Pituicytomas, a mis-diagnosed benign tumor of the neurohypophysis: report of three cases.

Pituicytoma is a rare benign primary tumor of the neurohypophysis, occurring in the sellar and suprasellar spaces. We report here three new cases with immunohistochemical and electron microscopic study. Particular attention was paid to the expression of some cell adhesion molecules. These tumors were characterized by bundles of elongated cells strongly immunoreactive to anti-vimentin, S-100 protein, neural cell adhesion molecule and neuron-specific enolase antibodies. Glial fibrillary acidic protein (GFAP) was not recorded. It expressed the very late antigen alpha2 (VLAalpha2), but not VLAalpha5, and lacked epithelial markers expression (epithelial membrane antigen, E-cadherin), and specific neuronal markers (synaptophysin, chromogranin, neurofilament). Staining for pituitary hormones was negative. At the ultrastructural level, tumor/blood vessel basal lamina and cytoplasmic intermediate filaments were observed but desmosome or pericellular basal lamina were lacking. In one case few secretory granules were recorded. Differential diagnoses include granular cell tumors, pilocytic astrocytomas and spindle cell tumors such as solitary fibrous tumors, fibroblastic meningiomas and schwannomas. However, the unique pattern of antigenic expression and ultrastructural features of pituicytomas distinguish this rare tumor. As a subpopulation of pituicytes (which are distinctive glial cells of the neurophypophysis), some pituicytomas do not expressed GFAP. This suggests that pituicytomas presumably arise from pituicytes at various stages of their differentiation.

Methicillin resistance of bacteria isolated from vitreous fluid from patients undergoing vitrectomy.

PURPOSE: The aim of this study was to compare the resistance patterns of bacteria in vitreous fluid from patients undergoing vitrectomy for diagnostic reasons, with bacteria of other nosocomial infections. METHODS: Vitreous fluid samples (n=144) were obtained from 133 patients undergoing vitrectomy for endophthalmitis, and 11 for uveitis as suspected endophthalmitis. They were Gram stained and cultured. Antibiotic susceptibility tests were run on all isolates. RESULTS: Gram stains were positive in 45/144 cases (31%), among which 38/45 (84%) were confirmed by a positive culture. Cultures were positive in 74/144 patients (51%) with mainly coagulase-negative staphylococci (n = 44) and Staphylococcus aureus (n = 13). In 133 patients endophthalmitis occurred after lens implantation (80 cases) and in 53 cases there was another origin (e.g. corneal transplantation, endogenous). In 26/80 post-lens implantation infections, culture remained negative; 32 infections occurred with coagulase-negative staphylococci, 10 with Staphylococcus aureus, 9 with streptococci and 3 with gram-negative bacteria. For endophthalmitis, ophthalmologists in our institution give an intraocular injection of vanccmycin and ceftazidim after vitrectomy. Among the 44 isolates of coagulase-negative staphylococci, 12 (27%) were resistant to methicillin. This is in contrast to other hospital-related coagulase-negative staphylococcus infections in general, and the resistance rate is 75% in our hospital. Only 2/13 Staphylococcus aureus isolates were methicillin-resistant. CONCLUSIONS: We conclude that isolates of coagulase-negative staphylococci from vitreous fluid are less resistant to methicillin than those isolated in other nosocomial infections.

[Atypical teratoid and rhabdoid tumor. Report of a congenital case]. / Tumeur rhabdoïde et tératoïde atypique. A propos d'un cas congénital.

The atypical teratoid rhabdoid tumor is a rare brain tumor of childhood. We report a congenital case, revealed by peripheral facial palsy. This polymorphous tumor consisted of rhabdoid cells associated with areas of primitive neuroectodermal tumor. The immunoreactivity for the three proteins vimentin, epithelial membrane antigen and smooth-muscle actin was suggestive of rhabdoid tumor. Genetic study showed a homozygous mutation in the tumoral DNA and a constitutional heterozygous mutation, as it was demonstrated in atypical teratoid rhabdoid tumors and in renal and extra-renal rhabdoid tumors.

[Value of cytokeratin 7 and 20 for the diagnosis of cerebral metastases of adenocarcinoma: study of 78 cases]. / Intérêt des cytokératines 7 et 20 pour le diagnostic des métastases cérébrales d'adénocarcinome: étude de 78 cas.

