Multicentric Astrocytomas of the Optic Chiasm, Brain Stem and Spinal Cord

Autopsy was performed on a 52 year old man with a 20-year history of neurological symptoms. At autopsy, both a brain stem tumor and a spinal cord tumor were found. These showed the features of pilocytic astrocytoma histologically. A pilocytic astrocytoma was also found in the optic chiasm upon microscopical examination. These three tumors were thought to be multicentric astrocytomas, because there was no continuity among them and no evidence of dissemination or metastasis by any pathway. From a review of the literature, the present case is considered to be an exceedingly rare one because of the multicentric sites of occurrence. Acta Pathol Jpn 39: 664 669, 1989.     

Clinicopathological and immunohistochemical features of three pilomyxoid astrocytomas: Comparative study with 11 pilocytic astrocytomas

Pilomyxoid astrocytoma, first described by Tihan et al ., was recently included as an established variant of pilocytic astrocytoma in the World Health Organization classification of CNS tumors. Histologically, it much resembles pilocytic astrocytoma, but monomorphic myxoid tumor of pilocytic cells with prominent angiocentric growth pattern without Rosenthal fibers or eosinophilic granular bodies is characteristic of pilomyxoid astrocytoma. Pilomyxoid astrocytoma is thought to be more aggressive with more frequent local recurrence as well as cerebrospinal spread. The authors recently encountered a case of pilomyxoid astrocytoma, therefore the purpose of the present study was undertake a retrospective review of pilocytic astrocytomas previously diagnosed during the past 10 years. Consequently, two of them were found to have histological features suggestive of pilomyxoid astrocytoma and both involved multiple recurrence, suggesting aggressive behavior in comparison to pilocytic astrocytoma. Therefore, knowledge of this entity is essential to surgical pathologists and clinicians for patient management.     

An unusual and misleading form of pilocytic astrocytoma

Pilocytic astrocytoma is histologically characterized by a biphasic pattern. We report a myxoid form of frontocallosal pilocytic astrocytoma in a 13-year-old girl. MRI showed a relatively well-defined tumor with necrosis and ring-like zone of contrast enhancement. Histological examination showed a monophasic tumor composed of piloid cells on a myxoid background corresponding to a pilomyxoid astrocytoma. This unusual form of pilocytic astrocytoma can be mistaken for a high grade infiltrating glioma. Pilomyxoid astrocytoma is more aggressive than classic pilocytic astrocytoma and has to be distinguished from it.     

May 1999--16 year old male with an unexpected MRI finding.

Four years after resection of a supratentorial pilocytic astrocytoma this 16-year-old boy displayed widespread leptomeningeal seeding. Although the primary tumor lacked contrast enhancement, the multiple metastatic nodules were markedly contrast enhancing. Both the initial and disseminated tumor were consistent with a pilocytic astrocytoma. He was treated with vincristin and carboplatinum and the tumor was stable up to Dec. 1998. Dissemination of low-grade intracranial astrocytoma in children occurs in only 4%. It is not a sign of malignancy.The present case is similar to previously published cases. The prognosis of these patients might be quite favorable when treated with radiotherapy and/or chemotherapy.     

毛细胞黏液样型星形细胞瘤的临床病理学观察

目的探讨毛细胞黏液样型星形细胞瘤的临床病理学特点。方法观察3例毛细胞黏液样型星形细胞瘤的光镜形态,采用EnVision法免疫组织化学标记胶质纤维酸性蛋白（GFAP）、CD34、Ki-67,并结合文献复习分析其生物学行为。结果3例均为女性,年龄分别为9个月、10岁和19岁。1例发生于视交叉,2例发生于第三脑室（近鞍区部位）。镜下由双极性的梭形细胞组成,间质内含有大量的黏液。肿瘤内的血管明显增生,部分区域内瘤细胞显示以血管为中心性生长。3例切片内均未见到经典型毛细胞星形细胞瘤中的双相性形态,也未见Rosenthal纤维和嗜酸性颗粒小体。免疫标记显示,瘤细胞强阳性表达GFAP,瘤细胞增殖指数（Ki-67）〈1％。CD34标记显示清晰瘤内增生的血管。结论毛细胞黏液样型星形细胞瘤是毛细胞星形细胞瘤的一种独特亚型,在组织学上与毛细胞星形细胞瘤有不同之处,临床上较毛细胞星形细胞瘤更具有侵袭性。部分病例也可发生于儿童和青少年。GFAP标记有助于该瘤的诊断和鉴别诊断。     

