MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry

Purpose: The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. Patients and methods: 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient’s survival. Results: In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). Conclusion: We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening (AU)

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MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry.

PURPOSE: The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. PATIENTS AND METHODS: 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient's survival. RESULTS: In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). CONCLUSION: We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.

Adult recurrent pilocytic astrocytoma: Clinical, histopathological and molecular study.

BACKGROUND: PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers. MATERIAL AND METHODS: We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor. RESULTS: Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity. CONCLUSION: Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses.

[A rare cause of recurrent meningitis in children: cochleovestibular dysplasia]. / Une cause rare de méningite récurrente chez l'enfant: la dysplasie cochléovestibulaire.

Recurrent bacterial meningitis is an uncommon disease of childhood. It occurs most often in children who have an underlying predisposing disorder that can result from anatomic fistula or immunodeficiency. Cochleovestibular dysplasia is a rare malformation of the inner ear that is often associated with translabyrinthine cerebrospinal fistula and then can cause recurrent bacterial meningitis. We report an unusual case of recurrent meningitis revealing cochleovestibular dysplasia in a 9-year-old child. The malformation was confirmed by imaging and the child had surgery. The outcome was favourable with no recurrence of meningitis during the 3 years after the operation.

Liposarcoma of the extremities: MR imaging features and their correlation with pathologic data.

OBJECTIVE: To describe the MRI features of liposarcomas of the extremities and correlate them with data from the histologic subtypes. MATERIAL AND METHODS: Retrospective study of 20 cases of liposarcoma of the extremities identified on MRI, surgically removed and confirmed at pathology. On MRI examination, T1- and T2-weighted fat-suppressed and non-fat-suppressed images were acquired then gadolinium-enhanced fat-suppressed T1-weighted images were obtained in at least two orthogonal planes. RESULTS: Sixteen female and four male patients aged 12 to 77 years old at presentation, in 16 cases, with a slowly enlarging painless mass (demonstrating no associated local or general inflammatory components), located in the lower extremity (16 cases) and predominantly located in the thigh (13 cases). Pathologic examination revealed three cases of well-differentiated liposarcoma, 12 cases of myxoid liposarcoma one of which with round cells, three cases of pleomorphic liposarcoma, one case of dedifferentiated liposarcoma and one case of mixed-type liposarcoma. MR images mostly showed well-circumscribed tumors (19 cases) . Well-differentiated liposarcomas typically demonstrated a very specific diagnostic appearance as a predominantly adipose mass containing nonlipomatous components seen as thick septa that may show nodularity. Other subtypes of liposarcoma demonstrated a small amount of adipose tissue thus producing a marbled textural pattern on T1-weighted images particularly in myxoid liposarcomas (9 cases), or even nonlipomatous elements in high-grade liposarcomas (in round cell liposarcoma and in two out of three pleomorphic liposarcomas). The myxoid subtype has also a relatively characteristic appearance as a low signal intensity noted on T1-weighted images and a marked high signal intensity on T2. The dedifferentiated liposarcoma has a very specific radiologic appearance as a nonlipomatous component within a predominantly adipose mass, simulating that of well-differentiated liposarcomas. CONCLUSION: MRI of extremity liposarcomas is a highly reliable and sensitive method to characterize liposarcomas. Besides its value in the diagnosis of liposarcoma and locoregional extension control, it allows proper identification of the specific histologic subtypes of liposarcoma. LEVEL OF EVIDENCE: Level IV. Rétrospective diagnostic study.

Acute disseminated encephalomyelitis following herpes simplex encephalitis.

Acute disseminated encephalomyelitis is an acute immunomediated demyelinating disorder of the central nervous system, usually encountered in children or adolescents and characterized by multifocal neurologic deficits of rapid onset. It is often preceded by various infectious diseases or vaccination, but acute disseminated encephalomyelitis developing after herpes simplex encephalitis is rare. We report such a case in a 2-year-old girl which illustrates the importance of MRI features to consider acute disseminated encephalomyelitis in a patient who develops neurologic signs after the onset of HVS encephalitis.

[Canavan disease or N-acetyl aspartic aciduria: a case report]. / La maladie de Canavan ou acidurie N-acétyl aspartique: à propos de 1 cas.

Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive leukodystrophy characterized by spongy degeneration of brain. The disease is an inborn error of metabolism caused by aspartoacylase deficiency resulting from accumulation of N-acetyl aspartic acid in the brain. The authors report a case in a 10-month-old boy who presented with developmental delay and megalencephaly noticeable after 4 months of age. Magnetic resonance imaging of the brain showed diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry.

[Discoid menisci in children: ultrasonographic features]. / Le ménisque discoïde chez l'enfant: aspects échographiques.

OBJECTIVE: Discoid meniscus is a rare congenital pathology affecting mainly the lateral meniscus. Radiological diagnosis, initially based on arthrographic findings, is now established on well defined MRI criteria. In this study, ultrasonography (US) was the modality proposed for diagnosing discoid meniscus and compared to the normal sonographic meniscal pattern. Subjects and methods. 8 children aged from 6 to 11 years, with a symptomatology highly suggestive of meniscal pathology, were investigated by US of both knees, followed by MRI in 3 and arthroscopy in all cases. RESULTS: In all 8 cases, a meniscus was diagnosed as discoid when it no longer had its normal triangular shape, was abnormally elongated and thick and demonstrated a heterogeneous central pattern. Associated lesions (fracture, cystic degeneration) were well demonstrated on US. The lateral meniscus was involved in all 8 cases, the pathology was bilateral in 5 cases and MRI/US correlation was good in 3 cases. Arthroscopy confirmed US findings in all cases. CONCLUSION: US, a more widely available imaging modality, is a reliable technique for the diagnosis of discoid meniscus in children.

[Biliary cystadenocarcinoma: a case report disease]. / A propos d'un cas de cystadénocarcinome biliaire.

Biliary cystadenocarcinoma is a rare tumour arising in a healthy liver. Prognosis is better than other malignant tumours of the liver. It frequently develops in a pre existing benign biliary cystadeonoma and usually occurs in middle-aged women. This tumour is difficult to diagnose because of the lack of specificity of clinical, biological and radiological features. We report the sonographic, computed tomographic and angiographic features of a case of biliary cystadenocarcinoma. A review of the literature is presented as well. The sonographic and CT findings suggestive of biliary cystadenocarcinoma are summarized. Treatment is surgical and diagnosis is confirmed at histopathology.

[Calcification of the cervical ligamentum flavum. Case report and review of the literature]. / Calcification du ligament jaune du rachis cervical. A propos d'un cas et revue de la littérature.

Calcification of the cervical ligamentum flavum is a rare entity observed exclusively in Japanese people. We report a new case in a 65-year-old man from Tunisia who presented with symptoms of cervical myelopathy with mild tetra paresis, sensory abnormalities and dysuria. Magnetic resonance imaging (MRI) showed a posterior compression of the spinal cord at C3-C4. CT-scan showed a calcification of the ligamentum flavum at level C3-C4, compressing the left postero-lateral aspect of the spinal cord. C3-C4 laminectomy was performed with removal of abnormal ligamentum flavum tissue. The postoperative course was uneventful and all symptoms resolved. Calcification of the cervical ligamentum flavum is a rare entity; the diagnosis is easy but the pathogenesis remains unclear. Literature regarding this pathology is reviewed.

[Computed tomography features in aorto-digestive fistula after abdominal aortic surgery. Report of two cases]. / Apport de la tomodensitométrie dans les fistules aorto-digestives compliquant la chirurgie de l'aorte abdominale. A propos de deux cas.

Aorto-enteric fistula is an uncommon late complication of aortic reconstructive surgery. Morbidity and mortality remain high despite progress in diagnosis and therapeutic procedures. We report two cases of complications of aortic interventions and present the diagnosis contribution of the CT scans. Our patients were two men aged 62 and 68 years. Both presented with abdominal pain and gastrointestinal bleeding. Endoscopy and CT scan with contrast enhancement were performed providing the diagnosis of aorto-enteric fistula before surgery. Both patients died after surgery. The fundamental principle in the management of late complications of abdominal aortic surgery is early and aggressive surgery. Cross sectional imaging and particularly CT scan plays an important role in diagnosis and in determining the extent of these complications. CT must be performed for life-long follow-up of these patients to allow assessment of early diagnosis of aortic reconstruction surgery complications.

[Aicardi syndrome with favorable outcome]. / Syndrome d'Aicardi d'évolution favorable.