OBJECTIVE: histological features of metastasis are not always specific of the origin. The usefulness of cytokeratin 7 and 20 (CK7 and CK20) in cerebral metastases from an adenocarcinoma was studied in a series of 78 patients. RESULTS: metastases from lung adenocarcinoma showed a CK7+/CK20- pattern in 79% of cases, CK7+/CK20+ in 19% and CK7-/CK20- in 2%. When observed, positivity for cytokeratin 20 was generally focal or weak. Breast adenocarcinoma metastases were CK7+/CK20- in 71% of cases and CK7-/CK20- in 29%. Less differentiated tumours were usually negative for both cytokeratins. Metastases by colonic adenocarcinoma were CK7-/CK20+ in 100% of cases. Cytokeratins 7 and 20 are useful to distinguish lung from colonic metastatic carcinoma. In case of double positivity, a more intense CK7 expression is rather suggestive of a lung origin. CONCLUSION: these results might modify paraclinic investigations in search of the primitive tumor.

[Contribution of immunohistochemistry and electron microscopy for the diagnosis of meningeal hemangiopericytomas. 15 case reports]. / Apport de l'immunohistochimie et de la microscopie électronique dans le diagnostic des hémangiopéricytomes méningés. A propos de 15 cas.

Meningeal hemangiopericytomas (HPC) are rare CNS tumors with a pour prognosis compared to meningiomas. In order to define diagnosis criteria, we performed an immunohistochemical and ultrastructural study in respectively 15 and 5 meningeal HPC. The following antibodies anti-KL1, EMA, vimentin, CD34, factor VIII, alpha-smooth actin, estrogen and progesteron receptors (RE, RP) were used in paraffin embedded sections whereas anti-NCAM and E-cadherin antibodies were used on frozen sections when available. We can differentiate meningeal HPC from meningioma because of a complete lack of immunostaining with epithelial markers as well as with NCAM antibody or RE and RP receptors. Besides a positivity with CD34 and alpha-smooth actin antibodies was always observed even focally in HPC. On the other hand, solitary fibrous tumor showed a strong and diffuse positivity with anti CD34 and anti-vimentin antibodies. Electron microscopy can be helpful in some instances showing membrane basal-like substance and absence of desmosomes.

Prognostic factors in intracranial ependymomas in children.

OBJECT: The occurrence of intracranial ependymomas in children is relatively infrequent, and their prognostic factors are still controversial, especially regarding histological composition. METHODS: A retrospective study was conducted of 37 children treated during the last 20 years for intracranial ependymomas at the Hôpital de la Timone. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of patient age and sex, extent of tumor removal, location of the tumor (supratentorial compared with infratentorial, median compared with lateral), tumor histological composition, and adjuvant therapies in affecting the 5-year progression-free survival (PFS) rate and overall survival (OS) rate. The following histopathological features, either alone or in combination, were analyzed: endothelial proliferation, necrosis, loss of differentiating structures (present compared with absent), the number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf). In addition, immunohistochemical detection of Ki-67 antigen was performed and the Ki-67 labeling index (LI) evaluated in all cases. The 5-year OS and PFS rates were 45% and 25%, respectively (median follow up 34 months). Four patients died of disease without remission (median 163 days) and disease in 21 patients relapsed: 18 in situ and three both in situ and distantly. On univariate analysis total surgical resection and median infratentorial location were associated with a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating structures was associated with poor prognosis (p < 0.008) and the combination of necrosis, endothelial proliferation, and mitotic index greater than 5 was also a negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS time was shorter in patients younger than 4 years of age and in patients in whom a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the 15 patients in whom total excision was achieved, OS was better in those who did not receive adjuvant therapies. In contrast, adjuvant therapies significantly enhanced PFS time in patients in whom tumor excision was incomplete. CONCLUSIONS: This study and analysis of the literature further highlight that total tumor removal is the treatment of choice for ependymomas in children. Postoperative measurement of residual tumor is required, especially because a subgroup of patients might be treated by surgery alone. Median infratentorial ependymomas have to be distinguished from the lateral type. Appropriate and reproducible histological parameters and Ki-67 LI are of interest as predictors of outcome.

Immunohistochemical localization of cytokines, C5b-9 and ICAM-1 in peripheral nerve of Guillain-Barré syndrome.

