骨小梁。
2.多指正常软骨和儿童HME瘤体软骨帽的扫描电镜观察结果
对照组(多指正常软骨)：冷冻断裂的软骨组织内见少量的软骨细胞位于软骨陷窝内,细胞呈圆形或不规则,细胞表面有少量的突起；软骨组织表面可见大量散乱、稀疏的胶原纤维。
实验组(儿童HME瘤体软骨帽)：冷冻断裂的软骨组织内见大量不规则的软骨陷窝,每个软骨陷窝内均含有软骨细胞,细胞增生明显,软骨细胞体积较大,形状不规则,细胞表面有丰富的细胞突起；软骨组织表面的胶原纤维较对照组结构致密。
3.多指正常软骨和儿童HME瘤体软骨帽的透射电镜观察结果
对照组(多指正常软骨)：软骨细胞数量不多,细胞多呈椭圆形,细胞表面有少量短小的微绒毛,细胞核形状不规则,核内染色质凝集、边集；细胞质内可见到少量的细胞器,线粒体较小,糖原颗粒呈簇状分布,粗面内质网成条索样分散在细胞质内。
实验组(儿童HME瘤体软骨帽)：大量的瘤样细胞增生,瘤细胞体积较大,聚集分布；细胞核较大,核内常染色质丰富,核仁明显,核质比较高；细胞质内可见到扩张的粗面内质网以及圆形或椭圆形的线粒体,溶酶体数量较少；瘤细胞间可见到毛细血管,血管腔内充满红细胞及血浆蛋白,细胞间亦有蛋白样物质的沉积；在瘤样细胞附近可见到明显增多的软骨细胞,软骨细胞体积较对照组增大,形态呈梭形,细胞核圆形,核内常染色质丰富,有明显的核仁；细胞质内可见到大量粗面内质网,粗面内质网呈池样扩张,扩张的池内充满细颗粒样物质：线粒体数量较少,游离核糖体常可见到。
结论
1.儿童HME瘤体软骨帽软骨组织代谢旺盛,细胞增生及蛋白质合成活动活跃,部分瘤体软骨帽胶原纤维致密有钙化倾向,具有使瘤体恶变的一定物质基础,这与儿童HME的发病、发展、转归等因素密切相关。
2.儿童HME软骨帽是瘤体恶变、复发的根源所在。
Children hereditary multiple osteochondroma (HME) is a genetic bone disease affecting the process of normal cartilage bone. This disease is the most common benign bone tumor in children. The incidence of HME is about1/50000, the incidence in male is higher than female, the ratio of male to female is approximately3:1. The tumor of children HME is consisted of the cap-like structure of cartilage tissue and the prominent bone tissue which is almost perpendicular to the bone surface. Children HME used to appear mostly around the joints, such as the metaphysis of long bones, ribs, scapula, pelvis, etc. The characteristic of the tumor is having a cartilage cap in the top of the tumor, the tumor continued to grow through its deep cartilage bone formation, tumor growth can cause local pain, bone deformities, movement disorder when the tumor is near joints, compress the adjacent blood vessels and nerves then cause corresponding symptoms. If the tumor suddenly grew up or rapid growth, malignant changes of the tumor should be considered. Many scholars have depth study of the HME from the genetic disease genes, pathogenesis, clinical manifestations and genotyping, imaging, and excessive cartilage cap growth has been considered to be one of the main reasons of the HME malignant transformation.
Objective
We observe the ultrastructure of children HME's cartilage cap by scanning electron microscopy and transmission electron microscopy, in order to improve the understanding of the ultrastructural pathology of children HME, explore the pathogenesis of the disease, provide diagnosisreliable basis for children HME Ultrastructural pathologic, evaluate the reasons for the recurrence of children HME, and to provide some guidance for surgical treatment.
Methods
1. Material
Experimental groups:select32HME childern in the pediatric orthopedic ward of our hospital between October2010and June2012. Control group:Select32cases of multi-fingered children, due to surgical resection of multi-fingered epiphyseal cartilage. The control group and the experimental group matched on age, gender, specimen processing methods; clear history of familial; preoperative examination without metabolic system and other bone diseases. The above cases were confirmed by the hospital ethics committee approval and their families signed informed consent.
2. Methods The tumor cartilage cap or multi-finger normal cartilage were freshed with saline, then fixed in10%formalin solution, making the optical microscope slice, observe the structural by light microscopy.
