Primary diffuse leptomeningeal glioneuronal tumors.

Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal cisterns and interhemispheric fissure of children but lacking intraparenchymal tumor. Histologically, the tumors are composed of sheets of monotonous rounded cells. Here, we report three cases of DL-GNTs, focusing on clinicopathologic features. Two patients were adult male, but one patient was child. The patients presented with seizures (n = 1) or headaches (n = 2). In all patients, radiography revealed characteristic leptomeningeal thickening and enhancement with minor superficial parenchymal lesions. All three cases were diffusely positive for both GFAP and synaptophysin, and scattered positive for OLIG2 and NeuN, but negative for IDH-1 (H09). Electron microscopic examination showed astrocytic and neuronal differentiation. The patient with the anaplastic tumor died due to aggressive progression of the tumor, but the remaining two patients were stable without tumor recurrence for 23 and 37 months. Thus, these findings suggest that DL-GNT can occur in both children and adult and both supra- and infra-tentorial leptomeninges. It has unique radiological and histopathological features and biological behavior. Further clinicopathological data with molecular genetic study are required for establishing DL-GNT as a unique entity.

Strong desmin expression in a congenital desmoplastic infantile ganglioglioma mimicking pleomorphic rhadomyosarcoma: a case report including ultrastructural and cytogenetic evaluation and review of the literature.

PURPOSE: Desmoplastic infantile gangliogliomas (DIGs) are rare tumors of infancy. Herein, we describe an unusual case of DIG diagnosed by prenatal ultrasound. METHODS: This 5-day-old newborn was delivered after a prenatal ultrasound revealed a large cystic mass in the left cerebral hemisphere along with an echogenic solid component. RESULTS: The tumor revealed a glial and neuronal proliferation in a background of desmoplasia more typical of DIG and a minor component with a more primitive, immature appearance to the glioneuronal elements. A significant component of the tumor was composed of pleomorphic eosinophilic spindle cells in whorls and interlacing fascicles that showed a strong, sharp, and diffuse positivity for desmin, thus mimicking rhabdomyosarcoma. However, the tumor cells were GFAP (+), INI-1 (+), and myogenin (-). Mitoses were seen both in the more spindle cell astroglial areas as well as the more primitive neuroepithelial cells. The MIB-1 proliferation index was brisk, exceeding 15 %, and in areas it was estimated to be as high as 30 %. Such high proliferation index has been described and accepted in the more primitive neuroepithelial areas, but not in the terminally differentiated, spindle cell astroglial areas as in our case. Our patient was incidentally diagnosed prenatally. To our knowledge, this case is the first documented congenital DIG diagnosed prenatally. CONCLUSIONS: This case highlights the pitfalls in diagnosing DIG, which can mimic a rhabdomyosarcoma. Furthermore, it underscores the importance of re-evaluating the grading of these tumors or at least segregating the variants where the prognosis may be more guarded.

A case of melanotic desmoplastic ganglioglioma.

We describe a case of desmoplastic infantile ganglioglioma (DIG) in a 9-month-old boy located in the temporal lobe. Grossly the tumor was brown and superficially located. Histologically the tumor contained pigment in numerous neoplastic cells, shown to be melanosomal melanin by ultrastructural examination. Pigmented neoplasms have been reported at various sites in the central and peripheral nervous system. Previous reports on pigmented neuroepithelial tumors include neoplasms containing melanin, while others have contained neuromelanin and or lipofuscin. This case represents the first description of pigmented neoplastic cells in DIG, enlarging the spectrum of pigmented primary CNS tumors.

Ultrastructural heterogeneity of gangliogliomas.

