Circumscribed astrocytic gliomas: Contribution of molecular analyses to histopathology diagnosis in the WHO CNS5 classification

The newest revision of the WHO classification of tumors of the central nervous system, also known as WHO 5th edition, introduces substantial changes, especially within the glial tumor category and separates adult-type and pediatric-type glial tumors into different categories for the first time. In addition, another category of glial tumors, “Circumscribed Astrocytic Gliomas” were also created. This group includes pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, astroblastoma, and the highly nebulous novel entity high-grade astrocytoma with piloid features. We present a brief and critical review of the pathological and molecular characteristics of these often well-demarcated tumors that can occur in adults as well as in the pediatric population.

Síndrome diencefálico en un niño con desnutrición crónica e hiperactividad / Diencephalic syndrome in a child with chronic malnutrition and hyperactivity

El síndrome diencefálico es una causa infrecuente de desnutrición. Se produce por la disfunción del hipotálamo y está asociado a tumores del encéfalo. Los pacientes presentan una grave y progresiva pérdida de peso, aunque el apetito y la ingesta calórica son, por lo general, adecuados. Característicamente, los síntomas neurológicos son tardíos, lo que retrasa la sospecha diagnóstica. Se presenta a un paciente de 2 años y 6 meses de edad con desnutrición crónica grado II, derivado con diagnóstico presuntivo de enfermedad celíaca con mala adherencia y fracaso del tratamiento. Durante la internación, se arribó al diagnóstico de síndrome diencefálico secundario a un astrocitoma pilocítico grado I.

Diencephalic syndrome is an infrequent cause of malnutrition. It is produced by a malfunctioning hypothalamus, and it is related to encephalic tumors. Patients present a serious and progressive weight loss although the appetite and calorie intake are, usually, adequate. Neurological symptoms typically have a late appearance, delaying diagnostic suspicion. We present a patient aged 2 years and a half with grade II chronic malnutrition, referred with presumptive diagnosis of celiac disease, with poor adherence and treatment failure. During hospitalization, diagnosis of diencephalic syndrome secondary to grade I pilocytic astrocytoma was reached.

Posterior Fossa Lesions– An Experience Of 32 Cases Over 2 Years

INTRODUCTION- 1 Posterior fossa tumours are common in paediatric population ; however their occurrence in adults is not rare. They form a major cause of morbidity and mortality in either population. Some of these tumours like pilocytic astrocytomas are rewarding, others, like medulloblastomas may have a poor outcome. This study aims to analyse the epidemiology and surgical outcomes of posterior fossa lesions. MATERIALS AND METHODS – This is a retrospective study done at Dr. B.R.A.M. Hospital between April 2016 and June 2018. It included 32 patients with posterior fossa lesions.Cerebellopontine angle lesions- schwannomas, epidermoids were excluded. Only lesions involving the cerebellum or occupying the fourth ventricle were included in the study. Their surgical outcome in terms of complications and mortality were analysed. RESULTS-Thirty –two patients, in the age group of 2years to 68 years were included in the study. Cerebello-pontine angle lesions were excluded. Only lesions involving the cerebellum or occupying the fourth ventricle were included in the study. Most common lesion was medulloblastoma, followed by pilocytic astrocytoma, cerebellar abscess, haemangioblastoma, arachnoid cyst, exophytic tectal gliomas, tuberculoma, metastasis, epidermoid. They underwent surgery depending upon the nature of lesion. Overall mortality was found in 9 of 32 patients. Mortality was especially high in medulloblastoma patients (54.55%). CONCLUSIONS – Various lesions may affect the posterior fossa, varying from neoplastic malignant or benign lesions to infective and developmental lesions. Medulloblastoma is a common tumour in the paediatric population and carries a bad prognosis

Massive Calcified Cerebellar Pilocytic Astrocytoma with Rapid Recurrence : A Rare Case

Pilocytic astrocytomas (PAs) are World Heath Organization Grade I tumors and are most common in children. PA calcification is not a common finding and has been reported more frequently in the optic nerve, hypothalamic/thalamus and superficially located cerebral tumors. We present a cerebellar PA in a 3-year-old male patient with cystic components and massive calcification areas. The residual tumor grew rapidly after the first operation, and the patient was operated on again. A histopathological examination revealed polar spongioblastoma-like cells. Massive calcification is not a common feature in PAs and can lead to difficulties in radiological and pathological differential diagnoses.

