Impact of Molecular Pathology on Classifying Diffuse Gliomas
Impact of Molecular Pathology on Classifying Diffuse Gliomas
The 3 morphological entities that exhibit IDH-mut are FA (grades 2–4), OD (grades 2 and 3), and MOA (grade 2 or 3). All other brain tumors are IDH-wt, including most pediatric cases, pilocytic astrocytoma of any age, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, EP, medulloblastoma, and meningioma. IDH-wt diffuse astrocytomas, including de novo GBM, gliomatosis cerebri, thalamic, and brainstem astrocytoma, harbor a variety of genetic changes, and they should be regarded as distinct from their IDH-mut counterparts despite being morphologically indistinguishable. Conversely, cases of OD are almost always IDH-mut. Rare IDH-wt exceptions, including most pediatric cases, should be segregated within this diagnostic category until their pathogenesis is resolved. Morphologically MOAs are frequently IDH-mut and subsequently classifiable as either FA or OD following further molecular testing. The appropriate pathological diagnosis for the rare IDH-wt MOA remains unsettled; however, such tumors should still be segregated from the IDH-mut categories.
Common Morphological Entities
The 3 morphological entities that exhibit IDH-mut are FA (grades 2–4), OD (grades 2 and 3), and MOA (grade 2 or 3). All other brain tumors are IDH-wt, including most pediatric cases, pilocytic astrocytoma of any age, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, EP, medulloblastoma, and meningioma. IDH-wt diffuse astrocytomas, including de novo GBM, gliomatosis cerebri, thalamic, and brainstem astrocytoma, harbor a variety of genetic changes, and they should be regarded as distinct from their IDH-mut counterparts despite being morphologically indistinguishable. Conversely, cases of OD are almost always IDH-mut. Rare IDH-wt exceptions, including most pediatric cases, should be segregated within this diagnostic category until their pathogenesis is resolved. Morphologically MOAs are frequently IDH-mut and subsequently classifiable as either FA or OD following further molecular testing. The appropriate pathological diagnosis for the rare IDH-wt MOA remains unsettled; however, such tumors should still be segregated from the IDH-mut categories.