Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc.

Gliomatosis cerebri: evolución a glioblastoma multiforme / Gliomatosis cerebri: evolution to glioblastoma multiforme

Introducción. La gliomatosis cerebri es un trastorno neoplásico caracterizado por una infiltración difusa de células gliales con relativa conservación de las estructuras subyacentes. Las crisis comiciales, la cefalea y los trastornos del comportamiento suelen ser las manifestaciones iniciales.Caso clínico. Hombre de 38 años que presenta crisis parciales complejas y trastorno del comportamiento de 3 meses de evolución. En la resonancia magnética cerebral presenta lesiones hiperintesas en T2 sugerentes de gliomatosis cerebri, confirmándose con la biopsia cerebral. Varios meses después sufre un empeoramiento clínico rápido, evidenciándose el desarrollo de un glioblastoma multiforme sobre la lesión.Conclusiones. La gliomatosis cerebri, pese a su rareza, debe tenerse en cuenta en el diagnóstico diferencial de las lesiones infiltrativas difusas de la sustancia blanca. El empeoramiento clínico de rápida evolución y la aparición de lesiones focales que captan contraste nos deben hacer sospechar una trasformación a lesiones de mayor malignidad

Introduction. Gliomatosis cerebri is a neoplastic disorder characterized by diffuse infiltration of glial cells with relative conservation of the underlying structures. Seizures, headache and behavior disorders are generally the initial manifestations.Clínical case. A 38 year-old male who had complex partial seizures and behavior disorder of three months' evolution. The brain magnetic resonance imaging showed hyperintense lesions in T2 suggestive of gliomatosis cerebri, this being confirmed with the brain biopsy. Several months later, he suffered rapid clinical deterioration, observing the development of a glioblastoma multiforme over the lesion.Conclusions. In spite of its rareness, gliomatosis cerebri should be taken into account in the differential diagnoses of diffuse infiltrative lesions of the white matter. Rapid evolution clinical deterioration and the appearance of focal lesions that capture contrast should make us suspect a transformation to lesions of greater malignancy

[Diagnosis and treatment of intraocular tumors in the child]. / Diagnostic et traitement des tumeurs intra-oculaires chez l'enfant.

PURPOSE: To remind of the absolute necessity for early diagnosis in the presence of ocular signs in children giving rise to possible intraocular tumours. METHOD: Based on our own experience of intraocular tumours in children, together with findings from the literature, diagnostic criteria and methods of treatment are presented. RESULTS: Retinoblastoma is the predominant cause of intraocular tumours in children, representing over 80% of cases under the age of 15 years. Other diseases may give rise to the same initial signs, usually leukocoria, sometimes strabismus, more rarely other atypical signs. Elements taken into account for diagnosis include age, sex, laterality, heredity, size of the globe, clinical aspect of the tumours, presence of calcifications and vitreous seeding. Full fundus examination under general anaesthetic is usually necessary. Biological examination, ultrasonography, computerized tomography and MRI enable an accurate diagnosis to be made in the majority of doubtful cases. The management of retinoblastoma is adapted for each individual case from the wide range of treatments available. Enucleation, radioactive applicators (...), brachytherapy (...), cryo- and photocoagulation represent classical measures. Primary chemotherapy, combined with other treatments such as thermotherapy, has become the treatment of choice in those cases where external beam radiotherapy has been used up to now, or in some instances before enucleation. Enucleation is usually carried out for medullo-epitheliomas, but brachytherapy may offer an alternative. CONCLUSION: Any unexplained ocular sign in children should be considered as a possible retinoblastoma, making an accurate and certain diagnosis imperative. Early treatment may save not only the life but also the vision of patients carrying this highly malignant lesion.