Gangliogliomas are rare brain tumors, composed of neuronal and glial cells mixed in a different proportion. The basic histopathological pattern of gangliogliomas is well recognized but the variable microscopic appearance still can pose a challenge to the neuropathologist. The authors reanalyzed their series of gangliogliomas in the files of two departments of neuropathology. All analyzed tumors fulfilled the WHO histological criteria of ganglioglioma. Seven tumors were examined by electron microscopy. The following ultrastructural features were graded: presence of dense-cored vesicles, synaptic vesicles, synapses and intermediate filaments, abundant basal membranes, dystrophic neurites, autophagic vacuoles, and multivesicular bodies. Most of the neoplastic neurons were large, polyglonal or oval with well-developed subcellular organelles, round nuclei, and prominent nucleoli. In most cases there were abundant dense core vesicles, observed in both the tumor cell bodies as well as in their processes. Synapses were typically observed. Intermediate filaments were abundant in all tumors. The most intriguing ultrastructural finding was abundant presence of autophagic vacuoles. In 4 cases, multivesicular bodies were observed. All of the tumors with multivesicular bodies also contained abundant autophagic vacuoles.

Unusual malignant glioneuronal tumors of the cerebrum of adults: a clinicopathologic study of three cases.

Malignant glioneuronal tumors of the brain are rare and poorly characterized. Herein, we report the clinicopathologic features of three examples with unusual morphologies including both glial and neuronal differentiation. Hematoxylin and eosin-stained slides were reviewed in all cases. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded sections. Transmission electron microscopy (EM) was performed on both formalin-fixed (n=1) and paraffin embedded tissue (n=2). The immunogold technique for localization of GFAP was also performed. Two patients were male and one was female, age 66, 84, and 34 years, respectively. Radiologic studies demonstrated hyperdensity on CT (n=3), multicentricity (n=2), and a cortical based solid component with a cystic extension into underlying white matter (n=2). At surgery, all three tumors were superficial and relatively circumscribed. Histologically, they were composed of large epithelioid cells (n=3), spindle cells (n=1), and poorly differentiated smaller cells with high nuclear/cytoplasmic ratios (n=1). Brisk mitotic activity and coagulative non-palisading necrosis were present in all cases. The tumors were immunopositive for GFAP (n=3), S-100 (n=3), synaptophysin (n=3), chromogranin (n=3), Neu-N (n=2), and neurofilament protein (n=2). Stains for EMA were negative. EM demonstrated convincing neurosecretory granules in one case, some in filament-containing cells immunogold labeled for GFAP. Two patients expired 3-5 weeks after surgery. True malignant neoplasms with glial and neuronal differentiation do occur in the central nervous system of adults and may pursue a highly aggressive course. The use of minimal diagnostic criteria, e.g., immunoreactivity for a single antigen like neurofilament protein, may not be sufficient and should be discouraged.

Angioganglioglioma: a transitional form between angioglioma and gangioglioma?

The authors describe for the first time an unusual cerebral tumor with unique clinical history, composed of 3 components: pilocytic astrocytoma, vascular proliferations similar to those described as arteriovanous malformations, and a neoplastic ganglion component. These three components were intimately entangled and created the tumor mass. Thus the authors propose the term angioganglioglioma for this entity. The relation to the historically defined anglioglioma and tumors related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed. The authors believe that this lesion, in regard to the clinical presentation (long course of the disease, clinical symptoms), is closely associated with ganglioglioma and, with other morphological features, also to angioglioma. Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features.

Applications of the neodymium:YAG laser in plastic surgery of the face and lacrimal surgery. Wound repair. A review.

The physical and clinical features of a number of laser energy sources presently being used in plastic and endonasal surgery, such as the Nd:YAG, KTP, Ho:YAG, Er:YAG and CO(2) lasers, are emphasized. Particular attention is paid to the Nd:YAG laser and to an Nd:YAG laser-powered quartz laser scalpel.

Mixed conventional and desmoplastic infantile ganglioglioma: an autopsied case with 6-year follow-up.

