Glioneuronal tumor with neuropil-like islands (GTNI) is a rare, recently described neoplasm, whose pathogenesis has not been studied extensively. The role of ATRX mutations, a class-defining alteration in diffuse astrocytic neoplasms, has not been assessed in GTNIs previously. We therefore aimed to assess the status of ATRX, along with IDH1, 1p/19q and p53, in cases of GTNI in order to evaluate the molecular profile of these tumors. All cases of GTNI diagnosed at our Institute were retrieved and clinicopathological features were reviewed. Immunohistochemistry for ATRX, IDH1 and p53 was performed. We identified four cases of GTNI, majority of which occurred in young adults. Loss of ATRX immunoexpression, a surrogate marker for ATRX mutation, was seen in all four cases. All cases were immunopositive for p53, while IDH1 positivity was seen in all three cases assessed. 1p/19q codeletion was absent in the three cases analyzed. These results indicate that the molecular pathogenesis of GTNIs similar to that of diffuse astrocytic tumors. Further, the loss of ATRX expression is seen in both the glial as well as neuronal components, indicating that both arise from the same tumor stem/progenitor cell and that the latter may be a metaplastic change. Thus, loss of ATRX immunoexpression, shown for the first time in these tumors, along with immunopositivity for p53 and IDH1, indicates that these tumors are molecular astrocytomas, and their clinical behaviour is likely to recapitulate that of ATRX-mutant and IDH-mutant diffuse astrocytomas of the same grade.
Keywords: ATRX; Astrocytoma; Brain tumors; Glioma; Glioneuronal tumor with neuropil-like islands; IDH.