Posterior fossa tumors in children with neurofibromatosis type 1 (NF1).

BACKGROUND: Tumours of the posterior fossa associated with neurofibromatosis type 1 (NF1) are very infrequent. Series studying this association are seldom reported. PERSONAL EXPERIENCE: In a series of 600 NF1 patients studied during 39 years (1965-2004) only five (0.83%) had posterior fossa tumours. They were studied clinically, radiologically by computerized tomography (CT) or magnetic resonance (MR) and histologically. Four of them had astrocytomas but only in one case was the tumour primarily cerebellar while the tumour was primarily of the brain stem with invasion of the adjacent regions of one or both cerebellar hemispheres in three patients. The fifth tumour was a medulloblastoma that had a survival of 3 years following treatment. The patient with primary cerebellar astrocytoma is apparently cured 7 years after the removal of the tumour. The patients with the brain stem tumours extending to the cerebellum, showed a chronic slowly progressive cerebellar disease, but remain alive at age of more than 20 years (one was lost to follow-up). DISCUSSION AND CONCLUSION: The aim of this study was to present five children (one male and four females) less than 16 years of age when they were initially seen in our service, who had NF1 associates with posterior fossa tumours. This location is very uncommon in patients with NF1, in contrast with those located in other regions, such as pathway optic tumours and brain stem tumours. Most of these tumours are histologically benign (low grade astrocytomas). Only one patient in this series had a medulloblastoma, an exceptionally rare tumour seldom reported in patients with NF1.

Complexity of the Hereditary Motor and Sensory Neuropathies: Clinical and Cellular Characterization of the MPZ p.D90E Mutation.

Early-onset hereditary motor and sensory neuropathies are rare diseases representing a broad clinical and genetic spectrum. Without a notable familial history, the clinical diagnosis is complicated because acquired causes of peripheral neuropathy, such as inflammatory neuropathies, neuropathies with toxic causes, and nutritional deficiencies, must be considered. We examined the clinical, electrophysiological, and pathologic manifestations of a boy with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. The progression of the disease despite treatment led to a suspicion of hereditary motor and sensory neuropathy. Genetic testing revealed the presence of the MPZ p.D90E mutation in heterozygosis. To clarify the pathogenicity of this mutation and achieve a conclusive diagnosis, we investigated the MPZ p.D90E mutation through in silico and cellular approaches. This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.

[Cerebral hemisphere tumours in neurofibromatosis type 1 during childhood]. / Tumores de los hemisferios cerebrales en la neurofibromatosis tipo 1 durante la infancia.

AIM: To present seven tumors of the cerebral hemispheres in 6 children with neurofibromatosis type 1 (NF1). PATIENTS AND METHODS: Six patients (three males and three females) of 600 cases of a series with NF1 showed features of cerebral hemispheres tumor (seizures, headache and hemiparesis). They were studied neurologically, by EEG and by image (MR and/or spectroscopic-MR) because of these features or simply because having NF1. RESULTS: All the patients had the two diagnostic criteria of the NF1. Six patients had seven tumors (it was because one of them had one tumor in every frontal lobe, both with the same image characteristics), but they did not were removed and they were not studied histologically. The histological study was made to the other five patients and showed that the histological nature corresponded to pilocytic astrocytoma in one patient, neuroepitelial dysembryoplastic tumor in one, polymorphe xanthoastrocytoma in one, neuroectodermic hamartoma in one, and inflammatory chronic non-granulomatose lesion in one. CONCLUSION: The prevalence of the tumors in the cerebral hemispheres is very low (1%) in the patients with NF1. The tumors commonly are histologically benign, and they can be found in peripheral or deep region of the cerebral hemispheres. Identity of the tumors by MR study commonly is easy and the treatment is surgical in most cases. However, urgent treatment very seldom is necessary in these tumors, and most frequently is possible to take the attitude of 'wait and see' before to decide the definite treatment.

Prevalence and progression of mitochondrial diseases: a study of 50 patients.