Wash the tissue with phosphate buffered saline or saline after removal of the take the HME cartilage cap and multi-finger normal cartilage specimens surface fixtures. Then fixed the specimens in glutaraldehyde (25g/L) at4℃for2h immediately. Required according to the needs of the experiment made into a scanning electron microscopy and transmission electron microscopy specimens, to prepare for experimental applications.
Results
1. Multi-finger normal cartilage and children the HME patients the tumor of cartilage cap observed by light microscopy
Multi-finger normal cartilage HE staining observed by light microscopy: Microscopically perichondrium and cartilage tissue near the perichondrium were scattered distribution, small volume, chondrocytes were flat; tissue deep the visible split hyperplasia, increased volume, washomologous group distribution of cartilage cells, cartilage lacunae obvious cartilage matrix the homogeneous-shaped distribution, purple-blue.
Children's the HME tumor cartilage cap observed by light microscopy:the cartilage cap visible on the surface of a pink fibrous periosteum; cartilage cells in the crypts, often perpendicular to the basal bone arranged in columnar formation of cartilage and bone in the base of them.
2. Scanning electron microscopy of multi-finger normal cartilage and children HME patients tumor cartilage cap
The control group (multi-finger normal cartilage):freeze-fracture of the cartilage tissue seen in a small number of chondrocytes in cartilage space within the cell is round or irregular, the cell had small bumps on the surface; cartilage surface a large number of scattered, sparse collagen fibres.
Experimental group (children HME the tumor cartilage cap):freeze-fracture of the cartilage tissue to see a large number of irregular cartilage lacunae, each lacuna containing cartilage cells, cell proliferation significantly larger chondrocytes irregular shape abundant cells, cell surface protrusions; the dense structure of the collagen fibers of the cartilage tissue surface compared to the control group.
3. Transmission electron microscopy observations of multi-finger normal cartilage and children HME patients tumor cartilage cap
Control group (multi-finger normal cartilage):a small number of chondrocytes, the cells were mostly oval cells in the surface of a small amount of short microvilli, nucleus irregularly shaped nuclear chromatin condensation, edge set; visible cytoplasmto a small number of cells, the rough endoplasmic reticulum into cord-like dispersed in the cytoplasm, mitochondria smaller glycogen granules were clustered distribution.
Experimental group (children HME the tumor cartilage cap):a large number of tumor-like cell hyperplasia, tumor cells larger aggregated distribution; nuclei were larger nuclei rich in euchromatin, prominent nucleoli, nucleoplasm; visible cytoplasm to round or oval mitochondria and expansion of the rough endoplasmic reticulum, a small number of lysosomes; tumor cells can be seen between the capillaries, vascular cavity filled with red blood cells and plasma proteins, cells, some protein-like substances deposited; cartilage cells, cartilage cell volume increased significantly compared with the control group increased fusiform morphology, the nucleus round nuclear euchromatin rich, prominent nucleoli can be seen near the tumor-like cells; cytoplasm can be seen within a large number of rough surface endoplasmic reticulum, rough endoplasmic reticulum was pool-like expansion, expansion tanks filled with fine granular material:the small number of mitochondria, free ribosomes can frequently be seen.
Conclusions
1. The cartilage cap in Children HME tumor cartilage metabolism,the cell proliferation and protein synthesis are active, some the tumor the cartilage caps collagen fiber dense calcification tendency has certain material foundation of the tumor malignant, child HME genetic disease, development, and outcome factors closely related.
