The 2016 WHO classification of CNS tumors included molecular parameters in addition to histology to redefine many tumor entities. Low-grade glioma (LGG) are divided into isocitrate dehydrogenase (IDH) wild type or mutant. Absence of IDH mutation is a rare event in LGG, and IDH wild type are considered a provisional entity. The technique used to assess IDH mutation is essential to determine the real impact of this tumor type.
The observation of a particularly favorable outcome in a group of 42 patients with a diagnosis of IDH wild type LGG (OS = 93.7 months) led us to retest IDH mutation with a more sensitive technique. Next Generation Sequencing (NGS) was used to retest IDH status in tumor samples, the results of NGS assay were compared with previous findings.
Initial assessment of IDH mutation in this 42 patients had been performed using PCR in 19 cases and immunohistochemistry in 2 cases. twenty-one (50%) of the 42 initial IDH wild type LGGs were discovered to be IDH mutant when tested with NGS. Four patients had R132H mutation while in the remaining 17 cases a rare IDH mutation was detected. In particular 4 patients showed IDH2 mutation, 5 patients had IDH1 R132C mutation, 5 patient had IDH1 R132G mutation and 3 patients had IDH1 R132S mutation. Median OS of NGS confirmed IDH mutated LGG was 164.0 months vs 32.2 months for NGS IDH wild type LGG reflecting the very distinct clinical course of these two entities.
Repeating testing in IDH wild type LGG cases is crucial, as well as the technique used to assess this mutation. NGS is able to assess IDH mutations in 50% of patients previously misdiagnosed. IDH wild type LGG remains a rare entity with dismal prognosis.
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All authors have declared no conflicts of interest.