PubMed HealthSearch

Biomedical subjects

B W Scheithauer

Publications and source records attributed to B W Scheithauer.

At least 55 records · Page 3Linked to original sources

Clear cell meningioma. A clinicopathologic study of a potentially aggressive variant of meningioma.

Since clear cell meningioma has only recently been recognized as a morphologic entity, its pathobiology has not been studied. Fourteen examples occurring in seven females and six males, ages 9 to 82 years (mean 29 years), were examined; one was associated with type 2 neurofibromatosis. Of these cases, seven (50%) were spinal-intradural (six lumbar, one thoracic), three (21%) arose in the posterior fossa (cerebellopontine angle), three (21%) were supratentorial, and one (7%) was centered upon the foramen magnum. In one case (8%), two tumors were considered to be independent primaries. One tumor (8%) appeared to show no dural attachment. Thirteen tumors were subject to complete study. All were composed of sheets of clear, glycogen-rich, polygonal cells forming only a few vague whorls. Hyalinization, both stromal and perivascular, was often extensive. Mitoses were rare in primary tumors. Immunohistochemistry showed vimentin and epithelial membrane antigen staining to be reactive in 100%. Stains for S-100 protein and CAM 5.2 were negative. Progesterone and estrogen receptor staining was observed in 77% and 0%, respectively. Ultrastructural study showed abundant cytoplasmic glycogen, a few cytoplasmic lumina, intermediate filaments, interdigitation of cell membranes, and desmosomal junctions. The means, medians, and ranges of proliferating cell nuclear antigen (PCNA) and MIB-1 antigen labeling indices for nonrecurring and recurring tumors were 10.4%, 8.8%, 0.8-23.4% and 11%, 1.4%, 0.1-50.3%, as compared with 7.4%, 6.7%, 2.9-17.2% and 13.3%, 13.4%, 3.3-25.7%, respectively. Twelve successful DNA ploidy studies showed that 11 tumors (85%) were diploid and one was tetraploid; percentage S-phase determinations varied from 4 to 9% (mean 6.0%). Recurrence was noted in eight patients (61%) (five of whom had multiple recurrences); there was local discontinuous spread in two cases (15%) and widespread cranial to spinal metastasis in one case (8%). Three patients (23%) are dead of disease. In summary, clear cell meningiomas are morphologically unique, show no sex predilection, affect primarily the lumbar region and cerebellopontine angle, and despite their benign appearance, may be inordinately aggressive, particularly intracranial examples. No close association was noted between recurrence or clinical outcome and such factors as mitotic activity, PCNA proliferation indices, percent S-phase determination, or DNA ploidy status. In contrast, MIB-1 proliferation indices were appreciably higher among recurring tumors.

Adolescent

Analysis of the chromogranin A post-translational cleavage product pancreastatin and the prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries.

Several members of the chromogranin/secretogranin (Cg/Sg) family are post-translationally processed in neuroendocrine cells and tumors to smaller peptides, some of which are biologically active. For example, CgA is processed to pancreastatin, parastatin, and other peptides. We analyzed the distribution of pancreastatin and CgA proteins in normal and neoplastic pituitaries as well as the prohormone convertases PC2 and PC3/1 (PC3), the putative processing enzymes for the Cg/Sg family, in 35 pituitary adenomas and 4 non-neoplastic pituitaries by immunohistochemistry and immunoblotting with highly specific antisera. CgA and CgB mRNAs were also examined. Pancreastatin was present in all subtypes of pituitary tumors, although prolactin-secreting adenomas expressed this peptide less frequently than did other tumor types. CgA protein and CgA mRNA expression were also restricted in prolactin adenomas and in normal prolactin cells, as shown by combined in situ hybridization and immunostaining. The prohormone convertases PC2 and PC3 were present in pituitary tumors and in non-neoplastic pituitaries. Immunoblot analysis and immunostaining showed a principal approximately 69-kd PC3 band and a approximately 68-kd PC2 band. Adrenocorticotrophic hormone-secreting adenomas expressed mainly PC3 as determined by immunoblotting and immunohistochemistry, whereas all other adenoma groups expressed predominantly PC2. These results indicate that the enzymes capable of processing CgA and other members of the Cg/Sg family to peptides with biological activity such as pancreastatin are widely expressed in human pituitary adenomas and in non-neoplastic pituitaries, with adrenocorticotrophic hormone tumors expressing predominantly PC3 and other adenomas expressing mainly PC2. The infrequent expression of CgA protein and pancreastatin peptides in normal and neoplastic prolactin cells suggests a unique role of CgA in these tumors.

