Biomedical subjects

B W Scheithauer

Publications and source records attributed to B W Scheithauer.

At least 253 records · Page 14Linked to original sources

PubMed1993

Intracranial parenchymal schwannoma. A clinicopathological and neuroimaging study of nine cases.

The clinical, radiological, and pathological features of nine cases of intracranial parenchymal schwannoma are described. The clinical course in four patients 23 years of age or younger mirrored the indolent nature of this neoplasm. Imaging studies included computerized tomography in eight patients and magnetic resonance imaging in three. The lesions were well demarcated with only mild surrounding edema. Five tumors were deep within the temporoparieto-occipital region, three were in the cerebellum, and one lay peripherally in the parietal lobe. Over two-thirds of the nine tumors were either cystic (five) or contained areas of cystic degeneration (two). One lesion was frankly hemorrhagic. A variety of imaging characteristics and contrast enhancement patterns were observed, including those of a cyst with a mural nodule and peripheral enhancement. Of the four solid neoplasms, two enhanced homogeneously while the other two demonstrated heterogeneous enhancement. Six tumors were resected totally. The follow-up period ranging from 2 months to 2 years has shown no recurrences. Microscopically, immunohistochemically, and ultrastructurally, the tumors were indistinguishable from peripheral schwannomas. A possible mechanism underlying the histogenesis of these rare lesions is discussed. The importance of recognizing this tumor is stressed, particularly in younger patients, given its benign nature, radiological resemblance to other tumors such as pilocytic astrocytoma, and favorable response to resection.

Adolescent↗

PubMed1993

p53 gene mutations in medulloblastoma. Immunohistochemistry, gel shift analysis, and sequencing.

Medulloblastoma (MB), the most common malignant tumor of the CNS in children, bears a loss of the short arm of chromosome 17 in almost half of the cases. The tumor suppressor gene p53 is located on this chromosome and its role in the pathogenesis of this primitive tumor is controversial. Twenty-two MBs were analyzed by single-strand conformation polymorphism (SSCP) of polymerase chain reaction-amplified conserved exons. Fragments displaying a gel mobility shift were subsequently analyzed by direct sequencing. Immunohistochemistry for p53 was performed in all cases; three had cytogenetic analysis. Two cases (9%) were found to harbor a mutation: one homozygous and one heterozygous. The latter showed focal p53 immunostaining. None of the cases with chromosome 17p abnormality by cytogenetic analysis were found to have a mutation in the remaining allele. Loss of heterozygosity (LOH) of 17p, however, was found in four cases (one by SSCP and three by cytogenetic analysis). Together with the homozygous deletion in one case, the overall incidence of p53 allelic involvement in MB is 23%. Although LOH for the p53 gene may confer a selective advantage to tumor cells harboring mutations with dominant negative oncogenic effect, the infrequent occurrence of p53 mutations in face of frequent LOH for this gene supports the previously formulated hypothesis of a novel tumor-related locus distal to p53 on chromosome 17p.

Adolescent↗

PubMed1993

Does the distribution of Schwann cells correlate with the observed occurrence of acoustic neuromas? .

Acoustic neuromas account for 75 to 80 percent of cerebellopontine angle tumors and 8 to 10 percent of all intracranial neoplasms. These tumors arise from the Schwann cell sheath that surrounds the peripheral portion of the facial, cochlear, superior, and inferior vestibular nerves. Theoretically, a schwannoma may arise from Schwann cells anywhere along these nerves from the glial-Schwann cell junction to the end organ. Clinically, however, they most frequently originate from the vestibular nerves, occasionally from the facial, and only rarely from the cochlear nerve. This investigation utilized light microscopy, immunochemistry, and digital optical morphologic analysis to determine the distribution of Schwann cells along the facial and vestibulocochlear nerves in an attempt to explain the observed distribution of tumors, and to evaluate currently accepted theories. No direct correlation between the distribution of Schwann cells and the observed distribution of schwannomas was found. Thus, this study did not confirm the currently held theories regarding schwannoma distribution in these nerves.

Cell Count↗

PubMed1992

Ultrastructure of the neurohypophysis.

