Jean-Michel Vignaud

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.

Respiratory epithelial adenomatoid hamartoma of the nose: an updated review.

Background This study was designed to update clinical and imaging features as well as treatment outcomes of the nasal respiratory epithelial adenomatoid hamartoma (REAH). Data sources included case reports, original articles, and reviews published in English or French in PubMed from 1995 to date. Methods Only published articles that met Wenigs histological criteria for the diagnosis of REAH were included. Results REAH is not rare and is probably underdiagnosed. It is usually observed in the fifth decade of life with a 3:2 male/female predilection. REAH can be represented in two forms: as an isolated lesion (less frequent) or in association with an inflammatory process (especially nasal polyposis). It was observed in 35–48% of patients undergoing endoscopic endonasal surgery for nasal polyposis. Its origin is found, in most cases, in the olfactory cleft, which is exhibited on computed tomography (CT) scans by widened opacified olfactory clefts without bone erosion. Resection of REAH from the olfactory clefts does not worsen, but instead, can improve the sense of smell after surgery. Conclusion Looking for REAH on CT scans and during endoscopic examination can lead to its diagnosis and help avoid aggressive surgical procedures and their complications. Endoscopic resection is the treatment of choice. The removal of REAH constitutes a specific surgery on the olfactory clefts, which can improve nasal obstruction as well as sense of smell. Whether REAH can be defined as a hamartoma, an inflammatory reactive process, or a neoplastic lesion remains to be determined.

Ethmoido-maxillary sinusitis caused by the basidiomycetous fungus Schizophyllum commune.

C. Lorentz, A. Rivier, A. Debourgogne, J. Sokolowska-Gillois, J-M. Vignaud, R. Jankowski and M. Machouart Service d Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, CHU de Nancy, Hopital Central, Nancy Cedex, France, Service de Parasitologie-Mycologie, CHU de Nancy, Hopital Brabois, Vandoeuvre-les-Nancy, France, Laboratoire de Parasitologie-Mycologie, Faculte de Medecine, Vandoeuvre-les-Nancy, France and Service d Anatomie et Cytologie Pathologiques, Hopital Central, CHU de Nancy, Nancy Cedex, France

Skin wounds vitality markers in forensic pathology: An updated review.

Wound age evaluation is one of the most challenging issues in forensic pathology. In the first minutes or hours, standard histological examination may not determine whether the wound was inflicted in the pre- or post-mortem period. While red blood cell infiltration is classically considered as a sign of vital reaction, several studies have shown that extravasation of blood cells may also occur after death and cannot be used as a reliable marker in the diagnosis of wound vitality. Numerous studies about wound vitality are available in the literature. They have evaluated markers involved in coagulation or inflammation, using various methods such as enzymology, molecular biology or immunohistochemistry. In this update, we first introduce some methodological principles. Then, we review the main studies available in the literature. Immunohistochemistry seems to be the most valuable method, given its easy application and the possibility to analyse the localization of the molecules of interest. Some markers are promising, such as CD15, TNFα, IL-6, IL-1β, TGFα or TGFβ1. Prior to their application in daily practice, these early results need to be confirmed with other studies, conducted by independent teams and integrating multiple controls. Most notably, the antibodies have to be tested in numerous post-mortem wounds. Indeed, a critical risk of overexpression in post-mortem wounds is present. Some promising markers have been later invalidated because of post-mortem false positivity. Finally, optimal sensitivity and specificity values could probably be reached by combining several markers, validated by large groups of pre- and post-mortem wounds.

Methyl(R217)HuR and MCM6 are inversely correlated and are prognostic markers in non small cell lung carcinoma.

