Biomedical subjects

B W Scheithauer

Publications and source records attributed to B W Scheithauer.

At least 37 records · Page 2Linked to original sources

PubMed2001

Management of malignant pineal germ cell tumors with residual mature teratoma.

OBJECTIVE: The treatment of intracranial mixed germ cell tumors presents a unique challenge, since eradication of malignant tumor by radiation and/or chemotherapy may spare the benign tumor component. We reviewed our surgical experience with residual malignant pineal germ cell tumors after neoadjuvant therapy. METHODS: Between 1987 and 1997, 16 patients with malignant intracranial germ cell tumors were treated at the Mayo Clinic with a protocol of neoadjuvant chemotherapy and radiation therapy. After the diagnosis was confirmed by histopathological examination, all patients were treated with four cycles of etoposide and cisplatin as well as external beam radiation therapy (range, 3030-5940 cGy). Six patients had an incomplete response to therapy, as demonstrated by observation of residual tumor on magnetic resonance imaging scans. Initial pathology in these six patients was germinoma in four and combinations of yolk sac tumor, embryonal carcinoma, malignant teratoma, and germinoma in two. Two patients had synchronous pineal and suprasellar tumors, with leptomeningeal dissemination. Tumor markers were elevated in four of the six patients at presentation. RESULTS: All patients with residual pineal tumors underwent surgical resection via an infratentorial, supracerebellar approach. Pathological examination revealed mature teratoma in five patients and amorphous debris in one patient. No patient had recurrent malignancy. Significant neurological morbidity occurred in one patient, with no mortality. At a mean follow-up of 23 months, no recurrence on magnetic resonance imaging has been documented. CONCLUSION: Residual pineal tumor occurring after treatment of malignant intracranial germ cell tumor with neoadjuvant therapy is likely to be mature teratoma. Operative resection of these benign recurrences is safe and effective.

Adolescent↗

PubMed2001

Combined oligodendroglioma/pleomorphic xanthoastrocytoma: a probable collision tumor: case report.

OBJECTIVE AND IMPORTANCE: We report the first case of combined oligodendroglioma and pleomorphic xanthoastrocytoma. CLINICAL PRESENTATION: A female college student and competitive cross-country runner presented to the Mayo Clinic at age 18 years with complaints of progressive headache and visual disturbances. Neuroimaging revealed a heavily calcified left parieto-occipital mass with focal enhancement and remodeling of the overlying calvarium. INTERVENTION: A histological examination of the nearly gross total resection specimen disclosed a low-grade oligodendroglioma discretely abutting a superficially situated focus of pleomorphic xanthoastrocytoma. Ten months thereafter, a recurrence was suspected on the basis of the detection of a new focus of nodular enhancement. This lesion stabilized after radiation therapy, and the patient is well, without apparent residual disease 2.8 years after surgery. CONCLUSION: This unique neoplasm is presumed to represent a collision tumor, its biological behavior being similar to that of oligodendroglioma alone. However, the possibility of an unusual, mixed oligoastrocytoma with pleomorphic xanthoastrocytoma as the astrocytic component cannot be excluded entirely. Potentially, both components have the capacity for recurrence and anaplastic transformation.

Adolescent↗

PubMed2001

Metastatic hepatocellular carcinoma presenting as epidural hematoma: case report.

OBJECTIVE AND IMPORTANCE: A case of acutely symptomatic epidural hematoma caused by metastatic hepatocellular carcinoma (HCC) to the cranium is reported. This is a rare case of metastatic HCC without known primary presenting as an epidural hematoma. CLINICAL PRESENTATION: The patient presented with an acute onset of headache, aphasia, and right hemiparesis 2 weeks after he experienced minor trauma to the cranium. An emergency computed tomographic scan of the head revealed the presence of a left parietal epidural hematoma. INTERVENTION: An emergency evacuation of the epidural hematoma was performed, and metastatic HCC was diagnosed. CONCLUSION: The patient's neurological deficits were reversed with surgical intervention, and he is now undergoing palliative chemotherapy. This was the first clinical manifestation of HCC in this patient. This case reaffirms the neurosurgeon's role in the complex, multidisciplinary care of patients with craniospinal metastasis.

