Accumulation of chromosomal changes in human glioma progression. A cytogenetic study of 50 cases.

Cytogenetic studies of 50 human gliomas, including three oligodendrogliomas, 16 grade I-III astrocytomas, and 31 glioblastomas multiforme, were performed using the short-term tissue culture method. The most common numerical chromosome aberrations were +7, -9, -10, -14, and loss of a sex chromosome. Structural changes involved predominantly the following chromosome arms: 1q, 2q, 6q, 7q, 9p, 14q, 17p, and 18p. Losses of chromosomes 9, 10, and 14, often occurring simultaneously and in polyploid clones, were observed almost exclusively in high-grade gliomas, and appear to constitute important events during glioma progression.

Comparative evaluation of p53-protein expression and the PCNA and Ki-67 proliferating cell indices in human astrocytomas.

Mutations of the p53 gene are one of the most frequent genomic alterations of human tumours of astrocytic lineage. Because the physiological role of this gene is a suppression of cellular proliferation and growth, the overexpression of p53-protein may correlate with the expression of PCNA or Ki-67, established markers of cell proliferation. Paraffin-embedded surgical specimens from 60 human astrocytomas (9 pilocytic tumours, 12 WHO grade II, 9 anaplastic astrocytomas [WHO grade III] and 30 glioblastomas [WHO grade IV]) were stained with anti-PCNA (PC10), anti-p53(DO-7) and anti-Ki-67 antibodies (DAKO). Approximately 40% of all the cases were p53-protein immunopositive (53.3% glioblastomas, 33.3% anaplastic, 41.7% low grade astrocytomas but no pilocytic tumor). Statistical analysis did not reveal statistically significant correlation between p53-immunopositivity and PCNA or Ki-67 labeling indices. The Ki-67- and PCNA LI-s were statistically correlated, and the former better discriminated groups of different grades of malignancy.

Immunohistochemical and ultrastructural studies of stromal cells in hemangioblastoma.

In order to shed more light on the controversial tissue histogenesis of the stromal cells (SC), light microscopic, immunohistochemical and electron microscopic studies were performed on surgical specimens of hemangioblastomas (36, 26 and 7 cases, respectively). SC were immunoreactive for vimentin, S-100 protein, and neuron specific enolase (NSE) in all cases. Occasional SC were also positive for desmin, smooth muscle actin, Factor VIII, Ulex europaeus lectin receptors, GFAP, and Factor XIIIa. However, majority of these cells were negative with all the endothelial and smooth muscle cell markers used. Electron microscopy demonstrated several different types of SC that were reminiscent of pericytes, smooth muscle cells and abnormal endothelium as well as the intermediate forms between all the above cell types. Few SC were found lining the vascular lumina. Some SC formed small cavities reminiscent of early capillaries. However, typical Weibel-Palade bodies were not found in these SC. It is concluded that SC represents a heterogeneous population of lipidized cells, derived predominantly from the vasogenic mesenchyme. Although immunohistochemistry failed to reveal any consistent antigenic property of SC, ultrastructural findings strongly support the hypothesis that these cells are modified or abnormally differentiated endothelial cells and pericytes.

Immunohistochemical study in two cases of dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos disease).

We report here immunohistochemical study of two cases of dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos disease) a rare entity which is recently classified as a tumor but which hamartomatous nature is also considered. Dysplastic cells of our cases expressed neuronal markers (synaptophysin and NFP), thus their origin from neurons or neuronal precursor is clearly demonstrated. The exact progenitor cell is, however, unknown. The glial involvement was not easily judged based on our histochemical study. While a few GFAP-immunopositive astrocytes were seen in all specimens, including the recurrence of the first case, they appeared of normal size and non hypertrophic in the second case. Furthermore, they did not much increased in number in the recurrent tumor. Thus, it seems that they are not the primary target for the pathogenetic process, whatever it is, of Lhermitte-Duclos disease.

Reactive and degenerative changes of tissues surrounding a brain tumor.

We report here immunohistochemical and ultrastructural studies of the pattern of brain degeneration being a consequence of the presence of brain tumors. Robust microglial reaction with upregulation of MHC II type antigens within and around the brain tumor were seen along with the purely degenerative phenomena like neuroaxonal dystrophy (NAD) and myelin dilatation ("ballooning"). The reaction was monotonous and independent of the histological type of the brain tumor.

Neoplastic vascular tumors of the central nervous system.

We report here neuropathology of vascular brain neoplastic tumors. These include haemangioblastoma, haemangiopericytoma, angiosarcoma. The most recent molecular data on the histogenesis of gliosarcoma are also discussed.

Expression of N-myc, c-myc and c-erbB-1 proto-oncogenes in cerebral primitive neuroectodermal tumors (PNET).