MRI features of pilomyxoid astrocytomas and pilocytic astrocytomas in hypothalamus/optic chiasma region / 实用放射学杂志

Objective To compare the difference of MRI characteristics of pilomyxoid astrocytomas (PMA)and pilocytic astrocy-tomas (PA)in hypothalamus/optic chiasma region.Methods The MR images and clinical materials of 20 PMAs and 20 PAs proved by pathology were reviewed retrospectively.Imaging characteristics and clinical materials were analyzed,including age,gender, size,the signal characteristics of the tumor,growth,enhancement pattern,hydrocephalus and leptomeningeal dissemination.Results There were statistically significant differences in streaky low signal intensity among the high intensity of T2 WI and leptomeningeal dissemination between PMA and PA (P <0.05).However,no statistically significant differences were found in the other character-istics and clinical materials between the two types of tumors.Conclusion PMA and PA in hypothalamus/optic chiasma region are difficult to make differential diagnosis.The streaky low signal intensity among the high intensity of T2 WI and more frequent lepto-meningeal dissemination are helpful differential features of PMA as compared to PA.

Radiation or Chemotherapy rather than Observation may be a Better Modality after Subtotal Resection for Pilocytic Astrocytoma in Children / 임상소아혈액종양

BACKGROUND: Pilocytic astrocytoma (PA) is a low-grade glioma that occurs primarily in children and young adults. The optimal postoperative treatment modality after subtotal resection (STR) of PAs remains to be elucidated. The aim of this study was to compare the efficacies of different post-STR treatment modalities and to examine the risk factors for the progression of PAs. METHODS: We reviewed the medical records of 91 pediatric PA patients in a single institute during a 30-year period. Kaplan-Meier analysis was used to assess overall survival (OS) and progression-free survival (PFS), and Cox proportional hazard models were used to calculate hazard ratios. RESULTS: The median age of 91 patients was 8.9 years (range, 0.3-17.9). GTR was perfomed, whenever possible. Patients who underwent STR afterwards received either radiotherapy, chemotherapy, or were observed without further treatment, according to clinician preference. In total group, 10-year OS was 97.4% and 10-year PFS was 57.2%. In GTR group (N=33), 10-year OS and PFS was 100%. In STR group (N=49), 10-year OS was 97.7%, while 10-year PFS was 38.6%. STR group underwent following postoperative (PO) modalities; observation (PO-Obs, N=32), radiotherapy (PO-RT, N=10), chemotherapy (PO-CTx, N=7). The 10-year PFS rate was higher in patients who received postoperative treatment (either PO-RT or PO-CTx) than in patients who received PO-Obs (62.5% vs 27.0%, P=0.039). In multivariate analysis for STR group, PO-CTx (Hazard ratio (HR)=0.20, P=0.035) and PO-RTx (HR=0.13, P=0.008) were superior to observation, respectively. CONCLUSION: Radiation and chemotherapy are better post-STR treatment modalities than observation for pediatric PA patients.

Radiation or Chemotherapy rather than Observation may be a Better Modality after Subtotal Resection for Pilocytic Astrocytoma in Children / 임상소아혈액종양

BACKGROUND: Pilocytic astrocytoma (PA) is a low-grade glioma that occurs primarily in children and young adults. The optimal postoperative treatment modality after subtotal resection (STR) of PAs remains to be elucidated. The aim of this study was to compare the efficacies of different post-STR treatment modalities and to examine the risk factors for the progression of PAs.METHODS: We reviewed the medical records of 91 pediatric PA patients in a single institute during a 30-year period. Kaplan-Meier analysis was used to assess overall survival (OS) and progression-free survival (PFS), and Cox proportional hazard models were used to calculate hazard ratios.RESULTS: The median age of 91 patients was 8.9 years (range, 0.3-17.9). GTR was perfomed, whenever possible. Patients who underwent STR afterwards received either radiotherapy, chemotherapy, or were observed without further treatment, according to clinician preference. In total group, 10-year OS was 97.4% and 10-year PFS was 57.2%. In GTR group (N=33), 10-year OS and PFS was 100%. In STR group (N=49), 10-year OS was 97.7%, while 10-year PFS was 38.6%. STR group underwent following postoperative (PO) modalities; observation (PO-Obs, N=32), radiotherapy (PO-RT, N=10), chemotherapy (PO-CTx, N=7). The 10-year PFS rate was higher in patients who received postoperative treatment (either PO-RT or PO-CTx) than in patients who received PO-Obs (62.5% vs 27.0%, P=0.039). In multivariate analysis for STR group, PO-CTx (Hazard ratio (HR)=0.20, P=0.035) and PO-RTx (HR=0.13, P=0.008) were superior to observation, respectively.CONCLUSION: Radiation and chemotherapy are better post-STR treatment modalities than observation for pediatric PA patients.