Adult

Gangliosides as diagnostic markers of human astrocytomas and primitive neuroectodermal tumors.

BACKGROUND: Limitations of classification schemes for brain tumors based solely on morphology have stimulated searches for molecular markers of nosologic and prognostic value. Gangliosides are logical candidates because there are high concentrations of them in the nervous system, there is evidence of their roles in regulation of growth and differentiation, and data from small series suggest correlations between ganglioside composition and glioma type. METHODS: Ganglioside compositions were determined for 70 primary human brain tumors: 16 low grade astrocytomas (LG), 12 anaplastic astrocytomas (AA), 34 glioblastoma multiformes (GBM), and 8 primitive neuroectodermal tumors (PNET). This method involved identification and quantitation of specific gangliosides using chemical analysis and immunoanalysis. RESULTS: Among all tumor types, histologic grade correlated with a progressive loss of 1b gangliosides (P < 0.0001). GQ1b was higher in LGs than in AAs (P < 0.001). Both GT1b and GD1b were higher in AAs than GBMs (P < 0.01 and 0.05, respectively) and lower in PNETs than in GBMs (P < 0.05). GM3 was higher in PNETs than in any astrocytoma group and higher in GBMs than in either AAs or LGs. There was a significant difference in the content of 3'-LM1 among all groups (P < 0.005), between AAs and GBMs (P < 0.05), and between low grade ordinary and juvenile pilocytic astrocyomas (P < 0.01). The lacto-series ganglioside 3'-isoLM1 was present in all groups except PNET. CONCLUSIONS: These results indicate that patterns of gangliosides could be of considerable value in refining the classification and diagnosis of primary human brain tumors.

Adult

Prognostic factors in gliomas. A multivariate analysis of clinical, pathologic, flow cytometric, cytogenetic, and molecular markers.

BACKGROUND: The ability to divide subsets of patients with glial neoplasms into prognostic groups currently is limited because only a few clinical and pathologic variables are available. The goal of this investigation was to identify biologic factors of potential prognostic value in patients with cerebral gliomas. METHODS: This prospective investigation used clinical, pathologic, flow cytometric, cytogenetic, and molecular genetic variables as potential prognostic factors in 207 patients with newly diagnosed gliomas (153 astrocytic tumors of the fibrillary type, 31 oligodendrogliomas, and 23 pilocytic astrocytomas). Classification and regression tree (CART) analysis was performed as part of the multivariate statistical analysis. RESULTS: The age of the patient and the grade of the tumor were confirmed as strong prognostic factors. Cytogenetic or molecular genetic abnormalities of chromosomes 7 and 10 were associated with poor survival in univariate analysis (P < 0.0001). CART multivariate analysis identified several subsets of patients with different prognoses. In the subset of patients younger than 66.5 years with Grade 4 tumors, the survival time was longer for those with aneuploid tumors than for those with nonaneuploid tumors. In the subset of patients with Grades 1-3 tumors, the survival time was longer for those whose tumors had a %G2M of less than 6.9 than for those whose tumors had a %G2M of 6.9 or greater. CONCLUSION: This investigation provides further evidence that flow cytometry, cytogenetic, and molecular genetic factors that may have prognostic value in patients with gliomas can be identified.

Adult

Mast cell-rich convexity meningioma presenting as chronic subdural hematoma: case report and review of the literature.

A 47-year-old woman with a convexity meningioma presenting as a chronic subdural hematoma is reported. This case is unique in that the symptoms were cyclical and stereotypic. The tumor contained an unusually high number of mast cells. A possible etiologic role of histamine-related vasodilation and tumoral hemorrhage is explored. The relationship between meningioma and subdural hematoma is discussed, and the literature is reviewed.

Brain

Aggressive medulloblastoma with high-level N-myc amplification.