August 2004: 64-year-old man with intermittent paresthesia of the abdomen and of the legs

A 64-year-old-man had a 2-year history beginning with a sense of abdominal "constriction." Additional slowly rising symptoms, such as tingling of the legs, mild gait ataxia and painful micturition, led to MRI investigation of the spinal cord. A fusiform enlargement of the cord extending from T5 to T8 was shown. The space occupying lesion infiltrated diffusely the spinal cord. A contrast medium enhancing exophytic tumor pellet was approached via a 2-level laminoplasty and resected. Biopsies were taken from different exophytic tumor areas whereas the intramedullary part was spared. The histologic examination confirmed the typical pattern of a pilocytic astrocytoma in all specimens. In our surgical experience with 226 intramedullary tumors and with 117 patients affected by intracranial pilocytic astrocytoma this case is unique because of its combination of tumor location, growth pattern and age of the patient.     

Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: A study of 48 cases

Pilocytic astrocytoma is an infrequently encountered, generally low-grade neoplasm. No study has extensively looked at both cyclin Dl and MIB-1 labeling indices in pilocytic astrocytoma and their relation to clinical outcome. This study retrospectively examines the clinicopathologic features of 48 patients with pilocytic astrocytoma including MIB-1 (cell proliferation marker) and cyclin Dl (protein that regulates progression from G1 to S phase of the cell cycle) immunohistochemistry. Of 48 patients (27 females and 21 males; mean age, 12.7 years; age range, 2 to 57 years), 26 initially underwent gross total resection; 17, subtotal resection; four, biopsy alone; in one patient, the extent of tumor resection was unknown. Histological features observed included Rosenthal fibers (83.3%), granular bodies (75%), vascular sclerosis (56.2%), vascular proliferation (56.2%), prominent nuclear pleomorphism (14.6%), necrosis (10.4%), and identifiable mitotic figures (2.1%). MIB-1 labeling indices (n = 45) (positive staining tumor nuclei per 1,000 nuclei evaluated) ranged from 0 to 3.5% (mean, 0.6%); seven tumors had a labeling index greater than 1.0%. Cyclin D1 labeling indices (n = 45) ranged from 0 to 0.8% (mean, 0.1%). Most tumors (N = 29, 66.7%) had no immunostaining. At last known follow-up, 27 patients were alive with no evidence of disease (mean, 49.2 months), 17 patients were alive with evidence of disease (mean, 36.8 months), three died with tumor at 2, 22, and 156 months, and one patient was lost to follow-up. Eight patients had at least one tumor recurrence requiring additional surgery; seven of these patients had an initial subtotal resection. In summary, MIB-1 labeling indices were generally low (mean, 0.6%) and are reflective of the slow growth of the tumors. Cyclin D1 immunostaining does not appear to be significantly increased in pilocytic astrocytoma. Adverse outcome in patients with pilocytic astrocytoma may be related to extent of surgical resection and does not seem to correlate with histology, MIB-1 labeling indices, or cyclin D1 immunoreactivity.     

August 2002: 21-year-old male with cystic intracerebral tumor

The August 2002 COM. A 21-year-old male presented with a single episode of generalized tonic clonic seizures. Radiology revealed a cystic tumor with mural nodule suggestive of a pilocytic astrocytoma. However, histopathological examination and electron microscopy revealed features of an intracerebral schwannoma. Therefore, although rare, in an intracerebral cystic lesion with mural nodule, the possibility of an intracerebral schwannoma should be entertained. This is important because this is a benign tumor with favourable response to resection.     

