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.

Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

Pigmented variant of pleomorphic xanthoastrocytoma - A rare long-term epilepsy associated neoplasm

Pleomorphic xanthoastrocytoma (PXA) is an uncommon, long-term epilepsy associated tumor of young adults. Its pigmented variant is exceedingly rare, with only five previously reported cases on record. We report the sixth case of pigmented PXA in a 24-year-old lady presenting with long-standing seizures. The MRI revealed a solid cystic lesion located in the right medial temporal lobe. Histopathologically, the superficially located tumor showed typical features of PXA with melanin-laden astrocytic component and was negative for V600E-mutant BRAF. The histogenesis is discussed.

Composite pleomorphic xanthoastrocytoma-ganglioglioma; assessing and addressing the dilemma of differential expression of neuronal markers: Case report with diagnostic perspective

We report the case of a 5-year-old male child presenting with seizures for 4 months. Magnetic resonance imaging (MRI) revealed a cortical-based solid cystic lesion in the right parietal lobe. Histopathological examination showed a tumour comprised of spindled glial fibrillary acid protein (GFAP) positive neoplastic cells interspersed with bizarre pleomorphic cells showing nuclear pseudoinclusions and intermingled dysplastic ganglion cells variably immunopositive for synaptophysin, chromogranin, Neu-N and immunonegative for neuron filament protein (NFP). This report highlights the occurrence of the rare composite pleomorphic xanthoastrocytoma-ganglioglioma and the vagaries of immunohistochemical analysis in highlighting neuronal differentiation in such a case setting. In addition, to the best of our knowledge this is the youngest patient till date to present with this entity.

MRI analysis of pleomorphic xanthoastrocytoma / 实用放射学杂志

Objective To investigate the MRI features of pleomorphic xanthoastrocytoma (PXA).Methods 1 5 pathologically confirmed PXA cases were analyzed retrospectively.Clinical history and imaging features including location,size,shape,signal intensi-ty,enhancement and surrounding changes of those lesions were analyzed.Results All 1 5 cases were supratentorial and solitary le-sions,of which 9 lesions located in temporal lobe(60%).14 lesions contacted with the leptomeninges,and 1 lesion contacted with lat-eral ventricle wall.All lesions were solid-cystic,with different proportion of solid/cystic components.8 large lesions were predomi-nantly cystic(53.3%),3 small lesions were predominantly solid(20%),and 4 lesions had roughly equal cystic and solid proportions (26.7%).Solid components showed iso-intense or mild hypo-intense on T1 WI,iso-intense or mild hyper-intense on T2 WI,and signif-icant enhancement with contrast.Cyst fluid showed slightly hyper-intense in some cases.Cyst wall or septa enhancement was seen in 7 cases,and leptomeningeal enhancement was seen in 8 cases.Conclusion The MRI features of PXA are the characteristic of suprat-entorial solid-cystic lesions commonly seen in temporal lobe and contacting with leptomeninges.The typical features include “cyst with mural nodule”and “multiple cysts with irregular eccentric nodule”with significant enhancement of solid component and some cyst wall.MRI features of PXA is valuable in diagnosis and differential diagnosis of PXA.

Pleomorphic xanthoastrocytoma with anaplastic features: A case report.

Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm. Recently, several patterns with relatively poor prognosis have been recorded and a new concept of “PXA with anaplastic features” has been proposed. The present case is about a 9-year–old girl who presented with symptoms of recurrent headache, seizures and poor academic performance. MRI revealed left frontoparietal irregular enhancing mass lesion with callosal involvement and right mid-brain arteriovenous malformation. Clinical and radiological examination was suggestive of a high grade glial neoplasm/PNET. A diagnosis of high grade glial neoplasm was rendered on the squash smears submitted for frozen sections based on the presence of spindle cells, admixed with pleomorphic bizarre, giant cells with multilobated nuclei showing few atypical mitosis and abundant eosinophilic cytoplasm. Frontal craniotomy with debulking of the tumor was performed and permanent sections revealed a biphasic glial neoplasm with spindle cells arranged in fascicles admixed with bizarre multinucleated giant cells showing abundant vacuolated and lipidized cytoplasm, nuclear hyperchromasia with intranuclear inclusions. Eosinophilic granular bodies, mitosis of 7/10 HPF, micro vascular proliferation, necrosis and invasion into the underlying brain parenchyma were noted. With these histomorphological fi ndings a diagnosis of pleomorphic xanthoastrocytoma with anaplastic features was rendered.

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.

