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Genomic Heterogeneity of Aggressive Pediatric and Adult Diffuse Astrocytomas

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Precision Molecular Pathology of Glioblastoma

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Abstract

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is remarkable for its degree of both morphologic and genomic heterogeneity. In children and adults, as defined by the World Health Organization (WHO), GBM is a grade IV neoplasm with a diffusely infiltrative growth pattern populated by cells showing predominately astrocytic differentiation. As discussed in previous chapters, GBM features prominent nuclear atypia and cellular pleomorphism, as well as high tumor cell mitotic activity accompanied by microvascular proliferation and/ or necrosis. As its former name indicates, GBM may include one or many morphologic patterns within a single tumor. In some tumors, this reflects underlying clonal evolution with newly acquired genetic changes in tumor cell subpopulations. Even more variable than GBM morphology is the range of genomic heterogeneity, creating multiple molecular signatures that define tumor behavior, prognosis and treatment response independent of tumor histopathology. Furthermore, while pediatric and adult glioblastoma share many histopathologic similarities, they are unequivocally biologically distinct neoplasms. In many pediatric and adult gliomas, the molecular subgroup is a better predictor of tumor behavior than histologic grade. In particular, WHO grade II or III diffuse astrocytomas lacking morphologic features associated with GBM (microvascular proliferation and necrosis), but with certain defined molecular alterations, should be considered GBM for prognostic and therapeutic purposes due to their expected WHO grade IV-like behavior. The focus of this chapter centers on the genomic heterogeneity and pathobiology of aggressive pediatric and adult diffuse astrocytomas with WHO grade IV behavior independent of morphologic features.

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Authors and Affiliations

  1. Department of Pathology, Nationwide Children’s Hospital, Columbus, OH, USA

    Christopher R. Pierson

  2. Department of Pathology, The Ohio State University and Nationwide Children’s Hospital, Columbus, OH, USA

    Diana L. Thomas

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  1. Christopher R. Pierson
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  2. Diana L. Thomas
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Correspondence to Diana L. Thomas .

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  1. Neuropathology, The Ohio State University, Columbus, OH, USA

    José Javier Otero

  2. Radiation Oncology, The Ohio State University, Columbus, OH, USA

    Aline Paixao Becker

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Pierson, C.R., Thomas, D.L. (2021). Genomic Heterogeneity of Aggressive Pediatric and Adult Diffuse Astrocytomas. In: Otero, J.J., Becker, A.P. (eds) Precision Molecular Pathology of Glioblastoma. Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-030-69170-7_9

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