Brain Neoplasms↗

PubMed2001

Mature teratoma of the middle ear.

OBJECTIVE: The authors report a case of mature teratoma of the middle ear in a 3-year-old girl with a 1-year history of otitis media. METHODS AND RESULTS: Radiologic investigation revealed a partially cystic lesion of the petrous portion of the right temporal bone. It produced opacification of the middle ear as well as destruction of septal air cells. The patient underwent a subtotal petrosectomy. Histologically, the tumor was composed of an intimate admixture of mature tissues representing all three germ layers, including brain, myelinated nerve trunks, skeletal muscle, bone, immature cartilage, seromucinous glands, and respiratory epithelium. Of note within the brain tissue was choroid plexus within an ependyma-lined rudimentary ventricle. Immunohistochemical studies were also performed. Twenty months after surgery, the patient was well, with complete recovery from symptoms. CONCLUSION: Teratomas of the middle ear are rare neoplasms. Only a few examples have been reported. As a rule, they are cured by resection and do not require adjuvant therapy.

Adipose Tissue↗

PubMed2001

PS6K amplification characterizes a small subset of anaplastic meningiomas.

PS6K, a putative oncogene mapped to chromosome 17q23, encodes a serine/threonine kinase, which phosphorylates ribosomal subunit 6 and is part of the insulin receptor signal transduction pathway involved in the regulation of messenger RNA translation, protein synthesis, cell cycle progression, and cell size. Comparative genomic hybridization studies have detected 17q23 amplifications in a subset of meningiomas, particularly those with aggressive histologic features. PS6K amplifications have been reported in breast cancer, another hormonally driven neoplasm. We assessed PS6K dosage in 94 archival paraffin-embedded meningiomas using dual-color fluorescence in situ hybridization. We found high-level PS6K amplifications in 3 of 22 anaplastic grade III meningiomas. Amplification was confirmed by differential polymerase chain reaction in 1 of these cases. In contrast, no amplifications were identified in 37 benign (grade I) and 35 atypical (grade II) meningiomas. To our knowledge, this represents the first report of gene amplification in primary human meningiomas. Given its exclusive association with anaplastic meningiomas, PS6K amplification likely occurs during the malignant progression of a small subset of anaplastic tumors. Further studies are needed to map the 17q23 amplicon to determine whether additional genes in this region are amplified in high-grade meningiomas.

DNA Primers↗

PubMed2001

Analysis of beta-catenin mutations and alpha-, beta-, and gamma-catenin expression in normal and neoplastic human pituitary tissues.

The cadherin-catenin system mediates Ca(2+)-dependent cell-cell adhesion, and genetic alterations in these molecules play a significant role in multistage carcinogenesis. Mutations in the beta-catenin gene, mostly affecting exon 3, have been detected in malignant cell lines and in primary tumors. Immunohistochemical abnormalities in alpha-, beta-, and gamma-catenin have been reported in malignant and benign tumors, and nuclear localization of beta-catenin has been associated with mutations in exon 3 of this gene. Mutational analysis of exon 3 of the beta-catenin gene was undertaken by polymerase chain reaction (PCR) and sequencing using genomic DNA extracted from frozen tissues, including 4 normal pituitaries, 22 pituitary adenomas, and one pituitary carcinoma. Frozen sections from these cases were used for immunohistochemical detection of beta-catenin. We also analyzed immunohistochemical expression of alpha-, beta-, and gamma-catenin by paraffin sections from 154 pituitary tumors, including 148 adenomas and 6 carcinomas. Genomic DNA was extracted from paraffin sections of 2 gonadotroph tumors showing nuclear staining for beta-catenin and was used for PCR and sequencing of exon 3 of the beta-catenin gene. No mutations in exon 3 of the beta-catenin gene were found in any of the 23 cases analyzed by PCR and sequencing. In addition, the 2 cases studied by paraffin section immunohistochemistry, with nuclear staining for beta-catenin, were negative for mutations in this exon. Normal pituitary expressed all three catenin proteins. Immunostaining usually showed a membranous pattern of reactivity and was generally stronger in normal pituitary than in the adjacent adenomas. Stains for alpha-catenin were positive in fewer tumors than for beta-catenin. The lowest frequency immunopositive tumors and the weakest immunostaining was for gamma-catenin. All medically treated prolactinomas were negative for gamma-catenin, whereas treated growth hormone adenomas were less often positive for both alpha- and gamma-catenin than for untreated tumors. The percentage of positive cases for beta-catenin was the same in these two groups. Most pituitary carcinomas were negative for both alpha- and gamma-catenin but were beta-catenin positive. These results indicate that (i) mutations in exon 3 of the beta-catenin gene are uncommon in pituitary tumors, and (ii) expression of alpha-, beta-, and gamma-catenin is decreased in pituitary adenomas compared to normal pituitary tissues.