The spectrum of the Guillain-Barré Syndrome (GBS) has recently been widened by the newly identified forms of acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN). An important question has been raised regarding the possibility for the axon to be a target in immune-mediated damage. Although myelin breakdown is the characteristic feature of classic acute inflammatory demyelinating polyradiculoneuropathy (AIDP), axonal degeneration may occasionally be observed in this form, especially in cases with explosive onset and severe clinical course. Immunohistochemical findings of five frozen sural nerves biopsies of patients with GBS (AIDP variant) tested with a panel of monoclonal antibodies raised against different molecules implicated in immune-mediated processes have principally disclosed an immunoreactivity of tumor necrosis factor-alpha (TNF-alpha) on both Schwann cell membranes and in myelinated and unmyelinated axons. On the other hand, interleukin 1-beta (IL1-beta) labeled Schwann cells, endothelial cells and macrophages; interferon-gamma (IFN-gamma) was observed both in endothelial cells and lymphocytes. Membrane attack complex (C5b-9) deposits were observed on Schwann cell membranes and finally intercellular adhesion molecule-1 (ICAM-1) was localized both on endothelial cells and macrophages. Our findings strongly suggest that TNF-alpha is an important factor in the cascade of events leading to immune-mediated demyelination and axonal damage in GBS.

Papillary glioneuronal tumour: clinicopathological and biochemical study of one case with 7-year follow up.

Among the mixed glioneuronal tumours, a new variant called papillary glioneuronal tumour has recently been delineated. A case occurring in a 23-year-old man is reported. The tumour was cystic with a mural nodule enhanced by gadolinium injection. It was located within the left parieto-occipital lobe. Surgical excision showed a greyish friable tumour with cystic areas. Histopathological examination revealed a pseudopapillary component comprising a single layer of regular cells, arranged around hyalinised vessels. These cells were immunoreactive with anti-glial fibrillary acidic protein and HNK1 antibodies. A neurocytoma-like component coexisted with round blind cells and focal fibrillary rosettes. These cells were immunostained by anti-neuron-specific enolase and anti-synaptophysin antibodies. Neither mitoses nor ganglioid cells were seen. HNK1, the three isoforms of NCAM, and the L1 adhesion molecule were detected by Western blot analysis. Ultrastructural study showed three different types of cells. The first contained gliofilaments, the second showed long processes with true synapses, and the third was poorly differentiated. However, all had identical nuclei and contained dense bodies. These findings suggest a common origin for the tumour cells derived from a bipotential neuroglial progenitor. As for other mature mixed neuroglial tumours, the prognosis is good. Our patient is free of disease 7 years after complete surgical treatment.

p16INK4a and p19INK4d mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index.

The INK4a-ARF locus encodes two unrelated proteins that both function in tumour suppression: p16INK4a and p19INK4d. Although p19INK4d expression has not been studied in central nervous system (CNS) tumours, it has been reported that p16INK4a inactivation is involved in the growth of glioblastomas. This observation has not been reported in relation to other CNS tumours. To understand further the role of p16INK4a and p19INK4d in neuroglial tumour growth, expression of both p16INK4a and p19INK4d mRNAs was studied by reverse transcription polymerase chain reaction RT-PCR in 59 neuroglial tumours, in which Ki67 labelling indices (LI) were also determined. P16INK4a mRNA was found in all pilocytic astrocytomas (7/7), in all grade II and III astrocytomas (7/7 and 4/4, respectively), in 4/12 glioblastomas, 8/8 oligodendrogliomas, 10/11 anaplastic oligodendrogliomas, 4/7 ependymomas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p19INK4d mRNA was detected in all tumours and control tissues. p16INK4a expression was associated with a low Ki67 LI in glioblastomas but not in other tumours. P16INK4a expression was not related to anaplasia in oligodendrogliomas and ependymomas. In tumours expressing p16INK4a, in situ hybridization showed a widespread expression of p16INK4a mRNA in tumour cells and in foci of microvascular proliferation. These results strongly support the concept that p16INK4a is involved in the regulation of proliferation in glioblastomas. Other cell cycle regulators which are yet unknown may also play a role in the control of oligodendrogliomas or ependymomas outgrowth. Further studies are required to evaluate the role of p19INK4d in neuroglial tumours.

Expression of PECAM-1/CD31 isoforms in human brain gliomas.

