Typical Pilocytic Astrocytoma Research Articles

CS-01 Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient

BACKGROUND: Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported. CASE DESCRIPTION: An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging (MRI) demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histological examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was less than 1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, MRI showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histological findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed. CONCLUSION: It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.

The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population

Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features—(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4–6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.

Pilomyxoid astrocytomas: a short review.

Pilomyxoid astrocytoma is a variant of pilocytic astrocytoma and the clinical, histological and molecular data point to a very close relationship as well as a more aggressive biological behavior for the former. WHO 2016 classification does not provide a specific grade for these neoplasms, but there is sufficient evidence in the literature that pilomyxoid astrocytoma has slightly worse prognosis than typical pilocytic astrocytoma. There is increasing evidence that in addition to the MAPK pathway alterations, pilomyxoid astrocytomas harbor genetic alterations that distinguish them from typical pilocytic astrocytoma.

Prechiasmatic transection of the optic nerve in optic nerve glioma: technical description and surgical outcome.

Optic pathway glioma (OPG) encompasses a spectrum of findings ranging from lesions confined to the optic nerve only, lesions affecting the optic chiasm and hypothalamus, and lesions with diffuse involvement of a large part of the optic pathway and neighboring structures. The majority of pediatric low-grade astrocytomas in the optic/chiasmatic region are typical pilocytic astrocytoma. The rest of them (10%) may be other gliomas such as fibrillary pilomyxoid astrocytoma (grade 2 WHO). The postsurgical local recurrence rate of 55 to 76% has been reported in some histological subtypes such as pilomyxoid astrocytoma (grade 2). Performing a prechiasmatic transection might offer a new surgical option to avoid further tumor growth toward the chiasm in the optic nerve glioma with predominantly orbital manifestations. In this retrospective study, four patients (three children, two without neurofibromatosis type 1 (NF1), and one with NF1 and one adult without NF1) with optic nerve glioma without involvement of the chiasm but blindness, disfiguring proptosis, and pain of the affected eye were included. The surgical approach was performed as a combined approach from pterional extradural and intradural. Without any exceptions, vision of the contralateral eye could be preserved and did not show any deterioration after surgery or during the follow-up time between 17 and 106months. Furthermore, in all patients, gross total tumor resection could be achieved. During follow-up observation in all patients, no further tumor progress or recurrences could be observed. None of the patients were treated postoperatively by radiotherapy or chemotherapy. Prechiasmatic transection of the optic nerve in optic nerve glioma without affecting the chiasm might offer a surgical treatment option to control tumor growth and to preserve vision of the contralateral eye.

Rosette-forming glioneuronal tumor of the fourth ventricle

Objective To explore the clinicopathological features of rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle. Methods The clinical manifestations, neuroimaging, histopathological and immunohistochemical features were analysed in one case of RGNT of the fourth ventricle, and related literatures were reviewed. Results A 24-year-old female presented with progressive dizziness under no obvious predisposing causes and dyskinesia such as stumbling. MRI revealed expansion of the fourth ventricle, and a mass with long T 1 WI and T 2 WI signal and clear boundary could be seen within the fourth ventricle. The border of tumor showed slight enhancement. At surgery, it was observed that the solitary tumor arised from the fourth ventricle and appeared well demarcated with rhomboid fossa. The tumor was blocking the aqueduct of sylvius before it was removed. Microscopically, the tumor exhibited both neuronic and astrocytic components. In the neuronic components, neurocytes formed neurocytic rosettes and perivascular pseudorosettes. At the center of the neurocytic rosettes, there was an eosinophilic core and some region consisted of microcysts. While the astrocytic components of the tumor revealed typical pilocytic astrocytoma structure. The center of neuronic rosettes and perivascular pseudorosettes displayed strong positive staining with synaptophysin (Syn) and oligodendrocytes transcription factor-2 (Olig-2). The astrocytic components showed positive immunostaining of glial fibrillary acidic protein (GFAP). There were focal and partial positive immunostaining of neuron-specific enolase (NSE) in both components of the tumor. The Ki-67 labeling index was 1.50%-2.00% in two components. Conclusions Rosette-forming glioneuronal tumor of the fourth ventricle is an unusual neuronal and mixed neuronal-glial tumors. The imaging examination showed solid or mixed solid-cystic mass at the fourth ventricle with well demarcated border. The lesion has two characteristic components and the distinctive immunostaining of GFAP and Syn expression will help the differential diagnosis. DOI: 10.3969/j.issn.1672-6731.2015.11.013

Radiologically typical pilocytic astrocytoma with histopathological signs of atypia

Pilocytic astrocytoma (PCA) is the most common CNS tumor in primary school-aged children. Herein, we report the case of a 7-month-old female child with a large cerebellar hypodense tumor on computer tomography occupying nearly the whole cerebellar hemisphere. Magnetic resonance imaging revealed characteristic features of a PCA, depicting a mass with hyperintense solid and cystic areas on T2-weighted images and with marked solid and ring-like enhancement pattern. Histopathological and immunohistochemical analysis showed partially typical features of a PCA, but also atypical features such as a high proliferation rate, hypercellularity, and focally diffuse infiltration pattern were present. However, definite signs of transformation to an anaplastic PCA were not observed. We therefore classified the tumor as pilocytic astrocytoma with signs of atypia instead of simple WHO grade I pilocytic astrocytoma. The case illustrates that neuroimaging features may give very important clues for the definite diagnosis in histopathologically atypical PCA.