Adenoma↗

PubMed2001

Inactivation of the p16 gene in human pituitary nonfunctioning tumors by hypermethylation is more common in null cell adenomas.

Recent studies have shown that methylation of the CpG island within the p16/CDKN2A/MTS1 (p16) gene is associated with loss of expression of p16 protein in pituitary tumors. We analyzed a series of 21 pituitary adenomas and three normal pituitaries along with a human pituitary cell line (HP75) for methylation of exon 1 by methylation-specific PCR, immunohistochemistry, and Western blotting. PCR analysis showed that 5/7 (71%) of null cell adenomas, but only 2/7 (29%) gonadotroph tumors were hypermethylated. In addition,1 of 2 ACTH tumors but no GH (n = 4) or PRL (n = 1) adenoma examined were hypermethylated. Immunostaining and Western blot analysis of protein expression supported the methylation-specific PCR analyses. These results show that p16 gene silencing by hypermethylation is more common in null cell adenomas compared to other nonfunctioning adenomas such as gonadotroph tumors and that the role of p16 in the pathogenesis of pituitary adenomas is restricted to specific tumor subtypes.

Adenoma↗

PubMed2001

Primary polymorphous hemangioendothelioma of the spinal cord. Case report.

A case of polymorphous hemangioendothelioma of the spinal cord is described. This 55-year-old woman presented with an 18-month history of lower-extremity sensorimotor deficit. A magnetic resonance image revealed an enhancing, intradural, extramedullary nodule at the T 1-2 level. On gross inspection, the lesion measured 3.5 cm and was firmly attached to spinal cord parenchyma and adjacent nerve roots. It was completely removed. Fourteen months after surgery the patient's neurological deficit had resolved. Polymorphous hemangioendothelioma is a rare vascular tumor of borderline malignancy. Most occur in lymph nodes. None has been reported to occur in the central and peripheral nervous system. Based on current experience, resection and close follow up seems the best therapeutic approach.

Female↗

PubMed2001

Chordoid glioma: a neoplasm unique to the hypothalamus and anterior third ventricle.

BACKGROUND AND PURPOSE: Chordoid glioma is a new clinicopathologic entity that occurs in the region of the hypothalamus/anterior third ventricle. The aims of this study were to describe the characteristic radiographic features of chordoid glioma, identify specific imaging features that may enable differentiation of chordoid glioma from other suprasellar tumors, and increase neuroradiologists' awareness of this newly described tumor, facilitating prospective diagnosis. METHODS: CT scans and/or MR images of six patients with chordoid glioma were reviewed retrospectively to determine whether any characteristic radiographic features would emerge. Reports of the clinical presentation, pathologic findings, and radiographic findings of another six patients were reviewed and included, for a total patient population of 12 (mean age +/- SD, 46 +/- 13 years). RESULTS: Imaging features were strikingly similar for all tumors. In each case, the mass was ovoid, was well circumscribed, was located in the region of the hypothalamus/anterior third ventricle, and enhanced uniformly and intensely. Tumors were hyperdense to gray matter on CT scans and were isointense on T1-weighted MR images and slightly hyperintense on long-TR MR images. In two patients, vasogenic edema extended into the optic tracts, and in three, there was hydrocephalus. CONCLUSION: Chordoid glioma is a recently described unique histopathologic entity that has been added to the World Health Organization glioma classification scheme and must be included in the differential diagnosis of a suprasellar mass. Distinctive imaging features are its location, ovoid shape, hyperdensity on CT scans, and uniform intense contrast enhancement.

