Rosette-forming glioneuronal tumor of the fourth ventricle with bilateral olivary degeneration.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been recognized as a new type of glioneuronal tumor. RGNTs are typically located in the infratentorial midline with involvement of the fourth ventricle. They occasionally involve the aqueduct and/or vermis. RGNTs of unusual anatomical sites or those with unusual findings have been reported. The present case reports describe RGNT of the fourth ventricle with bilateral olivary degeneration. It is important to accumulate imaging findings and biological behaviors of RGNTs given the limited number of cases.

Unclassified glioneuronal tumor with advanced lipidization.

Lipidization is observed only occasionally in primary neuroectodermal tumors of the central nervous system. It may reflect lipomatous transformation of tumor cells into xanthomatous and/or adipocyte-like cells. We report a unique case of mixed glioneuronal tumor with marked lipomatous changes in a young patient with intractable epilepsy. MRI revealed a well-circumscribed lesion in the right temporal lobe. Histopathological findings showed the pleomorphic tumor with numerous cells containing large lipid droplets, resembling mature adipocytes, that were arranged in clusters or scattered within the neoplastic tissue. The tumor was composed of both glial and neuronal elements. Some tumor cells displayed features intermediate between glial and neuronal cells. The reticulin fibers were limited to blood vessels. Mitotic figures, vascular proliferation, and necrosis were absent, and MIB-1 labeling index was less than 1%. Diffuse immunoreactivity for GFAP and S100-protein was observed. In some heavily lipidized cells, the lipid droplets were surrounded by a cytoplasmic rim of GFAP immunoreactivity. Numerous cells exhibited immunostaining for NSE and synaptophysin. This is the first documented case of glioneuronal tumor with extensive lipomatous transformation, which might be considered as a heavily lipidized unclassified pleomorphic glioneuronal tumor or a variant of lipoganglioglioma with marked pleomorphism and severe lipidization.

Immunization with a mimotope of GD2 ganglioside induces CD8+ T cells that recognize cell adhesion molecules on tumor cells.

The GD2 ganglioside expressed on neuroectodermal tumor cells has been used as a target for passive and active immunotherapy in patients with malignant melanoma and neuroblastoma. We have reported that immunization of mice with a 47-LDA mimotope of GD2, isolated from a phage display peptide library with anti-GD2 mAb 14G2a, induces MHC class I-restricted CD8(+) T cell responses to syngeneic neuroblastoma tumor cells. The cytotoxic activity of the vaccine-induced CTLs was independent of GD2 expression, suggesting recognition of a novel tumor-associated Ag cross-reacting with 47-LDA. Glycan microarray and immunoblotting studies using 14G2a mAb demonstrated that this Ab is highly specific for the entire carbohydrate motif of GD2 but also cross-reacts with a 105 kDa glycoprotein expressed by GD2(+) and GD2(-) neuroblastoma and melanoma cells. Functional studies of tumor cells grown in three-dimensional collagen cultures with 14G2a mAb showed decreases in matrix metalloproteinase-2 activation, a process regulated by the 105 kDa-activated leukocyte cell adhesion molecule (ALCAM/CD166). A recombinant CD166 glycoprotein was shown to be recognized by 14G2a Ab and inhibition of CD166 expression by RNA interference ablated the cell sensitivity to lysis by 47-LDA-induced CD8(+) T cells in vitro and in vivo. The binding of 14G2a to CD166 was not disruptable by a variety of exo- and endo-glycosidases, implying recognition of a non-glycan epitope on CD166. These results suggest that the vaccine-induced CTLs recognize a 47-LDA cross-reactive epitope expressed by CD166, and reveal a novel mechanism of induction of potent tumor-specific cellular responses by mimotopes of tumor-associated carbohydrate Ags.

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.