Microvascular proliferation is a histopathological hallmark of glioblastomas and anaplastic oligodendrogliomas. Platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31) is involved in angiogenesis. PECAM-1 mediates homophilic and heterophilic interactions (with glycosaminoglycans and alphaVbeta3), but deletion of exon 14 results in a loss of heterophilic adhesion. Expression of various PECAM-1 isoforms was searched for in brain gliomas, showing microvascular proliferation (glioblastomas and anaplastic oligodendrogliomas) or not (oligodendrogliomas). In addition, expression of alphaVbeta3 in some tumors was studied by immunohistochemistry. Various tissues and the HUVEC primary cell line were used as controls. Immunohistochemistry showed that PECAM-1 was expressed by all endothelial cells in all tissues and by some tumor cells in glioblastomas and anaplastic oligodendrogliomas. Microvascular proliferation always expressed alphaVbeta3. In addition, some tumor cells in anaplastic oligodendroglioma and glioblastomas expressed it. In all samples examined, PECAM-1 exists under at least two transcriptional isoforms: the whole length molecule and an isoform made by the splicing of exon 14. Western blot analysis revealed in all cases 130 and 110 kDa bands corresponding to the mature form and its precursor respectively. These results suggest that splicing of exon 14 occurs in vivo in various normal and tumoral tissues and may modulate PECAM-1 adhesion according to the presence or not of other PECAM-1 ligands such as alphaVbeta3. Expression of PECAM-1 by tumor cells in glioblastomas and anaplastic oligodendrogliomas may favour angiogenesis by specific PECAM-1 interactions between glial and endothelial cells.

Adult onset reducing body myopathy.

We report the case of a 28 year-old woman with left scapuloperoneal syndrome since the age of 24. The course was slowly progressive and diffuse weakness was observed 4 years later. Serum creatine kinase levels were moderately elevated (x3 normal value) and EMG showed mixed neurogenic and myogenic patterns. Muscle biopsy showed type I predominance and numerous reducing bodies in muscle fibers. Reducing bodies were strongly immunoreactive with antibodies to dystrophin, alpha-sarcoglycan, vimentin and ubiquitin. Desmin immunoreactivity was increased at the periphery of some reducing bodies but alphaB crystallin, alpha actinin, titin and nebulin were negative. Western blot analysis showed an increase in dystrophin, vimentin and desmin expression. Ultrastructurally, reducing bodies were composed of tubulofilamentous material, 17 nm in diameter, and immunoreactive with anti-Dys 2 antibody. Granulofilamentous material, immunoreactive with anti-desmin antibody was observed at the periphery of some reducing bodies. This report further highlights the proteinic composition of reducing bodies and shows that late onset reducing body myopathy may occur.

Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas.

Since glioblastomas in adults are uniformly fatal, evaluation of easily reproducible prognostic criteria which would attempt to define groups of patients is required. However, there is lack of a clear consensus regarding the expression of some markers in the literature. Therefore, an immunohistochemical study was performed to determine the prognostic significance of Ki67, p53, and epidermal growth factor receptor (EGFR) in a retrospective series of 63 glioblastomas. Image analysis was carried out in positive specimens to quantify the immunoprecipitates. p53 and EGFR expression were specifically addressed in the 36 primary glioblastomas reported in this series. In all cases, clinical data (age, Karnofsky performance scale index [KPS] before surgery, extent of surgery) and immunohistochemical features were analysed using univariate and multivariate analysis to ascertain whether any significant correlation exists between [1] EGFR expression [2], p53 accumulation [3], Ki67 labelling index and prognosis (survival time and disease-free survival time, DFST). The results showed that in this series of glioblastomas, none of these markers had any prognostic value. Among the clinical parameters, a high KPS before surgery was found to be indicative of a shorter DFST and survival time (P < 0.05), whereas a younger age at onset and total or subtotal surgical excision were associated with a longer survival (P < 0.001 and 0.05, respectively). EGFR protein accumulation was inversely correlated with p53 accumulation (P = 0.01). The percentage of the primary glioblastomas expressing EGFR was much lower in our study (33%) than in the literature suggesting that the molecular distinction between primary and secondary glioblastomas is not so clear-cut.

Adaptive motion-compensated wavelet filtering for image sequence coding.

