Histopathologic predictors of pilocytic astrocytoma event-free survival

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Acta Neuropathologica (Impact Factor: 10.76). 04/2009; 117(6):657-65. DOI: 10.1007/s00401-009-0506-3
Source: PubMed


Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. Most arise in the cerebellum, but they also can develop in the brainstem and optic nerve, where gross total resection (GTR) is not possible. In the absence of GTR, significant variability in both clinical behavior and histology exists. To identify potential markers associated with poor clinical outcome, we retrospectively assessed pathological features in 107 patients with PAs. We identified four pathological features (necrosis, oligodendroglioma-like features, vascular hyalinization, and calcification) that showed a significant correlation with decreased event-free survival (EFS). Similar to previous reports, we also found that PAs involving the optic pathway were associated with worse EFS compared with those arising in other locations. In contrast, mitotic index, p53 immunoreactivity and hyperactivation of several mitogenic signaling pathways (MAPK, CREB, mTOR) did not demonstrate a statistically significant relationship with EFS. Lastly, we did find a statistical trend between EFS and the number of CD68+ cells, suggesting that non-neoplastic elements of the tumor microenvironment may influence subsequent growth and clinical recurrence. Collectively, the identification of specific histopathologic features associated with clinical outcome may improve our ability to determine which PAs are more likely to exhibit clinical progression and require more vigilant observation.

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    • "Pilocytic astrocytoma (PA) is a rare, slow-growing glioma, classified as grade I by the World Health Organisation (WHO); it typically occurs in children and young adults [1, 2]. PA is the most common glial neoplasm in children. "
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    ABSTRACT: Pilocytic astrocytoma can be challenging to diagnose. Its clinical presentations can differ, directly related to its size and location, and are relatively unreliable. Similarly, imaging findings also vary with the location of the pilocytic astrocytoma. This review provides an overview of the different imaging findings regarding pilocytic astrocytomas using both conventional and advanced magnetic resonance imaging sequences according to tumour location; the findings are strongly related to the tumour's tendency to infiltrate surrounding structures, being able to carry out gross total resection, and finally the prognosis. Knowledge of these imaging manifestations of pilocytic astrocytoma may be helpful to arrive at an accurate diagnosis. • To recognise the various imaging findings of pilocytic astrocytoma on both conventional and advanced magnetic resonance imaging sequences. • To identify the characteristic imaging findings according to tumour location. • To discuss the relevant differential diagnoses of pilocytic astrocytoma in each tumour location.
    Full-text · Article · May 2014 · Insights into Imaging
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    • "Spongy patterns, Rosenthal fibers, hyalinized vessels, and honeycomb-like components have often been associated with PA [3]. However, PA is usually found in younger people. "
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    ABSTRACT: A 55-year-old man presented with a large tumor in his lateral ventricles. Magnetic resonance imaging revealed disseminated lesions in the third and fourth ventricles at the time of diagnosis. The patient underwent a partial removal of the tumor in the lateral ventricles. Histologically, the surgical specimens showed glioneuronal differentiation with ganglion or ganglioid cells, Rosenthal fibers, oligodendroglia-like honeycomb appearances, a spongy pattern, perivascular pseudorosettes, and many hyalinized blood vessels. Papillary structure was not observed. The neuronal component showed a moderately high labeling index of Ki-67/MIB-1. We diagnosed this tumor as atypical intraventricular glioneuronal tumor. The disseminated lesions disappeared after chemoradiation therapy with temozolomide, and the residual tumors in the lateral ventricles remained stable for 3 years after the surgery. We discuss the pathological diagnosis, therapy and clinical course with review of the literatures.
    Full-text · Article · Dec 2011 · Diagnostic Pathology
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    • "Additionally, we observed that potentially aggressive histological features were more commonly associated with tumors from younger patients. In particular, some series suggest that necrosis, oligodendroglioma-like features, and infiltrative growth are associated with decreased event-free survival.4,24 Evaluation of a larger series of tumor samples will be required to determine if the Hh pathway is activated to a greater extent in pilocytic astrocytomas from younger patients and whether this correlates with specific histopathologic features and tumor progression. "
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    ABSTRACT: Pilocytic astrocytoma is commonly viewed as a benign lesion. However, disease onset is most prevalent in the first two decades of life, and children are often left with residual or recurrent disease and significant morbidity. The Hedgehog (Hh) pathway regulates the growth of higher WHO grade gliomas, and in this study, we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas. Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed (ages 1-22 years) and correlated inversely with patient age. Evaluation of a tissue array revealed oligodendroglioma-like features, pilomyxoid features, infiltration, and necrosis more commonly in specimens from younger patients (below the median patient age of 10 years). Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10. A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured, and 86% of Ki67-positive cells also expressed PTCH. The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism. Taken together, these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth.
    Full-text · Article · Mar 2010 · Neuro-Oncology
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