This review summarizes our current knowledge of the ultrastructure of the human neurohypophysis and includes comments on its anatomy, physiology, and embryology. The neurohypophysis represents a unique tissue having neural and endocrine characteristics and possessing ultrastructural features distinct from those of conventional endocrine organs such as the anterior pituitary, thyroid, pancreatic islets, etc. In contrast to these glands, the neurohypophysis is composed of the processes of mature neurons. As such, it is not capable of synthesizing hormones but only of their storage and release. Neurosecretion is one of the most exciting areas of neuroendocrinology and, although spectacular progress has been achieved in elucidating the process, a number of aspects are incompletely understood. Recent evidence indicates that the magnocellular nuclei of the hypothalamus, the anatomic origin and functional basis of the neurohypophysis, produce not only vasopressin and oxytocin, the so-called "neurohypophyseal hormones," but a number of other biologically active peptides as well. The physiologic function of these substances is largely unknown but they may be of profound importance in endocrine homeostasis. Based on these novel findings, the role of the neurohypophysis in endocrine regulation has to be re-evaluated.

Exons↗

PubMed1992

Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole.

A cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5-fluorouracil and levamisole for adenocarcinoma of the colon. None of the patients had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5-fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patients presented with a subacute (2-3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demonstrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patients. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and perivascular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5-fluorouracil and levamisole. This syndrome may represent the pathological basis for 5-fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.

Adenocarcinoma↗

PubMed1992

Prognostic value of cytogenetic analysis in human cerebral astrocytomas.

Cytogenetic analysis has become an important part of the diagnostic evaluation of most hematological neoplasms. However, there is limited information on the value of cytogenetic analysis in most solid tumors, including cerebral astrocytomas. This report summarizes a prospective cytogenetic study of 99 human cerebral astrocytomas, 16 mixed oligoastrocytomas, and 2 gliosarcomas. The cytogenetic procedure involved in situ culture and robotic harvesting techniques. Correlative clinical and survival data were available on all patients. We successfully cultured and obtained suitable metaphases in 107 of the 117 tumors. One or more chromosomally abnormal clones were observed in 72 tumors, and nonclonal or normal karyotypes were observed in 35 tumors. In a multivariate analysis, survival time was significantly better in patients whose tumors had normal or nonclonal karyotypes on cytogenetic analyses than in those whose tumors had clonal abnormalities (p = 0.0071). Our study demonstrates that cytogenetic analysis provides independent prognostic information in patients with cerebral astrocytomas.

Astrocytoma↗

PubMed1992

Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas.

Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas.

Adolescent↗

PubMed1992

Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas.

The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo-astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo-astrocytomas (2 grade 4, 4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, -10, -13, -14, -17, +19, -22, and -Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TST1 on the 10q arm near the centromere or on the 10p arm.

Adult↗

PubMed1992

Cisplatin-based chemotherapy in primary central nervous system germ cell tumors.

We report a retrospective review of our experience with cisplatin-based chemotherapy in eight patients (ages 9-44 years) with histologically confirmed primary central nervous system germ cell tumors. Five patients received chemotherapy as the primary treatment, radiation therapy being administered either at completion of chemotherapy or between chemotherapy courses. Three patients received cisplatin-based chemotherapy for recurrent disease after prior radiation therapy and/or surgery. Four of five patients treated with chemotherapy at diagnosis are in complete remission at 11-14 months from diagnosis. The remaining patient twice achieved complete remission prior to dying of progressive disease 16 months after diagnosis. Two of three patients treated with chemotherapy for recurrent disease are in complete remission at 20 and 26 months; the remaining patient deteriorated after the first cycle of chemotherapy and expired six months thereafter. Overall, of seven patients evaluable for response, five achieved complete remission with chemotherapy alone, and two with chemotherapy and radiation therapy. Our results confirm previous reports of high complete remission rates utilizing cisplatin-based chemotherapy in conjunction with radiation therapy. Prospective evaluation of cisplatin-based chemotherapy followed by radiation therapy is warranted.

Adolescent↗

PubMed1992

Diffuse "fibrillary" astrocytomas: correlation of MRI features with histopathologic parameters and tumor grade.

MR images in 54 patients with biopsy-proven diffuse or "fibrillary" astrocytomas were analyzed and compared with the histopathologic features in order to determine which histopathologic characteristics underlie the radiographic findings in these gliomas and whether radiographic findings are more closely correlated with individual histopathologic characteristics than with histologically determined tumor grade. The MRI features studies included tumor heterogeneity, edema, mass effect, border sharpness, "anatomic invasion", contrast enhancement, hemorrhage, and the presence of flow voids, calcium and cyst formation. The histopathologic characteristics studied included cellular atypia, mitoses, cellularity, endothelial proliferation, necrosis and tumor grade. Edema (P less than 0.01), flow voids (P = 0.02) and contrast enhancement (P less than 0.01) demonstrated a direct correlation with tumor grade, but edema (P less than 0.01) and contrast enhancement (P less than 0.01) also demonstrated a significant correlation to tumor cellularity. Tumor heterogeneity was associated with the presence of necrosis (P = 0.01). Hemorrhage occurred only in high grade tumors, where it correlated with endothelial proliferation (P = 0.04).

