LAUSR

We previously described a series of localized intramedullary glioneuronal tumors limited to the spinal cord with histomorphologic, immunophenotypic, and molecular characteristics of diffuse leptomeningeal glioneuronal tumor (DLGNT), a newly added provisional entry in the current World Health Organization classification of central nervous system tumors [1, 3]. These localized spinal tumors and DLGNTs are characterized by the concomitant presence of KIAA1549–BRAF fusion and chromosome arm 1p deletion [6]. Both have OLIG2-expressing oligodendrocyte-like tumor cells that are positive for synaptophysin and negative for GFAP [5]. Neuropil-like islands surrounded by neurocytic cells and variable amounts of ganglion cell differentiation are additional distinct features of both diseases [1]. However, despite this histomorphologic, immunophenotypic, and molecular resemblance, it remains uncertain whether the localized spinal BRAF-fused and 1p-deleted glioneuronal tumors are nosologically related to DLGNT, in which predominant and widespread leptomeningeal dissemination at presentation, often without a recognizable parenchymal component, is a defining feature [3]. To answer this question, we have been closely following cases of localized spinal BRAF-fused and 1p-deleted glioneuronal tumors at St. Jude Children’s Research Hospital (St. Jude) by using serial magnetic resonance imaging of the brain and spinal cord, even when none of them showed evidence of detectable leptomeningeal dissemination at presentation and during a follow-up of up to 9.25 years. Herein, we report that one of the patients, who is now a 15-yearold boy, developed diffuse leptomeningeal dissemination (“sugarcoating”) involving supratentorial, posterior fossa, and spinal compartments, accompanied by non-resorptive (communicating) hydrocephalus, after 25 months of followup (Fig. 1a–e). The primary T10–12 intramedullary lesion, on the other hand, showed minimal volumetric increase at the time of leptomeningeal progression. The patient had not received any chemotherapy or radiation after the biopsy at diagnosis and was closely followed with periodic surveillance imaging and physical examination. This finding confirms that localized spinal tumors with KIAA1549–BRAF fusion and chromosome arm 1p deletion have the ability to develop diffuse leptomeningeal dissemination, which affirms the nosologic relationship between these localized spinal tumors and DLGNT and has significant clinical implications. Next, we sought to identify the risk factors that may predict disease progression and hence help guide clinical management and decision making of these patients upfront, since the prognosis of DLGNT is highly variable [1, 5]. However, next-generation sequencing analysis of 143 cancer-related genes by using the ClearSeq Cancer Panel (Agilent), and Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0040 1-018-1940-x) contains supplementary material, which is available to authorized users.