A Case of Huge Pilocytic Astrocytoma Causing Eyeball Subluxation

PURPOSE: To report a relatively rare case of huge pilocytic astrocytoma of the optic nerve and optic chiasm causing eyeball subluxation. CASE SUMMARY: An eight-year-old male presented with proptosis and visual loss in the left eye for one year. The radiological findings showed a 2.9 x 2.7 x 4.2-cm tumor on the left optic nerve and optic chiasm. For diagnosis and treatment, the patient underwent tumor resection and enucleation. Pathohistological analysis of the tumor specimen revealed pilocytic astrocytoma, which is classified by the World Health Organization as a grade I astrocytic tumor. CONCLUSIONS: Astrocytoma is a tumor of the brain that affects children more often than adults. In general, gross-total resection of pilocytic astrocytoma is expected to be curative due to the non-invasive feature of the tumor. Considering pilocytic astrocytoma as differential diagnosis of orbital tumor in children with symptoms of rapidly progressive proptosis and decreased visual acuity is important because occurrence in the optic nerve and optic chiasm is possible.

Ganglion cells in circumscribed astrocytic tumors: possible implication in classification and prognosis / Implicação da presença de células ganglionares na classificação e evolução de tumores astrocíticos circunscritos

INTRODUCTION: Glial and neuroglial cell neoplasms comprise pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA) and ganglioglioma (GG), which share various similarities, though PA has better prognosis. As ganglion cells (GC) may be scarce in GG and these gangliogliomas may recur or progress to grade III, an accurate diagnosis is essential. OBJECTIVES: The aim was to identify GC and eosinophilic granular bodies (EGB) in PA and PXA, to evaluate its effect on patient’s outcome and compare them with GG. METHODS: A retrospective analysis of radiological, morphological and follow-up aspects (disease free-survival, recurrence and death) of 30 cases (14 PA, 8 PXA, 8 GG). Hematoxylin and eosin (HE) stained sections were reviewed to identify the presence of neoplastic GC and EGB. They were immunostained for synaptophysin (SYN) and neurofilament (NF). Glial fibrillary acidic protein (GFAP) immunostaining was performed in selected cases. RESULTS: Six PA were reclassified as GG due to the presence of GC by HE or immunohistochemistry. Some EGB resembling degenerate GC were also immunostained for SYN/NF and most of them were negative for GFAP. The mean disease-free survival was 62.16 months. Four tumors recurred and one patient died. All PXA had GC, suggesting that they were variants of GG, 4 of which recurred and one patient died. Mean disease-free survival was 69 months. The radiological aspect was predominantly cystic. CONCLUSION: We propose that PA and PXA with GC or with EGB immunopositive for neuronal markers could be variants of GG, and some EGB may represent degenerate GC. However, the presence of GC does not seem to modify the biological behavior of these neoplasms.

INTRODUÇÃO: As neoplasias circunscritas incluem astrocitoma pilocítico (AP), xantoastrocitoma pleomórfico (XP) e ganglioglioma (GG), que compartilham diversas semelhanças, sendo o AP o de melhor prognóstico. Como as células ganglionares (CG) no GG podem ser escassas e os GGs podem recidivar ou evoluir (grau III), é fundamental o diagnóstico preciso. OBJETIVOS: Identificar CG e corpos granulares eosinofílicos (CGE) em AP e XP, avaliar sua implicação na evolução e comparar com o GG. MÉTODOS: Análise retrospectiva dos aspectos radiológicos, morfológicos e evolutivos (tempo livre de doença, recidiva e óbito) de 30 casos (14 AP, oito XP, oito GG). Cortes corados com hematoxilina e eosina (HE) foram revistos para a identificação da presença de CG neoplásicas e CGE. Estes foram imunomarcados para sinaptofisina (SIN) e neurofilamento (NF) e, em casos selecionados, para glial fibrillary acidic protein (GFAP). RESULTADOS: Seis AP foram reclassificados para GG pela presença de CG (HE ou imunomarcação). Alguns CGE, semelhantes às CG degeneradas, também imunomarcaram para SIN/NF, a maioria sendo negativa para GFAP. O tempo médio livre de doença foi de 62,16 meses. Quatro tumores recidivaram; um deles evoluiu para óbito. Todos os XP possuíam CG, sugerindo que são variantes de GG, dos quais quatro recidivaram (um óbito). O tempo médio livre de doença foi de 69 meses. O aspecto radiológico foi predominantemente cístico. CONCLUSÃO: Sugerimos que AP e XP com CG ou CGE imunopositivos para marcadores neuronais possam ser variantes de GG e alguns CGE representem CG degeneradas; entretanto, a presença de CG ganglionares parece não modificar o comportamento biológico dessas neoplasias.