This paper deals with new advances made in the field of discrete spatio-temporal filters applied to digital image sequences. Within time-varying images, the temporal correlation of the information is folded within the spatio-temporal domain by motions originating from both camera and object displacements. The spatio-temporal video information can be therefore reformulated in terms of motion trajectories and intensity variations along these trajectories. To yield that signal description, the spatio-temporal scenes will be segmented according to motion. Motion-compensated temporal filters have been used as convolutional filters applied along the assumed motion trajectories. Spectral interpretations show the efficiency of motion-compensated filtering for video signals. As a matter of fact, the whole signal analysis performed in this paper also includes a spatial filtering to achieve a complete spatio-temporal (2-D+T) decomposition. Motion-compensated filtering leads to multiresolution applications. It leads to optimum and adaptive signal-to-noise decomposition procedures based on the temporal correlative content. Such properties allow enhancing tasks like temporal interpolation, image sequence smoothing, and restoration. Simulation results are presented in this paper to illustrate the field of image sequence coding.

Functional downregulation of the E-cadherin/catenin complex leads to loss of contact inhibition of motility and of mitochondrial activity, but not of growth in confluent epithelial cell cultures.

When epithelial cells reach confluency in vitro, a number of energy-requiring activities such as growth and motility are contact-inhibited. We investigated the possible role of the E-cadherin/catenin complex, which acts as an invasion suppressor, in contact inhibition. Three strategies for modulation of the complex were used. Firstly, the cell-cell adhesion and signal transduction functions of E-cadherin were neutralized immunologically in human MCF-7/6 mammary carcinoma cells possessing a complete complex. Secondly, the effect of E-cadherin transfection in E-cadherin negative cell lines was investigated. Thirdly, alpha-catenin deficient variants of the human HCT-8/S11 colon carcinoma cell line were compared with their parent cells. In confluent cultures functional downregulation of the E-cadherin/catenin complex did not alter cell growth nor saturation density. This was shown by cell number counts, protein staining assays, cell cycle analysis, proliferation markers (Ki67 and Proliferating Cell Nuclear Antigen) and apoptosis assays. However, confluent cells with a functionally deficient complex showed positional instability and enhanced succinate dehydrogenase-mediated mitochondrial 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl) tetrazolium bromide (MTT) conversion, as compared to cells with an active complex. Our data indicate that contact inhibition of motility and of mitochondrial enzyme activity, but not of growth is regulated by the E-cadherin/catenin complex in epithelial cells.

Large chorioangioma associated with hydrops fetalis: prenatal diagnosis and management.

A large chorioangioma located at the insertion area of the umbilical cord was diagnosed at 19 weeks of gestation by ultrasound and color Doppler ultrasound. This chorioangioma led to a progressively appearing hydrops fetalis and to fetal distress. The infant presented at birth with edemas and ascites associated with severe hemolytic anemia and thrombocytopenia.

Tamoxifen restores the E-cadherin function in human breast cancer MCF-7/6 cells and suppresses their invasive phenotype.

Tamoxifen is an antiestrogen used in adjuvant therapy of breast carcinoma and could potentially prevent the development of mammary cancer. While it is widely clinically used, its exact mechanisms of action are not yet fully elucidated. MCF-7/6 cells are estrogen receptor-positive invasive human breast cancer cells with a functionally inactive cell surface E-cadherin. In this study, we report that tamoxifen, and to a lesser extent its metabolites 4-OH-tamoxifen and N-desmethyltamoxifen, restore the function of E-cadherin in MCF-7/6 cells. In an aggregation assay, 10(-6) M tamoxifen significantly increases the aggregation of MCF-7/6 cells. This effect is abrogated by a monoclonal antibody against E-cadherin (HECD-1), is fast (within 30 min), and does not require de novo protein synthesis. Tamoxifen was also found to inhibit the invasion of MCF-7/6 cells in organ culture. Our data is the first demonstration that tamoxifen can activate the function of an invasion suppressor molecule and suggest that the restoration of E-cadherin function may contribute to the therapeutic benefit of tamoxifen in breast cancer patients.

[Infantile polycystic hepatorenal disease. 2 consecutive cases in a patient. Ultrasonic diagnosis and indication for elective pregnancy termination]. / Maladie polykystique hépatorénale infantile. Deux cas consécutifs chez une patiente. Diagnostic échographique et indication d'interruption médicale de grossesse.

We report a case of infantile polycystic kidney disease, during the course of two consecutive pregnancies in the same woman. Observed rates of recurrence in families at risk is higher than theoretical rates (25%). Antenatal ultrasound can show signs of bilateral involvement, which is always lethal and generally leads to elective termination of pregnancy. Diagnosis can rarely be made before 24 weeks of pregnancy.