Adult↗

PubMed2000

Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers.

Allelic loss of chromosome arm 19q is a frequent event in human diffuse glioma, suggesting the presence of a tumor suppressor gene. Previous loss of heterozygosity (LOH) analyses have mapped this gene to a 1.4-megabase interval, between the genetic markers D19S412 and STD. Further narrowing of this interval has been limited by the resolution of mapped polymorphic markers. In the present study, we have used genomic clones mapped to 19q as fluorescence in situ hybridization (FISH) probes to map the breakpoints of 13 gliomas with 19q13.3 deletion boundaries. In addition, we have developed three new polymorphic microsatellite markers (D19S1180, D19S1181, and D19S1182) that map between D19S412 and STD and have used these new markers to identify two gliomas with small deletions between the D19S412 and STD markers. Collectively, these data suggest that the region of common deletion may be as narrow as 150 kb and should facilitate future efforts to identify the glioma 19q tumor suppressor gene.

Chromosome Deletion↗

PubMed2000

Transdifferentiation of somatotrophs to thyrotrophs in the pituitary of patients with protracted primary hypothyroidism.

In patients with protracted primary hypothyroidism, the pituitary is enlarged due to the lack of feedback inhibition by thyroid hormone. In the present work, adenohypophysial biopsies from three women with protracted primary hypothyroidism were investigated by routine histology, immunocytochemistry, double immunostaining, immunoelectron microscopy, and combined immunocytochemistry - in situ hybridization. These methods confirmed the presence of massive thyrotroph hyperplasia and the formation of "thyroidectomy" or "thyroid deficiency" cells. A number of thyroidectomy cells were found to be immunoreactive for growth hormone (GH). Double immunostaining and immunoelectron microscopy revealed the presence of bihormonal cells containing both GH and thyroid stimulating hormone (TSH). Immunostaining combined with in situ hybridization revealed GH immunoreactive cells expressing TSH mRNA as well as TSH immunopositive cells expressing GH mRNA. Our findings provide conclusive evidence that somatotrophs may transform to thyrotrophs. Thus, in addition to multiplication of thyrotrophs, transdifferentiation of GH cells to thyrotrophs contributes to the increase of TSH-producing cells. The presence of such bihormonal cells best termed "thyrosomatotrophs" supports the concept that adenohypophysial cells are not irreversibly committed to the production of one single hormone and that their phenotype can change in response to functional demand.

Adult↗

PubMed2000

Primary malignant rhabdoid tumour of the brain in an adult.

We report a mass in the left cerebral hemisphere of a 20-year-old man. Histological, ultrastructural and immunohistochemical features of the tumour were consistent with primary malignant rhabdoid tumour. The age of presentation, imaging features prior to histological examination, and prognosis in this case were unusual.

Adult↗

PubMed2000

Ganglion cells in the posterior pituitary: result of ectopia or transdifferentiation?

Histologic examination revealed large ganglion cells within the posterior pituitary of an 80-year-old woman who died of myocardial infarction. Apparently fully mature, the cells were an incidental finding scattered within hyperplastic foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic examination of the pituitary obtained at autopsy. Immunocytochemistry showed staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of the glycoprotein hormones and beta-endorphin. The presence of these ganglion cells with features similar to those of magnocellular hypothalamic neurons could be considered the result of abnormal migration during the early phase of embryonic life, or differentiation/maturation of neuroblasts, presumed to occur in the embryonic neurohypophysis. Alternatively, transdifferentiation from proliferating PI cells may explain the emergence of neurons; a hypothesis supported by the proximity and shared alpha subunit, and beta-endorphin immunoreactivities of the two cell types.

Aged↗

PubMed2000

Immunolocalization of vascular endothelial growth factor in the GH3 cell line.