Prognostic Factors and Therapeutic Outcomes in 22 Patients with Pleomorphic Xanthoastrocytoma

OBJECTIVE: Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor classified as WHO II. It is generally benign, but disease progression and malignant transformation have been reported. Prognostic factors for PXA and optimal therapies are not well known. METHODS: The study period was January 2000 to March 2012. Data on MR findings, histology, surgical extents and adjuvant therapies were reviewed in twenty-two patients diagnosed with PXA. RESULTS: The frequent symptoms of PXA included seizures, headaches and neurologic deficits. Tumors were most common in the temporal lobe followed by frontal, parietal and occipital lobes. One patient who died from immediate post-operative complications was excluded from the statistical analysis. Of the remaining 21 patients, 3 (14%) died and 7 (33%) showed disease progression. Atypical tumor location (p<0.001), peritumoral edema (p=0.022) and large tumor size (p=0.048) were correlated with disease progression, however, Ki-67 index and necrosis were not statistically significant. Disease progression occurred in three (21%) of 14 patients who underwent GTR, compared with 4 (57%) of 7 patients who did not undergo GTR, however, it was not statistically significant. Ten patients received adjuvant radiotherapy and the tumors were controlled in 5 of these patients. CONCLUSION: The prognosis for PXA is good; in our patients overall survival was 84%, and event-free survival was 59% at 3 years. Atypical tumor location, peritumoral edema and large tumor size are significantly correlated with disease progression. GTR may provide prolonged disease control, and adjuvant radiotherapy may be beneficial, but further study is needed.

Rapid Progression of Early Delayed Radiation Effect in Pleomorphic Xanthoastrocytoma

Early delayed radiation effects are known to occur within several months after completing radiotherapy for brain tumors. We present marked changes of magnetic resonance imaging (MRI) scan that occurred one month after radiotherapy in a patient with a pleomorphic xanthoastrocytoma, which was eventually diagnosed as an early delayed radiation effect. Such an early development of dramatic MRI change has not been reported in patients treated with radiotherapy for pleomorphic xanthoastrocytomas.

Pleomorphic Xanthoastrocytoma with an Intracystic Hemorrhage: A Case Report and Literature Review

Pleomorphic xanthoastrocytoma (PXA) has been considered as a low grade tumor of adolescents and young adults. Although this tumor often shows cystic component, the hemorrhage within the cyst is extremely rare. The authors report a rare case of cystic PXA with a hemorrhage within the cyst and the mural nodule in the left frontal lobe. A 64-year-old male presented with a week history of the right side hemiparesis. After gross total resection of the tumor, the patient was fully recovered from neurological deficit. It is suggested that this typically benign tumor could be presented with hemorrhage, causing a rapid neurological deterioration. Prompt surgical intervention, especially total removal of the tumor can provide an excellent functional recovery.

Analysis of Comparative Genomic Hybridization in Pleomorphic Xanthoastrocytoma / 上海第二医科大学学报

Objective To detect genetic alterations in pleomorphic xanthoastrocytoma (PXA), and to investigate the mechanism of development of this neoplasm. Methods Three patients with PXA were studied. Comparative genomic hybridization (CGH) was performed to study chromosomal imbalances in PXA. Using immunohistochemical analysis, the expression of EGFR was detected in PXA. Results Using CGH analysis, genetic imbalance was detected on at least one chromosome for each case. One patient revealed multiple genetic alterations, including gains of 2p14-pter, 4p15-pter, 7p21-qter, 11q24-qter, 12 and 15q14-qter,as well as losses of 8p11.2-pter, 9p11-p23, 10p12-pter, and 13q14-qter. This patient experienced tumor recurrence and died one year later. Gain on Chromosome 7 and loss on Chromosome 8p were demonstrated in 2 of the 3 patients. Immunohistochemically, no EGFR positive reaction was found in all cases. Conclusion Detection of genetic alterations is very important in understanding the pathogenesis of PXA.

Pleomorphic Xanthoastrocytoma: Report of 3 Cases

Pleomorphic xanthoastrocytoma(PXA) is a rare neoplasm with favorable prognosis despite of its aggressive histological features. The authors report three cases of pleomorphic xanthoastrocytomas. The masses were in the temporal or parietal lobe of children or adolscence and presented as complex partial seizures. Total removal of mass was performed in all three cases and the seizure was abscent postoperatively. It is important to differentiate of pleomorphic xanthoastrocytoma from other malignant brain tumors and identify this type of glioma as a distinct entity.

Coexistence of Arteriovenous Malformation and Pleomorphic Xanthoastrocytoma: Case Report

Coexistence of an intracerebral vascular malformation and a brain tumor is an infrequent occurrence. Seven such cases have been reported in the literatures. We report a case of coexistence of arteriovenous malformation and pleomorphic xanthoastrocytoma. A 29-year-old woman was admitted with presentation of headache for 20 days. MR images showed an intra-axial mass in the right lateral ventricle, which was coexisted with arteriovenous malformation in the right frontal region. Pathological findings indicated that the intracranial mass was pleomorphic xanthoastrocytoma. This case raises several questions about plausible pathogenesis for coexistence of arteriovenous malformation and pleomorphic xanthoastrocytoma: that is, the coexistence of two separate lesions, the evolution of one lesion into the other. The authors report an unusual case of pleomorphic xanthoastrocytoma coexisted with arteriovenous malformation with review of literatures.

Cerebellar Pleomorphic Xanthoastrocytoma in an Infant: Case Report

Pleomorphic xanthoastrocytoma is a rare type of glioma and usually occurs in the superficial cerebral hemisphere of the patients under the age of 30 years. We report a case of pleomorphic xanthoastrocytoma in the cerebellum of a 3-month-old infant. This is an unusual case in view of location and age. The literatures concerning the clinicopathological aspects of this unusual pleomorphic xanthoastrocytoma are reviewed.

