Infarctus de l´os fémoral révélant une drépanocytose composite SC chez un patient marocain

La double hétérozygotie SC est considérée comme un syndrome drépanocytaire majeur; en effet, son évolution peut être marquée par des complications sévegrave;res voire irréversibles, tel que l´infarctus osseux. Notre observation rapporte la découverte d´une hétérozygotie composite SC chez un patient de 17 ans à la suite de gonalgies intenses et met ainsi en exergue le retard diagnostic de cette maladie, et soulegrave;ve la nécessité de mise en place d´une politique de dépistage précoce afin d´améliorer la prise en charge et le pronostic des sujets atteints

Anémie de fanconi au CHU Hassan II Fès: à propos de 6 observations

L'anémie de Fanconi est une maladie récessive associée à une instabilité chromosomique, elle est marquée par une hétérogénéité phénotypique qui inclut une insuffisance médullaire, un syndrome malformatif variable, une prédisposition à développer des leucémies aiguës myéloïdes (LAM) et une hypersensibilité cellulaire aux agents pontant l'ADN. Le diagnostic est basé sur l'augmentation anormale du taux de cassures chromosomiques spontanées mais surtout, et de manière spécifique, sur une augmentation nette de ces cassures chromosomiques en présence d'agents alkylants bifonctionnels, ce qui est le cas pour nos six patients. Le conseil génétique rejoint celui des maladies autosomiques récessives. Nous rapportons nos premières observations au CHU Hassan II Fès, confirmées par la mise en évidence d'une grande instabilité chromosomique après culture sous Mitomycine C en comparaison avec un témoin normal. Le but de cet article est la mise à jour de nos connaissances sur la génétique de l'Anémie de Fanconi et à travers ces six observations nous illustrons le rôle de la cytogénétique dans le diagnostic et le conseil génétique pour une meilleure prise en charge aussi bien des enfants atteints que de leurs familles

Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez)

<p>Abstract</p> <p>Introduction</p> <p>Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).</p> <p>The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer.</p> <p>Methods</p> <p>This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome.</p> <p>Results</p> <p>A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.</p> <p>The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS).</p> <p>Conclusion</p> <p>TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.</p

EWSR1 Rearrangement and CD99 Expression as Diagnostic Biomarkers for Ewing/PNET Sarcomas in a Moroccan Population

Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) are a group of round cell tumors. Malignant round cell tumors form a large and diverse group that includes rhabdomyosarcoma, synovial sarcoma, non-Hodgkin’s lymphoma, neuroblastoma, hepatoblastoma, Wilm’s tumor, desmoplastic small round cell tumor, and other morphologically similar entities. Differential diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (Ewing/PNET sarcomas or EPS) is difficult. In addition to morphology and immunohistochemistry (IHC), differential diagnosis of these tumors is based on molecular analysis of the EWSR1 gene rearrangement using fluorescent in situ hybridization (FISH) technique. We investigated the diagnostic value of combined CD99 immunostaining and EWSR1 t(22q12) alteration using a dual-color, break-apart rearrangement probe in forty-one formalin-fixed paraffin-embedded (FFPE) tissue samples from pediatric and adult patients diagnosed with EPS. IHC was performed in all cases using the CD99 antibody and showed a positivity of 92.7% in the enrolled cases (38/41) followed by FISH analysis where 48.8% of the cases (20/41) were rearranged. Sensitivity and specificity for IHC assays were 88% and 58%, respectively. Notably, FISH had a sensitivity of 100% and a specificity of 87%. In addition, CD99 positivity was found to correlate with EWSR1 rearrangement (p<0.05). This report shows that FISH has better sensitivity and specificity than IHC in the Moroccan population, and supports its combination with CD99 immunostaining as diagnostic biomarkers for this rare malignant entity.