Astrocitoma pilocítico da região selar/suprasselar determinando manifestações endócrinas / Pilocytic astrocytoma of sellar/suprasellar region determining endocrine manifestations

Pilocytic astrocytoma (PA) is a grade I glial neoplasm arising mainly in the cerebellum of children. Herein, the authors report a case of PA in a 21 year-old male patient, who presented headache, vomiting and delayed pubertal development. Serum level of cortisol and testosterone corresponded to 32.8 ug/dl and 0.19 ng/ml, respectively. The computed tomography/magnetic resonance (CT/RM) imaging showed an expansive process compromising suprasellar/hypothalamic region and determining hydrocephalus. The patient underwent resection of the process. Histological evaluation revealed a glial neoplasm constituted by loose glial tissue, small microcysts, areas of dense piloid tissue and Rosenthal fibers. The neoplastic cells were immunoreactive for glial fibrillary acidic protein (GFAP) and negative for chromogranin and synaptophysin. The diagnosis of PA was then established.

O astrocitoma pilocítico (AP) é uma neoplasia glial grau I encontrada principalmente no cerebelo de crianças. Os autores relatam um caso de AP em paciente masculino, 21 anos de idade, que apresenta cefaleia, vômitos e retardo do desenvolvimento puberal. Os níveis séricos de cortisol e testesterona corresponderam a 32,8 ug/dl e 0,19 ng/ml. A tomografia computadorizada/ressonância magnética (TC/RM) identificaram um processo expansivo que comprometia a região suprasselar/hipotalâmica e determinava hidrocefalia.O paciente foi submetido à ressecção do processo. À microscopia, foi identificada uma neoplasia glial constituída por tecido glial frouxo, pequenos microcistos, áreas de tecido piloide denso e fibras de Rosenthal. As células neoplásicas foram imunopositivas para glial fibrillary acidic protein (GFAP) e negativas para cromogranina e sinaptofisina. O diagnóstico de AP foi, então, estabelecido.

A Case of Malignant Transformation of Juvenile Pilocytic Astrocytoma with Neurofibromatosis Type 1 / 대한소아신경학회지

Pilocytic astrocytoma (PA) is a World Health Organization (WHO) grade I tumor typically affecting children and young adults. In general, surgical resection for PA is thought to be curative, and tumor recurrence or malignant transformation is relatively rare. Herein, we report an extremely rare case of a malignant transformation of PA. Five years prior, the patient underwent subtotal resection for PA in the left suprasellar area and left side brain parenchyma of the third ventricle, followed by gamma knife radiosurgery for remnants of the tumor. Four years after surgery, recurrent PA developed, and surgery was performed through an anterior interhemispheric transcallosal approach. One year after surgery, a rapidly growing tumor in the left basal ganglia and hypothalamus was discovered, and subtotal removal was performed. The histological diagnosis was glioblastoma. To the best of our knowledge, malignant transformation of PA has not been reported in Korea. Through review of the literature, we found malignant transformation to be limited solely to patients treated with radiotherapy, which is an observation that should be validated in future studies.

Cerebellar Pilocytic Astrocytomas with Spontaneous Intratumoral Hemorrhage in Adult

Cerebellar pilocytic astrocytomas (PAs) are benign gliomas predominantly found in the pediatric population. Intracranial hemorrhages are extremely rare in initial presentations of cerebellar PAs. There are no reports in the medical literature of adult cerebellar PA cases presenting with intratumoral hemorrhage. We report 2 cases of adult cerebellar pilocytic astrocytomas with intratumoral hemorrhage. The first case is a 37-year-old woman presenting with severe headache, nausea, and vomitting. Computed tomography demonstrated an acute hemorrhage adjacent to the right cerebellar hemisphere and hydrocephalus. Magnetic resonance imaging (MRI) revealed a cerebellar vermian tumor with the hemorrhage as a mixed isointense area in the T2-weighted image, and as a mixed hyperintense area in the contrast-enhanced T1-weighted image. The second case is a 53-year-old man presenting with headache for 3 weeks. MRI revealed a cerebellar hemispheric tumor with the hemorrhage as a mixed hyperintense area. It had a cystic mass with a heterogeneous enhanced mural nodule in the gadolinium-enhanced T1-weighted image and a fluid-fluid level within the cyst in the T2-weighted image. Both of them underwent radical resections of their respective lesions. Histological examination of the specimens revealed typical astrocytoma, including a hemorrhagic portion. Both patients recovered postoperatively and continue to do well at present. The medical literature on hemorrhagic cerebellar PAs is also reviewed.