Overexpression of vascular adhesion protein‐1 is associated with poor prognosis of astrocytomas

Vascular adhesion protein‐1 (VAP‐1) is one of the endothelial adhesion molecules that is believed to play a role in tumor progression and metastasis, supporting cancer cell extravasation. Very few studies have been performed on analyzing the contribution of VAP‐1 in brain tumor. Astrocytomas are the most common type of brain tumors, which are classified by World Health Organization (WHO) into four grades according to the degree of malignancy. This study was designed to investigate VAP‐1 expression level in different astrocytoma grades and its correlation with clinicopathological features as well as prognosis of astrocytoma patients. Eighty‐seven patients with different grades of astrocytoma (WHO Grade I–Grade IV) were enrolled in this study. The expression of VAP‐1 was assayed by immunohistochemistry. The correlation between VAP‐1 expression and clinicopathological features was evaluated by Chi‐square test, and overall survival was analyzed by Kaplan–Meier method. Cox regression analysis was applied to analyze the independent influence of each parameter on overall survival. The expression level of VAP‐1 was significantly higher in diffuse astrocytoma than those of pilocytic astrocytoma (p < 0.0001). In the subgroup analysis, upregulated VAP‐1 expression was frequently found in older age patients (≥50 years). The VAP‐1 expression was found to be significantly correlated with the overall survival (p = 0.0002). There was a statistical correlation between VAP‐1^high tumors in diffuse astrocytoma and VAP‐1^low tumors in pilocytic astrocytoma (p < 0.0001). Multivariate Cox analysis indicated VAP‐1 was an independent predictive marker for poorer prognosis (p = 0.0036). Therefore, VAP‐1 could be a promising prognostic biomarker in astrocytoma.     

December 1996 — Cervicomedullary Tumor

A cervicomedullary tumor in a 22-month-old female with an eight-month history of symptoms showed the histological features of a pilocytic astrocytoma but had many areas of palisading cells identical to those described in polar spongioblastomas. The tumor recurred 18 months later and showed predominately pilocytic features. The case is used to discuss polar spongioblastomas and tumors which can histologically simulate them.     

Pilomyxoid astrocytoma of the pineal region: Cytopathological features and differential diagnostic considerations by intraoperative smear preparation

Pilomyxoid astrocytoma (PMA) is a recently identified type of pilocytic astrocytoma (PA) with shorter progression‐free and overall survival, higher rate of recurrence, and higher risk of leptomeningeal spread compared to pilocytic tumors (WHO grade 2 designation). A case is presented here in which intraoperative imprint smears of a pineal region tumor in a 14‐year‐old girl revealed cytologic monomorphism, elongated cells with bland nuclei embedded in a myxoid background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and angiocentric arrangement were observed but Rosenthal fibers or eosinophilic granular bodies were absent. A cytologic diagnosis of PMA of the pineal region was suggested by intraoperative smear preparation. Histology and immunohistochemical results confirmed the final diagnosis. This report shows that smear preparation can be trustworthy for the intraoperative diagnosis of PMA, helping to determine the appropriate neurosurgical procedure and therapeutic implications. Diagn. Cytopathol. 2015;43:121–124. © 2014 Wiley Periodicals, Inc.     

