[show abstract][hide abstract] ABSTRACT: BACKGROUND: The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. OBJECTIVES: To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. STUDY DESIGN: We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients' PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. RESULTS: Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. CONCLUSION: We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2013; · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: About 90 % of meningiomas are benign (WHO grade I), atypical and anaplastic variants exist (WHO grade II/III, 10 %). Tumour grade has important implications for management. Non-invasive diagnosis of tumour grade is still not feasible. The purpose of this survey was to analyse epidemiological risk factors such as sex, age and location for a higher grade (WHO grade II/III) meningioma in a large surgical series. METHODS: A retrospective study comprising 1,663 patients operated on for an intracranial meningioma in a single tertiary-care centre. The population was analysed for correlations including WHO grade, histological subtype, tumour localisation, patient age and gender. Additionally correlations between Ki67 index/WHO grade and localisation were analysed. RESULTS: A binary logistic regression analysis revealed non-skull base localisation (OR 1.779 [CI 1.069-2.960, p = 0.0027]) and age ≥65 years (OR 1.549 [CI 1.214-2.624, p = 0.012]) as significant risk factors for a higher WHO grade. Male gender showed a trend for a higher risk in χ(2) analysis. An analysis of the Ki67 index revealed an increased index for non-skull base localisation compared with skull base (p < 0.001). Correlation analysis of Ki67 distribution in WHO grade I meningiomas revealed higher Ki67 indices for non skull base localisation (p = 0.0024). CONCLUSIONS: Non-skull base localisation and age ≥65 years are independent risk factors for higher grade meningiomas. In other terms, the malignant potential of skull base meningiomas is low. This information is important when advising a patient about individual treatment options (observation, surgery or radio-surgery) and prognosis.
[show abstract][hide abstract] ABSTRACT: Aim. We aimed to analyze the diagnostic criteria proposed by the Bethesda System for Reporting Thyroid Cytopathology for follicular lesions of undetermined significance (FLUS), the risk of cancer and diagnostic improvement with use of immunocytochemistry. Methods. For each FLUS diagnosis, we analyzed the cytological criteria (9 Bethesda criteria), secondary fine-needle aspiration (FNA) results, surgical procedures, contribution of immunocytochemistry with the antibodies cytokeratin 19 (CK19) and monoclonal anti-human mesothelial cell (HBME1). Results. Among patients with 2,210 thyroid FNAs, 244 lesions (337 nodules) were classified as FLUS (11% of all thyroid FNAs). The 3 criteria most often applied were cytological atypia suggesting papillary carcinoma (36%), microfollicular architecture but sparse cellularity (23.1%), cytological atypia (21.5%). With secondary FNA, 48.8% of nodules were reclassified as benign. For about half of all cases (41.4% for the first FNA, 57.6% for the second FNA), immunocytochemistry helped establishing a diagnosis favoring malignant or benign. No benign immunocytochemistry results were associated with a malignant lesion. In all, 22.5% of the 39 removed nodules were malignant. Conclusion. The FLUS category is supported by well-described criteria. The risk of malignancy in our series was 22.5%. Because we had no false-negative immunocytochemistry results, immunocytochemistry could be helpful in FLUS management.
Journal of thyroid research. 01/2013; 2013:250347.
[show abstract][hide abstract] ABSTRACT: To detect the presence of hypoxic tissue, which is known to increase the radioresistant phenotype, by its uptake of fluoromisonidazole (18F) (FMISO) using hybrid positron emission tomography/computed tomography (PET/CT) imaging, and to compare it with the glucose-avid tumor tissue imaged with fluorodeoxyglucose (18F) (FDG), in residual postsurgical skull base chordoma scheduled for radiotherapy.
Seven patients with incompletely resected skull base chordomas were planned for high-dose radiotherapy (dose ≥70 Gy). All 7 patients underwent FDG and FMISO PET/CT. Images were analyzed qualitatively by visual examination and semiquantitatively by computing the ratio of the maximal standardized uptake value (SUVmax) of the tumor and cerebellum (T/C R), with delineation of lesions on conventional imaging.