OBJECTIVES In non small cell lung carcinoma (NSCLC), earlier studies supported a prognostic value of intra-cytoplasmic HuR expression. HuR is a RNA binding protein previously shown to stimulate proliferation, but the link between HuR and proliferation in NSCLC has not yet been evaluated. The first objective of this study was to analyze the expression of HuR in a series of NSCLC and to correlate this to two proliferation markers, Ki-67 and MCM6. As potential post-transcriptional regulatory mechanisms for HuR expression, two miRNAs, miR16 and miR519, were also analyzed. Finally, because HuR methylation could be involved in its nucleocytoplasmic shuttling, the expression of methyl(R217)HuR and its relation to cancer survival were determined. MATERIALS AND METHODS Immunohistochemistry was used to evaluate the expression of HuR, methy(R217)HuR, Ki-67 and MCM6 in a series of 190 NSCLCs. The level of miR16 and miR519 was determined by qRT-PCR. RESULTS Higher cytoplasmic HuR staining was found in tumor vs. control paired normal lung (p<0.0001), but without correlation with survival. The level of methyl(R217)HuR was correlated both significantly with intra-cytoplasmic HuR staining (p<0.001), and overall survival (p=0.01). MCM6 correlated to a poorer overall survival (p<0.01). Both MCM6 and Ki-67 were positively correlated with HuR nuclear staining (p<0.0001 and p<0.001, respectively). On the contrary, MCM6 and Ki-67 correlated inversely to methyl(R217)HuR (p<0.001 and p=0.01, respectively). The levels of miR16 and miR519 were significantly lower in tumor tissue vs. paired normal lung (p<0.0001), but only miR519 correlated inversely to HuR expression (p=0.01). CONCLUSION While overall cytoplasmic HuR level was higher in tumor tissues, we found unexpectedly that methyl(R217)HuR was a marker of good prognosis. Furthermore, our data suggest that HuR level could be regulated by miR519. Finally, we demonstrated that Ki-67 and MCM6, both correlated with HuR, are valuable markers of poor prognosis in NSCLC.

Is pneumosinus dilatans an osteogenic disease that mimics the formation of a paranasal sinus

PurposePneumosinus dilatans is a disease that produces an abnormal expansion of a paranasal sinus cavity, which contains only air and is lined by normal mucosa, and whose bony walls are displaced outwardly to cause facial embossing or intracranial, orbital or ethmoidal encroachment. Objective was to evaluate the hypothesis that pneumosinus dilatans is primarily an osteogenic disease.MethodsA detailed clinical history of three consecutive patients with pneumosinus dilatans was taken. Each patient also underwent computed tomography (CT), fluorine-deoxyglucose positron emission tomography-CT (FDG PET-CT), fluorine 18-labeled sodium fluoride PET-CT (NaF PET-CT), and bone pathology.ResultsThe FDG PET-CT and pathology confirmed that the mucosa inside the pneumosinus dilatans was normal and devoid of inflammatory cell infiltrate. Significant uptake of 18F-NaF on PET-CT images correlated well with bone pathology, showing intense and diffuse bone remodeling. At a 1-year follow-up, following a frontotomy for case #1 and a middle antrostomy for case #2, there was a marked resolution of the patients’ clinical symptoms and deformities, new bone formation on the walls, stabilization of the new sinus shape and volume, and persistence of significant uptake of 18F-NaF.ConclusionsPneumosinus dilatans is a rare disease. Its diagnosis is based on CT scan images. This study has shown that 18F-NaF PET-CT and bone pathology are useful modalities for the positive diagnosis of difficult cases. Pneumosinus dilatans appears to be an osteogenic disease. Further research is needed to investigate a possible link between mechanisms involved in paranasal sinus formation and those involved in pneumosinus dilatans.

Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Diffuse adult high‐grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into “anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO,” restricted to tumors showing intermingled astrocytic and oligodendroglial component, and “GBM/GBMO” based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co‐deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10−4). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co‐deleted AO, IDH1 R132H‐GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

Pleomorphic malignant fibrous histiocytoma at the site of an arthroscopic reconstruction of the anterior cruciate ligament. A case report.