2. The cartilage cap in Children HME is the root of malignant transformation and recurrent.
目的
本课题通过扫描电镜和透射电镜观察儿童遗传性多发性骨软骨瘤软骨帽的超微结构,以提高对儿童HME的超微病理认识,探寻该病的发病机制,为儿童HME超微病理诊断提供可靠依据。阐述儿童HME复发原因,为手术治疗提供一定的指导。
方法
1.研究对象
实验组：病例选择我院小儿骨科病区2010年10月-2012年6月收治的32例HME患儿。对照组：病例选择我院小儿骨科病区相同时期收治的多指患儿32例,因手术切除的多指骨骺软骨。对照组与实验组在年龄、性别、标本处理方法等相配对；明确无家族遗传病史；术前检查无代谢系统及它处骨骼疾病。以上病例均经医院伦理委员会审批和家属签署知情同意书。
2.研究方法
将所取新鲜的瘤体软骨帽或多指正常软骨用生理盐水冲洗后,放入10%福尔马林溶液中,制作光学显微镜切片,应用光镜观察。
去除所取HME软骨帽及多指正常软骨标本表面附着物并用磷酸盐缓冲液或生理盐水将标本清洗后,立即置于25g/L的戊二醛固定液中4℃恒温固定2h以上。根据实验的需要,按要求制作成扫描电镜及透射电镜标本,应用扫描电镜及透射电镜观察研究。
结果
1.多指正常软骨和儿童HME瘤体软骨帽的光镜观察
多指正常软骨HE染色后光镜观察：镜下见软骨膜以及软骨组织,近软骨膜处有呈散在分布,体积较小,呈扁平状的软骨细胞；组织深部可见分裂增生,体积增大,呈同源群分布的软骨细胞,软骨陷窝明显,软骨基质均质状分布,呈紫蓝色。
儿童HME瘤体软骨帽光镜观察：软骨帽表面可见粉红色纤维性骨膜；软骨细胞都在隐窝内,常垂直于基底骨排列成柱状,在基底部它们形成骨小梁。
2.多指正常软骨和儿童HME瘤体软骨帽的扫描电镜观察结果
对照组(多指正常软骨)：冷冻断裂的软骨组织内见少量的软骨细胞位于软骨陷窝内,细胞呈圆形或不规则,细胞表面有少量的突起；软骨组织表面可见大量散乱、稀疏的胶原纤维。
实验组(儿童HME瘤体软骨帽)：冷冻断裂的软骨组织内见大量不规则的软骨陷窝,每个软骨陷窝内均含有软骨细胞,细胞增生明显,软骨细胞体积较大,形状不规则,细胞表面有丰富的细胞突起；软骨组织表面的胶原纤维较对照组结构致密。
3.多指正常软骨和儿童HME瘤体软骨帽的透射电镜观察结果
对照组(多指正常软骨)：软骨细胞数量不多,细胞多呈椭圆形,细胞表面有少量短小的微绒毛,细胞核形状不规则,核内染色质凝集、边集；细胞质内可见到少量的细胞器,线粒体较小,糖原颗粒呈簇状分布,粗面内质网成条索样分散在细胞质内。
实验组(儿童HME瘤体软骨帽)：大量的瘤样细胞增生,瘤细胞体积较大,聚集分布；细胞核较大,核内常染色质丰富,核仁明显,核质比较高；细胞质内可见到扩张的粗面内质网以及圆形或椭圆形的线粒体,溶酶体数量较少；瘤细胞间可见到毛细血管,血管腔内充满红细胞及血浆蛋白,细胞间亦有蛋白样物质的沉积；在瘤样细胞附近可见到明显增多的软骨细胞,软骨细胞体积较对照组增大,形态呈梭形,细胞核圆形,核内常染色质丰富,有明显的核仁；细胞质内可见到大量粗面内质网,粗面内质网呈池样扩张,扩张的池内充满细颗粒样物质：线粒体数量较少,游离核糖体常可见到。
结论
1.儿童HME瘤体软骨帽软骨组织代谢旺盛,细胞增生及蛋白质合成活动活跃,部分瘤体软骨帽胶原纤维致密有钙化倾向,具有使瘤体恶变的一定物质基础,这与儿童HME的发病、发展、转归等因素密切相关。
2.儿童HME软骨帽是瘤体恶变、复发的根源所在。
Children hereditary multiple osteochondroma (HME) is a genetic bone disease affecting the process of normal cartilage bone. This disease is the most common benign bone tumor in children. The incidence of HME is about1/50000, the incidence in male is higher than female, the ratio of male to female is approximately3:1. The tumor of children HME is consisted of the cap-like structure of cartilage tissue and the prominent bone tissue which is almost perpendicular to the bone surface. Children HME used to appear mostly around the joints, such as the metaphysis of long bones, ribs, scapula, pelvis, etc. The characteristic of the tumor is having a cartilage cap in the top of the tumor, the tumor continued to grow through its deep cartilage bone formation, tumor growth can cause local pain, bone deformities, movement disorder when the tumor is near joints, compress the adjacent blood vessels and nerves then cause corresponding symptoms. If the tumor suddenly grew up or rapid growth, malignant changes of the tumor should be considered. Many scholars have depth study of the HME from the genetic disease genes, pathogenesis, clinical manifestations and genotyping, imaging, and excessive cartilage cap growth has been considered to be one of the main reasons of the HME malignant transformation.