Of the eight lesion sites imaged with FDG PET/CT, only one was visible, whereas seven of nine lesions were visible on FMISO PET/CT. The median SUVmax in the tumor area was 2.8 g/mL (minimum 2.1; maximum 3.5) for FDG and 0.83 g/mL (minimum 0.3; maximum 1.2) for FMISO. The T/C R values ranged between 0.30 and 0.63 for FDG (median, 0.41) and between 0.75 and 2.20 for FMISO (median,1.59). FMISO T/C R >1 in six lesions suggested the presence of hypoxic tissue. There was no correlation between FMISO and FDG uptake in individual chordomas (r = 0.18, p = 0.7).
FMISO PET/CT enables imaging of the hypoxic component in residual chordomas. In the future, it could help to better define boosted volumes for irradiation and to overcome the radioresistance of these lesions. No relationship was founded between hypoxia and glucose metabolism in these tumors after initial surgery.
International journal of radiation oncology, biology, physics 03/2012; 84(3):681-7. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: To describe the pseudotumoural presentation of neuro-Behçet's disease (NBD).
We report here the main characteristics, treatment and outcome of 23 patients (5 personal cases and 18 patients from the literature) with a pseudotumoural presentation of NBD. Pseudotumoural NBD patients were compared with 69 consecutive patients, with a classical form of NBD.
The median age was 39 (range 27-48 years) years, with a male predominance (65.2%). Clinical features of the pseudotumoural NBD included hemi- or tetra-pyramidal symptoms (n = 20), headache (n = 17), cerebellar syndrome (n = 3), sphincter impotence (n = 3) and pseudobulbar signs (n = 2). CNS imaging showed pseudotumoural lesions mainly in the capsulo-thalamic area (69.6 vs 11.6% for classical NBD; P < 0.01). Histological analysis revealed necrotic lesions with perivascular inflammatory infiltrate without signs of tumoural or infectious lesions. Patients with pseudotumoural NBD had more severe initial disability status (Rankin's score ≥3 in 65.2 vs 24.7%; P < 0.01) and had a 3 years' longer duration between neurological signs and BD diagnosis (P = 0.01) compared with patients with classical NBD. Treatment consisted of CSs (n = 21, 95.5%) and immunosuppressive agents (n = 10, 35.7%) that led to complete clinical and imaging remission in 60.9% of patients. Two (8.7%) of the 23 patients with pseudotumoural NBD died of bedridden state complications.
The pseudotumoural form of NBD is a rare and life-threatening condition.
[show abstract][hide abstract] ABSTRACT: The endoscopic approach has gained an increased popularity in recent years for the biopsy and, in selected cases, the removal of tumors of the posterior third ventricle and pineal region. The authors report their experience on a series of 20 patients discussing also the technical limitations and complication avoidance. This is a prospective study of 20 patients with posterior third ventricle and pineal region tumors surgically managed by endoscopic biopsy and/or excision and simultaneous third ventriculostomy. The removal of the lesion could be achieved in 12 cases whereas in 8, only a biopsy could be performed. A histological diagnosis could be obtained in all cases. No delayed third ventricular stoma failures were recorded in any patient at the latest follow-up (mean follow-up, 39 months). Severe postoperative complications were recorded in 2 out of 12 cases of tumor removal attempt and in zero out of eight cases of biopsy. A delayed (3 weeks) postoperative mortality occurred in a patient harboring a GBM that developed an intratumoral hematoma 48 h postoperatively, one patient was in a vegetative state. Transient postoperative complications included: nausea and vomiting (five cases) and diplopia (two cases). One patient developed a bilateral ophthalmoplegia that recovered within 6 months due to residual tumor hemorrhage. Higher rate of complications was found in the case of vascularized and/or larger lesions. Endoscopic management of posterior third ventricle lesions may represent an effective option. However, though biopsies remain often a safe procedure, tumor excision should be limited to highly selected cases (cystic, poorly vascularized, and/or smaller than 2.5-cm lesions).
[show abstract][hide abstract] ABSTRACT: Thyroid nodules are relatively common (7% of the population) but are malignant in only 5%-10% of cases. Fine-needle aspiration (FNA) to detect cancer can have > 90% sensitivity but only 50%-65% specificity because of false-positive results, which necessitates surgical controls. We aimed to assess the diagnostic accuracy of immunocytochemistry (ICC) of thyroid FNA to improve its sensitivity and specificity.
