[show abstract][hide abstract] ABSTRACT: We report on an 85-year-old woman with hypertensive cerebral arteriolosclerosis who presented with rapidly progressive encephalopathy
leading to death within 4months. Magnetic resonance imaging showed mild cortical atrophy consistent with her age and diffuse
leukoaraiosis. Her CSF 14–3–3 protein was positive. Neuropathology showed severe spongiform change and gliosis in the grey
matter and immunohistochemistry revealed diffuse prion protein deposition in a predominant synaptic pattern. She had no family
history of neurological disorder and genotyping did not show any prion protein gene mutation, in keeping with a diagnosis
of sporadic Creutzfeldt–Jakob disease. There was also diffuse amyloid angiopathy involving the cortical and leptomeningeal
arterioles of the cerebral hemispheres and cerebellum and the capillaries of the grey matter. The amyloid angiopathy expressed
beta-amyloid but also prion protein and double immunostaining confirmed co-localization of both proteins in many vessel walls.
Alzheimer’s type pathology was restricted to a few diffuse beta-amyloid plaques in the entorhinal cortex and rare tangles
in the hippocampus. Deposition of prion protein in cerebral vessels has been reported in a single case of stop codon 145 mutation
of the PRNP gene. Co-localization of beta-amyloid and prion protein in the same amyloid plaque has been described in elderly patients
with Creutzfeldt–Jakob or Gerstmann–Sträussler–Scheinker diseases but only exceptionally in cerebral amyloid angiopathy. In
this patient, hypertensive cerebrovascular disease may have contributed to the failure to eliminate both proteins from the
[show abstract][hide abstract] ABSTRACT: Pineal parenchymal tumours (PPTs) are rare neoplasms that are divided into pineocytoma (PC), pineoblastoma (PB) and PPT of intermediate differentiation (PPTID). Factors affecting the survival of patients with PPTs are morphological subtype and histological grading according to mitotic index and neurofilament immunostaining. Grading criteria to distinguish PPTIDs are difficult to define, particularly when using small specimens. The Ki67 labelling index (LI) might be helpful in distinguishing between grade II and III PPTIDs. Our study was performed to assess the predictive value of the Ki67 LI in a large cooperative series of PPTs and to evaluate whether inclusion of this data would improve and refine the World Health Organization classification.
A retrospective analysis of 33 PPTs was performed. The histological features of the tumours were reviewed and Ki67 LI scoring was evaluated by immunohistochemistry. Data were correlated with the patients' survival.
The mean Ki67 LI was significantly different for tumour grades (0 in PC, 5.2 ± 0.4 in PPTID grade II, 11.2 ± 2.0 in PPTID grade III, 36.4 ± 6.2 in PB; P < 0.0001). However, there was no statistically significant difference in either overall or disease-free survival evaluated by the Kaplan-Meier method for patients with different grade tumours or Ki67 LI, possibly due to the different clinical management of patients in different centres.
The Ki67 LI may be a useful additional tool for grading PPTs, more particularly in small tumour samples.
Neuropathology and Applied Neurobiology 06/2011; 38(1):87-94. · 4.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.
Journal of Neuro-Oncology 04/2011; 105(2):219-24. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Infectious myositis can be a life-threatening condition. We describe the clinical presentation, diagnosis, treatment, and outcome of a patient with Aspergillus-related myositis and review the relevant literature on Aspergillus-related myositis.
We report on a patient with acquired immunodeficiency syndrome who presented with Aspergillus myo-fasciitis, which was unusual because of its relapsing-remitting course and favorable outcome. We analyze the clinical features, diagnosis, and treatment of 9 additional patients identified through a PubMed literature review between 1964 and early 2010.
A 64-year-old human immunodeficiency virus positive African woman was hospitalized for a relapsing-remitting history of bilateral myo-fasciitis for more than 15 years. She had already undergone 3 previous muscle biopsies without definite diagnosis. A computed tomographic scan-guided biopsy revealed numerous septae hyphae with focal necrosis. Cultures yielded Aspergillus flavus as the underlying pathogen and the diagnosis of Aspergillus-related myo-fasciitis was finally made. On reviewing the literature, only 9 other cases have been described. However, no similar case with such a chronic and favorable course was reported.
As compared with the reported cases in the literature, our case is unusual because of its relapsing-remitting course for more than 15 years and favorable outcome. Our case emphasizes the difficulty of the diagnosis, and the importance of early and appropriate management of this rare myositis, which should be systematically evoked in patients with immune deficiency.
Seminars in arthritis and rheumatism 03/2011; 41(2):230-5. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gliomatosis cerebri is a rare glial neoplasm, characterized by diffuse brain infiltration with relative preservation of the underlying cytoarchitecture. Its clinical and radiologic features are not specific and its antemortem diagnosis is difficult. We report a case of gliomatosis cerebri in a 68-year-old woman presenting with gait disturbances and episodic seizures. MRI showed bilateral white matter hypersignal intensities on Flair sequences and brain biopsy revealed a poorly cellular proliferation of neoplasic glial cells strongly expressing OLIG-2, Ki-67 and occasionally GFAP, without alpha-internexin expression. The patient status worsened rapidly and she died 2 months after the initial symptoms. Postmortem brain examination confirmed gliomatosis cerebri and revealed a focal glioblastoma in the frontal cortex, with nuclear p53 expression in the highest malignant areas. Gliomatosis cerebri should be included in the differential diagnostic of diffuse brain lesions. Antemortem diagnosis, although difficult, can be assessed by IRM and careful biopsy examination. Progression to glioblastoma has been seldom reported, enhancing the controversy about the etiopathogenesis of this rare tumour.
