LAUSR

We report the case of a 29-year-old female who presented with headaches and papilledema and found to have a right cerebellar T2/FLAIR hyperintense mass with restricted diffusion and minimal patchy enhancement resulting in fourth ventricular effacement and right transverse sinus stenosis (Fig. 1). She underwent an uncomplicated right retrosigmoid suboccipital craniectomy with neuro-monitoring and intraoperative MRI for gross total resection. The patient was discharged home four days after surgery, neurologically intact. Pathology was consistent with a WNT-negative, GFAP/synaptophysin positive tumor comprised of clusters and sheets of ovoid irregular pleiomorphic nuclei with retained INI1 and elevated Ki67 (10–15%), consistent with classic World Health Organization (WHO) Grade IV medulloblastoma (MB). Postoperative MRI of the neuroaxis showed no evidence of disease. Whole exome sequencing was performed and identified 70 somatic mutations, including an IDH2 p.R172S (NM_002168) hotspot missense mutation, never previously reported in MBs (Fig. 1). Additionally, there was identification of a deactivating missense mutation in the Sonic Hedgehog (SHH) receptor PTCH1 p.T1078M (NM_001083606) [1–3]. We noted chr.9 LOH overlapping with PTCH1, suggestive of bi-allelic PTCH1 loss. We also identified a passenger SMO p.G416D (NM_005631) mutation and a ROS1 p.Y1011C (NM_002944) missense mutation of unknown significance. Neither have been reported in Cosmic database. Copy number variation analysis detected chr. 3p and chr. 9q deletions; the latter previously reported in SHH-MBs [1–3]. A somatic TERT promoter mutation (chr5:1,295,228: G>A), previously detailed as highly recurrent in adult SHH-MBs, was also identified [4]. The integrated diagnosis was SHH-MB and our Precision Brain Tumor Board recommended craniospinal irradiation (CSI-proton beam vs conformal IMRT/VMAT 27 Gy with tumor boost of 55.8 Gy) with adjuvant lomustine/CCNU, cisplatin and vincristine. Three full cycles of chemotherapy have been completed to date, with no evidence of disease recurrence 8 months after surgery.