Immunohistochemical and ultrastructural study of chordoid glioma of the third ventricle: its tanycytic differentiation

A chordoid glioma in the third ventricle was studied immunohistochemically and ultrastructurally. In this report, special attention is paid to the histogenesis in relation to the pathological appearance and unique anatomic location of this tumor. Light microscopic and immunohistochemical findings were similar to those reported previously. Ultrastructurally, microvilli were frequently seen, but three types of abnormal cilia were rarely observed. Basement membrane around the tumor cells and microvessels was extensive. Poorly to moderately developed intermediate (adherent) junctions were frequently seen. Resemblance of these ultrastructural features of the tumor to embryonic tanycytes suggests the tanycytic differentiation of chordoid glioma. Neuroradiologically, all of the previously reported cases of chordoid gliomas seem to arise in the anterior part of the third ventricular floor. This region includes the lamina terminalis, infundibular recess and median eminence, which corresponds to a tanycyte-rich area. These findings suggest a tanycytic origin of chordoid glioma.     

Astroblastoma: Report of a case with microsatellite analysis

A 5‐year‐old girl who developed progressive headache, vomiting, and left hemiparesis was found to have a cystic tumor with an enhanced mural nodule in the right frontoparietal region on a computed tomography examination. The lesion was histologically and ultrastructurally verified as an astroblastoma, an uncommon neuroepithelial tumor of uncertain origin. Molecular analysis using 17 microsatellite markers on chromosomes 9, 10, 11, 17, 19, and 22 showed loss of heterozygosity at the D19S412 locus on the long arm of chromsome 19. This observation suggests that there is a tumor suppressor gene in this chromosomal region, which plays a role in the pathogenesis of astroblastoma.     

Astroblastoma with unusual signet‐ring‐like cell components: A case report and literature review

We report a case of astroblastoma with unusual signet‐ring‐like cell components. A 33‐year‐old‐woman presented with occasional partial seizures of the face. Radiological studies revealed an enhanced frontal mass lesion. At surgery, a gray, soft, well‐circumscribed mass was seen and shelled out. Histologically, the tumor showed a perivascular arrangement and papillary‐like patterns with compact cellularity. The tumor cells radiating from the hyalinized vessels showed broader, shorter, less tapered processes. A part of each tumor cell displayed prominent islands of signet‐ring‐like cells. Glial fibrillary acidic protein reaction revealed strongly positive staining of tumor cells and signet‐ring‐like cells. Eight years after the operation the patient remains well with no tumor recurrence. It remains to be determined whether, in this astroblastoma, the unusual signet‐ring‐like cell components were related to benign biological characteristics or to the tumor's low‐grade form with incidental signet‐ring‐like cell appearance.     

Hemangioblastomas: Immunohistochemical and ultrastructural study of the stromal cells

An immunohistochemical study of 36 hemangioblastomas (Hmbl) from 32 patients was performed to clarify the cytogenesis of stromal cells (SC). In 19 of 29 Hmbl, SC revealed glial fibrillary acidic protein-immunolabeling with an antigen retrieval by trypsinization, and were also positive for S-100 protein, αB crystallin, neuron-specific enolase and vimentin. Ultrastructurally, SC contained lipid droplets, unevenly distributed intermediate filaments with occasional myelin figures, primitive desmosomal junctions and, although rare, Rosenthal fibers or a cilium. It is concluded that SC associated with Hmbl exhibit markers consistent with an astrocytic origin.     

Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease

Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.     