A 27-year-old man was treated for an aggressive cerebellar medulloblastoma that, at operation, exhibited dural invasion. Six months after gross total resection and radiation therapy, a "surgical metastasis" developed in the lower portion of the surgical scar. The tumor grew rapidly down into the right side of his neck. Chemotherapy failed, and he subsequently died. Cytogenetic and molecular genetic studies revealed multiple numeric and structural chromosome abnormalities, including an abnormal chromosome 17p arm, more than 100-fold N-myc amplification, a rearranged c-myc gene, and a 16-base pair deletion involving exon 7 of the p53 gene. We postulate that these genetic features may have contributed to the aggressive behavior of the tumor.

Adult

Dysembryoplastic neuroeptihelial tumor (DNT): an immunohistochemical and ultrastructural study.

To assess the range of differentiation of the cells comprising dysembryoplastic neuroepithelial tumor (DNT), particularly the oligodendrocyte-like cells (OLC), 14 DNT were immunochemically studied with a spectrum of neuronal and glial markers. Eight tumors were also studied ultrastructurally. Neurofilament protein, class III beta-tubulin, and synaptophysin preparations stained a few OLC in two, six and one lesion, respectively. In addition, many OLC within a single cortical nodule were reactive for class III beta-tubulin. The vast majority of OLC were strongly S-100 protein positive. Glial fibrillary acidic protein labeled a fair number of OLC in two cases and one nodule consisted almost entirely of immunoreactive astrocytes. Ultrastructurally, many OLC resembled oligodendrocytes in exhibiting microtubules, prominent Golgi and short cell processes; pericellular lamination of cell processes, a characteristic of oligodendroglia, was noted in only one tumor. In two cases, OLC with astrocytic features were seen to contain small numbers of intermediate filaments. In four cases, a few OLC resembled immature neurons with scant dense-core granules or synapses. This study confirms the glioneuronal nature of DNT, a lesion composed of heterogeneous cells, many resembling oligodendrocytes and a few showing early astrocytic and neuronal differentiation. Although their relation to OLC is unclear, the presence and peculiar distribution of mature neurons is nonetheless an integral diagnostic feature of the lesion.

Adolescent

The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study.

Biologically malignant pilocytic astrocytomas are rare. Precise morphologic criteria permitting their identification and clinically meaningful distinction from more ordinary pilocytic astrocytomas have not been developed. The histologic grading schemes applied to fibrillary astrocytomas--ones based on nuclear atypia, increased cellularity, mitotic activity, endothelial proliferation, and necrosis--are thought not to correlate with prognosis in pilocytic astrocytomas. Nonetheless, these features were systematically sought in 107 cerebellar pilocytic astrocytomas, four of which were histologically malignant. The clinical, morphologic, and flow cytometric features of these cases were studied. The incidence of histologic malignancy occurring spontaneously in otherwise typical pilocytic astrocytomas was 0.9%; that occurring after radiation was 1.8%. The four histologically malignant tumors occurred in two males and two females, ages 6 to 18 years. All showed increased mitotic activity (three to five mitoses per high-power microscopic field [250x]). Endothelial proliferation and necrosis were present in three and two cases each. DNA ploidy analysis showed the spontaneously occurring malignant-appearing tumors to be aneuploid, whereas both previously radiated tumors were tetraploid; 5% to 11% of cells were in S phase. The appearance of histologic malignancy in pilocytic astrocytoma is rare and less reliably correlated with prognosis than in patients with fibrillary astrocytomas. Essential features of such tumors include a high mitotic index and perhaps a high percentage of cells in S phase.

Adolescent

ras mutations in human prolactinomas and pituitary carcinomas.

Pituitary adenomas have been shown to be clonal in origin, indicating that one or more somatic mutations underlie tumor pathogenesis. Mutated oncogenic forms of ras protein have been identified in a number of human neoplasms, including thyroid adenomas and carcinomas. However, the potential role of activated ras in the development of specific human pituitary tumor phenotypes has not been determined. Although ras mutations were not found in glycoprotein hormone-secreting or somatotroph adenomas, we recently identified a mutation in the H-ras gene (Gly-Val) at codon 12 in a highly invasive prolactinoma. These data raise the possibility that ras mutations might play a role in the pathogenesis of PRL-secreting pituitary tumors and/or may be a marker for tumor invasiveness and malignant transformation. Therefore, we investigated 78 pituitary tumors (59 prolactinomas, 13 invasive prolactinomas, and 6 pituitary carcinomas) for activating point mutation in the three ras genes using oligonucleotide-specific hybridization. In contrast to the relatively high frequency of ras mutations in many different tumor types, no ras mutations were identified in either prolactinomas or pituitary carcinomas. Our data indicate that ras mutations are rare in prolactinomas and pituitary carcinomas.