We describe a case of desmoplastic infantile ganglioglioma (DIG) arising in the ventral diencephalon of a 3-1/2-month-old boy. On biopsy, the tumor featured a desmoplastic, S-100 protein and GFAP immunoreactive stromal element, as well as a variable spectrum of ganglion cells. Electron microscopy demonstrated astrocytes, and morphologically fibroblasts, as well as neurons containing 120-nm dense core granules. In addition, tubular structures composed of tightly apposed cells with features of astrocytes and of Schwann-like cells were also noted. Devoid of fibroblasts, the tubular structures were surrounded by a single basal lamina. At autopsy 6 years later, the multinodular, cystic mass had replaced the diencephalon, extended into both temporal lobes as well as the optic nerves, and showed marked leptomeningeal involvement. Microscopically, superficial portions of the tumor consisted of typical DIG, whereas deep, nondesmoplastic portions exhibited pattern variation ranging from pilocytic astrocytoma to ganglioglioma and gangliocytoma. There was also a minor element of small, 'primitive-appearing' neuroepithelial cells. Dysplastic ganglion cells variously reactive for neurofilament protein and synaptophysin were present throughout the tumor. Our study not only confirms DIG as a variant of ganglioglioma, one capable of slow growth, infiltration, and fatal progression but suggests that its differentiating potential includes elements of both the central and peripheral nervous systems. If so, their derivation may be from multipotential cells of the neural plate.

Class III beta-tubulin immunoreactive intranuclear inclusions in human ependymomas and gangliogliomas.

We have observed intranuclear inclusion bodies immunoreactive for the cytoskeletal protein class III beta tubulin (C3betaT) in neurons and ependymal cells of post-mortem human brain. The relationship of these inclusions, detected by light microscopy, to the intranuclear rodlets described by the classical microscopists is unknown. The present study was conducted to determine whether these proteinaceous inclusions (C3betaT-NIIs) exist in the neoplastic counterparts of these cell types. Immunohistochemical staining for C3betaT revealed intensely stained, predominantly rod-shaped intranuclear inclusions in a variable proportion of tumor cells in five of ten ependymomas. In addition, C3betaT-NIIs were encountered in less than 1% of neuronal cells in two of five gangliogliomas. This study represents the first report of tubulin-containing intranuclear inclusions in brain tumors. The functional significance of these inclusions in normal human brain and in cerebral neuroepithelial neoplasms remains to be determined.

Ganglioglioma with a tanycytic ependymoma as the glial component.

We studied a cystic ganglioglioma (GG) located in the right frontal lobe of the brain. Interestingly, the fibrillary spindle glial cells were often arranged in a fascicular pattern, and the generally uniform, round-to-oval delicate nuclei appeared to resemble those of ependymoma; and the neoplastic neurons often contained neurofibrillary tangles (NFTs). The glial component was positive for glial fibrillary acidic protein and occasionally contained granular or microvesicular structures positive for epithelial membrane antigen. Ultrastructural investigation revealed that the glial cells were ependymal in nature; intracytoplasmic lumina and intercellular microrosettes lined with cilia and microvilli, as well as long zonulae adherentes, were evident. In addition, chromogranin A-positive granular staining, neurosecretory-granule-like structures, and parallel arrays of microtubules were sometimes associated with the blood vessels. We considered the present case to be an unusual example of GG with an ependymoma, more precisely a tanycytic ependymoma, as the glial component; to our knowledge, the existence of ependymoma as the main glial component of this particular tumor has not been described before. The occurrence of NFTs, which has been reported in several cases of GG, was an additional, unusual feature.

Papillary glioneuronal tumour: clinicopathological and biochemical study of one case with 7-year follow up.

Among the mixed glioneuronal tumours, a new variant called papillary glioneuronal tumour has recently been delineated. A case occurring in a 23-year-old man is reported. The tumour was cystic with a mural nodule enhanced by gadolinium injection. It was located within the left parieto-occipital lobe. Surgical excision showed a greyish friable tumour with cystic areas. Histopathological examination revealed a pseudopapillary component comprising a single layer of regular cells, arranged around hyalinised vessels. These cells were immunoreactive with anti-glial fibrillary acidic protein and HNK1 antibodies. A neurocytoma-like component coexisted with round blind cells and focal fibrillary rosettes. These cells were immunostained by anti-neuron-specific enolase and anti-synaptophysin antibodies. Neither mitoses nor ganglioid cells were seen. HNK1, the three isoforms of NCAM, and the L1 adhesion molecule were detected by Western blot analysis. Ultrastructural study showed three different types of cells. The first contained gliofilaments, the second showed long processes with true synapses, and the third was poorly differentiated. However, all had identical nuclei and contained dense bodies. These findings suggest a common origin for the tumour cells derived from a bipotential neuroglial progenitor. As for other mature mixed neuroglial tumours, the prognosis is good. Our patient is free of disease 7 years after complete surgical treatment.