Pleomorphic Xanthoastrocytomas: Report of Three Cases

We report three cases of patient with pleomorphic xanthoastrocytoma(PXA). PXA is a clinicopathologically distinct variant of cerebral astrocytoma which is a low-grade leptomeningeal glioma affecting under the age of 30 years. This tumor has a favorable prognosis, but histological and neuroradiological findings suggest malignant brain tumor. Occasionally these may be confused with malignant gliomas. Clinical features from our three patients were manifestation of increased intracranial pressure and all cases were under the age of 30 years and females. Two patients had superficial location in the right frontal and left temporal respectively, but remaining one(case 2) which was associated with arteriovenous malformation in the left frontal region was in the right lateral ventricle. The intraoperative histological evidence by frozen biopsy suggested glioblastoma or anaplastic astrocytoma in all cases which confirmed to be PXA by postoperative histological examination. Two cases which had been resected subtotally were followed by cranial irradiation without therapeutic efficacy. Optimal management of PXA is primary surgical resection to reduce recurrence of tumor and to secure long-term survival. Therefore, differentiation of PXA from malignant brain tumors and intraoperative diagnosis of PXA is imperative to treat PXA effectively.

Pleomorphic Xanthoastrocytoma: Report of 2 Cases

Pleomorphic xanthoastrocytoma is a recently characterized neoplasm with relatively favorable prognosis despite aggressive histological features. Two cases of pleomorphic xanthoastrocytoma involving the left temporal lobe are reported, both occurring in adolescents. The tumor is considered to arise from the subpial astrocytes of the superficial cortex. Electron microscopic examination and immunoperoxidase stains for glial fibrillary acidic protein(GFAP) are helpful in making a definitive histologic diagnosis. In contrast to malignant gliomas, pleomorphic xanthoastrocytoma does not appear to require aggressive postoperative radiation therapy or chemotherapy. Therefore, It is important to recognize and identify this type of glioma as a distinct entity.

Pleomorphic Xanthoastrocytoma in a 58-year-old Woman: A case report

A case of left parietal pleomorphic xanthoastrocytoma that occurred in a 58-year-old woman is reported clinicopathologically. Histopathologic diagnosis of pleomorphic xanthoastrocytoma was made because of the unique pleomorphic histologic features, positive glial fibrillary acidic protein in immunohistochemical staining. The flow cytometric analysis reveals DNA aneuploidy and relatively high S-phase fraction. The pleomorphic xanthoastrocytoma is considered as a special subgroup of glioma on the basis of superficial cortical location, GFAP expression, marked cellular atypia, xanthomatous cells, and relatively favorable prognosis.

Pleomorphic Xanthoastrocytoma: Report of Three Cases

Pleomorphic xanthoastrocytoma is known as a rare specialized type of cerebral astrocytoma, which occurs mainly in the temporal loe of the brain in young ages in spite of marked pleomorphism with multinucleated giant cells, lipid-laden xantomatous cells, rich reticulin net-works, and the demonstration of glial fibrillary acidic protein, the prognosis is usually favorable. The authors report three cases of pleomorphic xanthoastrocytoma which were presented with headache and review the past literature.

Spinal Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma is a rare tumor, presenting superficially over the cerebral hemispheres of young subjects. We report a case of Pleomorphic xanthoastrocytoma of the cervical cord in view of its unusual location. The patient is a 20-year-old female, presenting with left neck pain radiating to the left shoulder one month before the admission. Magnetic resonance imaging revealed a high signal lesion in the upper cervical cord lower brainstem in T2 weighted image. On operation, intramedullary tumor was present and it was relatively well delineated. Near-total removal of the spinal cord mass was done. Microscopically, the tumor was composed of pleomorphic astrocytes, which were spindle-shaped with cytoplasmic processes and hyperchromatic nuclei. Other cells were round with vesicular nuclei and abundant eosinophilic cytoplasm. A few giant cells were seen. Despite the marked pleomorphism, mitosis or necrosis was not encountered. Scattered foamy cells were also seen, which showed negative staining in GFAP immunostaining in contrast to other GFAP-positive tumors cells.

Pleomorphic Xanthoastrocytoma: A Case Report

Pleomorphic xanthoastrocytoma is histologically characterized by marked cellular pleomorphism of lipid-laden neoplastic astrocytes and bizarre giant cells showing mitotic figures and high cellularity. Inspite of its ominous-looking microscopic features, howerver, the prognosis is usually favorable. This tumor develops mainly in the supratentorial area of young people and frequently involves the leptomeninges. We experienced a case of pleomorphic xanthoastrocytoma in 18 year-old-male. In addition to the cellular pleomophism, the prominent reticulin fibers surround the individual tumor cells or the tumor cells nests. Immunohistochemical staining and electron microscopy revealed glial fibrillary acidic protein(GFAP) expression and pericytoplasmic basal lamina in the tumor cells.