Adolescent

Pituitary adenomas in childhood and adolescence.

A clinicopathological study of 56 pediatric patients with non-ACTH-secreting pituitary adenomas removed by a transsphenoidal neurosurgical approach was undertaken to better define the clinical presentation, to assess demographic factors, to determine the immunohistochemical staining characteristics of the tumors, and to evaluate the outcome of transsphenoidal surgical treatment and other adjuvant therapies. A separate analysis of prolactinoma patients was performed. All tumors were confirmed histologically and immunophenotyped for pituitary hormones. Forty-one patients had tumors that stained for PRL alone, eight patients had tumors that stained for PRL and GH, six patients had plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas (1.4:1). There were no male patients with microadenomas of any type. Females outnumbered males (3.3:1). Patients presented most frequently with headache, menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but one of the patients with hypopituitarism at presentation had macroadenomas. Tumor staining characteristics did not always correlate well with clinical status, especially with regard to GH-containing tumors. Pediatric pituitary tumors did not appear to be more invasive or more aggressive than adult pituitary tumors, contrary to some previous reports. The patients with microadenomas had a 70% operative cure rate and a 65% long term cure rate; the recurrence rate for microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma and macroadenoma patients had similar long term cure rates, but macroadenoma patients required more aggressive adjuvant therapy (second surgery, radiation, or bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma patients vs. 0% of microadenoma patients required long term hormone replacement).

Adenoma

Mixed oligoastrocytomas: a survival and prognostic factor analysis.

Seventy-one patients with supratentorial mixed oligoastrocytomas underwent surgery only (5 patients) or surgery with postoperative radiation therapy (66 patients) between 1960 and 1982. The median survival for these 71 patients was 5.8 years and the 5-, 10-, and 15-year survival rates were 55, 29, and 17%, respectively--values significantly different from those of an age- and sex-matched normal reference population. Uni- and multivariate survival analyses were applied to 14 possible prognostic factors, including the following: patient factors--age, sex, and seizures; tumor factors--site, size, side, computed tomographic enhancement, and calcification; pathological factors--tumor grade and dominant cellular component; and treatment factors--extent of surgical resection, lobectomy, and radiation dose and field. Of these factors, tumor grade, as determined by the Kernohan method, was the most strongly associated with survival. The 60 patients with Grades 1 and 2 tumors had a median survival of approximately 6.3 years and 5- and 10-year survival rates of 58% and 32%, respectively, compared with 2.8 years (36 and 9%, respectively) for the 11 patients with Grades 3 and 4 tumors. Age < 37 years, gross total resection, partial brain radiation, and radiation dose > or = 5000 cGy were other factors significantly associated with improved survival in both uni- and multivariate models. Three of five patients not receiving postoperative radiation therapy experienced tumor recurrence and died. Seven of eight patients from whom tissue was obtained at the time of tumor progression demonstrated anaplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Chronic meningitis: the role of meningeal or cortical biopsy.

Meningeal and cortical biopsies were evaluated in 37 patients (25 men and 12 women; mean age, 54 yr) who had chronic meningitis of an unknown cause between 1985 and 1993 (the era of magnetic resonance imaging). Magnetic resonance imaging with gadolinium contrast was the most useful diagnostic imaging technique, demonstrating meningeal enhancement in 15 of 32 patients (47%). Only 2 of 32 (6%) computed tomographic scans revealed enhancement. A definitive diagnosis was made in 16 of 41 biopsies (39%), but in cases where enhancement was present on either magnetic resonance imaging or computed tomography, a diagnosis was obtained in 80% (12 of 15 cases). Only 2 of 22 biopsies (9%) from nonenhancing regions were diagnostic. Although the locations of enhancement were distributed evenly, biopsies through suboccipital and pterional craniotomies gave the highest diagnostic yields (50%). Furthermore, if the biopsies were obtained from enhancing regions, the yield of these two approaches increased to 84 and 100%, respectively. Of 18 cases in which biopsy samples were taken from both the meninges and cortex, only 1 had cortical involvement alone. The meninges were therefore diagnostic in 15 of the 16 definitive diagnostic cases (94%). Second biopsies were necessary in four cases, of which the three biopsies from enhancing regions were diagnostic. The most frequent causes of chronic meningitis were sarcoid (31%) and metastatic adenocarcinoma (25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Angiographically occult vascular malformations: a correlative study of features on magnetic resonance imaging and histological examination.

