Diffuse intrinsic brainstem glioma (DIPG) accounts for 10-15% of all new pediatric brain tumor diagnoses and is the leading cause of brain tumor-related death in children.1 Median age at diagnosis is 6 to 7 years2,3, and patients commonly present with cranial nerve deficits, upper motor neuron signs, and ataxia.1 Typical MRI appearance is a T1-hypointense, T2-hyperintense, variably contrast enhancing, expansile mass involving ≥ 50% of the pons. Though often not apparent at diagnosis, several recent studies have demonstrated leptomeningeal dissemination and spread to proximal areas of brain at autopsy.3,4 Prognosis for DIPG is dismal, with a median overall survival of less than one year.1 Standard treatment at diagnosis consists of local radiation therapy, but this intervention is only useful to improve symptoms and prolong survival by 2 to 3 months in some.4 Chemotherapeutic strategies, including targeted agents, have proven uniformly ineffectual to date.1,5,6
DIPG is generally diagnosed on the basis of clinical and radiographic findings. Historically, histopathological diagnosis has not been routinely performed due to perceived risks of brainstem biopsy7 but was instead reserved for patients with atypical imaging characteristics. The consequence of this paradigm is scarcity of tissue and thus grave limitation of our understanding of the molecular biology of DIPG. In recent years, tissue has become more available through collaborative determination to overcome barriers to tissue procurement. This has been accomplished in the following ways:
- Efforts to study and implement safe surgical techniques for brainstem biopsy, which were pioneered in Europe8-11 and have become more recently accepted in the United States12, and
- Initiation of programs for tissue collection at autopsy, which have been instigated by family advocacy groups and physicians.3,13,14
- Jansen MHA, van Vuurden DG, Vandertop WP, Kaspers GJL. Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat. Rev. 2012;38(1):27–35.
- Saratsis AM, Kambhampati M, Snyder K, et al. Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes. Acta Neuropathol. 2014;127(6):881–895.
- Buczkowicz P, Bartels U, Bouffet E, Becher O, Hawkins C. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropathol. 2014.
- Caretti V, Bugiani M, Freret M, et al. Subventricular spread of diffuse intrinsic pontine glioma. Acta Neuropathol. 2014.
- Haas-Kogan DA, Banerjee A, Kocak M, et al. Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma. Neuro-Oncology. 2008;10(3):341–347.
- Bartels U, Wolff J, Gore L, et al. Phase 2 study of safety and efficacy of nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma. Neuro-Oncology. 2014.
- Epstein F, McCleary EL. Intrinsic brain-stem tumors of childhood: surgical indications. J. Neurosurg. 1986;64(1):11–15.
- Cartmill M, Punt J. Diffuse brain stem glioma. A review of stereotactic biopsies. Childs Nerv Syst. 1999;15(5):235–7– discussion 238.
- Pincus DW, Richter EO, Yachnis AT, et al. Brainstem stereotactic biopsy sampling in children. J. Neurosurg. 2006;104(2 Suppl):108–114.
- Roujeau T, Machado G, Garnett MR, et al. Stereotactic biopsy of diffuse pontine lesions in children. J. Neurosurg. 2007;107(1 Suppl):1–4.
- Puget S, Philippe C, Bax DA, et al. Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLoS ONE. 2012;7(2):e30313.
- MacDonald TJ. Diffuse intrinsic pontine glioma (DIPG): time to biopsy again? Pediatr. Blood Cancer. 2012;58(4):487–488.
- Angelini P, Hawkins C, Laperriere N, Bouffet E, Bartels U. Post mortem examinations in diffuse intrinsic pontine glioma: challenges and chances. J Neurooncol. 2011;101(1):75–81.
- Broniscer A, Baker JN, Baker SJ, et al. Prospective collection of tissue samples at autopsy in children with diffuse intrinsic pontine glioma. Cancer. 2010;116(19):4632–4637. .