J Pathol Transl Med.  2018 Jan;52(1):28-36. 10.4132/jptm.2017.09.25.

Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach

• Kim SI
• Lee Y
• Won JK
• Park CK
• Choi SH
• Park SH

• KMID: 2403255
• DOI: http://doi.org/10.4132/jptm.2017.09.25

Abstract

BACKGROUND
Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients.
METHODS
Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups.
RESULTS
We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old).
CONCLUSIONS
Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.

Keyword

Oligoastrocytoma; Glioblastoma with oligodendroglioma component; WHO classification; Genetics; Integrated diagnosis

MeSH Terms

Astrocytoma
Classification
Diagnosis
Disease-Free Survival
Genetics
Glioblastoma
Glioma
Humans
Necrosis
Oligodendroglioma
Pathology
Prognosis
Seoul

Figure

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  Fig. 1. Hematoxylin and eosin features of a case that was previously diagnosed as glioblastoma with oligodendroglial component. This case turned out to be glioblastoma, IDH-wildtype in new classifications.

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  Fig. 2. Change in diagnosis after applying molecular genetics integrated diagnostic criteria. OA, oligoastrocytoma; AOA, anaplastic oligoastrocytoma; GBMO, glioblastomas with an oligodendroglial component; DA, diffuse astrocytoma; m, mutant; w, wildtype; AA, anaplastic astrocytoma; AO, anaplastic oligodendroglioma; GBM, glioblastoma.

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  Fig. 3. Overall survival (OS) in different clinical, histological, and molecular subgroups. (A) Age over 45 years. (B) Necrosis. (C) IDH mutation status. (D) ATRX methylation status. (E) p53 positivity (more than 20% of tumor in immunohistochemistry). (F) 1p/19q-codeletion status.

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  Fig. 4. Progression-free survival (PFS) in different clinical, histological, and molecular subgroups. (A) Age over 45. (B) Necrosis. (C) IDH mutation status. (D) ATRX methylation status. (E) p53 positivity (more than 20% of tumor in IHC). (F) 1p/19q-codeletion status.

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  Fig. 5. Overall survival (A) and progression-free survival (B) in rediagnosed subgroups. AA, anaplastic astrocytoma; DA, diffuse astrocytoma; AO, anaplastic oligodendroglioma; GBM, glioblastoma; IDH-m, IDH-mutant; IDH-w, IDH-wildtype.

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