With reference to vascular malformations, the term cavernous has architectural as well as histologic connotations. It refers to a compact pattern of growth wherein no intervening brain parenchyma is evident, as well as to the histological nature of the vessels, which are hyaline and collagenous in appearance, lacking the microscopic features of arteries or veins. Historically, cavernous angioma has been defined as exhibiting both features. Twenty-five patients with neurological symptoms and neuroimaging abnormalities who underwent surgery for cerebral vascular malformations between 1987 and 1990 satisfied the following study criteria: their lesions were angiographically occult and both magnetic resonance imaging (MRI) and histological sections were available for review. The patients' ages ranged from 4 to 49 years (mean, 30 years), the male to female ratio being 1:2. Two thirds of the lesions were supratentorial in location and all were intraparenchymal. All patients had clinical improvement after resection. In 24 of the 25 lesions, the vascular channels were histologically cavernous in nature; one inadequate specimen precluded classification. Three demonstrated a purely compact or cavernous pattern, 20 a mixed cavernous and racemose pattern, and one a purely racemose pattern. The authors conclude that 1) histologically cavernous lesions are the commonest form of occult vascular malformation; 2) a purely compact or cavernous architectural pattern is uncommon, most lesions showing a partially racemose architecture; 3) some histologically cavernous malformations possess a capillary component; 4) clinical growth of cavernous malformations may have its basis in intraluminal thrombosis and subsequent recanalization; 5) the T2-weighted MRI pattern of cavernous malformations varies, the most common being a multifocal hyperintense center surrounded by a hypointense ring; 6) the MRI pattern reflects the histological appearance; 7) since no thrombosed arteriovenous malformations were encountered, such lesions must be rare; 8) in that the pathophysiological hallmark of a cavernous lesion is recurrent thrombosis and hemorrhage, a resolving hematoma cannot always be distinguished from a cavernous lesion; 9) MRI is the examination of choice in evaluating occult vascular malformations; and 10) microsurgical excision is a satisfactory method of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins

Cerebellar pleomorphic xanthoastrocytoma: case report.

We report a case of pleomorphic xanthoastrocytoma occurring in the midline cerebellum of a 48-year-old woman. Radiological, histological, immunohistochemical, and flow cytometric findings are discussed. Pleomorphic xanthoastrocytoma typically occurs in the superficial cerebral hemispheres of young patients. To our knowledge, this is the first report of the occurrence of this neoplasm in the cerebellum. The English literature is reviewed with regard to the clinicopathological features of this uncommon form of astrocytoma.

Astrocytoma

Estrogen receptor gene expression in craniopharyngiomas: an in situ hybridization study.

Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation.

Cell Division

Changes in proliferating cell nuclear antigen expression in glioblastoma multiforme cells along a stereotactic biopsy trajectory.

Proliferating cell nuclear antigen, an auxiliary protein of deoxyribonucleic acid polymerase-delta, has been shown to be a reliable marker of nuclear deoxyribonucleic acid synthetic activity. We applied a monoclonal antibody to proliferating cell nuclear antigen to a series of serial stereotactic biopsies from patients with glioblastoma multiforme and found the proliferative activity to vary relative to biopsy location within or surrounding the solid tissue component of the tumor. Twenty-seven trajectories in 26 patients were analyzed, each consisting of two to five sequential 10 x 1.5 mm core biopsies (mean = 3). The proliferative index (PI) was greatest in those cells located at the solid tumor-infiltrated parenchyma interface. PI values were significantly lower in those biopsy cores located proximal (within infiltrated parenchyma) and distal (within solid tumor tissue) to the solid tumor-infiltrated parenchyma interface (median PI values, proximal to distal: 0.38, 0.66, 5.45 solid tumor-infiltrated parenchyma interface], 0.39, 0.09%). The mean PI values were significantly lower in neoplastic cells samples from regions of peripheral hypodensity on computed tomographic scans compared with those sampled from contrast-enhancing regions (0.9 and 3.91%, respectively). There was no significant difference in the mean PI values of neoplastic cells sampled from regions of contrast enhancement or central hypodensity (3.91 and 4.31%, respectively).

Biomarkers, Tumor