We prospectively collected 2038 thyroid FNAs, of which 1397 were FNA biopsies with liquid-based cytology (Thin-Prep-Hologic®). ICC with cytokeratin 19 and HBME1 antibodies (Dako® A/S) was used for all malignant cases and cases of atypical cells of undetermined significance (AUS), follicular neoplasm (FN), and nodules suspicious for malignancy-papillary thyroid carcinoma (SM-PTC) as well as some benign cases (abnormal features on radiography or benign on secondary FNA). ICC results were defined as "non-contributory," "favoring benign," "favoring malignant," or "indeterminate." Results for 150 cases were compared with histological controls for diagnostic accuracy.
Of these 150 cases ICC was helpful for benign or malignant triage of 48 cases of AUS, FN, and SM-PTC (42% of these lesions). Six (4%) ICC results were false positive (favoring malignant with benign histology) but none were false negative (favoring benign with malignant histology). Results for indeterminate cytological cases favored malignant or benign disease with sensitivity, specificity, and negative and positive predictive values of 100%, 85.2%, 100%, and 86.2%, respectively.
ICC of thyroid FNAs with cytokeratin 19 and HBME1 antibodies can reduce the false-positive and false-negative results of single morphological analyses. It can increase the sensitivity and specificity of diagnosis, thus improving diagnostic accuracy and reducing the need for surgical controls.
Thyroid: official journal of the American Thyroid Association 08/2011; 21(10):1067-73. · 2.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations. Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median follow-up was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P = 0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P = 0.008 and P < 0.001, respectively). The CCJ location was also related to a lower OS (P = 0.043) and it was more common in young patients (P = 0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease. Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.
[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: The authors report a case of a thoracic epidural spinal lipomatosis causing severe neurological deficits along the review of pertinent literature. The patient is a 56-year-old woman who presented with acute onset of severe paraparesis; she was investigated with cervical and thoracic MRI and then surgically managed because of an intraspinal mass compressing the cord. The operation consisted in the excision of the mass confirmed to be a fibrolipoma by pathological analysis. The patient attained complete neurological recovery and at 18 months follow-up she reported a generalised well-being. Thoracic lipomas are rare lesions that presenting mostly with back pain; however, in rare instances they may cause progressive and/or abrupt neurological dysfunction. Appropriate imaging can help in the diagnosis and management of such cases.
[show abstract][hide abstract] ABSTRACT: Many techniques are described to treat Chiari type I malformation. One of them is a splitting of the dura, removing its outer layer only to reduce the risks of cerebrospinal fluid (CSF) leak. We try to show the effectiveness of this technique from histological and biomechanical observations of dura mater. Study was performed on 25 posterior fossa dura mater specimens from fresh human cadavers. Dural composition and architecture was assessed on 47 transversal and sagittal sections. Uniaxial mechanical tests were performed on 22 dural samples (15 entire, 7 split) to focus on the dural macroscopic mechanical behavior comparing entire and split samples and also to understand deformation mechanisms. We finally created a model of volume expansion after splitting. Dura mater was composed of predominant collagen fibers with a few elastin fibers, cranio-caudally orientated. The classical description of two distinct layers remained inconstant. Biomechanical tests showed a significant difference between entire dura, which presents an elastic fragile behavior, with a small domain where deformation is reversible with stress, and split dura, which presents an elasto-plastic behavior with a large domain of permanent strain and a lower stress level. From these experimental results, the model showed a volume increase of approximately 50% below the split area. We demonstrated the capability of the split dura mater to enlarge for suitable stress conditions and we quantified it by biomechanical tests and experimental model. Thus, dural splitting decompression seems to have a real biomechanical substrate to envision the efficacy of this Chiari type I malformation surgical technique.
[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: Distinctive hyaline inclusion bodies in the cytoplasm of neocortical astrocytes were observed in surgical resection specimens of a frontal epileptic focus, in 2 patients aged 16 and 10 who had suffered intractable partial seizures since the age of 2 years. One case had minimal neurological impairment and no brain malformation on MRI and recovered completely following surgery. The second case had mental retardation and surgery reduced the frequency and generalization of seizures. In both cases, the astrocytic inclusions were strongly eosinophilic, hyaline and refractile. They were PAS negative. Electron microscopy in the first case, confirmed their granular osmiophilic structure. By immunohistochemistry, the inclusions were strongly positive for filamin in the first case, only some were weakly positive in the second case. They also variably expressed other proteins such as alpha-B-crystallin, GFAP, S-100 protein and cytoglobin. We compare our findings with previously reported cases and discuss the clinical significance of the inclusions and the pathophysiologic relevance of filamin A and other proteins accumulation in astrocytes.
[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.