Hashimoto's encephalopathy mimicking Creutzfeldt-Jakob disease: brain biopsy findings.
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Biomedical subjects
Publications and source records attributed to R Folkerth.
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OBJECTIVE: Parathyroid hormone-related protein (PTHrP) and its mRNA have been found to be expressed in a variety of human tumors including breast, prostate, colon, lung, renal and ovarian cancers. The purpose of this study is to evaluate the expression of PTH/PTHrP receptor and ligand in human glial tumors. METHODS: We examined the coexpression of PTH/PTHrP receptor and ligand in 73 glial tumors of different histological grades and 4 nonneoplastic human brain specimens and three glioblastoma cell lines, by using Western Blot analysis and immunohistochemical analysis. RESULTS: PTHrP and PTH/PTHrP receptors were shown in the neurons, reactive astrocytes and the endothelial cells of normal brain tissue as well as tumor cells, reactive astrocytes and vasculature of nonneoplastic tissue. They were expressed at higher levels in pure astrocytic tumors as compared to tumors with oligodendroglial components. CONCLUSION: PTH/PTHrP receptor and PTHrP ligand are co-expressed in human glial tumors. There increased expression suggests an autocrine and/or paracrine loop may exist.
Glioblastomas only rarely metastasize to sites outside the central nervous system, for reasons that are poorly understood. We report the clinicopathological and molecular genetic findings in 6 patients with metastatic glioblastoma. Four patients were under the age of 32 and all but 1 patient died within 2 yr of diagnosis. The number of metastases ranged from 1 to 3. At the time of death, 3 patients had apparent tumor control at their primary site. We evaluated DNA from both primary and metastatic glioblastomas for genetic alterations commonly found in glioblastomas: TP53 mutations, CDKN2A/p16 deletions, EGFR amplification, and allelic loss of chromosomes 1p, 10q and 19q. Four of 6 cases had TP53 mutations and only single cases had EGFR amplification, CDKN2A/p16 deletions, or allelic loss of 1p, 10q and 19q; 2 cases had no detectable genetic alterations. In 2 cases, the primary and metastatic tumors had identical genotypes. Remarkably, however, 2 cases had different TP53 alterations in the primary and metastatic lesions, or among the metastatic tumors, which suggests that some metastatic deposits may represent emergence of subclones that were not necessarily dominant in the primary tumor. The present observations and a review of the recent literature demonstrate that metastatic glioblastomas tend to occur in younger adults who do not follow long clinical courses, and may be characterized by TP53 mutations and differential clonal selection.
OBJECT: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.
Telepathology affords the means to provide pathological diagnosis and consultation to remote sites. However, before telepathology can become an acceptable medical tool, it will be vital to determine the diagnostic accuracy of this technology. We report the results of a single-blind study of the accuracy of diagnosis performed using computerized still images obtained from a telepathology workstation used in a French telepathology network. Four pathologists, each working alone, reviewed a total of 200 cases of routine surgical pathology (50 cases each), and performed diagnosis based on both computer CD-ROM still images (CD) and conventional glass slides (GS). Concordance between GS and CD diagnosis, as well as accuracy, were determined. Other factors related to performance were also measured, including diagnostic certainty, reasons for uncertainty, and causes of diagnostic error. Overall, there was good agreement between CS and CD diagnosis. There was 87.5% concordance between CS and CD diagnosis, and comparison to consensus (correct) diagnosis showed accuracy of 95.5% and 88.5% for GS and CD diagnosis, respectively. Marked variability in accuracy of CD diagnosis was observed among the four pathologists, and issues related to image selection and/or quality appeared responsible for 60% of the diagnostic errors. The lack of sufficient images and clinical information were frequently cited as reasons for diagnostic uncertainty, as well as feelings of insufficient expertise. It is likely that the opportunity for interaction with the referring pathologist and the use of subspecialty consultants would likely improve the performance of telepathology.
A cavernous angioma of the posterior fossa dura was discovered incidentally on neuroimaging studies. The clinical and pathologic features of this lesion are described. Although it has been reported to arise in the posterior fossa and the tentorium cerebelli, we present the first case of such a malformation arising from the dura of the posterior fossa.
In the oral cavity, differentiation between reactive and neoplastic lymphoproliferative lesions can, at times, be very difficult. We report an unusual case in which immunohistochemical findings were necessary to determine that the lesion was reactive despite the original interpretation of malignant lymphoma. The relationship of this lesion to atypical histiocytic granuloma, angiolymphoid hyperplasia with eosinophilia, and traumatic ulcerative granuloma with stromal eosinophilia is discussed and possible pathogenetic mechanisms are proposed. The value of immunohistochemistry in the diagnosis of extranodal lymphoproliferative lesions is emphasized.
Conventional imaging techniques are often unreliable in distinguishing between radiation necrosis and recurrent glioma in patients who are symptomatic after high-dose radiotherapy. We performed dual-isotope single-photon emission computed tomography (SPECT) with the use of thallium-201 (201TI) and the perfusion agent 99mTc-hexamethyl-propyleneamine oxime (HMPAO) to aid in this differentiation in 15 patients with glioma prior to biopsy. We found that dual-isotope SPECT scanning correlated with the pathologic findings in 14 of the 15 cases. All patients with high 201TI uptake in their treated tumor beds had local tumor recurrence, and all patients with low 201TI uptake showed only radiation changes without evidence of solid tumor. In patients with an intermediate level of 201TI concentration in their tumor bed, 99mTc-HMPAO uptake differentiated those patients with active tumor from those without; three of four patients with preserved or increased perfusion had pathologic evidence of solid tumor, whereas none of the four patients with decreased perfusion to the tumor bed had evidence of local recurrence. We believe that dual-isotope SPECT with 201TI and 99mTc-HMPAO may be useful in differentiating sites of likely tumor growth from nonspecific radiation changes in patients treated for malignant glioma.