PATH-43. INFRATENTORIAL IDH-MUTANT ASTROCYTOMAS REQUIRE HIGH INDEX OF SUSPICION FOR ACCURATE DIAGNOSIS

Abstract

Abstract BACKGROUND Banan et al (PMID 2776277) recently identified infratentorial IDH-mutant astrocytomas (Inf-IDHmt) as a distinct subtype in which 80% have non-canonical mutations, precluding the use of IDH1 R132H immunohistochemistry (IHC) for diagnosis. They note “molecular testing is critical for detection of these tumors”. Only 47% have ATRX loss by IHC and only 56% have MGMT promotor methylation. Thus, it is critical that neurosurgeons take this into account during surgical planning due to the requirement for adequate tissue sample volume necessary for diagnosis. We review these diagnostic challenges in our recent single institution experience with these tumors. METHODS Database text word searches were conducted for the years 2007-2023 to generate cases, coupled with chart review. RESULTS 7 cases were identified: 3 male and 4 female, ages 27-44. All cases were small stereotactic biopsies. The histological diagnosis was made exceptionally challenging by paucity of tumor cells (especially in grade 2), coupled with the fact that 5 of 7 had non-canonical IDH-mutation and 5 of 7 showed ATRX retention by IHC, necessitating a very high index of suspicion on the part of the pathologist to send for next-generation sequencing (NGS). Due to the rare co-expression of IDH and histone mutations in this subtype, 6 of 7 had H3 K27M IHC conducted; all were negative. Due to small tissue volumes, MGMT promotor methylation testing could only be conducted on 3 of 7 cases; testing was uninformative on these 3. CONCLUSION Preoperative high index of suspicion is required to obtain maximal safe biopsy volumes of tissue for molecular and MGMT methylation testing, which should be conducted on virtually all brainstem and cerebellar biopsies.