Differential over-expression ofmdr1 genes in multidrug-resistant rat glioblastoma cell lines selected with doxorubicin or vincristine

International audienceWe have compared the pharmacological and molecular characteristics of 2 cell lines derived from the C6 rat glioblastoma, and selected for resistance either to doxorubicin (C6 0.5 line) or to vincristine (C6 IV line). Each line displays a preferential 400-fold resistance towards the drug used for selection, the C6 IV line being especially weakly resistant to doxorubicin (13-fold). Verapamil completely restored doxorubicin sensitivity in the C6 IV line as well as vincristine resistance in the C6 0.5 line, but could not completely reverse doxorubicin resistance in the C6 0.5 line or vincristine resistance in the C6 IV line. This suggests that specific mechanisms of resistance against each drug were added to a common P-glycoprotein-mediated multidrug-resistance mechanism. Doxorubicin efflux was total within 2 hr in the C6 IV line, whereas it remained 8 to 10% of drug in the C6 0.5 line 4 hr after drug removal, despite a more rapid efflux of the drug in the first 30 min. This 2-compartment behavior could be related to a special sub-cellular distribution of doxorubicin in C6 0.5 cells. Northern and Western blot analysis of the mdrI gene and of the P-glycoprotein expressed by the 2 resistant cell lines made it possible to quantify their degree of over-expression; when compared with the C6 wild strain, the C6 0.5 line over-expressed both the mdrI gene and the P-glycoprotein to a slightly higher level than the C6 IV line. Northern and Western blot analysis also suggested that C6 0.5 cell preferentially over-expressed the mdrIa gene, whereas the C6 IV cells preferentially over-expressed the mdrIb gene. This differential over-expression was confirmed after polymerase-chain-reaction amplification of the cDNA sequences transcribed from total RNA extracted from the 2 lines. It can be concluded therefore that the mdrIa gene product is more efficient than the mdrIb gene product in extruding anti-cancer drugs from the cells; and that the mdrIb gene product might preferentially extrude vincristine rather than doxorubicin

Astroblastoma – a rare and challenging tumor: a case report and review of the literature

Abstract Background Astroblastoma is a controversial and an extremely rare central nervous system neoplasm. Although its histogenesis has been clarified recently, controversies exist regarding its cellular origin and validity as a distinct entity. Because of its extreme rarity and because its common features are shared with other glial neoplasms, this tumor is prone to misdiagnosis and remains challenging not only in terms of diagnosis and classification but also in the subsequent management. This case report describes a new case of astroblastoma. It discusses clinical, radiologic, pathological, and therapeutic features and differential diagnosis of this rare neoplasm, with a review of the recent literature. Case presentation We report the case of an 8-year-old Moroccan girl who presented with a 1-year history of epileptic seizure, headache, and decreased visual acuity. Cranial magnetic resonance imaging revealed a right occipito-temporal mass. A tumor resection was performed and histological examination combined with immunohistochemical study confirmed the diagnosis of low-grade astroblastoma. Conclusions Astroblastoma is a very rare primary brain tumor. Its diagnosis is often challenging because of the astroblastic aspects that can be found in astrocytic tumors, in ependymomas, and in non-neuroepithelial tumors. Considerable confusion surrounds its histogenesis and classification. The low incidence rate makes it difficult to conduct studies to examine tumor characteristics

