颅咽管瘤的个体化治疗分析

目的 探讨颅咽管瘤个体化治疗方法以及不同治疗方法的适应症。方法 2011~2013年收治颅咽管瘤83例,首次发病者行手术切除,不能耐受开颅手术者行立体定向囊液抽吸+32P囊内放疗或伽玛刀治疗;囊性为主复发者行立体定向囊液抽吸+32P囊内放疗,合并实体病变者结合伽玛刀治疗;病变体积小,未侵及下丘脑以及第三脑室的实体复发者采取开颅手术治疗;术后残余、复发实体病灶无法实施手术切除者行伽玛刀治疗。结果 开颅手术切除46例;采取立体定向囊液抽吸+32P囊内放疗32例,其中11例同时接受伽玛刀治疗;单独接受伽玛刀治疗5例。所有患者随访11~40个月,治疗有效75例,稳定4例,进展4例。并发症发生率为45.8%。结论 颅咽管瘤患者的治疗方案,应根据患者具体临床表现及影像学特征,个体化制定、实施。     

Nerve connections between mouse and rat hippocampal brain tissue: ultrastructural observations after intracerebral xenografting

Fascia dentata tissue from embryonic mice was grafted to the hippocampal region of newborn Kyoto rats. After 1–7 months the recipients received lesions of the entorhinal cortex on the side of transplantation. Three days later their brains were processed for electron microscopy. The xenografts were identified by their content of mouse dentate granule cells which have smaller cell nuclei with more nucleoli than the corresponding host rat granule cells. Electron dense, degenerating host rat entorhinal fibers terminated in the outer parts of the mouse dentate molecular layer corresponding to the normal perforant path zones. They formed the normal type of synaptic contacts with dendritic spines. The findings demonstrate that precise synaptic contacts can be made across a species barrier.     

Gliosarcomas: Histological,immunohistochemical, ultrastructural,and tissue culture studies

Summary Thirty-nine cases of gliosarcomas, two initiating as fibrosarcomas, 25 as mixed gliomas and sarcomas, and 12 as anaplastic gliomas with secondary sarcomas, were studied by light microscopy, immunohistochemistry, using GFAP, factor VIII/RAg, andUlex europaeus I agglutinin (UEA I), electron microscopy and tissue culture. GFAP was found variably positive in the glial areas; F VIII/RAg and UEA I, markers of both normal and neoplastic endothelial cells and their derivatives, were found in vessels of both gliomatous and sarcomatous parts of GS, less intensive in hyperplastic glomeruloid structures and, with decreasing intensity, in adjacent fibrosarcomatous areas, while UEA I, giving stronger reaction than F VIII/RAg, was occasionally demonstrated in sarcomatous cells. In vitro studies confirmed previous data of a separate growth of glial and mesenchymal cells with a divergent migratory speed. Electron microscopy demonstrated the frequent close admixture of glial and mesenchymal tumor cells, which showed the feature of either fibrosarcoma or angiosarcoma. The frequent resemblance of the latter with endothelial cells was supported by the occasional demonstration of Weibel-Palade-like bodies in both vascular endothelial and adjacent sarcomatous cells. These observations confirm the hypothesis that at least part of the sarcomatous components in many GS originate from vascular endothelial proliferation and obviously represent the final stage of a process starting with the endothelial hyperplasia in anaplastic gliomas.     

Comparative ultrastructural observations on peripheral nerve abnormalities in the late infantile,juvenile and late onset forms of metachromatic leukodystrophy

Summary The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons.     