Annales de Pathologie 02/2010; 30(1):25-9. · 0.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gliomatosis cerebri is a rare glial neoplasm, characterized by diffuse brain infiltration with relative preservation of the underlying cytoarchitecture. Its clinical and radiologic features are not specific and its antemortem diagnosis is difficult. We report a case of gliomatosis cerebri in a 68-year-old woman presenting with gait disturbances and episodic seizures. MRI showed bilateral white matter hypersignal intensities on Flair sequences and brain biopsy revealed a poorly cellular proliferation of neoplasic glial cells strongly expressing OLIG-2, Ki-67 and occasionally GFAP, without α-internexin expression. The patient status worsened rapidly and she died 2 months after the initial symptoms. Postmortem brain examination confirmed gliomatosis cerebri and revealed a focal glioblastoma in the frontal cortex, with nuclear p53 expression in the highest malignant areas. Gliomatosis cerebri should be included in the differential diagnostic of diffuse brain lesions. Antemortem diagnosis, although difficult, can be assessed by IRM and careful biopsy examination. Progression to glioblastoma has been seldom reported, enhancing the controversy about the etiopathogenesis of this rare tumour.
Annales De Pathologie - ANN PATHOL. 01/2010; 30(1):25-29.
[show abstract][hide abstract] ABSTRACT: Adult leukodystrophies with neuroaxonal spheroids (LNS) constitute a heterogeneous group of genetic diseases. Herein, we report on two unrelated patients with LNS characterized by rapid onset, predominant involvement of the frontal white matter, and areas of decreased apparent diffusion coefficient on diffusion-weighted imaging. We found similar cases in the literature and propose that they represent a distinct entity within the group of LNS. Further studies will be required to identify its molecular basis.
Journal of Neurology 06/2009; 256(10):1649-54. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.
Journal of Neuropathology and Experimental Neurology 02/2009; 68(2):190-8. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cytologic pleomorphism has been described in a limited number of benign pineal tumors, namely pineocytoma (PC) and pineal parenchymal tumors (PPTs) of intermediate differentiation (PPTID). We examined the clinicopathologic features in a retrospective series of 14 cases (seven females and seven males aged from 10 to 65 years) of pleomorphic PPT. Seven cases were PC, with no mitoses and with areas of tumoral cells forming large pineocytomatous rosettes and other areas with giant cells containing hyperchromatic nuclei. The other seven were PPTID, presenting few mitoses (< or =2), a Ki67 proliferation index between 3% and 7%, and predominantly composed of small neoplastic cells and scattered giant cells, sometimes multinucleated. In the 14 tumors, the proportion of pleomorphic areas was variable. Most tumoral cells showed extensive neuronal differentiation with strong expression of neuron-specific enolase, synaptophysin and neurofilaments. Some of the neoplastic cells expressed S100 protein. The follow-up period ranged from 1.2 to 13 years and only one PC and one PPTID progressed after stereotactic biopsy or incomplete resection. The lack of invasiveness and the low proliferation index of these tumors suggest a benign clinical course despite the marked pleomorphism, the latter of which can lead to upgrading.
[show abstract][hide abstract] ABSTRACT: MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.
Journal of Neuro-Oncology 07/2007; 83(2):173-9. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival.
The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression.
The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas.
The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.
Cancer 11/2006; 107(8):1891-7. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Search for loss of heterozygosity on chromosomes 1p, 9p, 10q, and 19q, epidermal growth factor receptor (EGFR) gene amplification, and p53 expression was performed in a series of 131 low-grade gliomas. The profile of molecular changes, clinical findings, and histology were subsequently correlated with the course of the disease, mainly progression-free survival. When these parameters were considered as candidate variables in a multivariate analysis, only loss of heterozygosity on chromosome 1p was associated with increased progression-free survival (hazard ratio, 0.521), indicating a major favorable prognostic role of this genetic alteration in low-grade gliomas.
Annals of Neurology 09/2005; 58(2):322-6. · 11.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 38-year-old man living near Phnom Penh (Cambodia) was admitted to a hospital in Paris in June 2001 for a single episode of a generalized grand mal seizure. This episode was preceded by a 9-month history of headaches. Magnetic resonance imaging (MRI) of the head revealed a rounded lesion immediately ahead of the left central sulcus. The resected lesion was about 20 mm in diameter. Histologic examination revealed an elongated but unsegmented metacestode at the center of the lesion. Polymerase chain reaction (PCR) analysis was inconclusive due to formalin-based histologic processing of the tissue. Morphologic analysis based on the histologic sections revealed that the metacestode was a tetra-acetabulate plerocercoid of the order Cyclophyllidea, with a distinct rostellum and pseudosegmentation of the dorsoventrally flattened hindbody. This is the first report of a tetra-acetabulate plerocercoid from a human host and the first report of any cyclophyllidean plerocercoid from the human brain. After 6 weeks, the patient was asymptomatic, neurologic examination was normal, and the brain MRI showed only surgical cavitation. The patient returned to Cambodia.
The American journal of tropical medicine and hygiene 06/2005; 72(5):513-7. · 2.53 Impact Factor