Neuroectodermal tumors demonstrate a relatively high incidence of proto-oncogenes amplification. This study attempted to determine the frequency of overexpression of three genes: N-myc, c-myc and c-erbB-1, in human PNET. Immunohistochemical studies revealed 5 to 74% neoplastic cells with positive immunoreactivity to anti-c-myc antibody in all investigated samples. In 3 cases the reactivity was particularly strong and present in more than 50% of tumor cells. Northern blot analysis revealed normal (2.3-kb in size) but significantly higher level of c-myc transcripts in these cases. By using anti-EGFR antibody 3 tumors disclosed 10 to 65% neoplastic cells with positive immunoreactivity. There was no rearrangement detected of their c-erbB-1 or N-myc genes by means of applied methods. Our results suggest that overexpression of c-myc gene is present in 10% of PNET but it is not the consequence of gene amplification. Amplification of N-myc and c-erbB-1 are rare events during PNET development.

Expression of p53-protein, epidermal growth factor receptor (EGFR) and proliferating cell antigens in human gliomas.

Paraffin-embedded surgical specimens from 56 human astrocytomas (8 pilocytic [I degree] astrocytomas, 9 low grade [II degrees] fibrillary astrocytomas, 9 high grade [III degrees] astrocytomas and 30 glioblastomas) were immunostained with the anti-PCNA, anti-p53, anti-Ki-67 and anti EGFR antibodies. Approximately 41% of all cases were p53 protein-positive while 23% were EGFR positive. Five cases (8.9%) were positive for both p53 protein and EGFR. Low grade gliomas showed low PCNA LI while high PCNA LI was observed in high grade gliomas. The same trend was observed with anti-Ki-67 antibodies but the proportion of Ki-67 immunolabelled cells was always much lower. In conclusion, we found two populations of astrocytic tumors with EGFR and with p53 protein overexpression but no dependence between p53 immunoreactivity and PCNA or Ki-67 LI.

Pleomorphic xanthoastrocytoma and desmoplastic infantile ganglioglioma--have these neoplasms a common origin?

We report a case of a 24-year-old woman with left temporal pleomorphic xanthoastrocytoma (PXA) with atypical neuronal cells. Many neoplastic cells, otherwise typical of PXA, expressed glial fibrillary acidic protein, while neuronal cells with marked atypia were immunopositive for synaptophysin and neurofilament protein. This report supports a notion that PXA, like other astrocytic tumors, may has its gangliogliomatous counterpart as superficial cerebral astrocytoma of infancy has it in desmoplastic infantile ganglioglioma.

Metaplastic meningioma with lipomatous changes.

We report here relatively rare lipomatous metaplastic changes, probably related to a prolonged clinical course, in not otherwise specified transitional meningioma. This lesion appears to have evolved over 30 years, with the initial diagnosis of multiple sclerosis. Histologically, it was composed of clusters and whorls of polygonal and spindle cells characteristic for transitional meningioma, with large areas of cells with lipid cytoplasmic accumulation, closely resembling mature adipocytes. The lipidization of other brain tumors and the histogenesis of these lesions in meningiomas on the background of meningeal embryogenesis are also discussed.

Desmoplastic cerebral astrocytoma of infancy: a case report.

We report a case of desmoplastic cerebral astrocytoma of infancy (DCAI), in a 7-month-old boy. DCAI belongs to a group of recently described central nervous system (CNS) tumors, which also includes desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA) and dysembryoplastic neuroepithelial tumor (DNT), all characterized by relatively favorable prognosis and occurring mostly in children and young adults. DCAI is a rare neoplasm arising in the cerebral hemispheres within the first two years of life, and histologically is characterized by dense fibrous desmoplasia. In our case, CT scan presents a massive partially cystic tumor of the left cerebral hemisphere with an enlargement of the ventricular system. Histologically, the tumor was composed of cells arranged in fascicles and whorls forming storiform pattern. Immunohistochemical stainings for glial fibrillary acidic protein proved glial histogenesis of this tumor, while no cells were unequivocally immunopositive for neuron specific enolase, neurofilament proteins and synaptophysin what excludes a diagnosis of DIG--a similar entity but containing also a neuronal elements. Our studies, comprising a complete clinical, radiological, histopathological and immunohistochemical data, correspond to a cases of DCAI published before and it is the first one described in Poland.

Clinical, radiological and histological presentations of dysembryoplastic neuroepithelial tumors (DNT). Report of two cases.

Dysembryoplastic neuroepithelial tumor (DNT) is a recently described rare brain neoplasm with characteristic clinical and morphological features and favorable prognosis. We report here two cases of DNT. The first concerned a 12 years old girl who presented complex seizures preceded by acoustic aura (melodies). Computed tomography revealed a hypodense tumor measuring 2 x 2.5 cm in diameter, located paracortically in the left temporal lobe. The second tumor was removed from a 21-year-old man with partial complex seizures. Nine years earlier patient underwent neurosurgery with partial removal of the tumor The tumor's histopathologic diagnosis is unfortunately lacking. Computed and magnetic resonance imaging showed a mass occupying the cortex and paracortical areas of the anterior pole of the temporal lobe. Histologically, both tumors consisted of small, S-100 protein immunopositive oligodendrocyte-like cells (OLCs) arranged between synaptophysin- and, to a lesser degree, NFP-immunopositive axons (glioneuronal element). In the second case, an area of pilocytic astrocytoma-like appearance was also found, these cells were immunopositive for GFAP. The present study provides clinical, radiological and histological data, which may be helpful in differential diagnosis of this newly recognised brain tumor.