Ultrastructural identification of protein bodies, cellular markers of human catecholamine neurons, in a temporal lobe ganglioglioma.

A temporal lobe ganglioglioma, surgically removed from an 8-year-old body, and a human brainstem at the level of locus coeruleus (LC) were processed for light microscopy (LM), with formalin fixation and paraffin embedding, and for electron microscopy (EM) with glutaraldehyde fixation, potassium permanganate postfixation, phosphotungstic acid-hematoxylin block-staining, and epoxy resin embedding. The paraffin sections were stained with toluidine blue O/rhodamine B and observed under epi-fluorescence. The thin sections for EM were viewed directly without further staining. The neuronal neoplastic cells of ganglioglioma and the neurons of LC are known to produce catecholamines. Both also contain spherical protein bodies (pb), cellular markers that identify catecholamine neurons in humans. The ultrastructural characteristics of the pb in LC were compared with those of the pb in neoplastic ganglion cells. These bodies had an identical ultrastructure, in both tissues, consisting of electron-lucent core surrounded by an electron-dense thin rim. The rhodamine B-stained sections also emphasized the identical morphology of the pb in ganglioglioma and LC. Based on the EM comparison, these brightly fluorescing spherical bodies are ideal markers for identifying in LM, the clusters of large neoplastic cells, representing neurons, which are the most important clue to the correct diagnosis of gangliogliomas.

Ganglioma desmoplásico da infância: estudo clínico, histológico, imumoistoquímico e ultra-estrutural de um caso / Desmoplastic infantile ganglioglioma: a clinical, histological, immunohistochemical and ultrastructural study of one case

O ganglioma desmoplásico da infância (GDI) representa uma entidade clinicopatológica distinta e rara, comprometendo 0,5-1,0 por cento de todos os tumores intracranianos. Os autores relatam um caso de GDI, e um uma criança de quatro meses de idade do sexo feminino, que apresentava crises convulsivas mais evidentes no hemicorpo direito e exame neurológico normal. A ressonância magnética evidenciou uma massa sólido-cística em regiäo frontotemporoparietal esquerda. Foi submetida a cirurgia para exérese do tumor, sendo realizado exame de congelaçäo intra-operatório, onde foi suspeitado GDI e astrocitoma desmoplásico. No exame histopatológico observavam-se áreas desmoplásicas com astrócitos de padräo fibrilar ao lado de células fusiformes semelhantes a fibroblastos, ambas com imunoexpressäo de proteína ácida gliofibrilar. A célula fusiforme apresentou na ultra-estrutura retículo endoplasmático granular bem desenvolvido, com cisternas dilatadas pelo conteúdo protéico secretado. Em áreas focais notavam-se ainda células ganglionares que imunoexpressavam proteína S100 e enolase neurônio-esoecífica. A confirmaçäo diagnóstica de GDI utilizando a imunoistoquímica e a microscopia eletrônica para descartar outras neoplasias semelhantes é muito importante para o paciente, já que esta entidade clinocopatológica apresenta um prognóstico favorável

Ganglioglioma: an ultrastructural and immunohistochemical study.

