Abstract
Background: H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas (DIPGs), but has been recently recognized to occur also in adult midline diffuse gliomas, as well as midline tumors with other morphologies, including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas. In a few patients with H3 K27M-mutant tumors with these alternate morphologies, longer survival has been reported, making grading difficult for the neuropathologist. Few series compare tumors in adult vs. pediatric cohorts; we report our 4-year experience. Materials and methods: Text Word database searches using “H3 K27M” in reports generated between January 2013 and November 10, 2017 were used to identify patients. Clinical and histological features as well as survival were evaluated for each case. Results: 28 H3 K27M-mutant tumors were identified, with equal numbers of adults (13) vs. children (15). For adults, mean and median age was 52 years (range = 27 – 81 years), 2 decades older than a recently-published adult series. Tumors involved thalamic (adult = 7; pediatric = 7), spinal cord (adult = 4; pediatric = 2), pons (adult = 1; pediatric = 6), and hypothalamic (n = 1) sites. Other morphologies at presentation included pure GG (n = 3, pediatric) and PA (n = 1, adult). One adult and 1 pediatric patient each presented with leptomeningeal dissemination or developed leptomeningeal dissemination within 1 year after diagnosis, with transformation from PA or GG histology to glioblastoma. Mean survival was 9.3 (adults) vs. 8.9 (pediatric) months. Patients with tumors of other morphologies (GG, PA) did not enjoy extended survival. Conclusion: H3 K27M-mutant tumors can affect patients at advanced ages, may show leptomeningeal dissemination at time of presentation, and “pure” GG or PA morphology is not rare. Regardless of patient age or tumor morphology, patients fare equally poorly.
Highlights
H3 K27M mutations were first described in pediatric diffuse pontine gliomas (D IPGs) [1], but soon thereafter were found in midline gliomas in adults by our group [2] and Solomon et al [3]
H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas (DIPGs), but has been recently recognized to occur in adult midline diffuse gliomas, as well as midline tumors with other morphologies, including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas
Our 28 cases are similar in number to the 21 H3 K27M-mutant adult patients recently published by Meyronet et al [10], that series was derived from multiple French institutions
Summary
H3 K27M mutations were first described in pediatric diffuse pontine gliomas (D IPGs) [1], but soon thereafter were found in midline gliomas in adults by our group [2] and Solomon et al [3]. More of a nomenclature/grading problem for the neuropathologist are the H3 K27Mmutant tumors with “pure” histologies other than diffuse infiltrating astrocytoma In the past, these have been published almost exclusively under the diagnosis made by histological appearance and some of these patients have enjoyed several years of survival before undergoing recurrence and eventual demise. These have been published almost exclusively under the diagnosis made by histological appearance and some of these patients have enjoyed several years of survival before undergoing recurrence and eventual demise These have included a midline, histologically-classic “pure” pilocytic astrocytoma [6] and ganglioglioma [7] with H3 K27M mutation, but such cases at the time were considered quite exceptional [8]. Regardless of patient age or tumor morphology, patients fare poorly
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