Analysis of 200 consecutive neuropathologically verified brain tumors of childhood.

Brain tumors are the most frequent solid neoplasms of childhood. We present here a series of 200 consecutive cases of neuropathologically verified brain tumors in children under 18, operated on between 1990-1996 at the Polish Mother Memorial Hospital in Lódz. The respective diagnoses were established on the basis of light microscopy, ultrastructure and immunohistochemistry. The criteria of the World Health Organization (WHO) classification of central nervous system (CNS) tumors were used in all but one (superficial desmoplastic cerebral astrocytoma of infancy) case. The location of tumors, age and sex of children and tumors' histology in our material were compared with those of previously published series of pediatric brain tumors.

Expression of synaptophysin and neurofilament protein confirms predominantly neuroblastic differentiation of primitive neuroectodermal tumors (PNET).

We report here that neuronal and glial differentiation is easily detected using synaptophysin (SF) and neurofilament protein (NFP) immunohistochemistry in primitive neuroectodermal tumors (PNET). Thus, for all practical reasons, every PNET should be regarded as PNET with "hidden" multipotential or bipotential differentiation.

Diagnosis of Alzheimer's disease with commercially available anti-beta peptide (beta A4) antibodies following microwave oven pretreatment.

Alzheimer's disease (AD), the most common presenile dementia is underdiagnosed in Poland, thus every attempt to make the frequency of this diagnosis approaching standards of Western countries should be recommended. Deposits of beta A4 amyloid in a form of amyloid (senile) plaques, diffuse amyloid deposits and congophilic angiopathy is central to the pathogenesis of AD. These amyloid deposits are virtually invisible in routine pathological stainings like HE but may be visualized with Bielschowsky silver impregnation, other metallic impregnations, and following Thioflavine S or Congo red stainings. We report here that amyloid deposits are as easily immunolabeled with commercially available antibodies against beta A4 (DAKO) and such a staining was greatly enhanced by microwave oven pretreatment. In all cases of AD, the diagnosis could be easily made using either 4GM or commercial DAKO anti-beta A4 antibodies following pretreatment with formic acid or processing in microwave oven. Pretreatment in microwave oven even for only one second was already sufficient to visualize beta A4-immunopositive plaques while after 5 second the intensity of staining approached that obtained after formic acid pretreatment.

Ultrastructure of the primitive neuroectodermal tumors (PNET).

We report a prospective series of consecutive cases of primitive neuroectodermal tumor (PNET) studied by electron microscopy. Virtually all specimens showed a differentiation along neuroblastic lines as evidenced by the presence of neurites, dense-cored vesicles, microtubules and adhesive plaque junctions. We observed also numerous intracytoplasmic cilia and autophagic vacuoles. Synaptic specializations were only rarely seen. We conclude that PNET is a tumor category which is not undifferentiated ("primitive") and clearly exhibits features of neuroblastic differentiation.

Ultrastructural study of subependymal giant cell astrocytoma: unusual paracrystalloid inclusions in tumour cells.

Subependymal giant cell astrocytoma (SEGA) is a tumour with a broad range of morphological, immunohistochemical and ultrastructural neoplastic cellular features. We report here the presence of this tumor in two 7-year-old-boys presented with a lateral intraventricular mass. Further clinical investigation confirmed the diagnosis of tuberous sclerosis. Ultrastructural and immunohistochemical investigation revealed that glial differentiation was more pronounced in these cases. Interestingly, tumour cells containing unusual paracrystalline inclusions, infrequently described in SEGA, were identified ultrastructurally. These inclusions are probably not related to other cellular organelles.

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.

[Favorable outcome using indomethacin in a case of temporal arteritis]. / Pomyslny wynik zastosowania indometacyny w przypadku zapalenia tetnicy skroniowej.

The authors described a case of temporal arteritis in which only biopsy of the artery made the correct diagnosis possible. The patient had contraindications to steroid treatment and thus a trial of Metindol therapy was undertaken. After the treatment a rapid regression of symptoms occurred.

[Primary malignant lymphoma of the central and peripheral nervous systems]. / Pierwotny chloniak zlosliwy osrodkowegó i obwodowego ukladu nerwowego.

The authors present a case of malignant lymphoma in a man aged 64 years. Neoplastic infiltrations mainly in the form of perivascular accumulations were limited to the central nervous system (both central and peripheral). In the histological examinations of internal organs including lymph nodes and spleen no neoplastic tissue was found.