P reviously regarded as a distinct tumor type representing the most common adult soft-tissue sarcoma1,2, the term malignant fibrous histiocytoma is now reserved for a small group of undifferentiated pleomorphic sarcomas3. The tumor is most often primary, but rare cases of secondary malignant fibrous histiocytoma in burn scars4-8 or infected or noninfected surgical scars9-12 have been reported (see Appendix). Secondary malignant fibrous histiocytoma has been described in contact with prostheses13-28, osteosynthesis material29-35, or implanted Dacron grafts36. Malignant degeneration of benign tumors35, Paget disease37, osseous infarcts38, or fibrous dysplasia39 also has been reported (see Appendix). We report a unique case of a patient with soft-tissue malignant fibrous histiocytoma that developed on the medial side of the knee six years after arthroscopic reconstruction of the anterior cruciate ligament with use of the patellar tendon. D uring a soccer game in June 1993, a nineteen-year-old man experienced an indirect injury to the right knee that caused a rupture of the anterior cruciate ligament. A magnetic resonance imaging scan confirmed the diagnosis. An arthroscopic reconstruction of the anterior cruciate ligament was carried out in October 1993 with use of the patellar tendon. Stainless-steel (alloy-316L) screws (with a diameter of 6.5 mm) were used for the femoral and tibial fixation. The rest of the intra-articular examination was normal, and the postoperative course was uneventful. In 1995, a hemarthrosis developed in the right knee subsequent to a new injury. The knee was stable, and the hemarthrosis resolved with symptomatic treatment. In 1997, the patient experienced a locking episode of the right knee, which was found to be caused by a bucket-handle tear of the medial meniscus at …

Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and resistance to hypoxia

HuR regulates cytoplasmic mRNA stability and translatability, and the HuR expression level has been shown to correlate with poor disease outcome in several cancer types; however, the prognostic value and potential pro‐oncogenic properties of HuR in meningioma remain unclear. Thus, in the present study, we analysed 85 meningioma tissue samples to establish the relationship between HuR expression, tumour cell proliferation, and/or patient survival. In addition, we examined the anti‐proliferative effects of HuR knockdown in two meningioma cell lines (IOMM‐Lee and Ben‐Men‐1) and conducted transcriptome‐wide analyses (IOMM‐Lee cells) to elucidate the molecular consequences of HuR knockdown. The results of the present study showed HuR cytoplasmic expression to correlate positively with tumour grade (p = 1.2 × 10−8) and negatively with progression‐free and overall survival (p = 0.01) time in human meningioma tissues. In vitro, siHuR‐induced HuR knockdown was shown to reduce the growth of both Ben‐Men‐1 (p = 2 × 10−8) and IOMM‐Lee (p = 4 × 10−9) cells. Transcriptome analyses revealed HuR knockdown in IOMM‐Lee cells to deregulate the HIF1A signalling pathway (p = 1.5 × 10−6) and to up‐regulate the expression of genes essential for the assembly of the cytoplasmic mRNA processing body, global genome nucleotide‐excision repair, poly(A)‐specific ribonuclease activity, the positive regulation of apoptosis and of cell cycle arrest, and the negative regulation of RNA splicing [p(FDR) < 0.001]. Interestingly, HuR knockdown under hypoxic culture conditions further potentiated the effects of HuR knockdown on cell growth, apoptosis, and HIF1A expression. We thus conclude that cytoplasmic HuR expression is a marker of poor prognosis in meningioma and that HuR is a promising potential therapeutic target for use in tumours refractory to standard therapies. Copyright

Successful management of rhinosinusal zygomycosis in a renal transplant recipient

Patrice Gallet, Anne Debourgogne, Alexandre Rivier, Nathalie Marcon, Thomas Georgel, Marc Ladrière, Jean-Michel Vignaud, Roger Jankowski and Marie Machouart Service d Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, CHU de Nancy, Hôpital Central, Nancy Cedex, France, Service de Parasitologie-Mycologie, CHU de Nancy, Hôpital Brabois, Vandoeuvre-les-Nancy, France, Service d Anatomie et Cytologie Pathologiques, Hôpital Central, CHU de Nancy, Nancy Cedex, France and Service de Néphrologie-Hémodialyse, CHU de Nancy, Hôpital Brabois, Vandoeuvre-lès-Nancy, France