BACKGROUND: Ganglioglioma is a rare, mixed neuronal-glial neoplasm of the central nervous system that occurs in young patients and has a benign clinical course. METHODS: To define the immunophenotypic and morphologic features of ganglioglioma precisely, 27 specimens were studied by routine histochemistry, 21 specimens by immunochemistry, and 14 specimens were examined at the ultrastructural level. RESULTS: The age of the 27 patients, 14 males and 13 females, ranged from 3 to 52 years (mean, 22 years). The most commonly affected site was the temporal lobe (13 patients). Three patients experienced a local recurrence. Microscopically, the tumors were comprised of well differentiated, somewhat abnormal neurons as well as glial cells, the latter including astrocytes of fibrillary (59%) and pilocytic (41%) type. Scant mitotic activity was observed in 2 tumors (7%). Glial cells of all tumors were immunoreactive for glial fibrillary acidic protein, S-100 protein, and vimentin. Ki-67 labeling indices (LI) ranged from 0.6 to 10.5% (mean, 2.7%) and p53 LI from 1.1 to 42.4% (mean, 15.6%). Ki-67 and p53 LI in recurrent tumors were significantly higher than those of nonrecurrent ones (P = 0.036 and 0.026, respectively). No examples of anaplastic transformation were encountered. Immunohistochemically, many neuronal cells were positive for synaptophysin (100%), Class 3 beta-tubulin (100%), neurofilament protein (90%), and chromogranin A (86%), in addition to S-100 protein (71%) and, occasionally, vimentin (24%). Ultrastructural characteristics of neuronal cells included the presence of numerous, 100-230-nanometer dense core granules within both perikarya and cell processes, well developed rough endoplasmic reticulum, microtubules within cell processes, and synapses associated with clear vesicles. Astrocytic cells usually contained abundant intermediate filaments; their cell membranes, when abutting the stroma, were covered by basal lamina. CONCLUSIONS: Gangliogliomas are comprised of well differentiated neuronal cells and glial cells that are very often of pilocytic type. No cells with features intermediate between neurons and glia were observed. Neuronal cells are characterized by prominent neurosecretory features distinct from those of normal neurons in the central nervous system. Higher Ki-67 and p53 LI may indicate more aggressive behavior.

Ultrastructural characterization of oligodendroglial-like cells in central nervous system tumors.

Cells with uniform, small-round nucleus and clear cytoplasm (oligodendroglial-like cell, OLC) are commonly observed in central nervous system (CNS) neoplasm of glial and neuronal lineage, such as oligodendroglioma, clear-cell ependymoma, and central neurocytoma. Immunohistochemistry does not always contribute to the characterization of OLC because of (1) loss of antigen expression; (2) lack of specific markers for oligodendrogliomas; and (3) occasional coexpression of neuronal and glial antigens. An ultrastructural analysis associated with an immunohistochemical study of 20 cases of CNS tumors largely constituted by OLCs has been performed. Neurocytomas (12 cases), medullocytomas (2 cases), cerebral neuroblastoma (1 case), and ganglioglioma (1 case) showed OLCs with ultrastructural features of neuronal differentiation (neuritic processes, dense-core granules, synaptic structures). Oligodendroglioma (3 cases) OLCs were characterized by mitochondrial-rich cytoplasm, and ependymoma (1 case) OLCs showed microrosettes and scattered cilia. The electron microscopic analysis can provide a more precise diagnosis of these OLC-containing tumors despite their uniform morphological appearance.

Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells. Case report.

A total resection of a left frontal lobe tumor in a 26-year-old man revealed differentiated ganglioglioma with small foci of atypical glial cells exhibiting mild atypia. Six and one-half years later, a large, well-demarcated tumor recurred; at that time, histological analysis revealed both typical ganglioglioma and highly cellular anaplastic areas, the latter predominating. Although the patient subsequently underwent total and subtotal resections, radiation therapy, and chemotherapy, tumors continued to recur at progressively shorter intervals and he died at the age of 35 years. Biopsies of tissue obtained at the last three resections and the autopsy revealed only anaplastic tumor cells. Routine histological examinations indicated that these tumors were uniformly composed of undifferentiated cells. However, pathological studies using immunohistochemical analysis, electron microscopy, and immunoblot analysis demonstrated that a small number of recurrent anaplastic cells had astrocytic features. Results of Ki-67/MIB-1 labeling and silver nucleolar organizer region counts for those cells were high for glial tumors. A retrospective study of the initial tumor showed slightly high MIB-1 labeling for atypical glial cells. This case is characterized by pathological findings of recurrent tumors that correspond to an unusual form of malignant glioma exhibiting slight astrocytic differentiation. The present case suggests that a longer follow-up period ( > 5 years) is necessary in cases of ganglioglioma with mild atypia and that careful examinations, including proliferating potential analysis of initial tumor cells, could be important for the diagnosis and treatment of ganglioglioma.