BACKGROUND: Aicardi syndrome is usually associated with a very poor outcome. CASE REPORT: We report a particular case of Aicardi syndrome characterised by a partial agenesis of the corpus callosum associated with an arachnoidal interhemispheric cystic formation, and by a complete control of epilepsy and a favorable outcome regarding visual and psychomotor performances. CONCLUSION: A better prognosis could be expected in Aicardi syndrome when spasms occur lately and are not preceded by partial seizures, when agenesis of corpus callosum is partial and especially when chorioretinal lacunae are small, isolated, few and spare the macula.

[Primary cardiac sarcoma: report of 3 cases and review of the literature]. / Les sarcomes primitifs du coeur: revue de la littérature, illustrée par 3 cas.

Primary cardiac sarcoma is a rare tumor with a poor prognosis. We report 3 cases with a review of literature about this disease. There were 2 males and 1 woman. The main symptoms were thoracic pain. The clinical features were various and the thoracic ultra sonography exam allowed the diagnosis in the 3 cases. All patients had surgical remove of their cardiac tumor followed by chemotherapy. All of them died within 13 to 36 months after the diagnosis. Primary cardiac sarcoma has a poor prognosis with a mean survival less than 12 months.

[Primary lymphoma of bone: imaging features]. / Lymphomes osseux primitifs: apport de l'imagerie médicale.

Primary lymphoma of bone (PLB) has benefited from recent advances in medical imaging and immunohistochemical study that are of prognostic and therapeutic value. From 3 case reports of PLB involving the iliac bone and the skull base, we review the definition of PLB and their main features. The importance of complete initial workup for staging in order to exclude secondary bone lymphomas, more frequent and of worse prognosis, is emphasized. Diagnosis of PLB involving the skull base is more difficult to obtain and nearly always requires neurosurgical biopsy unlike PLB of peripheral bones that are more readily amenable to percutaneous biopsy.

[Tuberculous mesenteric lymphadenitis: a case report]. / La lymphadénite mésentérique d'origine tuberculeuse: à propos d'un cas.

The authors report a case of mesenteric tuberculous lymphadenitis which mimic a pancreatic cystadenoma. They emphasize ultrasound and CT scan features which lead to the recognition of tuberculosis and permit a percutaneous fine needle biopsy. Laparotomy seems the most reliable method for a positive diagnosis. The place of different imaging methods is discussed.

[Radioclinical profile of cardiopericardial hydatid: report of 17 cases]. / Profil radioclinique du kyste hydatique cardiopéricardique: à propos de 17 cas.

Hydatid cysts concerning the heart are rare, accounting for 0.5 to 2% of all hydatic sites. The risk of serious complications in this location makes rapid diagnosis and surgical treatment essential. The aim of our study is to clarify the role of imaging in the diagnosis of the disease and to propose an adequate strategy. We report on 17 patients who underwent surgery for cardiopericardial hydatid cyst in the cardiovascular and thoracic unit of Sahloul hospital in Sousse from January 1988 to December 1998. Clinical investigation included in all cases chest X ray, ECG and ultrasonography (US). A computed tomography (CT) scan was performed in 14 cases, magnetic resonance imaging in three cases, transesophageal US in five cases, and coronary angiography in fsix cases. Examination for other hydatic sites was realized in all cases, and brain CT was performed in four cases. The hydatid cyst was variably localized in the left ventricle wall (five cases), the right ventricle (five cases), the pericardium (five cases), the interventricular septum (four cases), the right auricle (one case) and the left auricle (one case). The existence of other cardiac hydatid sites was found in 12 cases. All patients underwent surgery. Outcome was favorable in 14 cases, with a mean of 3 years and 5 months survey. Three patients died. The combination US-CT scan allowed a precise topographical inventory, reducing the need for MRI to the complicated cases and to the rare cases of inconclusive results by US-CT scan.

[Post-traumatic adenoid cystic carcinoma of the lacrimal gland]. / Carcinome adénoïde kystique post-traumatique de la glande lacrymale.

A young 17-year-old man was injured on the external orbital canthus and developed a tumefaction which remained stable. After 2 years the tumefaction with exophthalmia and visual troubles. Radiological investigations suggested two diagnosis: Organized hematoma or a lacrimal gland tumor. Surgical exploration found an apparently benign tumor but histologically it was a cystic adenoid carcinoma.