ABSTRACT
Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.