Pineal ganglioglioma with premature thelarche. Report of a case and review of the literature.

We report a case of a 6-year-old girl with a ganglioglioma in the pineal region presenting with a rare clinical picture of premature thelarche. Intracranial gangliogliomas are rare, especially in the pineal region. Their character, origin, treatment, and prognosis remain controversial. The pathophysiology of precocious puberty associated with pineal ganglioglioma is discussed.

The immunohistochemistry and ultrastructure of ganglioglioma with chromosomal alterations: a case report.

Ganglioglioma, together with its counterparts-ganglioneuroma and gangliocytoma are relatively uncommon neoplasms of the brain composed of neoplastic neurons (ganglion and ganglioid cells) and glial cells. We report here a case of ganglioglioma studied by electron microscopy. The case was further characterized by peculiar chromosomal alterations, 46,XX[6]/43,XX[1], der(1)t(1;5)(q21;q12), der(8;13)(q10;q10),-9,i(10)(q10). Routine light microscopy revealed mixed neuro-glial tumor composed of pilocytic astrocytes with abundant Rosenthal fibers and relatively numerous ganglion cells. The latter were immunoreactive with antibodies (Abs) against synaptophysin and neurofilament protein (NFP). Anti-NFP Abs also immunostained numerous distorted axons embedded in the tumor mass. Some of these showed bullous swellings and thus were analogous to dystrophic neurites or spheroids. Ganglion cells were characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers were seen. Dense-cored vesicles were pleomorphic and ranged in diameter from small synaptic vesicles to large lysosome-like neurosecretory granules. The former occasionally formed characteristic dumbbell shapes. Neoplastic astrocytes were identical to those of other glial tumors of astrocytic lineage; numerous Rosenthal fibers were frequently seen.

Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors.

Gangliogliomas are generally low grade neoplasms composed of mixtures of neoplastic glial and neuronal elements whose origin and exact nature are still controversial. We studied a series of 60 intracranial gangliogliomas looking for coexistent cortical architectural abnormalities (cortical dysplasia, microdysgenesis) and to determine if tumor behavior correlates with MIB1 (marker of cellular proliferation) labeling. The patients included 34 males and 26 females who ranged in age from 6 months to 55 years (mean 20 years). Thirty-eight tumors (63%) were located in the temporal lobe and 6 (10%) in the frontal lobe. Fifty-four patients (90%) presented with seizures (most with intractable epilepsy) and the duration of seizures ranged from 1 to 38 years (mean 14 years). In all cases, the predominant glioma component resembled a low grade fibrillary astrocytoma. In 14 tumors (23%), an oligodendroglial component was present. In one case, the glial component resembled an anaplastic astrocytoma. The tumors were characterized variously by perivascular chronic inflammation (N = 45, 75%), vascular proliferation (N = 36, 60%), granular bodies (N = 54, 90%), binucleated neurons (N = 36, 60%), calcification (N = 28, 47%), and cystic degeneration (N = 26, 43%). Meningeal involvement by tumor was observed in five (8%) cases. In 38 patients, sufficient tissue was resected to evaluate for the presence of concomitant cortical architectural abnormalities. Cortical architectural abnormalities were identified near to but clearly separate from the tumor in 19 (50%) patients. Only four patients including the anaplastic tumor died with tumor progression. MIB1 indices (positive tumor cells/1,000 tumor cells counted) in 54 cases ranged from 0 to 10.2 (mean 1.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)