Astrocytoma↗

PubMed1992

Pituitary lactotrophs and somatotrophs in pregnancy: a correlative in situ hybridization and immunocytochemical study.

Lactotroph hyperplasia is a prominent finding in the adenohypophyses of pregnant women. In order to elucidate the morphogenesis of this change, pituitaries from 16 women in various phases of pregnancy were collected at autopsy and studied by histology, immunocytochemistry and in situ hybridization. The results showed that the increase in the amount of prolactin (PRL) mRNA paralleled the progressive lactotroph hyperplasia. The presence of mitoses in PRL-immunoreactive cells provided evidence that proliferation of preexisting lactotrophs contribute to lactotroph accumulation. Growth hormone (GH) immunoreactive cells showed a marked reduction in GH mRNA indicating that GH synthesis was inhibited. In many GH-immunoreactive cells, PRL mRNA became apparent. These findings demonstrate that GH is stored following discontinuation of GH synthesis. It appears that, when PRL is secreted in excess during pregnancy, somatotrophs are recruited to produce PRL. These somatotrophs begin to express PRL mRNA, transform to bihormonal mammosomatotrophs and possibly later to lactotrophs, contributing to PRL production. Mature somatotrophs may be regarded as reserve cells in the adenohypophysis, having the potential to switch hormone synthesis and to convert to mammosomatotrophs and possibly lactotrophs.

Adolescent↗

PubMed1992

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.

Adenoma↗

PubMed1992

Distribution of transforming growth factor-beta 1 in human astrocytomas.

We used immunohistochemical techniques to study the distribution of transforming growth factor-beta 1 (TGF-beta 1) and infiltrating lymphocytes and macrophages in human astrocytomas. Thirteen of 15 grade 4 astrocytomas (glioblastomas) showed staining with anti-TGF-beta 1 antibody, predominantly in proliferating endothelial complexes and surrounding small and medium-sized blood vessels. Brain tissue microscopically free of tumor cells (n = 8) and more differentiated astrocytomas of varying grade (1 to 3; n = 6) devoid of endothelial proliferation did not stain with anti-TGF-beta 1. Normal brain contained only rare lymphoreticular cells. The majority of astrocytomas studied, however, contained T lymphocytes and macrophages with smaller numbers of B lymphocytes. The lymphoreticular infiltrates were concentrated primarily in close proximity to blood vessels. Within an individual tumor perivascular regions staining for TGF-beta 1 never contained more than occasional T lymphocytes. Perivascular regions not staining for TGF-beta 1 frequently contained low to high numbers of T lymphocytes. The inverse relationship in the distribution of TGF-beta 1 and lymphocyte infiltrates is compatible with a functional relationship between this cytokine and an immune effector cell response to glioblastomas.

Astrocytoma↗

PubMed1992

The pituitary gland in hyperthyroidism.

The pituitary glands of 33 patients (24 women and 9 men, 18 to 78 years old) who died in thyrotoxicosis (18 with Graves' disease and 15 with toxic multinodular goiter [Plummer's disease]) were examined by histologic and immunocytologic methods. Thirteen patients (39%) died in "thyroid storm." The avidin-biotin-peroxidase complex immunostaining method was used to demonstrate the spectrum of pituitary hormones, including growth hormone, prolactin, adrenocorticotropic hormone, thyrotropin, follicle-stimulating hormone, luteinizing hormone, and alpha-subunit. The most striking finding was a pronounced decrease or loss of immunoreactivity to thyrotropin in all thyrotoxic cases, a consistent change that allowed ready distinction of thyrotoxic from euthyroid pituitary glands. When immunoreactive thyrotrophs were identified, they were sparse and small and demonstrated only faint thyrotropin reactivity. No morphologic differences were noted between the pituitary glands of patients with Graves' disease or Plummer's disease or between sexes. Loss of thyrotropin immunoreactivity was found to be reversible in that thyrotropic cells in the pituitary glands of 16 additional concurrently studied patients, who had thyrotoxicosis but were treated and subsequently had normal thyroid function or hypothyroidism, appeared normal or even hyperplastic. Other types of adenohypophysial cells in both the thyrotoxic and the successfully treated groups exhibited no abnormalities. Pituitary adenomas were incidental findings in 6 of the 33 patients (18%). Their immunotypic spectrum included three prolactin-immunoreactive tumors, two growth hormone-containing adenomas (one of which was plurihormonal), and one tumor with follicle-stimulating hormone and luteinizing hormone; no thyrotropin-containing adenomas were noted. No examples of pituitary hyperplasia were encountered in pituitary glands of thyrotoxic patients, and no hypophysitis or fibrosis was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1992

The pituitary gland in patients with breast carcinoma: a histologic and immunocytochemical study of 125 cases.

