Article
Distinct morphology in molecular subgroups of glioblastoma in young patients
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Published: | August 25, 2015 |
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Introduction: Glioblastoma is a malignant primary brain tumor that occurs in all age groups and corresponds to WHO°IV. Based on genetics, global gene expression, and methylation patterns, glioblastoma can be categorized in six different molecular subgroups named “IDH”, “K27”, “G34”, “RTK I”, “Mesenchymal”, and “RTK II” (Sturm et al. 2012). ”IDH” glioblastomas, which carry mutations within IDH1 or IDH2 as well as the “K27” and “G34” subgroups, which are characterized by distinct mutations within the H3F3A gene, are particularly often found in younger patients below 30 years of age.
Objective: We aimed to analyze the histomorphology of glioblastoma found in younger patients with known molecular subgroups.
Patients & methods: Patients <30 years were included in the study. IDH1 R132H and H3F3A K27M mutation status was defined by immunohistochemistry and verified by pyrosequencing. Other IDH1 or IDH2 mutations, as well as H3F3A G34R mutations were analyzed by pyrosequencing.
Results: Besides disparities in cell density, cellular morphology and nuclear pleomorphism, we detected different extents of vessel proliferation and geographic or pseudopallisading necroses in the distinct molecular subgroups. Specifically, glioblastoma cases carrying H3F3A G34R mutations displayed a very undifferentiated morphology with densely packed cells and high nuclear pleomorphism. H3F3A K27M mutated cases more often showed necroses and commonly showed tumor cells with large and sometimes vacuolated nuclei. IDH mutated cases displayed lower cell density, an astroglial morphology and often harbored microcystic features or gemistocytic tumor cells.
Conclusions: Molecular glioblastoma subgroups are characterized by distinct histomorphological features that can be detected by routine histology. This underlines the diversity of glioblastoma and suggests that distinct morphological features reflect the underlying molecular changes.