We report 50 patients with various clinical phenotypes of mitochondrial disease studied over the past 10 years in a large urban area (Madrid Health Area 5). The clinical phenotypes showed a large variety of abnormalities in molecular biology and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7 per 100,000 in the population over 14 years of age. Clinical and electrophysiological assessment reveal signs of neuropathy in 10 patients. Electromyographic findings consistent with myopathy were obtained in 37 cases. Six patients died of medical complications. Disease phenotype influenced survival to some degree (P < 0.01). Age of onset and gender were not associated with differences in survival. Mitochondrial disease is thus far more common than expected and a common cause of chronic morbidity.

Neuroblastoma anaplásico del bulbo olfatorio con áreas de diferenciación rabdomioblástica. Descripción de un caso / Anaplastic olfactory neuroblastoma with areas of rhabdomyoblastic differentiation. A case report

El neuroblastoma de bulbo olfatorio es un tumor de células pequeñas y origen neuroectodérmico que aparece en el área superior de la cavidad nasal en la región de la lámina cribosa y puede mostrar un patrón de agresividad y afectar a estructuras intracraneales. Presentamos el caso de un paciente de 25 años de edad con una masa a nivel de fosas nasales que invade la órbita y muestra afectación intracraneal extracerebral. Fue intervenido mediante un abordaje combinado por neurocirugía y cirugía maxilofacial, siendo el diagnóstico de neuroblastoma. Al mes de realizarse esta cirugía radical se produjo una recidiva muy agresiva fundamentalmente a nivel intracerebral, que es nuevamente intervenida, mostrando en el estudio histopatológico áreas de diferenciación rabdomioblástica dentro del neuroblastoma. A pesar de lo infrecuente de la aparición de áreas rabdomioblásticas en el seno de un neuroblastoma, la existencia de este dato anatomopatológico confiere al neuroblastoma un grado de agresividad y capacidad de recidiva extremadamente elevado. La cirugía debe ser lo más radical posible, lo cual no garantiza una supervivencia prolongada(AU)

Olfactory neuroblastoma is a small-cell tumour of neuroectodermal origin occurring in the upper nasal cavity in the region of the cribriform plate, which can show aggressive behaviour and affect intracranial structures. We report a case of a 25 year old male with a mass at the level of nasal cavity that invaded the orbit and the intracranial extracerebral compartment. The mass was removed using a combined neurosurgical and maxillofacial approach and a neuroblastoma was diagnosed. One month later, the patient had an aggressive, mostly intracerebral, recurrence. He underwent further surgery and the neuroblastoma was found to contain areas of rabdomyoblastic differentiation. Although rabdomyoblastic areas within neuroblastoma are extremely rare, when they are present the degree of aggressivity and possibility of recurrence are greatly increased. Thus, surgery should be as radical as possible, even though it does not guarantee long term survival(AU)

Tumores de los hemisferios cerebrales en la neurofibromatosis tipo 1 durante la infancia / Cerebral hemisphere tumours in neurofibromatosis type 1 during childhood

Objetivo. Presentar siete tumores en los hemisferios cerebrales en seis niños con neurofibromatosis tipo 1 (NF1). Pacientes y métodos. Seis pacientes (tres mujeres y tres varones) entre 600 casos con NF1 presentaban síntomas de tumor de los hemisferios cerebrales (crisis epilépticas, cefaleas y hemiparesia). Fueron estudiados por estos hechos o simplemente por la NF1 desde el punto de vista neurológico, mediante electroencefalograma e imagen (resonancia magnética o resonancia magnética espectroscópica). Resultados. Todos los pacientes presentaban los dos criterios diagnósticos de la NF1. Seis pacientes presentaban siete tumores (una paciente tenía un tumor en cada lóbulo frontal; las imágenes radiológicas de ambos fueron de similares características, pero no se extirparon y no se realizó el estudio histológico). El estudio histológico de los tumores extirpados se realizó a los otros cinco pacientes, y mostró que correspondía a astrocitoma pilocítico en el primero, tumor neuroepitelial disembrioplásico en el segundo, hamartoma neuroectodérmico en el tercero, xantoastrocitoma polimorfo en el cuarto y lesión inflamatoria crónica no granulomatosa en el quinto. Conclusión. La prevalencia de los tumores de los hemisferios cerebrales es muy baja (1%) en los pacientes con NF1. Los tumores son generalmente de naturaleza histológica benigna y pueden localizarse en zonas periféricas o centrales de los hemisferios cerebrales. La identificación tumoral mediante resonancia magnética es comúnmente fácil y el tratamiento es quirúrgico en la mayoría de los casos. En pocas ocasiones hay que actuar con urgencia en estos tumores, y la mayoría de las veces se puede adoptar la actitud prudente de ‘esperar y ver’ hasta tomar la decisión definitiva (AU)

