Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation

Mohammed Ali Alvi, Cristiane M. Ida, Michael A. Paolini, Panagiotis Kerezoudis, Jenna Meyer, Emily G. Barr Fritcher, Sandy Goncalves, Fredric Meyer, Mohammed Bydon, Aditya Raghunathan

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6 Scopus citations

Abstract

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18–69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Original languageEnglish (US)
Pages (from-to)1236-1243
Number of pages8
JournalModern Pathology
Volume32
Issue number9
DOIs
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Alvi, M. A., Ida, C. M., Paolini, M. A., Kerezoudis, P., Meyer, J., Barr Fritcher, E. G., Goncalves, S., Meyer, F., Bydon, M., & Raghunathan, A. (2019). Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation. Modern Pathology, 32(9), 1236-1243. https://doi.org/10.1038/s41379-019-0271-3