Immunohistochemical localization of enkephalin in the human striatum: a postmortem ultrastructural study

Within the basal ganglia, the functionally defined region referred to as the striatum contains a subset of GABAergic medium spiny neurons expressing the neuropeptide enkephalin. Although the major features of ultrastructural enkephalin localization in striatum have been characterized among various species, its ultrastructural organization has never been studied in the human brain. Human striatal tissue was obtained from the Maryland and Alabama Brain Collections from eight normal controls. The brains were received and fixed within 8 h of death allowing for excellent preservation suitable for electron microscopy. Tissue from the dorsal striatum was processed for enkephalin immunoreactivity and prepared for electron microscopy. General morphology of the dorsal striatum was consistent with light microscopy in human. The majority of neurons labeled with enkephalin was medium-sized and had a large nonindented nucleus with a moderate amount of cytoplasm, characteristic of medium spiny neurons. Of the spines receiving synapses in dorsal striatum, 39% were labeled for enkephalin and were of varied morphologies. Small percentages (2%) of synapses were formed by labeled axon terminals. Most (82%) labeled terminals formed symmetric synapses. Enkephalin-labeled terminals showed no preference toward spines or dendrites for postsynaptic targets, whereas in rat and monkey, the vast majority of synapses in the neuropil are formed with dendritic shafts. Thus, there is an increase in the prevalence of axospinous synapses formed by enkephalin-labeled axon terminals in human compared with other species. Quantitative differences in synaptic features were also seen between the caudate nucleus and the putamen in the human tissue.     

Immunohistochemical and ultrastructural study of basophilic inclusions in adult-onset motor neuron disease

We immunohistochemically and ultrastructurally studied basophilic inclusions (BI) in a patient with adult-onset sporadic motor neuron disease (MND). BI were frequently observed not only in degenerated anterior horn cells, such as central chromatolytic neurons, but also in normal-appearing large anterior horn neurons. They had various shapes, round, elliptical or irregular, and occasionally they had distinct basophilic rims. They also varied in size. There were no halos around them nor core in their centers. Immunohistochemically, some BI were immunostained for ubiquitin or SOD1, but BI were not immunoreactive with anti-phosphorylated neurofilament (SMI 31), phosphorylated tau, cystatin C or Golgi (MG-160) antibodies. Ubiquitin-positive skein-like inclusions (SI) were occasionally observed in the somata of anterior horn neurons. Ultrastructurally, BI consisted of filamentous structures associated with granules, which were attached to thick filaments. The thick filaments were straight without constriction or side arms and their diameter was twice that of the neurofilaments. BI occasionally contained tubular structures among the granule-associated filaments. The granulo-filamentous profiles varied from being compactly arranged to being more loosely packed. The structure of BI resembles that of the Lewy body-like hyaline inclusions (LBHI) observed in sporadic MND patients. Bundles of filaments resembling SI, which were composed of compactly packed filaments without fine granules running parallel to the longitudinal axis, were frequently observed inside or at the periphery of BI, and occasionally clustered in the perikarya. Each filament measured approximately 15-25 nm in diameter, and a bundle of these grouped filaments was sometimes surrounded by a unit membrane. We also occasionally observed in-between structures of BI and bundles of filaments resembling SI. These findings suggest a certain relationship between BI, SI and LBHI in the pathomechanism of BI development. Further studies are needed to elucidate whether sporadic adult-onset MND characterized by BI forms a different subtype of MND.     

Chordoid glioma of the third ventricle: A report of two cases,one with ultrastructural findings

Chordoid glioma, which generally occurs in adults, is a rare CNS tumor arising in the anterior part of the third ventricle. We report two cases of chordoid glioma of the third ventricle in a 42‐year‐old woman and a 51‐year‐old man, respectively. Both tumors showed essentially the same histological and immunohistochemical features; the tumors were composed of cords and nests of epithelioid, GFAP‐immunoreactive cells in a mucinous stroma with lymphoplasmacytic infiltrates at the tumor periphery. Ultrastructural examination in one case revealed that the tumor cells were characterized by the presence of hemidesmosomes and associated focal basal lamina formation, intermediate junctions, microvilli and cilia, and intercellular microrosettes with microvilli. Of interest was that small blood vessels with fenestrated endothelial cells were present in the stroma. In the brain, the presence of fenestrated endothelial cells is a feature of the circumventricular organs (except the subcommissural organ), among which the organum vasculosum of the lamina terminalis is located in the anterior part of the third ventricular floor that is lined by specialized ependymal cells known as tanycytes. These findings further strengthen the hypothesis that chordoid glioma may represent a peculiar clinicopathological subtype of ependymoma (chordoid ependymoma) originating from the lamina terminalis area.     