Aim. To present seven tumors of the cerebral hemispheres in 6 children with neurofibromatosis type 1 (NF1). Patients and methods. Six patients (three males and three females) of 600 cases of a series with NF1 showed features of cerebral hemispheres tumor (seizures, headache and hemiparesis). They were studied neurologically, by EEG and by image (MR and/or spectroscopic-MR) because of these features or simply because having NF1. Results. All the patients had the two diagnostic criteria of the NF1. Six patients had seven tumors (it was because one of them had one tumor in every frontal lobe, both with the same image characteristics), but they did not were removed and they were not studied histologically. The histological study was made to the other five patients and showed that the histological nature corresponded to pilocytic astrocytoma in one patient, neuroepitelial dysembryoplastic tumor in one, polymorphe xanthoastrocytoma in one, neuroectodermic hamartoma in one, and inflammatory chronic nongranulomatose lesion in one. Conclusion. The prevalence of the tumors in the cerebral hemispheres is very low (1%) in the patients with NF1. The tumors commonly are histologically benign, and they can be found in peripheral or deep region of the cerebral hemispheres. Identity of the tumors by MR study commonly is easy and the treatment is surgical in most cases. However, urgent treatment very seldom is necessary in these tumors, and most frequently is possible to take the attitude of ‘wait and see’ before to decide the definite treatment (AU)

Astrocitos en oligodendrogliomas. Estudio con impregnaciones argénticas, inmunohistoquímica y cultivo de tejidos / Astrocytes in oligodendroglyomas, studied by silver impregnation, immunohistochemistry and tissue culture

La existencia de oligodendrocitos y astrocitos en los tumores mixtos se ha querido explicar por varias teorías: 1. Un origen a partir de dos líneas celulares distintas; 2. Inducción neoplásica de un tumor sobre las células vecinas; 3. Existencia de una única célula originaria procedente de la línea celular A2B5, capaz de dar lugar a oligodendrocitos y astrocitos. Hemos estudiado una serie de 124 oligodendrogliomas con los siguientes métodos: 47 casos con impregnación argéntica de Rio-Hortega; 77 casos con inmunotinción para GFAP; 11 casos con cultivo de tejidos a corto plazo y 8 líneas permanentes en monocapa. Este estudio demuestra que: 1. Una parte de los astrocitos son células atrapadas dependientes de la gliosis peritumoral; 2. Existen numerosos oligodendrocitos capaces de expresar GFAP y con argentofilia pertenecientes a la población tumoral; 3. Las células explantadas en los dos tipos de cultivo han expresado GFAP. En base a ello consideramos que, bajo ciertas condiciones, la oligodendroglía es capaz de exhibir rasgos astrocíticos y que, en consecuencia, los tumores mixtos son oligodendrogliomas con metaplasia astrocítica (AU)

The existence of tumoral oligodendrocytes and astrocytes in mixed gliomas has been explained in several ways: 1. Originating from two distinct cell lines; 2. Resulting from neoplastic induction of a previous tumor on the peripheral cells or; 3. From a single original cell of A2B5 lineage, capable of developing into oligodendrocytes and astrocytes. 124 oligodendrogliomas were revised: 47 cases underwent Rio-Hortega silver staining; 77 cases were stained for GFAP; 11 cases by short term tissue cultures; 8 cases by permanent cell lines established in monolayer cultures. Our findings are as follows: 1. A part of the astrocytes were trapped cells dependent on the peritumoral gliosis. 2. Several oligodendroglial cells in the tumoral population ex-pressed GFAP and showed argentofilia. 3. Both types of cultures developed expression of GFAP in vitro. In conclusion, we consider that oligodendroglia can, under certain conditions, develop some astrocytic features and that the so-called «mixed tumors» are the consequence of an astrocytic metaplasia in oligodendroglioma (AU)