Pituitary glands obtained at autopsy of 125 women with disseminated breast carcinoma were studied to determine whether pituitary prolactin cell abnormalities (hyperplasia or adenoma) might be involved in the pathogenesis of breast carcinoma. In addition, we studied 85 pituitary glands obtained from unselected, consecutive autopsies in women without breast carcinoma but who died of other diseases (control group). The frequency of lactotroph hyperplasia was slightly higher in patients with breast carcinoma than in the control group, but the difference was not statistically significant, nor were differences in the frequency and size of pituitary adenomas, prolactin-producing or otherwise. No correlation was found between the presence of lactotroph hyperplasia or prolactin-producing adenomas (or both) and such factors as the patient's age, bilaterality of the carcinoma, previous treatment with tamoxifen citrate or oophorectomy, stage of disease, or survival. The frequency of breast carcinoma metastatic to the pituitary gland was higher in the study group than in the control group; however, the difference was not statistically significant. No preferential site of metastatic involvement in the pituitary gland was noted. Relative proportions of other lesions such as infarcts, cysts, lymphocytic infiltrates, and basophilic invasion were similar in the study and control groups. This study indicates that accumulation of prolactin cells, whether hyperplastic or adenomatous, cannot be considered a major risk factor for the genesis or progression of breast carcinoma.

Adenoma↗

PubMed1992

Biochemical evaluation of adrenal dysfunction: the laboratory perspective.

In this study, we reviewed the diagnostic efficiency of laboratory tests that are performed for assessment of patients with Cushing's syndrome or adrenal insufficiency. Baseline laboratory data from patients subsequently diagnosed with adrenal dysfunction were analyzed for tests performed between 1987 and 1989 at our institution. Results were analyzed for 36 patients diagnosed with pituitary-dependent Cushing's syndrome, 15 with ectopic Cushing's syndrome, 12 with adrenal-dependent Cushing's syndrome, 20 with primary adrenal insufficiency, and 7 with secondary adrenal insufficiency. Tests reviewed were plasma cortisol, plasma corticotropin, urinary free cortisol, urinary 17-ketosteroids, urinary ketogenic steroids, low-dose and high-dose dexamethasone suppression, and metyrapone stimulation. Our findings suggest that a substantial proportion of diagnoses could be based on the results of three tests--plasma corticotropin, plasma cortisol, and urinary free cortisol. We present a nomogram that combines the results of plasma corticotropin and plasma cortisol testing to enhance the diagnostic efficiency of these tests.

Adolescent↗

PubMed1992

Primary malignant ependymoma of the lung.

In a 64-year-old woman, a solitary pulmonary nodule developed 30 months after combination chemotherapy and thoracic irradiation had been administered for small-cell carcinoma of the ipsilateral lung. No evidence of extrapulmonary tumor was identified, and the nodule was excised. The well-circumscribed tumor had histologic features of a malignant ependymoma. Immunohistochemical staining showed strong reactivity for glial fibrillary acidic protein; staining for S-100 protein, Leu-7, and vimentin was less intense. Focal reactivity for epithelial membrane antigen was also present. Stains for keratin, synaptophysin, and chromogranin were negative. Electron microscopy showed cohesive cells, the cytoplasm of which contained intermediate filaments. Rare well-formed junctions were also noted. Flow cytometry of formalin-fixed paraffin-embedded tissue demonstrated DNA aneuploidy. Six months after the ependymoma was diagnosed, the patient, who had a history of hypertension, died of an intracerebral hemorrhage.

Ependymoma↗

PubMed1992

The neuropathology of tuberous sclerosis.

Tuberous sclerosis, an autosomal dominant disorder associated with hamartomas in multiple organs, prominently affects the central nervous system; principle lesions include subependymal nodules and giant cell astrocytomas, white matter heterotopias, and cortical tubers. Histologic, immunocytochemical, and ultrastructural features of these processes suggest they have their basis in abnormal cell migration and differentiation. Aberrant expression of cystoskeletal proteins appears to be common to the multisystem hamartomas of this disorder and may, in part, underlie their pathogenesis.

Astrocytoma↗