Endothelial ultrastructural alterations of intramuscular capillaries in infantile mitochondrial cytopathies: “Mitochondrial angiopathy”

Electron microscopy (EM) is a reliable method for diagnosing mitochondrial diseases in striated muscle biopsy in infancy. Ultrastructural alterations in mitochondria of myofibers are well documented, but there are few studies of endothelial involvement in intramuscular capillaries. Quadriceps femoris biopsies of five representative infants and toddlers, ages neonate to 3.5 years, were performed because of clinical and laboratory data consistent with mitochondrial disease without mitochondrial DNA (mtDNA) mutations and likely with nuclear DNA mutations. Pathological studies included histochemistry, EM, respiratory chain enzymatic assay and mtDNA sequencing and deletion/duplication analysis. EM demonstrated frequent and severe alterations of mitochondria in capillary endothelium. The most constant changes included: either too few or fragmented cristae; stacked and whorled cristae; paracrystallin structures that often were large and spheroid with stress fractures; closely apposed membranes of granular endoplasmic reticulum surrounding mitochondria with loss of the normal intervening layer of cytoplasm; long narrow, thin looped microvilli extending into the lumen; and thick microvilli containing large, abnormal mitochondria. We conclude that mitochondrial cytopathies in early life exhibit more severe ultrastructural alterations in the endothelium than in myofibers and that paracrystallin body structure differs, perhaps due to less rigid surrounding structures. This distribution may explain the frequent lack of prominent histochemical and biochemical abnormalities in muscle biopsies of young patients. Endothelial changes do not distinguish the genetic defects. Vascular involvement in brain contributes to cerebral lesions and neuronal death by impairment of molecular and nutrient transport and ischemia; endothelium in muscle may reflect similar changes.     

Induced glial differentiation of fetal rat brain cells in culture: An ultrastructural study

Primary and secondary cultures of fetal rat brain cells (FBC) from 18th day of gestation have been investigated by scanning and transmission electron microscopy. Primary cultures consisted of a monolayer of flat, undifferentiated epithelioid cells, with some oligodendrocytes, astrocytes and immature neuronal cells. In secondary cultures, cells with glia morphology disappeared. Following addition of extracts from adult rat brains to secondary cultures, a dramatic of the epithelioid cells took place. They detached from the plastic surface, extruded long cytoplasmic processes with numerous microvilli and cytoplasmic blebs as well as parallel arrays of microtubules and filaments. The differentiated cells resembled astrocytes, and characteristic glia filaments were also observed. An increase of ribosomes and rough endoplasmatic reticulum suggested enhancement of protein synthesis. At the same time S-100 protein and glial fibrillary acidic protein accumulated within the cells. The morphological changes were mostly reversible within 48 h of removal of the brain extract.     

Tanycytic ependymoma arising from the right lateral ventricle: A case report and review of the literature

A 38‐year‐old man presented with a year‐long history of worsening headache. Neuroradiological findings showed that a solid cystic mass occupied the right lateral ventricle. Histologically, the tumor composed of nuclear dense zones consisting of a cluster of spindle cells and fibrillary zones consisting of streaming of cell processes. The tumor cells showed the characteristics of monopolar or bipolar processes. Some tumor cell processes extended to the vessel wall and formed ill‐defined perivascular rosettes. No mitoses or necrosis were found. The cells presented positive for GFAP, S‐100 protein, vimentin, Nestin and neurofilament, and dotlike positive for epithelial membrane antigen, but negative for Syn and NeuN. Four cases of tanycytic ependymoma arising from the lateral ventricle have been reported in literature. Histological differential diagnosis includes spindle‐shaped neuroepithelial tumors, such as pilocytic astrocytoma, fibrillary astrocytoma and schwannoma. Tanycytic ependymoma has slightly better prognosis than other ependymoma subtypes.     

