Michel Peoc'h

Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing.

Background The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. Methodology/Principal Findings From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). Conclusions/Significance The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas.

Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma

OBJECTIVE Our objective was to evaluate the levels of miR-210 in tumor and serum samples of conventional renal cell cancer (cRCC) patients to explore whether circulating miR-210 in serum can be used as a biomarker for the detection of cRCC. METHODS The paired samples from primary cRCC tumors and adjacent non-tumoral renal parenchyma were collected from 32 patients with cRCC. Serum samples were obtained from 68 patients with a cRCC before surgery, 10 samples after one week of surgery, and 42 healthy individuals were included in this study. Real-time PCR was used to measure the microRNA level. The expression of miRNAs was normalized using the dCT method. Expression levels of miR-210 were compared using the Mann-Whitney U test or Wilcoxon test. Diagnostic performance of serum miR-210 level was calculated by using the receiver operating characteristic (ROC) curve. RESULTS The average miR-210 level was higher in primary cRCC tissues than in normal tissue (p=0.004). For serum samples, the average level of miR-210 was significantly higher in cRCC patients than in controls (p<0.001). The serum miR-210 level yielded an AUC (the areas under the ROC curve) of 0.874 with a sensitivity of 81.0% and a specificity of 79.4%. Furthermore, the average serum level of miR-210 was significantly decreased in the patients one week after the operation (p=0.001). CONCLUSION Serum mi-210 may have a potential as a novel noninvasive biomarker for the detection of cRCC.

Chordoid glioma of the third ventricle: a report of two new cases, with further evidence supporting an ependymal differentiation, and review of the literature.

The term chordoid glioma of the third ventricle was first used to describe a rare and slowly growing neoplasm of uncertain histogenesis, with chordoid appearance, occurring preferentially in middle-aged women. Herein we report two additional examples of this novel entity together with a literature review based on the 25 cases previously published. Our review fully confirms the strikingly stereotyped clinical, neuroradiologic, and pathologic features of this unique tumor. The female/male ratio was 1.7:1, and the age range was 24–70 years (mean 44.9 years). In all 27 cases imaging findings were similar showing a well-defined mass (mean 2.8 cm in largest dimension), ovoid in shape, hyperdense on CT scans, with uniform and intense contrast enhancement, arising in the hypothalamic/suprasellar/third ventricular region. Histologically, the main consistent characteristics were cords and clusters of epithelioid cells within an abundant mucinous and often vacuolated background. Mitoses were sparse or absent and anaplastic features, endothelial proliferation, and necrosis were not identified. Lymphoplasmacytic infiltrates with Russell bodies were frequent throughout the tumor and its interface with adjacent brain parenchyma. Most of the tumor cells revealed a strong and diffuse expression of vimentin and glial fibrillary acidic protein. Additionally, the vast majority of tumors showed focal coexpression of cytokeratins, CD34, S-100 protein, and epithelial membrane antigen; the MIB-1 labeling indices were uniformly low. Surprisingly for a glioma assigned WHO grade II, the 19 patients with an available but short follow-up (mean 22.5 months; range 6–68 months) experienced a rather poor outcome (three recurrences and seven deaths), probably reflecting the anatomic site of the neoplasm that precludes a complete surgical excision rather than its histologic composition. Ultrastructural examination of 10 cases demonstrated findings in line with a glial derivation and a putative ependymal origin such as cytoplasmic intermediate filaments, microvilli, intermediate junctions or desmosomes, and focal basal lamina formation. In our case no. 1, and for the first time in this tumor, we observed sparse and abnormal cilia in an aberrant juxtanuclear location, a further argument for considering chordoid glioma as a subtype of ependymoma. However, a better understanding of the biologic behavior and histogenesis of this distinctive clinicopathologic entity needs to be investigated with a larger series. Nevertheless, taking into account its strikingly consistent anatomic localization, its unique histopathologic and immunohistochemical profile, in conjunction with the most recent and convincing ultrastructural arguments, we suggest that chordoid glioma of the third ventricle could be better classified as chordoid ependymoma of the lamina terminalis area.

Revisited Microanatomy of the Corneal Endothelial Periphery: New Evidence for Continuous Centripetal Migration of Endothelial Cells in Humans

The control of corneal transparency depends on the integrity of its endothelial monolayer, which is considered nonregenerative in adult humans. In pathological situations, endothelial cell (EC) loss, not offset by mitosis, can lead to irreversible corneal edema and blindness. However, the hypothesis of a slow, clinically insufficient regeneration starting from the corneal periphery remains debatable. The authors have re‐evaluated the microanatomy of the endothelium in order to identify structures likely to support this homeostasis model. Whole endothelia of 88 human corneas (not stored, and stored in organ culture) with mean donor age of 80 ± 12 years were analyzed using an original flat‐mounting technique. In 61% of corneas, cells located at the extreme periphery (last 200 μm of the endothelium) were organized in small clusters with two to three cell layers around Hassall‐Henle bodies. In 68% of corneas, peripheral ECs formed centripetal rows 830 ± 295 μm long, with Descemet membrane furrows visible by scanning electron microscopy. EC density was significantly higher in zones with cell rows. When immunostained, ECs in the extreme periphery exhibited lesser differentiation (ZO‐1, Actin, Na/K ATPase, CoxIV) than ECs in the center of the cornea but preferentially expressed stem cell markers (Nestin, Telomerase, and occasionally breast cancer resistance protein) and, in rare cases, the proliferation marker Ki67. Stored corneas had fewer cell clusters but more Ki67‐positive ECs. We identified a novel anatomic organization in the periphery of the human corneal endothelium, suggesting a continuous slow centripetal migration, throughout life, of ECs from specific niches. STEM CELLS2012;30:2523–2534

Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients.