Objective
We observe the ultrastructure of children HME's cartilage cap by scanning electron microscopy and transmission electron microscopy, in order to improve the understanding of the ultrastructural pathology of children HME, explore the pathogenesis of the disease, provide diagnosisreliable basis for children HME Ultrastructural pathologic, evaluate the reasons for the recurrence of children HME, and to provide some guidance for surgical treatment.
Methods
1. Material
Experimental groups:select32HME childern in the pediatric orthopedic ward of our hospital between October2010and June2012. Control group:Select32cases of multi-fingered children, due to surgical resection of multi-fingered epiphyseal cartilage. The control group and the experimental group matched on age, gender, specimen processing methods; clear history of familial; preoperative examination without metabolic system and other bone diseases. The above cases were confirmed by the hospital ethics committee approval and their families signed informed consent.
2. Methods The tumor cartilage cap or multi-finger normal cartilage were freshed with saline, then fixed in10%formalin solution, making the optical microscope slice, observe the structural by light microscopy.
Wash the tissue with phosphate buffered saline or saline after removal of the take the HME cartilage cap and multi-finger normal cartilage specimens surface fixtures. Then fixed the specimens in glutaraldehyde (25g/L) at4℃for2h immediately. Required according to the needs of the experiment made into a scanning electron microscopy and transmission electron microscopy specimens, to prepare for experimental applications.
Results
1. Multi-finger normal cartilage and children the HME patients the tumor of cartilage cap observed by light microscopy
Multi-finger normal cartilage HE staining observed by light microscopy: Microscopically perichondrium and cartilage tissue near the perichondrium were scattered distribution, small volume, chondrocytes were flat; tissue deep the visible split hyperplasia, increased volume, washomologous group distribution of cartilage cells, cartilage lacunae obvious cartilage matrix the homogeneous-shaped distribution, purple-blue.
Children's the HME tumor cartilage cap observed by light microscopy:the cartilage cap visible on the surface of a pink fibrous periosteum; cartilage cells in the crypts, often perpendicular to the basal bone arranged in columnar formation of cartilage and bone in the base of them.
2. Scanning electron microscopy of multi-finger normal cartilage and children HME patients tumor cartilage cap
The control group (multi-finger normal cartilage):freeze-fracture of the cartilage tissue seen in a small number of chondrocytes in cartilage space within the cell is round or irregular, the cell had small bumps on the surface; cartilage surface a large number of scattered, sparse collagen fibres.
Experimental group (children HME the tumor cartilage cap):freeze-fracture of the cartilage tissue to see a large number of irregular cartilage lacunae, each lacuna containing cartilage cells, cell proliferation significantly larger chondrocytes irregular shape abundant cells, cell surface protrusions; the dense structure of the collagen fibers of the cartilage tissue surface compared to the control group.
3. Transmission electron microscopy observations of multi-finger normal cartilage and children HME patients tumor cartilage cap
Control group (multi-finger normal cartilage):a small number of chondrocytes, the cells were mostly oval cells in the surface of a small amount of short microvilli, nucleus irregularly shaped nuclear chromatin condensation, edge set; visible cytoplasmto a small number of cells, the rough endoplasmic reticulum into cord-like dispersed in the cytoplasm, mitochondria smaller glycogen granules were clustered distribution.
Experimental group (children HME the tumor cartilage cap):a large number of tumor-like cell hyperplasia, tumor cells larger aggregated distribution; nuclei were larger nuclei rich in euchromatin, prominent nucleoli, nucleoplasm; visible cytoplasm to round or oval mitochondria and expansion of the rough endoplasmic reticulum, a small number of lysosomes; tumor cells can be seen between the capillaries, vascular cavity filled with red blood cells and plasma proteins, cells, some protein-like substances deposited; cartilage cells, cartilage cell volume increased significantly compared with the control group increased fusiform morphology, the nucleus round nuclear euchromatin rich, prominent nucleoli can be seen near the tumor-like cells; cytoplasm can be seen within a large number of rough surface endoplasmic reticulum, rough endoplasmic reticulum was pool-like expansion, expansion tanks filled with fine granular material:the small number of mitochondria, free ribosomes can frequently be seen.
Conclusions
1. The cartilage cap in Children HME tumor cartilage metabolism,the cell proliferation and protein synthesis are active, some the tumor the cartilage caps collagen fiber dense calcification tendency has certain material foundation of the tumor malignant, child HME genetic disease, development, and outcome factors closely related.
2. The cartilage cap in Children HME is the root of malignant transformation and recurrent.
引文
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