DIPG-19. PROLONGED SURVIVAL AND EVENTUAL DEATH BY DISSEMINATED PULMONARY METASTASIS IN A PEDIATRIC PATIENT WITH DIFFUSE PONTINE H3.1K27M GLIOMA: A CASE REPORT

Abstract

Background: Diffuse intrinsic pontine gliomas (DIPG) with H3.1K27M mutation are associated with dismal prognosis and median survival of 15.0 months. Objective(s): To describe a case of DIPG with an unusual natural history. Design/Method: Case Report Results: In this case report, we present a patient with diffuse H3.1K27M pontine glioma treated with craniospinal irradiation and anti-angiogenic therapy, who survived 38months and ultimately died of pulmonary disease. A previously healthy 7-year-old female presented with headache and altered mental status. Neuroimaging revealed T2/FLAIR hyperintensity centered within and expanding the pons, as well as enhancement along pituitary infundibulum and ventral C6-T5 spinal cord concerning for synchronous metastatic disease. Ventriculoperitoneal shunt placement and brainstem biopsy were performed, biopsy revealed infiltrative astrocytoma with positive nuclear histone H3-K27M staining. She received 6 weeks of craniospinal irradiation followed by 10 months of triple anti-angiogenic medication with thalidomide, celecoxib and etoposide per modified Angiocomb protocol. She eventually developed progressive interstitial lung disease with no concurrent clinical signs of CNS disease progression. She ultimately died of respiratory failure 38 months from diagnosis. Next generation sequencing performed on diagnostic tissue found HIST1H3B p.K28M hotspot and PTPN11 gene missense mutations, lung biopsy tissue prior to death revealed the same H3.1K27M and PTPN11 mutations, as well as frameshift mutations in NF1 and CREBBP genes. Postmortem examination revealed presence of metastases in lungs, kidneys, liver, fallopian tube, perihepatic soft tissue, diaphragm, as well as progression of her primary disease. Conclusion(s): Our case is the first report of documented DIPG pulmonary metastasis and subsequent death by pulmonary disease, and the longest documented survival of HIST1H3B K27M pontine glioma by several months.Further thought should be given to whether cerebrospinal fluid diversion and radiation strategy affected her clinical course. References: 1 Mackay A, et al. Integrated molecular meta-analysis of 1000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell. 2017 Oct 9; 32(4):520-537. 2 Castel D, et al, Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015; 130(6):815-827. 3 Barajas Jr, R, et al. Metastatic diffuse intrinsic pontine glioma to the peritoneal cavity via ventriculoperitoneal shunt: Case report and literature review. J Neurol Surg Rep. 2015 Jul;76(1):e91-e96. 4 Porkholm M, et al. Radiation therapy and concurrent topotecan followed by maintenance triple anti-angiogenic therapy with thalidomide, etoposide, and celecoxib for pediatric diffuse intrinsic pontine glioma.