NTRK2 gene fusions are uncommon in pilocytic astrocytoma.

BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.

Pediatric Skull Base Tumors: A Management Challenge.

CONTEXT: Skull base tumors are varied in children and are particularly challenging to pediatric neurosurgeons, with few papers in the literature describing the evolution, complications, and outcome. The authors evaluated long-term outcomes in children submitted to skull base tumor surgery and performed a literature review. AIMS: The aim of this study was to analyze surgical results, complications, and outcomes, on comparison with previous publications. MATERIALS AND METHODS: A retrospective analysis of children undergoing surgery at a single institution between 2000 and 2018 for lesions of the cranial base was carried out. In addition, a literature review was carried out describing a total of 115 children operated on for skull base tumors. STATISTICAL ANALYSIS: Chi-squared and Fisher's exact tests were performed to compare the distribution of categorical variables and a nonparametric Mann-Whitney U test was used to perform intergroup comparisons of continuous variables. RESULTS: Seventeen children ranging in age from 8 months to 17 years (mean, 10.9 years) underwent skull base approaches. Tumor types included schwannoma, meningioma, chondroid chordoma, mature teratoma, epidermoid cyst, hemangiopericytoma, rhabdomyosarcoma, myofibroblastic inflammatory tumor, fibromyxoid sarcoma, Crooke's cell adenoma, ossifying fibroma, osteoblastoma, nasopharyngeal angiofibroma and Ewing's sarcoma. Gross total resection was achieved in 6 patients (35.3%), 12 patients (70.6%) had benign histology, and 5 patients (29.4%) had a malignant tumor. Transient postoperative cerebrospinal fluid leak affected only one patient. Thirteen children (76.4%) had a residual neurological deficit at last follow-up evaluation. Three (17.6%) surviving patients received adjuvant therapy. The rate of recurrence or lesion progression was 17.6%. CONCLUSIONS: Skull base tumors in children present a therapeutic challenge because of their unique pathological composition and can lead to considerable morbidity and mortality in pediatric age.

Visceral leishmaniasis: historical series of hospitalized patients and correlation with climate in an endemic area in Minas Gerais, Brazil / Leishmaniose visceral: série histórica de pacientes hospitalizados e correlação com o clima em área endêmica de Minas Gerais, Brasil

RESUMEN Introducción La leishmaniasis visceral (LV) es una enfermedad infecciosa causada por protozoos del género Leishmania; predomina en las regiones tropicales, subtropicales y templadas. Objetivo Caracterizar una serie de casos de LV en pacientes mayores de 18 años atendidos en un hospital de referencia del norte de Minas Gerais, así como describir la ocurrencia de casos, según la caracterización climatológica, y correlacionar la distribución de los casos con la lluvia y la temperatura ambiente. Métodos El diseño del estudio fue una serie de casos recopilados entre 1999 y 2016. Los datos se extrajeron de historias clínicas seleccionadas cronológicamente. La información climática se recopiló en el Centro de estudios del Semiárido de la Universidad Federal de Montes Claros (Unimontes). Resultados Hubo un ligero predominio del sexo masculino (54,4%) y de edades comprendidas entre uno y cuatro años (42,9%). El tiempo de evolución de las manifestaciones clínicas hasta el momento de la hospitalización osciló entre cinco y 120 días, siendo la duración más frecuente entre 16 y 30 días (34,4%). Hepatomegalia, esplenomegalia, palidez cutánea y fiebre fueron manifestaciones presentes en más del 90% de los pacientes al ingreso. El diagnóstico se realizó por métodos serológicos en la mayoría de los casos (85,9%). La mayor parte de los ingresos duró entre 16 y 30 días (44%) y el alta hospitalaria con orientación para el control ambulatorio fue el resultado más frecuente de los ingresos. El porcentaje de muertes fue del 2%. Conclusión Las características predominantes son niños varones de 1 a 4 años, que acudió al servicio de salud con la clásica tríada LV: hepatoesplenomegalia, palidez y fiebre prolongada. En este estudio no hubo asociación estadísticamente significativa entre temperatura, precipitación y número de casos, sin embargo, existen matices en los factores ambientales que influyen en la dinámica de transmisión de LV, los cuales varían de región a otra.

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas.

BACKGROUND/OBJECTIVES: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. METHODS: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. RESULTS: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. CONCLUSIONS: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas.

Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.

Metachronous occurrence of nonradiation-induced brain cavernous hemangioma and medulloblastoma in a child with neurofibromatosis type I phenotype.

Cavernous hemangioma (CH) is a sporadic vascular malformation occurring either as an autosomal dominant condition or as a well-known complication of radiation exposure. Medulloblastoma is a primitive neuroectodermal tumor common in children and currently treated with surgical resection, chemotherapy, and radiotherapy. Neurofibromatosis is the most common single-gene disorder of the central nervous system. Posterior fossa malignant tumors in the context of neurofibromatosis type I (NF1) are very infrequent. This is the first documented case of an unusual metachronous occurrence of non-radiation-induced CH and medulloblastoma in a child with NF1 phenotype. We report the case of a 13-month-old boy with café-au-lait skin lesions associated with NF1-like phenotype who underwent surgical resection of a single CH in the temporal lobe due to recurrent seizures. Four years later he presented with signs of raised intracranial pressure associated with a posterior fossa tumor and hydrocephalus, thus requiring gross total resection of the lesion. Histological analysis revealed a medulloblastoma. After being treated with radiotherapy and chemotherapy, he achieved total remission. Six years later a massive recurrence of the tumor was observed and the child eventually died. The interest in this case lies in the rarity of NF1-like phenotype associated with a non-radiation-induced brain CH and medulloblastoma in a child.

[Giant internal carotid artery aneurysm simulating pituitary adenoma]. / Aneurisma gigante de carótida interna simulando macroadenoma de hipófise.

Giant aneurysm projected into the sellar region is a rare cause of hypopituitarism and is usually associated with atherosclerosis, fibromuscular dysplasia and pituitary radiation therapy. We report the case of a 78-year-old patient presenting a giant internal carotid artery aneurysm disclosed by clinical features of hypopituitarism and cranial nerves compression (optic and abducent). Computed tomographic scans, magnetic resonance images and cerebral angiography were performed and showed the aneurysm. Cerebral angiography confirmed concomitant atherosclerosis and fibromuscular dysplasia. After evaluation of risk/benefit, no surgical treatment was proposed. Replacement endocrine therapy with glucocorticoid and levothyroxine was initiated followed by a satisfactory clinical response.

Aneurisma gigante de carótida interna simulando macroadenoma de hipófise / Giant internal carotid artery aneurism simulating pituitary adenoma

O aneurisma gigante com extensão selar é uma causa rara de hipopituitarismo, e está freqüentemente associado com aterosclerose, displasia fibromuscular ou radioterapia hipofisária. O presente caso é de uma paciente de 78 anos com aneurisma gigante de carótida interna esquerda, somente diagnosticado devido a quadro de pan-hipopituitarismo e síndrome de nervos cranianos (compressão dos nervos abducente e ópticos). A etiologia foi definida após tomografia computadorizada, ressonância nuclear magnética e arteriografia cerebral compatíveis com aneurisma. Ficou demonstrada associação com aterosclerose e displasia fibromuscular pela arteriografia. Não foi realizado tratamento cirúrgico após avaliação de risco/benefício. Obteve-se melhora clínica significativa após instituição de reposição hormonal com glicocorticóide e levotiroxina.