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1.
  • Andersson, Elin Möller, et al. (author)
  • Clinicopathological concordance in cognitive disease diagnostics
  • 2020
  • In: Clinical Neuropathology. - 0722-5091. ; 39:3, s. 99-104
  • Journal article (peer-reviewed)abstract
    • Neurocognitive disorder encompasses many separate diagnoses, such as frontotemporal dementia (FTD), Alzheimer's disease (AD), Lewy body dementia (LBD), vascular dementia (VaD), and mixed dementia (MD). Because of the many variations between and within each subtype, it may be a challenge to clinically diagnose each condition. In a previous study on 176 dementia patients in a university hospital cohort between the years 1996 and 2006, a full diagnostic concordance of 49% was demonstrated between clinical diagnoses and pathological morphology [1]. The aims of this study were to do a follow-up on diagnostic concordance from the subsequent 10 years (2007 - 2016) and to compare the results with the previous study from 2009. In all cases of neuropathologically diagnosed dementia disorders (n = 324), the clinical records were searched for information on the clinical diagnosis of dementia, including on subtype. All individuals who had been diagnosed by a specialist were selected (n = 210). In this study, a full concordance between clinical diagnoses and neuropathological morphology was found in 61% of individuals, with marked variations between subgroups, including the lowest (31%) in the group of VaD. Vigilance in clinicopathological concordance is important for quality maintenance as well as the improvement of skills in diagnostic work. In light of the previous study, VaD one decade later remains elusive. The unmasking of this complicated and multifaceted disorder may be beneficial to the overall diagnostic accuracy in cognitive disease investigations.
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2.
  • Andersson, Ulrika, et al. (author)
  • Heterogeneity in the expression of markers for drug resistance in brain tumors
  • 2004
  • In: Clinical Neuropathology. - 0722-5091. ; 23:1, s. 21-27
  • Journal article (peer-reviewed)abstract
    • Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (> 50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p < 0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.
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3.
  • Asklund, Thomas, et al. (author)
  • PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma
  • 2011
  • In: Clinical Neuropathology. - Deisenhofen : Dustri-Verlag Feistle. - 0722-5091. ; 30:5, s. 242-246
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.
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4.
  • Brunnström, Hans, et al. (author)
  • Comparison of four neuropathological scales for Alzheimer's disease.
  • 2011
  • In: Clinical Neuropathology. - 0722-5091. ; 30:2, s. 56-69
  • Journal article (peer-reviewed)abstract
    • Objective: There are several neuropathological scales for staging of Alzheimer pathology. The system proposed by Braak and Braak is based on the topographic distribution of neurofibrillary tangles and neuropil threads, while that of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is based on the quantity of neocortical neuritic plaques. A combination of the Braak and CERAD staging scales was recommended by the National Institute on Aging and Reagan Institute (NIA-RI). The Poly-Pathology Alzheimer's Disease assessment, nine areas (PPAD9) is a staging system based on the extent of neuronal degeneration, microvacuolization, cytoarchitectural disorder and gliosis, in addition to neurofibrillary tangles and neuritic plaques, in nine cerebral regions. The aim of the present study was to critically compare these four neuropathological staging scales. Methods: We assessed the Alzheimer pathology, using the four scales, in 43 patients with various dementia disorders, with focus on concordance and differences between the staging systems. Results: Comparing the staging systems, the Spearman's rho value for PPAD9 vs. Braak was 0.65, for PPAD9 vs. CERAD 0.72, for PPAD9 vs. NIA-RI 0.67, and for Braak vs. CERAD 0.46. Conclusion: The correlation between the neuropathological staging systems was suboptimal, and we conclude that the choice of staging system affects the evaluation of Alzheimer pathology, and hence the final diagnosis.
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5.
  • Brunnström, Hans, et al. (author)
  • Differential degeneration of the locus coeruleus in dementia subtypes.
  • 2011
  • In: Clinical Neuropathology. - 0722-5091. ; 30:3, s. 104-110
  • Journal article (peer-reviewed)abstract
    • Objective: Neuronal loss in the locus coeruleus (LC) is common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The aims of the present study were to investigate LC degeneration in different dementia disorders including vascular dementia (VaD) and frontotemporal lobar degeneration (FTLD), to compare LC degeneration with severity of pathology in AD and DLB/PDD, to further evaluate the usefulness of a previously presented scoring system and to examine the predictive value of macroscopic assessment of the LC. Methods: A horizontal mid-level section of the pons was examined in 200 neuropathologically examined cases with clinical dementia. A previous macroscopic assessment of the LC was performed in 149 of the cases. Results: Cases with DLB/ PDD and AD presented with the highest microscopic LC degeneration scores, with significant differences compared to combined AD + VaD, in turn with a higher score than VaD, FTLD and other dementia disorders. Interrater agreement (weighted kappa;) for LC degeneration scoring was 0.83 - 0.91. DLB/ PDD, AD and AD + VaD were the diagnoses for 85% of the cases with macroscopic LC depigmentation. Conclusion: LC degeneration, which may be macroscopically noted, often indicates synuclein and/or Alzheimer pathology among demented. When clinical information is scarce or inconsistent, a macroscopic assessment of the LC may facilitate focusing of the subsequent neuropathological investigation. Also, the semiquantitative scoring system is a reliable tool for histological assessment of LC degeneration.
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6.