Co‐occurrence of astrocytoma and astroblastoma: Case report and literature review

A 41‐year‐old man presented to us with left arm and leg weakness and mild word finding difficulties. His preoperative magnetic resonance imaging (MRI) demonstrated abnormal T1 and T2 signal changes in the right temporal lobe and basal ganglia, indicative of possible glioma. An awake craniotomy for right temporal lobectomy was performed and the tumor was resected. Full pathologic workup later revealed the patient had two distinct tumors occurring simultaneously, anaplastic astrocytoma and astroblastoma. We review the literature regarding the treatment of anaplastic astrocytoma and astroblastoma and discuss their co‐occurrence.     

Embryonal tumor with abundant neuropil and true rosettes: Morphological,immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation

Embryonal tumors are a group of malignant neoplasms that most commonly affect the pediatric population. Embryonal tumor with abundant neuropil and true rosettes is a recently recognized rare tumor. It is composed of neurocytes and undifferentiated neuroepithelial cells arranged in clusters, cords and several types of rosettes in a prominent neuropil‐rich background. We describe a new case of this tumor. The patient, a 24‐month‐old female infant, was referred to the Meyer Children's Hospital with a history of right brachio‐crural deficit associated with occasional episodes of headache and vomiting. Computed tomography scan and MRI revealed a large bihemispheric mass. The patient underwent two consecutive surgeries. The resultant surgical resection of the tumor was macroscopically complete. The postoperative period was uneventful. On light microscopy the tumor showed a composite morphology: embryonal tumor with abundant neuropil and true rosettes (specimen from the first surgery); medulloepithelioma with mesenchymal and epithelial areas (specimen from the second surgery). The immunohistochemistry evidenced the heterogeneous (neuronal, mesenchymal and epithelial) immunoprofile of tumoral cells. By real‐time polymerase chain reaction (RT‐PCR), the PTEN gene expression in the tumor was lower than in the five non‐neoplastic brain tissues used as control. Mutation analysis did not show any variation in INI‐1 and PTEN sequence while P53 analysis showed the presence of homozygote P72R variation. Fluorescent in situ hybridization analysis showed polysomy of chromosome 2 while amplification of N‐MYC was not detected. Owing to the rarity of embryonal tumor with abundant neuropil and true rosettes, each new case should be recorded to produce a better clinical, pathological and molecular characterization of this lesion.     

Chorea,transverse myelitis,neuropathy and a distinctive MRI: Paraneoplastic manifestations of probable small cell lung cancer

Paraneoplastic chorea occurs most commonly in association with small cell lung cancer, often in combination with other paraneoplastic phenomena and sometimes with distinctive basal ganglia T2-weighted MRI hyperintensities. A case of acute-onset chorea is presented in which this phenomenon, combined with transverse myelitis, neuropathy and the described characteristic MRI changes prompted positron emission tomography scanning, in which evidence of probable small cell cancer was uncovered.     

Central neurocytoma: immunohistochemical and ultrastructural study

Summary Eight cases of central neurocytomas were studied by immunohistochemistry and electron microscopy. Seven tumors were located in the lateral ventricles and one in the subependymal region. All but one patient had a favorable postoperative course. The tumors were composed of small uniform cells possessing amitotic round nuclei with frequent perinuclear halos, a few Homer Wright rosettes and no ganglion cells; an appearance resembling that of oligodendroglioma. Immunohistochemical studies disclosed neuron-specific enolase and Leu-7 positivity in all tumors, S-100 protein-positive cells were found in six, while glial fibrillary acidic protein —and vimentin-positive cells were confined to the blood vessels. Myelin basic protein as well as neurofilament were not detected in the tumors. Synaptophysin-positive areas were seen in one tumor. Ultrastructural examination showed distinctive neuronal tumor cells which had a cytoplasm with sparse dense-core vesicles and thin cell processes containing parallel microtubules. They were classified into three different types of tumor cells according to the extent of differentiation. The most consistent finding for histological diagnosis was the presence of typical or abortive synapses with clear and dense-core vesicles. Additionally, synaptophysin may be a specific marker for some central neurocytomas.     

Nephrosialidosis: ultrastructural and lectin histochemical study

Summary The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherryred spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of -neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system; lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis.     

