Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference

Abstract

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and advances in molecularly targeted treatment and potential immunologic treatment of these tumors. Next steps are recommended to advance the management and outcomes for NF1-associated gliomas.

Keywords: gliomas; immunotherapy; molecular-targeted therapy; neurofibromatosis type 1; pilocytic astrocytomas.

Fig. 1

Anaplastic astrocytoma with piloid features (pilocytic astrocytoma with anaplasia) arising in the cerebellum of a 29-year-old NF1-patient. Well-differentiated pilocytic astrocytoma component (top a, b) and sharp interface with an anaplastic component characterized by high cellularity and brisk mitotic activity (bottom a, d). ATRX loss detected by immunohistochemistry in well-differentiated (c) and anaplastic (e) components. Positive cells in the stroma and vessels serve as an important internal control (scale bar representing 100 µm applicable to panel a; scale bar representing 50 µm applicable to panels b–e).