  • Brunnström, Hans, et al. (author)
  • Staging of Lewy-related pathology in dementia
  • 2012
  • In: Clinical Neuropathology. - 0722-5091. ; 31:4, s. 216-223
  • Journal article (peer-reviewed)abstract
    • Objective: Lewy-related pathology is the characteristic feature of Parkinson's disease with and without dementia and dementia with Lewy bodies (DLB). There are two neuropathological staging systems for Lewy-related pathology commonly employed today: the staging system for Parkinson-related pathology by Braak et al., and the staging system by the Consortium on DLB. There are also several modified systems based on these two scales. Methods: We applied a total of eight different staging systems for Lewy-related pathology to 36 consecutive demented patients with various dementia disorders. Results: The staging systems varied considerably in number of unclassifiable cases (range 0 - 16 out of 36 cases), while the diagnostic agreement between the systems that were able to classify all or the very majority of cases varied only slightly (weighted kappa 0.86 - 0.92 and Spearman's sigma 0.80 - 1.0). Conclusion: The different staging systems for Lewy-related pathology that exist today vary in staging procedure and proportion of unclassifiable cases. The choice of system may affect the stage of Lewy-related pathology and ultimately final diagnosis.
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7.
  • Casar-Borota, Olivera, et al. (author)
  • Gliosarcoma with liposarcomatous component, bone infiltration and extracranial growth.
  • 2006
  • In: Clinical Neuropathology. - 0722-5091. ; 25:4, s. 200-3
  • Journal article (peer-reviewed)abstract
    • Gliosarcoma is a highly malignant brain tumor consisting of both a glioblastoma and a mesenchymal component. The latter typically resembles fibrosarcoma, but differentiation patterns resembling osteosarcoma, chondrosarcoma, angiosarcoma and rhabdomyosarcoma have also been described. Molecular-genetic studies have shown that both glioblastoma and the mesenchymal component share identical cytogenetic abnormalities or mutations, suggesting a monoclonal origin from glial cells. We report an unusual case of gliosarcoma that presented as a large intracerebral tumor with infiltration of the temporal bone and the soft tissues in the infratemporal fossa. Microscopically, the tumor consisted of alternating areas of glioblastoma and fibrosarcoma. Focally, areas ofosteosarcomatous and liposarcomatous differentiation were found. Although gliosarcoma with transcranial penetration is very rare, it should be suspected in case of intracranial tumor with glioblastoma-imaging features, infiltration of bone and extracranial growth. Our case of liposarcomatous differentiation in gliosarcoma--together with another very recently reported similar case--expands the morphologic heterogeneity of this peculiar brain tumor.
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8.
  • Casar-Borota, Olivera, et al. (author)
  • Spindle cell oncocytoma of the adenohypophysis : report of a case with marked cellular atypia and recurrence despite adjuvant treatment.
  • 2009
  • In: Clinical Neuropathology. - 0722-5091. ; 28:2, s. 91-95
  • Journal article (peer-reviewed)abstract
    • Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.
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9.
  • Dahlin, Lars B., et al. (author)
  • Intraneural glomus tumor of "uncertain malignant potential" and with BRAF mutation in the median nerve - an unusual case
  • 2017
  • In: Clinical Neuropathology. - 0722-5091. ; 36:7, s. 164-170
  • Journal article (peer-reviewed)abstract
    • A glomus tumor of uncertain malignant potential is defined as a glomus tumor with some, but not all, criteria for malignancy and without a known metastasis. Here, we present a rare example presenting in the median nerve in a 40-year-old woman with a long history of severely impaired left median nerve function. A large panel of immunohistochemical stains excluded other diagnoses, and the designation of a "uncertain malignant potential" was based on the high proliferative activity, the tumor size and location, and the lack of WHO malignancy criteria such as marked nuclear atypia, necrosis, or atypical mitoses. A BRAF mutation was found in the tumor. Although extremely rare, both benign and malignant glomus tumors may present in large peripheral nerves and should therefore be considered in the differential diagnosis.
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10.
  • Haglund, Mattias, et al. (author)
  • A methodological study of locus coeruleus degeneration in dementing disorders
  • 2016
  • In: Clinical Neuropathology. - 0722-5091. ; 35:5, s. 287-294
  • Journal article (peer-reviewed)abstract
    • Background: Degeneration of the locus coeruleus (LC) of the brain stem is a recognized phenomenon in Alzheimer's disease (AD), in dementia with Lewy bodies (DLB), and in Parkinson's disease with dementia (PDD). Prior studies have suggested that LC degeneration can be used to differentiate various dementing disorders histologically, but the paucity of methodological data may hamper systematic research on this nucleus. Purpose: The purpose of this study was to evaluate various approaches to quantifying LC degeneration in dementing disorders, and to inform future decisions regarding the most appropriate method for diagnostics and research. Methods: 105 LCs from brains of demented individuals with AD, DLB/PDD, vascular dementia (VaD), mixed dementia (AD+VaD), or frontotemporal lobar degeneration (FTLD) were examined, and the extent of LC degeneration was assessed using macroscopic evaluation, cell counting, and two degeneration scales. Scores were compared across diagnostic categories; diagnostic utility and intra- and interobserver reliability were assessed. Results: AD and DLB/PDD were associated with greater LC damage using either assessment method, significantly different from VaD and FTLD. Macroscopic appearance was informative, but cell counting was more sensitive and specific. The degeneration scales did not add significant diagnostic value over cell counting and were associated with greater observer variability. Conclusions: The LC degenerates in certain dementia subtypes, especially in AD and DLB/PDD. Macroscopic assessment of the LC postmortem can be used to differentiate between disorders associated with degeneration (AD, DLB/PDD) or sparing (VaD) of the LC, but counting LC cells in a representative pontine section is the most appropriate method by which to assess LC degeneration.
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