Ultrastructural Pathology of Glial Brain Tumors Revisited: A Review

The ultrastructural pathology of primary brain tumors of glial origin is examined. These are divided into two major groups. The first category comprises astrocytoma with the variants: fibrillary, protoplasmic, gemistocytic, and anaplastic. These are biologically aggressive tumors of a relatively high proliferative potential and include a substantial proportion of cases that transform into the most malignant secondary glioblastoma. The second category, comprised of rather benign tumors of a limited proliferative capacity and a reasonable good prognosis, includes such clinico-pathological entities as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma of tuberous sclerosis. There is no ultrastructural feature, however, which makes it possible to discriminate between major subclasses of astrocytes; but secondary glioblastoma cells, while still retaining the stigmata of neoplastic astrocytes, are characterized by nuclei that seem to be more indented, cisterns of the endoplastic reticulum may be distended, and intranuclear pseudoinclusions are frequently observed. Primary glioblastoma, which probably originates de novo, is characterized by poorly differentiated cells with a paucity of subcellular organelles and no obvious features of astrocytic origin. Granular cell tumor also belongs to neoplasms of astrocytic lineage and the hallmark of this entity is a cell characterized by the presence of numerous membrane-bound, electron-dense autophagic vacuoles. Its malignant analogue is the granular cell glioblastoma. Two subtypes of granular cell glioblastoma have been distinguished. The first is characterized by the presence of numerous granular, electron-dense bodies which correspond to autophagic vacuoles. The second type is characterized by numerous electron-dense, amorphous masses within cellular processes. These electron-dense inclusions are virtually indistinguishable from minute Rosenthal fibers. The pilocytic astrocytoma is virtually indistinguishable at the ultrastructural level from fibrillary astrocytomas but cells tend to be more elongated. Besides Rosenthal fibers, two types of distinctive structures are relatively common in pilocytic astrocytomas: eosinophilic hyaline droplets and round granular bodies, which are composed of large aggregates of electron-dense secondary lysosomes or small electron-dense bodies, respectively. Pleomorphic xanthoastrocytoma is characterized by astrocytes surrounded by basal membranes. It belongs to a peculiar category of astrocytic “desmoplastic” brain tumors occurring in younger patients, the common denominator for which is the presence of basal lamina. The last category in this group is subependymal giant cell astrocytoma, a tumor of bivalent (glial and neuronal) differentiation, the cells of which are characterized by the presence of peculiar crystalloids. The hallmark of oligodendroglioma is the presence of concentric arrays of membranes (so-called membrane laminations, whorls, or scrolls). A fragment of the cytoplasm sequestrated within a particular whorl may contain mitochondria, lysosomes, or abundant glycogen granules. Ependymomas are characterized by a florid picture dominated by the presence of microlumina, cilia with basal bodies (blepharoplasts), microvilli, and long, interdigitating intercellular junctions of the zonulae adherentiae type. Ganglioglioma, the last category covered by this review, is a mixed glio-neuronal tumor. While glial cells are indistinguishable from their counterparts encountered elsewhere (mostly pilocytic astrocytes), the ganglion cells are characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments, and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers is seen. Dense-core vesicles are pleomorphic and ranged in a diameter from small synaptic vesicles to large lysosome-like neurosecretory granules.     

Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology

AIMS: NeuN is considered to be a marker of neuronal differentiation in brain tumours. Our aim was to perform, for the first time, a systematic and comparative analysis of NeuN expression in all major brain tumour subtypes to provide guidance for the rational use of NeuN immunohistochemistry in diagnostic histopathology. METHODS AND RESULTS: Anti-NeuN immunohistochemistry was performed on paraffin-embedded biopsy specimens of 106 diffuse astrocytomas, 100 pilocytic astrocytomas, 107 ependymomas, 59 1p-aberrant oligodendroglial neoplasms, 115 glioblastomas, 115 medulloblastomas, 14 gangliogliomas/gangliocytomas and 10 central neurocytomas. We found no NeuN expression in pilocytic astrocytoma, whereas all other investigated tumour subtypes showed focal or widespread expression in varying proportions of cases. Comparing NeuN expression in clear cell tumours, widespread NeuN expression had a positive predictive value of 76.9% (95% confidence interval 46.2, 95.0) for central neurocytoma. Lack of NeuN expression had a positive predictive value of 87.3% (76.5, 94.4) for oligodendroglioma. CONCLUSIONS: Immunohistochemistry can detect NeuN expression in all major brain tumour subtypes except pilocytic astrocytoma. In the individual case, assessment of NeuN expression may be helpful in the differential diagnosis of clear cell primary brain tumours but does not seem to be useful for the differential diagnosis of other brain tumour subtypes.     