Syndrome de Lynch: à propos d’un cas et revue de la litterature

Le syndrome de Lynch, ou cancer colorectal héréditaire sans polypose ou HNPCC (hereditary non-polyposis colorectal cancer), est la forme la plus fréquente de cancer colorectal héréditaire. Il conduit à une augmentation de la susceptibilité à développer des cancers, au premier rang le cancer colorectal, le cancer de l’endomètre chez les femmes, et dans une moindre mesure, d’autres cancers (ovaire, intestin grêle, estomac, voies excrétrices urinaires et hépatobiliaires). Ainsi, le risque cumulé de développer un cancer colorectal ou de l’endomètre à l’âge de 80 ans s’élève respectivement à 20 et 40 %. Ces cancers sont caractérisés par leur contexte d’atteinte familiale, leur survenue à un âge précoce, ainsi que par le développement de cancers métachrones chez un même individu. Ce syndrome se transmet de manière autosomique dominante. Les gènes dont l'altération est associée à l'existence d'un syndrome HNPCC appartiennent à la famille des gènes de réparation des mésappariements de l'ADN (DNA mismatch repair ou MMR): MSH2, MLH1 et MSH6 sont impliqués, par ordre décroissant de fréquence, dans respectivement 35%, 25% et 2% des cas. Une surveillance coloscopique et gynécologique est proposée aux personnes porteuses d'une mutation constitutionnelle du gène MSH2, MLH1 ou MSH6. Nous rapportons une des premières observations marocaines d’un syndrome de Lynch dont la mutation constitutionnelle du gène MLH1 a été identifiée chez un des membres de la famille atteint d’un cancer du côlon. Suite à la demande d’autres sujets sains de la même famille, un diagnostic presymptomatique a été effectué conduisant à une stratégie de surveillance adaptée. A travers notre observation nous illustrons le rôle de l’oncogénétique dans la prise en charge des patients cancéreux et de leurs familles.The Pan African Medical Journal 2016;2

Correlates of HPV: a cross-sectional study in women with normal cytology in north-central Morocco

International audienceIntroduction: Epidemiological studies have shown the association between risk of developing cervical cancer and the persistence of high-risk papillomavirus types in addition to some co-factors. However, little is known about co-factors associated with human papillomavirus (HPV) infection, especially in developing countries. This study aims to determine HPV status and associated risk factors in women with normal cytology living in the north-central area of Morocco.Methodology: From February 2007 to December 2008, a total of 925 women consulting in the gynaecological department of Fez University Hospital were asked about sociodemographic characteristics and reproductive and sexual health. Cervical samples were collected for cytological examination and HPV DNA detection. Data collected from 751 women with normal cytology were used in this study to assess the correlation between HPV infection and potential risk factors.Results: High prevalence of HPV infection was detected (42.5%). The highest infection rate was observed in women aged >45 years and in those with history of abortion (OR:3.76; 95%CI[1.77-7.98]) fibroma, polyp or cysts (OR:1.68; 95%CI[1.07-2.65]). No significant association was detected with other reproductive health and risk factors including oral contraception.Conclusion: In spite of the insignificant association of HPV infection with age, health authorities should seriously consider and implement strategies to increase and maintain a cervical cancer screening programme in women aged 45 and above. More attention must be given to women with gynaecological history (abortion, fibroma, polyp or cysts) since these events may be predictors of HPV infection. Investigations on partner sexual behaviour and some specific hygienic habits, especially public Turkish bath use, are needed to clarify the HPV incidence in this region

EGFR Amplification and IDH Mutations in Glioblastoma Patients of the Northeast of Morocco

Glioblastomas are the most frequent and aggressive primary brain tumors which are expressing various evolutions, aggressiveness, and prognosis. Thus, the 2007 World Health Organization classification based solely on the histological criteria is no longer sufficient. It should be complemented by molecular analysis for a true histomolecular classification. The new 2016 WHO classification of tumors of the central nervous system uses molecular parameters in addition to histology to reclassify these tumors and reduce the interobserver variability. The aim of this study is to determine the prevalence of IDH mutations and EGFR amplifications in the population of the northeast region of Morocco and then to compare the results with other studies. Methods. IDH1 codon 132 and IDH2 codon 172 were directly sequenced and the amplification of exon 20 of EGFR gene was investigated by qPCR in 65 glioblastoma tumors diagnosed at the University Hospital of Fez between 2010 and 2014. Results. The R132H IDH1 mutation was observed in 8 of 65 tumor samples (12.31%). No mutation of IDH2 was detected. EGFR amplification was identified in 17 cases (26.15%). Conclusion. A systematic search of both histological and molecular markers should be requisite for a good diagnosis and a better management of glioblastomas