IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology

Abstract

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

A microdeletion event at 19q13.43 in IDH-mutant astrocytomas is strongly correlated with MYC overexpression

“…Such IDH-mutant astrocytomas with 19q loss were associated with better prognosis compared to those without [35]. IDH-mutant astrocytomas with 19q13 have also been reported before, but the authors have suggested that the underlying cause is the loss of the CIC gene, which resulted in oligodendroglioma like appearance [36].…”

Adult type diffuse gliomas in the new 2021 WHO Classification

“…Microcystic changes, oligodendroglial-like appearance and presence of gemistocytic differentiation may be present. Interestingly, oligodendroglioma-like morphological features are more common in IDH-mutant astrocytoma than in the IDH-wildtype counterpart 11 . Depending on tumor grade, histological features vary from low-cell-density tumors with mild nuclear atypia and low mitotic rate, referring to CNS WHO grade 2 tumors, to lesions with increased cell density, atypia and higher mitotic rate, referred to CNS WHO grade 3 or 4 ( Fig.…”

“…Concurrent mutations in TP53 and ATRX gene are also a typical feature of IDH-mutated astrocytomas, molecular features that are usually related to strong and intense p53 immunoreactivity and loss of ATRX expression 9 . IDH-mutant astrocytomas usually show a reliably expression of GFAP, even if some lesions may have a subset of GFAP negative cells, particularly in tumors with an oligodendroglial-like appearance 11 . In the latter case, Synaptophysin may be focally expressed.…”