IDH-1 polymorphisms in pilocytic astrocytomas

As of 2016, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations are part of the definition of an oligodendroglioma and may be seen in a significant subset of grade II-IV fibrillary astrocytomas. Reports of IDH-1 and IDH-2 alterations in pilocytic astrocytomas have been rare. This study reports two cases of pilocytic astrocytomas which harbored IDH-1 polymorphisms (G105G) (c.315C > T) discovered on polymerase chain reaction (PCR) testing and sequencing. The first was encountered in a 21-year-old male with a right orbital frontal pole mass. The second occurred in a 19-year-old female with a right frontal tumor. Neither tumor stained with antibody to IDH-1 (R132H). No BRAF V600E immunostaining, minimal p53 staining (<5%) and no loss of ATRX staining was noted in both cases. The significance of the IDH-1 findings at this juncture is uncertain. Misdiagnosis of the tumor as a fibrillary astrocytoma or oligodendroglioma due to the presence of an IDH alteration should be avoided.     

Post-traumatic astrocytoma

A 25 year old woman developed a mixed pilocytic and fibrillary astrocytoma in scar tissue 20 years after the brain contusion. The case fulfilled the criteria of traumatic etiology of this brain tumor.     

Cerebral astrocytic neoplasms in the adult: contribution of histologic examination to the assessment of prognosis

Cerebral astrocytomas are the most common primary central nervous system (CNS) tumors in adults. As a group these tumors are characterized by histologic variability and inconstant prognosis. Nevertheless, microscopic examination of these tumors with identification of certain histologic features provides useful prognostic information. Evidence of anaplasia including necrosis, vascular endothelial proliferation, mitotic activity, cytologic pleomorphism, and foci of increased cellularity, when present in diffusely infiltrating astrocytic gliomas, is associated with aggressive behavior. In particular, the occurrence of tumor necrosis in anaplastic astrocytomas is reliably predictive of a highly unfavorable outcome. Specific histologic subtypes of cerebral astrocytoma with relatively benign course may also be identified. These include juvenile pilocytic astrocytoma, subependymal giant-cell astrocytoma, and, in some cases, pleomorphic xanthoastrocytoma. The critical influence of tumor location and the limitations imposed by potentially nonrepresentative biopsy material must be appreciated when assessing prognosis in cerebral astrocytomas. Prognostic data provided by histologic examination are useful in selecting treatment regimens and for evaluation of newly proposed therapies.     

Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas

AIMS: While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas. METHODS AND RESULTS: By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein. CONCLUSION: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.     

Crystalline Cytoplasmic Inclusions in an Anaplastic Oligodendroglioma

The authors describe for the first time an unusual cerebral tumor with unique clinical history, composed of 3 components: pilocytic astrocytoma, vascular proliferations similar to those described as arteriovanous malformations, and a neoplastic ganglion component. These three components were intimately entangled and created the tumor mass. Thus the authors propose the term angioganglioglioma for this entity. The relation to the historically defined anglioglioma and tumors related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed. The authors believe that this lesion, in regard to the clinical presentation (long course of the disease, clinical symptoms), is closely associated with ganglioglioma and, with other morphological features, also to angioglioma. Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features.     

Angioganglioglioma: a transitional form between angioglioma and gangioglioma?

The authors describe for the first time an unusual cerebral tumor with unique clinical history, composed of 3 components: pilocytic astrocytoma, vascular proliferations similar to those described as arteriovanous malformations, and a neoplastic ganglion component. These three components were intimately entangled and created the tumor mass. Thus the authors propose the term angioganglioglioma for this entity. The relation to the historically defined anglioglioma and tumors related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed. The authors believe that this lesion, in regard to the clinical presentation (long course of the disease, clinical symptoms), is closely associated with ganglioglioma and, with other morphological features, also to angioglioma. Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features.     

毛细胞黏液样星形细胞瘤的研究进展

毛细胞黏液样星形细胞瘤（pilomyxoid astrocytoma,PMA）是2007年WHO中枢神经系统肿瘤病理学中新提出的一个分类。它是毛细胞星形细胞瘤（pilocytic astrocytoma,PA）的特殊亚型,患者发病年龄更早,视交叉/下丘脑是病变的常见部位。近些年也有成人PMA及特殊部位PMA的报道。组织学见双极梭形细胞围绕血管生长,有黏液样背景,无PA常见的Rosenthal纤维和嗜酸性颗粒小体。与PA相比,患者预后较差,易局部多次复发或经脑脊液转移甚至死亡。PMA复发后可演变呈典型的PA。