The purpose of this prospective multicenter study was to assess one‐step nucleic acid amplification (OSNA) for intraoperative sentinel lymph node (SLN) metastasis detection in breast cancer patients, using final histology as the reference standard. OSNA results were also compared to intraoperative histology SLN evaluation and to standard clinicopathological risk markers. For this study, fresh SLNs were cut in four blocks, and alternate blocks were used for OSNA and histology. CK19 mRNA copy number was categorized as strongly positive, positive or negative. Positive histology was defined as presence of macrometastasis or micrometastasis. When discrepancies occurred, the entire SLNs were subjected to histological studies and the node lysates to additional molecular studies. Five hundred three SLN samples from 233 patients were studied. Mean time to evaluate two SLNs was 40 min. Sensitivity per patient was 91.4% (95% CI, 76.9–98.2%), specificity 93.3% (95% CI, 88.6–96.6%), positive likelihood ratio 13.7 and negative likelihood ratio 0.1. Sensitivity was 63.6% for frozen sections and 47.1% for touch imprint cytology. Both methods were 100% specific. Positive histology and positive OSNA were significantly associated with highest clinical stage, N1 status and vascular invasion; and OSNA results correlated with HER2/neu status and benefited patients with negative histology. These findings show that OSNA assay can allow detection of SLN metastasis in breast cancer patients intraoperatively with a good sensitivity, thus minimizing the need for second surgeries for axillary lymph node detection.

Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

BACKGROUND The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

Mapping the Zonal Organization of Tumor Perfusion and Permeability in a Rat Glioma Model by Using Dynamic Contrast-enhanced Synchrotron Radiation CT

PURPOSE To depict and analyze in vivo the tumor zone organization of C6 gliomas depicted on quantitative parametric maps obtained with dynamic contrast material-enhanced synchrotron radiation computed tomography (CT) in a tightly controlled data-processing protocol. MATERIALS AND METHODS Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Fifteen Wistar rats with orthotopically implanted gliomas were studied at monochromatic synchrotron radiation CT after receiving a bolus injection of contrast material. The iodine concentration maps were analyzed by using a compartmental model selected from among a package of models. Choice of model and assessment of the relevance of the model were guided by quality criteria. Tissue blood flow (F(T)), tissue blood volume fraction (V(T)), permeability-surface area product (PS), artery-to-tissue delay (D(A-T)), and vascular mean transit time (MTT) maps were obtained. Parametric map findings were compared with histologic findings. Local regions of interest were selected in the contralateral hemisphere and in several tumor structures to characterize the tumor microvasculature. Differences in parameter values between regions were assessed with the Wilcoxon method. RESULTS Whole-tumor parameters were expressed as means +/- standard errors of the mean: Mean F(T), V(T), PS, and D(A-T) values and MTT were 61.4 mL/min/100 mL +/- 15.3, 2.4% +/- 0.4, 0.37 mL/min/100 mL +/- 0.11, 0.24 second +/- 0.06; and 3.9 seconds +/- 0.83, respectively. MTT and mean PS were significantly lower (P < .01) in the normal contralateral tissue: 1.10 seconds +/- 0.06 and < or = 10(-5) mL/min/100 mL, respectively. Tumor regions were characterized by significantly different (P < .05) F(T) and V(T) pairs: 108 mL/min/100 mL and 3.66%, respectively, at the periphery; 45.9 mL/min/100 mL and 1.91%, respectively, in the intermediate zone; 5.1 mL/min/100 mL and 0.42%, respectively, in the center; and 210 mL/min/100 mL and 6.82%, respectively, in the maximal value region. CONCLUSION Fine mapping of the glioma microcirculation is feasible with dynamic contrast-enhanced synchrotron radiation CT performed with well-controlled analytic protocols. SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/2501071929/DC1.

Perfusion-sensitive MRI of pilocytic astrocytomas: initial results

PurposeTo present the imaging and perfusion data obtained in nine patients with pilocytic astrocytomas (PA) and to discuss the original functional issues of this technique.MethodNine patients with pathologically proven PA underwent conventional and perfusion MR imaging. Various areas of relative cerebral blood volume (rCBV) within the tumors were obtained. The maximum rCBV ratios were identified and considered as representative of the tumor. The results were compared with the pathological findings.ResultsIn all patients, rCBV was <1.5 (mean 1) and the signal intensity curve overshot the baseline.ConclusionPA tend to have low rCBV values and a first-pass curve that crosses the baseline. These characteristics may be explained by the histological profile of the tumoral vascularity and are of relevance in the identification of these rare tumors.

Imaging the microvessel caliber and density: Principles and applications of microvascular MRI

Twenty years ago, theoretical developments were initiated to model the behavior of the NMR transverse relaxation rates in presence of vessels. These developments enabled the MRI‐based mapping of mean vessel diameter, microvascular density, and vessel size index with comparable results to those obtained by a pathologist. The transfer of these techniques to routine clinical use has been hindered by the unavailability of the required sequences, namely fast gradient‐echo spin‐echo sequences. Based on the increasing accessibility of such sequences on MRI scanners over recent years, we review the principles governing microvascular MRI, the validation studies, and the applications that have been tested worldwide by several teams. We also provide some recommendations on how to measure microvessel caliber and density with MRI. Magn Reson Med 73:325–341, 2015.

Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets

Reliable information regarding the current prevalence of peripheral T-cell lymphoma (PTCL) entities is missing. Herein we report on the frequency of PTCL entities in France between 2010 and 2013. Using Lymphopath , a national lymphoma network established by the French National Cancer Agency, which