The question of whether vascular endothelial growth factor (VEGF) is expressed in the GH3 cell line was investigated using immunocytochemistry, immunoelectron microscopy, and Western blotting. Using immunocytochemistry, VEGF was demonstrated in approximately 90% of the cells. Immunopositivity was localized mainly in the paranuclear Golgi region. In a small minority of cells, diffuse cytoplasmic immunostaining was also noted. By immunoelectron microscopy VEGF was evident in the secretory granules, cytoplasmic vesicles, rough endoplasmic reticulum, and the Golgi apparatus. Western blotting confirmed the results of the morphologic studies. It can be concluded that VEGF, which is know to induce angiogenesis and to increase vascular permeability, is produced in the prolactin- and growth hormone (GH)-secreting GH3 cell line. The functional role of VEGF in the GH3 cells is unknown. It is possible that this growth factor affects endocrine activity of GH3 cells by a paracrine mechanism.

Animals↗

PubMed2000

Comparative genomic hybridization of medulloblastomas and clinical relevance: eleven new cases and a review of the literature.

Medulloblastomas are highly malignant primitive neuroectodermal tumors of the cerebellum that display a wide variety of histopathological patterns. However, these patterns do not provide an accurate prediction of clinical-biological behavior and no satisfactory morphological grading system has ever been presented. Genetic alterations may provide additional diagnostic information and allow clinically relevant subgrouping of primitive neuroectodermal tumors. We examined 10 medulloblastomas and one medulloblastoma cell line. One amplification site on chromosome 8q24 was detected in the cell line corresponding to the known amplification of the c-myc gene in this cell line. The gain of 2p21-24 in two tumors was shown to represent amplification of the N-myc gene by Southern blot hybridization and fluorescence in situ hybridization. The data show that the isochromosome 17 can be recognized using comparative genomic hybridization (CGH) by the typical combination of loss of 17p combined with gain of 17q. No specific pattern of genetic alterations could be linked to the clinical behavior of the tumors. We have compared our results with previous CGH studies on medulloblastomas.

Adolescent↗

PubMed2000

A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas.

Current systemic treatment options for patients with relapsed gliomas are limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor activity in both preclinical studies as well as a number of phase I and II trials in humans. Studies in primates have shown good cerebrospinal fluid levels of topotecan following systemic administration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5 consecutive days repeated every three weeks. For patients who had received prior nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response and toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patients were not taking anticonvulsants during treatment. Nine patients developed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsants. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response rate of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at this dose and schedule showed no substantial activity in relapsed gliomas.

Adult↗

PubMed2000

A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma.

We conducted a randomized phase II study to determine the efficacy of dacarbazine (DTIC) in recurrent gliomas. Patients were randomly assigned to receive either DTIC 750 mg/m2 IV day 1 every 28 days (Arm A) or DTIC 200 mg/m2 IV days 1-5 every 28 days (Arm B). Pharmacokinetics were studied in 6 patients on each arm using HPLC analysis. Thirty-nine patients (30 male, 9 female), ages 27-67 years (median 53) were entered on the study (20 on Arm A, 19 on Arm B). No objective responses were seen. Median time to progression was 3 months. Median survival was 8 months. Treatment was generally well tolerated. Major toxicities were grade 1-2 nausea (33%). lethargy (28%), diarrhea (15%), alopecia (15%), and grade 3 neutropenia (8%). Four patients on Arm A had mild self-limited episodes of intravascular hemolysis occurring immediately after drug infusion, the mechanism of which is unknown. Mean AUC for DTIC, HMMTIC (5-[3-hydroxymethyl-3-methyl-1-triazeno] imidazole-4-carboxamide), and MTIC (5-[3-methyl-1-triazenol imidazole-4-carboxamide), in Arm A were 14.8, 0.17, and 1.15 mM min, respectively. Corresponding values for Arm B (on day 1 of 5) were 1.7, 0.06, and 0.29 mM min, respectively. The predicted HMMTIC and MTIC exposure over 5 days for Arm B, based on the day 1 data, is higher than with Arm A. We conclude that DTIC is well tolerated but does not have activity in patients with recurrent gliomas. The 5-day schedule appears less toxic, and pharmacokinetic studies show that it provides greater exposure to MTIC and HMMTIC compared to the one-day schedule.

Adult↗

PubMed2000

Leptin signal transduction in the HP75 human pituitary cell line.

Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OBR). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS-3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary.

Adenoma↗