Recurrence in pediatric craniopharyngiomas: analysis of clinical and histological features

Objective The purpose of this study was to investigate the recurrence pattern and significance of various clinical and histological features as predictors of recurrence in pediatric craniopharyngiomas.Methods A series of 116 pediatric craniopharyngiomas (68 boys and 48 girls; age range, 1.6–18 years) was reviewed. Mean follow-up period was 18.53 months. Tumors recurred in 15 patients within 96 months [mean recurrence-free survival (RFS), 12.67 months]. Of the recurrence cases, 2 had complete (mean RFS, 16 months) and 13 had subtotal tumor excision (mean RFS, 9.03 months). Histologically, an adamantinous pattern was seen in 95% of cases, whereas a papillary pattern was noted in 5%. Brain tissue was included in 41 cases. In 32 of 41 cases, brain invasion was noted, and all were of adamantinous histology. No correlation was noted of histopathological subtyping or brain invasion with recurrence.Conclusions The significant clinical factors associated with recurrence included extent of resection, tumor size >4 cm, and cystic tumors.     

微血管减压术治疗原发性典型与不典型三叉神经痛对比研究

目的探讨原发性典型与不典型三叉神经痛微血管减压术治疗的临床效果。方法选择原发性典型与不典型三叉神经痛患者各40例,在全身麻醉气管插管下完成微血管减压术,比较2组术中所见血管压迫来源、压迫程度及血管压迫位置。结果典型三叉神经痛组压迫血管来源为单纯动脉占85.0%,显著高于非典型三叉神经痛组的57.5%(P0.05);来源为动静脉混合占15.0%,显著低于非典型三叉神经痛组的42.5%(P0.05);典型三叉神经痛组血管与神经位置接触者显著高于非典型三叉神经痛者(P0.05),术中发生三叉神经出现萎缩者比例显著少于非典型三叉神经痛者(P0.05),典型三叉神经痛者其压迫血管在近端者显著多于非典型三叉神经痛者(P0.05),压迫血管在远端者显著少于非典型三叉神经痛者(P0.05)。结论原发性三叉神经痛实施血管减压术,术前鉴定其发病特点,在预测其压迫血管类型、位置及其与神经的关系具有一定临床价值。     

Light and electron microscopic analysis of insulin binding sites on neurons in dissociated brain cell cultures

The distribution of insulin binding sites on primary cultured neurons and glia from the fetal rat was examined by the immunoperoxidase method using a specific insulin receptor antiserum. Light and electron microscopic analysis revealed a homogenous distribution of insulin binding sites on selective neuron-like cells of the dissociated cell culture system. To determine the influence of medium insulin on the distribution of insulin binding sites, dissociated cell cultures were maintained in the presence or absence of porcine insulin for varying time periods. We observed a significant increase in the number of insulin stained neuron-like cells maintained in insulin free defined medium compared to neuron-like cells maintained in insulin supplemented defined medium. Further, we examined the distribution of insulin binding sites after incubation with the antibody, which has agonistic properties in peripheral tissues, for varying time periods prior to fixation. Under these conditions, the light microscopic analysis revealed a heterogeneous (patchy) distribution of immunoreactive insulin binding sites, suggesting that the ligand receptor complex migrates. These results demonstrate the presence and distribution of insulin binding sites on neurons maintained in vitro, and provide morphological evidence to support a functional role for insulin in CNS tissues.     

Central neurocytoma: an immunohistochemical, ultrastructural and cell culture study

To clarify the histogenesis and differentiation potential of central neurocytoma, a pathological investigation of seven tumors from three patients was conducted using immunohistochemistry and ultrastructural analysis in addition to systematic in vitro studies. Six tumors were studied immunohistochemically and five were examined ultrastructurally. All cases that were immunostained were positive for synaptophysin in nuclear-free neuropil islands. In five tumors, a few tumor cells, in addition to reactive astrocytes, were positive for glial fibrillary acidic protein (GFAP). Vimentin staining was also positive in a few tumor cells of five specimens. Neurofilament staining was always negative. All cases for which ultrastructure was examined showed various synaptic abnormalities. Cultured cells were subdivided into three distinct tumor cell types: neuronal cells which stained for neurofilament proteins with neurosecretory granules; small flat undifferentiated cells with a high nuclear-cytoplasmic ratio and scant cytoplasmic organelles; and small round or multipolar astrocytic cells with 10-nm intermediate filaments which stained for GFAP. Our tissue culture studies disclosed that cultured neurocytoma cells form a cellular mosaic similar to subependymal plate layers that are composed of mitotically active cells, neurons and glia. Received: 21 October 1996 / Revised, accepted: 26 February 1997     

Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems II. Electron microscopy observations

Summary The sequential electron microscopic features of six malignant nerve sheath tumors (three cranial and three spinal) induced in rats by transplacental ethylnitrosourea and maintained in organ culture systems were compared with those of a human acoustic Schwannoma similarly cultured. After 4 weeks in vitro, the malignant tumor cells often showed progressive elongation of their processes, with the development of an interdigitating pattern resembling that seen in well-differentiated Schwannomas. This was accompanied by an increase of microtubules. Basal lamina formation, less well-developed and less complete than in the benign Schwannoma in this study, was maintained in culture. Some explants demonstrated an increase in number and width of collagen fibrils, accompanied by a relative concomitant decrease of intercellular basement membrane material. The malignant tumor cells also showed numerous micropinocytotic vesicles and various junctional complexes, which are characteristic of perineurial cells. Since the origin of the experimental tumors from adult Schwann cells seems well established, this apparent contradiction is best resolved by the concept that Schwann cells and perineurial fibroblasts are functional variants of the same cell type.Supported by Research Grant CA 11689 from the National Cancer Institute, Graduate Neuropathology Training Grant 5 T01 NS 5500-09 and by Special Fellowships 1F11 NS 2629 (F.K.C.) and 1F03 NS 55632 (A.M.S.) from the National Institute of Neurological Diseases and Stroke, U.S.P.H.S.     

In vitro characteristics of a sacrococcygeal chordoma maintained in tissue and organ culture systems

Summary Explants of a human sacral chordoma were successfully maintained on collagen-coated coverslips, gelfoam sponge matrices, and Millipore filter platforms for up to 30 days. Tumor cells cultured on collagen-coated coverslips became increasingly vacuolated whereas those maintained in organ culture were entirely free of vacuoles after 22 days in vitro. A single basic tumor cell, small and polygonal with a large central spherical nucleus and abundant endoplasmic reticulum and Golgi apparatus, was recognized. Vacuoles were formed as the result of the progressive expansion of smooth endoplasmic reticulum. Coalescence of these vacuoles produced the physaliferous cell of light microscopy.Supported by Research Grant CA-11689 from the National Cancer Institute and Graduate Neuropathology Training Grant 5T01 NS 5500-10 from the National Institute of Neurological Diseases and Stroke, U.S.P.H.S.     

Adult-onset lysosomal storage disease in a Schipperke dog: clinical,morphological and biochemical studies

Summary An adult-onset lysosomal storage disorder was diagnosed in a 5-year-old Schipperke dog with progressive cerebellar and central vestibular signs. It was characterized by cerebellar atrophy with extensive loss of Purkinje and granular cells, and hydrocephalus. Enlarged and vacuolated neurons were observed in spinal cord and brain; pancreatic centrolobular and islet cells were also vacuolated. Ultrastructurally, enlarged secondary lysosomes laden with lamellated membrane structures were present in neurons and empty enlarged vacuoles were found in pancreatic centroacinar, ductal, and islet cells. On frozen sections neurons stained with Ricinus communis agglutinin-I and wheat germ agglutinin. On paraffin sections neurons stained with luxol fast blue, periodic acid-Schiff, Concanavalia ensiformis agglutinin, and were autofluorescent. These findings indicate an accumulation of glycolipids containing terminal -galactosyl and -sialyl residues, and N-linked oligosaccharides. Tissue activity of lysosomal -galactosidase was 50% of normal and the activity of -hexosaminidase was elevated. Brain lipid-bound sialic acid was twice normal, with a small increase of G_M1-ganglioside, but there was a significant elevation of G_M2 (G_D2) and G_M3 (G_D3). In addition, significant elevations of sialylated and non-sialylated oligosaccharides were noted. These clinical, biochemical and pathological findings are similar to those observed in human patients with adult-onset galactosialidosis.     