Congenital toxoplasmosis: histological and ultrastructural study

A case of congenital toxoplasmosis is reported in which the patient died at 32 days following seizures, coma and respiratory disturbances. Neuropathological examination showed numerous foci of softening throughout the brain. Histological examination disclosed widespread areas of inflammatory necrosis. Circumscribed areas of granulomatous inflammation were also found. Cysts containing a variable number of microorganisms and toxoplasmas free in the damaged areas were frequently observed. Small calcifications were scattered in the cerebral cortex and basal ganglia. Electron microscopy of postmortem brain specimens demonstrated toxoplasmas at various stages of development. The microorganism is enveloped by a two-layered membrane, the pellicle. Replication occurs in a vacuole inside the host cell. Following replication the newly formed parasites, the trophozoites, are released. Several replications without release may also occur with consequent cyst formation. The motile form of the toxoplasma, the tachyzoite, is fusiform with truncated cone shape of the anterior ending which is the presenting surface modified for host cell penetration. The modality of transplacental transmission and the clinical syndromes associated with toxoplasma infection are discussed. EM even of post mortem material contributes to knowledge of the structure of the parasite and of its life cycles.

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Sommario Si descrive un caso di toxoplasmosi congenita. La bambina era deceduta all'età di 32 giorni dopo un decorso clinico caratterizzato da convulsioni, coma e disturbi respiratori. L'esame neuropatologico dimostrò numerose aree di rammollimento cerebrale e lo studio istologico evidenziò zone estese di necrosi infiammatorie ed aree circoscritte di infiammazione granulomatosa. Calcificazioni erano presenti nella corteccia cerebrale e nei gangli della base. Si osservarono sia cisti, contenenti un numero variabile di microorganismi, che toxoplasmi liberi nelle zone interessate dal processo patologico. L'esame al Microscopio Elettronico di materiale autoptico mostrò toxoplasmi in vari stadi di sviluppo. Il microorganismo è avvolto da una doppia membrana, la pellicola. La sua replicazione ha luogo all'interno di vacuoli nella cellula ospite, dopodiché i trofozoiti possono essere rilasciati oppure, qualora più replicazioni avvengano all'interno della stessa cellula, si ha la formazione di una cisti. La forma invasiva del toxoplasma, il tachizoita, si presenta fusiforme con la parte anteriore strutturalmente modificata per favorire la penetrazione nella cellula ospite. Si discutono le modalità di trasmissione e le sindromi cliniche conseguenti all'infezione congenita, sottolineando in particolare come anche lo studio su materiale autoptico possa contribuire alla conoscenza del ciclo vitale del parassita.

     

Immunohistochemical and ultrastructural study of gap junction proteins connexin26 and 43 in human arachnoid villi and meningeal tumors

Human arachnoid villi and meningiomas are known to have gap junctions formed by connexin (Cx) proteins. We examined the expression and localization of Cxs in normal human arachnoid villi and meningeal tumors (meningiomas and hemangiopericytomas) by immunohistochemistry and Western blots. In arachnoid villi, strong immunopositivity for connexin26 (Cx26) and connexin43 (Cx43) was detected in the cap cell layer, cap cell cluster, and central core. They were weakly expressed in the fibrous capsule. In meningiomas they were strongly expressed in the meningotheliomatous area and weakly positive in the fibrous area. None of them were expressed in hemangiopericytomas. By immunoelectron microscopy, Cx26 and Cx43 were distributed on the cell membranes in arachnoid villi and meningiomas. In the Western blots in arachnoid villi and meningiomas, Cx26 and Cx43 were shown at bands with molecular weights of 26 kD and 42-47 kD, respectively. The degree of positivity for Cxs was different between subtypes of meningiomas. These findings suggest that expression of Cx26 and Cx43 might be related to the differentiation of the arachnoid villi and meningiomas, and exhibit the different origin of various subtypes of meningiomas. We proposed that Cx expression is one of the useful markers for the differentiation of meningioma and hemangiopericytoma.