Anaplasia in Pilocytic Astrocytoma Predicts Aggressive Behavior

The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients.

There are few pathologic studies of gliomas in patients with neurofibromatosis type 1. We analyzed clinical and pathologic features of gliomas from 100 neurofibromatosis type 1 patients (57 men; 43 women). The median age at tumor diagnosis was 13 years (range, 4 months to 68 years). Most tumors were typical pilocytic astrocytoma (PA) (49%) or diffusely infiltrating astrocytoma (DA) (27%) that included World Health Organization Grades II (5%), III (15%), and IV (7%); others were designated as low-grade astrocytoma, subtype indeterminate (LGSI; 17%). Two pilomyxoid astrocytomas, 1 desmoplastic infantile ganglioglioma and 1 conventional ganglioglioma, were also identified. The tumors in 24 cases arose in the optic pathways and included PA (n = 14), LGSI (n = 4), DA (n = 4), pilomyxoid astrocytoma (n = 1), and ganglioglioma (n = 1). The prognoses of the PA and LGSI gliomas overall were generally favorable; there were no survival differences between PA and LGSI groups based on site, tumor size, mitotic activity, or MIB-1 labeling index. In the combined PA and LGSI group, age younger than 10 years and gross total resection were associated with an increased overall survival rate (p = 0.047 and 0.002, respectively). Compared with the combined group (PA + LGSI), patients with DA at all sites had decreased overall and recurrence-free survival times (p < 0.001 and p = 0.003, respectively). This study emphasizes the wide histologic spectrum of gliomas that occur in patients with neurofibromatosis type 1. Classic PA and LGSI are the most common, and most have favorable prognoses. By contrast, DAs are more aggressive, similar to those that arise sporadically.

The Pilomyxoid Astrocytoma and its Relationship to Pilocytic Astrocytoma: Report of a Case and a Critical Review of the Entity

Pilomyxoid astrocytoma (PMA) is a rare glioma that shares histopathological similarities with pilocytic astrocytoma (PA). Yet, typical examples of both can be distinguished on clinical and histological grounds. The reported aggressive behavior of PMA provides a rationale for distinguishing this entity from typical PA. We report a 6(1/2) -year-old girl who had suffered poor weight gain, irritability and progressively worsening abnormal eye movements since approximately 2 months of age. Radiographic studies at 6 months of age (age at initial presentation) revealed a large hypothalamic lesion occupying proximal portions of the optic nerves, chiasm and right posterior optic tract. The first biopsy obtained after two chemotherapy regimens was consistent with a diagnosis of PMA. The patient suffered multiple recurrences, and underwent three subsequent surgical procedures. The last two surgical specimens revealed a tumor with histopathological features of PA. She is alive with residual disease 6 years after initial presentation. While earlier studies focused on the similarities between PA and PMA, considering the latter as the "infantile" form of the former, subsequent work outlined their histological and clinical differences. Some even suggested a different cell type, such as the tanycytic cell as the origin for PMA. This report provides evidence in favor of the earlier argument that there is a close relationship between PA and PMA, and presents a rare "maturation" phenomenon, at least from a morphological perspective. More systematic review of such cases will provide a better answer for the origin of PMA, and its relation to PA.

Pilomyxoid Astrocytoma of the Spinal Cord: Report of Three Cases

Pilomyxoid astrocytoma (PMA) is a recently described, rare, circumscribed glioma similar to pilocytic astrocytoma. Despite its circumscribed nature, PMA implies a worse overall outcome than typical pilocytic astrocytoma. All PMAs reported to date involved the hypothalamic/chiasmatic region. Since these original reports, we have encountered three tumors in the spinal cord with histological features identical to those of PMA. We report three male pediatric patients. The first patient presented at age 6 with back pain and constipation. The second patient presented at age 8 with back pain and a bout of urinary incontinence. The third patient, a neonate, presented with respiratory failure and hypotonia. The first patient's cervical and thoracic neoplasm was treated with subtotal resection and multiple laminectomies and spinal fusion for recurrence. The second patient underwent gross total resection of his thoracic neoplasm. The neonate underwent laminectomy and biopsy of his holocord tumor. PMAs typically occur in the hypothalamic region and within the first 4 years of life. Tumors with identical histological features are being recognized outside this typical clinical setting. The cases presented in this report suggest that PMA can occur at a later age and can involve the spinal cord. We believe that increased recognition of these circumscribed gliomas will help to elucidate their nature and lead to better management decisions.