A case of cerebral composite ganglioneuroblastoma: an immunohistochemical and ultrastructural study

Summary An unusual cerebral tumor is reported in a 14-year-old boy. On light and electron microscopy, the constituent cells were very complex; the majority of the neoplastic cells were primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma. Neoplastic neuronal cells and hypertrophic astrocytes were also observed in these areas. The neuronal cells showed a continuous spectrum of differentiation from very primitive to mature ganglion cells. Furthermore, the tumor contained a highly cellular discrete area consisting of neuroblasts and their precursor cells. From these findings, a diagnosis of composite ganglioneuroblastoma was made.     

Cerebellar liponeurocytoma: Morphological,immunohistochemical, and ultrastructural study of a relapsed case

Cerebellar liponeurocytoma is a rare and newly identified neoplasm found in adults which is reputed to be benign. Its salient morphological characteristics are advanced neuronal/neurocytic differentiation, the presence of lipomatous areas, low mitotic rate, and the absence of necrosis, pleomorphism and vascular hyperplasia. Reported is a case of relapsing liponeurocytoma which occurred 3 and a half years after the radical excision of the primary lesion. Histopathological aggressive features (mitoses and a high proliferation index as evaluated by MIB‐1) were shown in the primary lesion and recurrence of the tumor. We suggest that liponeurocytoma is an uncertain malignant potential lesion when mitoses are present and the MIB‐1 positive cells are more than 10%.     

Schilder's diffuse sclerosis: A biochemical and ultrastructural study of myelinoclastic demyelination

Summary A case of Schilder's diffuse sclerosis with a four-year history of progressive neurologic deterioration in a boy dying at ten years of age is reported. The asymmetry of the process was indicated during life by the clinical findings. A unicentric focus of demyelination was found with the initial stages in the occipital and temporal white matter and a subacute reaction in the rostral cerebral white matter, brain stem, and cerebellum. Electron microscopic study confirmed the extensive axonal loss. No particles compatible with a virus structure were identified.Analysis of the regional composition of cerebral lipids demonstrated large deficits of cerebroside, sulfatide, cholesterol, total phospholipid, sphingomyelin, and ganglioside in the occipital lesion. A significant but less complete deficit of lipids was found at the lesion margin in frontal white matter. An increase of cholesterol esters was demonstrated at this site as well. The normal-appearing white matter of rostral frontal lobe showed a decreased level of ganglioside and normal concentrations of the other structural lipids. This decreased ganglioside concentration of grossly normal white matter suggest the advisability of considering Wallerian degeneration in interpreting the analytical data obtained in the study of the demyelinating disorders.The morphological and biochemical findings indicate the progressive spread of the axonolytic and myelinolytic process in the pathogenesis of Schilder's diffuse sclerosis.Supported by U. S. Public Health grants NS 06926 and HE 11078. K.C.J. is a research trainee supported by U. S. Public Health grant GM 00404 and J. P. H. is a Special Fellow of USPHS in Neuropathology.Presented in part at Meeting of American Association of Pathologists and Bacteriologists, March, 1970.     

Mu opioid receptors are in somatodendritic and axonal compartments of GABAergic neurons in rat hippocampal formation

Activation of mu opioid receptors (MORs) has a net excitatory effect in the hippocampal formation through inhibition of gamma-amino butyric acid (GABA)-containing interneurons. To determine the precise subcellular targets of MOR agonists, immunoreactivity against MOR1 and GABA was examined in single sections of the hippocampal formation prepared for dual-labeling electron microscopy. In both the CA1 region of hippocampus and the dentate gyrus, MOR-like immunoreactivity (-li) was present in neuronal somata, dendrites, axons, and axon terminals, as well as a very few glial processes. Axon terminals with MOR-li formed symmetric synapses with principal cell dendrites and somata. Many MOR-labeled profiles of all types also contained GABA-li, and the vast majority possessed the ultrastructural characteristics of interneurons. Additionally, in the dentate gyrus a very small proportion of granule cell dendrites contained MOR-li. MOR-li, identified using immunogold-silver particles, was often affiliated with the extrasynaptic regions of neuronal plasma membranes, consistent with responsiveness to diffusing endogenous neuropeptide ligands. Semiquantitative analysis of the distribution of MOR-li revealed significantly more "presynaptic" (axons and terminals) than "postsynaptic" (somata and dendrites) labeled profiles in most laminae. We conclude that in addition to previously described somatodendritic MOR-li, a substantial amount of MOR-li in hippocampal formation is presynaptic. Furthermore, MORs are almost exclusively in GABAergic interneurons.     

