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The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features

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Abstract

Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF–KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF–KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF–KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.

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Acknowledgments

This study was sponsored by the OUHSC Department of Pathology.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Matthew D. Cykowski, Richard A. Allen, Angela C. Kanaly, Kar-Ming Fung, Ethan D. Stolzenberg & S. Terence Dunn

  2. Department of Pathology, Oklahoma City Veterans Administration Medical Center, Oklahoma City, OK, USA

    Kar-Ming Fung

  3. Department of Pathology, University of California, San Francisco, San Francisco, CA, USA

    Roxanne Marshall & Arie Perry

  4. University of Oklahoma Health Sciences Center, P.O. Box 26901, BMSB, Room 415, Oklahoma City, OK, 73190, USA

    S. Terence Dunn

Authors
  1. Matthew D. Cykowski
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  2. Richard A. Allen
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  4. Kar-Ming Fung
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Corresponding author

Correspondence to S. Terence Dunn.

Additional information

This study was presented at the 101st meeting of the United States and Canadian Academy of Pathology.

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Cykowski, M.D., Allen, R.A., Kanaly, A.C. et al. The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features. J Neurooncol 115, 477–486 (2013). https://doi.org/10.1007/s11060-013-1249-5

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  • DOI: https://doi.org/10.1007/s11060-013-1249-5

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