H magnetic resonance spectroscopy assessment of the temozolomide response in peaditric pilocytic astrocytomas

Pilocytic Astrocytomas (PA) treatment and prognosis is variable depending on location. ¹H Magnetic Resonance Spectroscopy (MRS) is used to characterize tumor metabolism providing additional information to the Magnetic Resonance Imaging (MRI) evaluation assessing the therapy response. This study was designed to evaluate brain metabolic changes that result from Temozolomide (TMZ) administration on pediatric PA using MRS. Twenty children with PA were studied. We performed MRI and MRS pretreatment and after 12 months of therapy on a 3.0 Tesla scanner in order to monitor the chemotherapy response to 5-day treatment with oral TMZ (200 mg/mt² x day) given every 28 days for 12 cycles. Multivoxel Proton Spectroscopic Imaging was performed using a Point Resolved Spectroscopy sequence (PRESS). Analysis of Variance (ANOVA) was applied to the results in order to evaluate the possible statistical differences. Pairwise comparisons with Bonferroni correction test were assessed in order to verify the differences among ratio means. It was observed a significant decrease in Cho/Cr ratio (p<0.05) and a significant increase in NAA/Cr ratio (p<0.05) while TMZ therapy was taking place. These results are linked with tumor size reduction (r = 0.95, p< 0.05) detected by MRI. Results show MRS can detect early tumor reaction to therapy prior to MRI. Therefore, MRS could provide a useful tool to monitor the answer of pediatric PA to TMZ. The link between metabolic markers changes due to TMZ treatment assessed by MRS and the tumor volume reduction may also provide a fertile ground to developa TMZ-based therapy for pediatric PA and to predict its efficacy to improve PA’s response to treatment.

Unusual dissemination patterns of low-grade astrocytomas in childhood

CONTEXT: Low-grade astrocytomas are intracerebral lesions of relatively high frequency in the under-18 pediatric population. They often present indolent behaviour, and complete surgical resection is the choice treatment. In cases where the surgery is not possible, chemotherapy and radiotherapy may be used. Medical reports do not recommend examination of the spinal cord at diagnosis or during treatment, since the risk of dissemination of the lesion to the spine is minimal according to medical experience. We describe here four cases of children with low-grade astrocytoma with aggressive dissemination to the neuroaxis.

CONTEXTO: Gliomas de baixo grau de malignidade são lesões intracerebrais relativamente freqüentes na população pediátrica menor de 18 anos de idade. Eles freqüentemente são indolentes em seu comportamento e a ressecção cirúrgica completa é o tratmento de eleição. Nos casos em que a cirurgia não é possível, a quimioterapia e a radioterapia podem ser utilizadas. Relatos da literatura não recomendam a avaliação radiológica da coluna espinhal ao diagnóstico ou durante o tratamento, desde que o risco de disseminação destas lesões para a coluna é considerado mínimo. Descrevemos aqui quatro casos de crianças com gliomas de baixo grau de malignidade com disseminação agressiva para o neuroeixo.

Intracranial Hemorrhage from Pilocytic Astrocytoma in Pons

We report a case of brain-stem glioma with hemorrhage. A 24-year-old female presented with a 2-month history of headache, vomiting, right hemiparesis. Magnetic resonance image showed a 4X2.5cm sized mass with subacute stage hemorrhage in the left cerebellopontine angle. The mass and hemorrhage was surgically removed and pathological findings were consistent with pilocytic astrocytoma with recent hemorrhage. The patient discharged with mild neurological deficit.

MRI Diagnosis of Cystic Pilocytic Astrocytoma / 实用放射学杂志

Objective To investigate the diagnostic value of cystic pilocytic astrocytoma by MRI.Methods MRI features of cysticpilocytic astrocytoma proved pathologically in 26 patients were reviewed retrospectively.The location,morphology and signal characteristics of the tumors were analyzed.Results Among 26 cases the tumors localized in cerebellum(n=20) and cerebrum(n=6).This tumor could be divided into simple cystic and cystic type with node on the wall.Conclusion Cystic pilocytic astrocytoma usually occur in children andadolescents with typical MRI features.MRI features in combination with clinical manifestation,it is possible to diagnose cystic pilocyticastrocytoma correctly before operation.