Epithelial properties of pleomorphic xanthoastrocytomas determined in ultrastructural and immunohistochemical studies

Summary Three cases of pleomorphic xanthoastrocytoma (PXA), one of which showed anaplastic evolution, are described. In all three the PXA tumors were well circumscribed and could be totally removed. Light-microscopically, pleomorphic tumor cells clustered gregariously and often formed alveolar structures. Electron microscopy revealed various epithelial properties, such as junctions and interdigitations between apposing tumor cells, and prominent basal laminae surrounding tumor nests. The circumscribed growth of PXA, as contrasted with an infiltrative growth of usual astrocytoma, can be attributed to the cellular cohesion based on the epithelial properties of the tumor cells. In the third patient, tumor recurred 6 months postoperatively. Although the recurrent tumor retained the alveolar structures, pleomorphism and various degenerative features of the tumor cells diminished with advance in the proliferative activities.Supported in part by grant in aid 60480328 from the Ministry of Education, Science, and Culture, Japan     

Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems

Summary Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas.These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.Supported by Research Grant CA 11689 from the National Cancer Institute, Graduate Neuropathology Training Grant 5 T01 NS 5500-09 and by Special Fellowships 1F03 NS 55632 (A.M.S.) and 1F11 NS 2629 (F.K.C.) from the National Institute of Neurological Diseases and Stroke, U.S.P.H.S.     

A quantitative and ultrastructural study of substantia nigra and nucleus centralis superior in Alzheimer's disease

Summary In four patients with presenile Alzheimer's disease (AD) and three age-matched controls a quantitative study of neurons and neurofibrillary tangles (NFT) in the substantia nigra (SN) and nucleus centralis superior (NCS) was performed. A significant neuronal loss, similar in both nuclei, was found in AD cases, while the incidence of NFT was remarkably higher in NCS. Moreover, no significant correlation between neuronal loss and number of NFT was detected. An electron-microscopic study revealed that the subcortical NFT in NCS are made up of paired helical filaments in spite of their globose round shape.Supported by CNR contract no. 83.02062.04     

Electron microscopic observations of rat medullary reticular tissue after short-term,whole body gamma irradiation

Summary The ultrastructural observations recorded after shortterm, whole body gamma irradiation on medullary reticular tissue were evaluated. Twenty-five adult rats were divided into one control and four irradiated groups which received 1,000 rads, 2,000 rads, 5,000 rads, and 10,000 rads, respectively. Tissue preparations in each group consisted of immersion fixation in veronal acetate buffered OsO₄ and a perfusion technique utilizing s-collidine buffered glutaraldehyde.The micrographs from the control group revealed conformity to neurological ultrastructures as reported by other authors, with one exception. A structure termed concentric membranous body (CMB) was observed in the s-collidine buffered, perfused animals. This structure was noted to be associated with neuronal membranes and to contain laminated repeating intraperiodicity of 40–50Å.In all irradiated groups (1,000, 2,000, 5,000, 10,000 rads) membranous swirls were observed. These structures appeared to be of CMB origin in the lower exposure groups and from both CMB and myelin sheath breakdown in the higher groups. Progressive cytoplasmic vacuolization, mitochondrial, and myelin sheath damage were noted as being related to dose level. Since no apparent capillary bed damage was observed in any irradiated animal, it was concluded that the cellular abnormalities recorded were the result of direct or localized irradiation damage of the brain.Submitted to the Faculty of the Graduate School, Texas A & M University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy.