Journal article
Desmoplastic Infantile Ganglioglioma: A MAPK Pathway-Driven and Microglia/Macrophage-Rich Neuroepithelial Tumor
Journal of neuropathology and experimental neurology, Vol.78(11), pp.1011-1021
11/01/2019
DOI: 10.1093/jnen/nlz086
PMID: 31562743
Abstract
MAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG. Activating MAPK pathway alterations were identified in 4 (57%) cases: 3 had a BRAF mutation (V600E/V600D/V600_W604delinsDQTDG, at 8%-27% variant allele frequency) and 1 showed a TPM3-NRTK1 fusion. Copy number changes were infrequent and nonrecurrent. All tumors had at least 30% of cells morphologically and immunophenotypically consistent with microglial/macrophage lineage. Two subtotally resected tumors regrew; 1 was re-excised and received adjuvant treatment (chemotherapy/targeted therapy), with clinical response to targeted therapy only. Even with residual tumor, all patients are alive (median follow-up, 83months; 19-139). This study further supports DIG as another MAPK pathway-driven neuroepithelial tumor, thus expanding potential treatment options for tumors not amenable to surgical cure, and suggests that DIG is a microglia/macrophage-rich neuroepithelial tumor with frequent low driver mutation allele frequencies.
Details
- Title: Subtitle
- Desmoplastic Infantile Ganglioglioma: A MAPK Pathway-Driven and Microglia/Macrophage-Rich Neuroepithelial Tumor
- Creators
- Melissa M. Blessing - Dell Children's Medical Center of Central TexasPatrick R. Blackburn - Dell Children's Medical Center of Central TexasChandra Krishnan - Dell Children's Medical Center of Central TexasVirginia L. Harrod - Dell Children's Medical Center of Central TexasEmily G Barr Fritcher - Mayo ClinicChristopher D. Zysk - Dell Children's Medical Center of Central TexasRory A. Jackson - Dell Children's Medical Center of Central TexasDragana Milosevic - Dell Children's Medical Center of Central TexasAsha A. Nair - Dell Children's Medical Center of Central TexasJaime Davila - Mayo ClinicJessica R. Balcom - Dell Children's Medical Center of Central TexasRobert B. Jenkins - Mayo ClinicKevin C. Halling - Mayo ClinicBenjamin R. Kipp - Mayo ClinicAmulya A. Nageswara Rao - Dell Children's Medical Center of Central TexasNadia N. Laack - Dell Children's Medical Center of Central TexasDavid J. Daniels - Mayo ClinicWilliam R. Macon - Mayo ClinicCristiane M. Ida - Dell Children's Medical Center of Central Texas
- Resource Type
- Journal article
- Publication Details
- Journal of neuropathology and experimental neurology, Vol.78(11), pp.1011-1021
- DOI
- 10.1093/jnen/nlz086
- PMID
- 31562743
- NLM abbreviation
- J Neuropathol Exp Neurol
- ISSN
- 0022-3069
- eISSN
- 1554-6578
- Publisher
- Oxford Univ Press
- Number of pages
- 11
- Grant note
- Anatomic Pathology Division, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
- Language
- English
- Date published
- 11/01/2019
- Academic Unit
- Pathology
- Record Identifier
- 9984756268102771
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