Diagnosis -- Synchronous IDH-mutant Anaplastic Astrocytoma and Oligodendroglioma

FINAL DIAGNOSIS

Synchronous IDH-mutant anaplastic astrocytoma and oligodendroglioma:

• Left Frontal Lesion: ANAPLASTIC ASTROCYTOMA, IDH-mutant, WHO grade 3;
• Right Parietooccipital Lesion: OLIGODENDROGLIOMA, IDH-mutant and 1p/19q co-deleted, WHO grade 2

DISCUSSION

IDH-mutant gliomas occur most often in adults between the ages of 30-50 and present as single parenchymal lesion. Multicentric gliomas are defined as multiple anatomically separated lesions, located in different lobes or hemispheres, with no apparent hematogenous or CSF dissemination or local spread of tumor cells. This clinical and radiologic picture is typically encountered in high-grade tumors such as glioblastomas and is a well-documented phenomenon, reported in 2-16.2% of cases [1]. Despite the lack of MRI signal abnormalities in the intervening brain tissue, at the histopathologic level these tumors can be widely invasive, with sparse malignant cells invading far from the main tumor mass. In many cases, therefore, multicentric gliomas likely arise from a single tumor cell population that expands into a radiologically identifiable mass in multiple locations.

In contrast, the simultaneous development of two primary gliomas with different histological types and distinct molecular profiles is much rarer and the etiology is unclear. In a small case series of multicentric diffuse low-grade gliomas, a 35-year-old man with WHO Grade II oligodendroglioma and astrocytoma found in separate hemispheres was described [2]. Most recently, Vaubel and colleagues reported a synchronous gemistocytic astrocytoma and oligodendroglioma in a 49-year-old man harboring rs55705857 polymorphism at 8q24 near CCDC26 [3], a risk allele associated with IDH-mutant gliomas [4][5]. Several theories have been proposed attempting to explain the synchronicity of primary brain tumors with different phenotypes and genotypes, but they are largely speculative. Some authors have postulated that an oncogenic stimulus could yield a malignant transformation in different cell lineages or could cause a transformation only in susceptible regions. Others have suggested that one neoplasm may act as an irritant which stimulates the development of the other. Another possibility that should be taken into consideration, especially in biopsy only cases, is intratumoral heterogeneity, which has been discussed in rare dual-genotype oligoastrocytomas with shared IDH alteration and biphasic components harboring ATRX/TP53 mutation and 1p/19q-codeletion, respectively [6][7].

In our case, the lesions demonstrated distant locations, different phenotypes and WHO grades, and distinct molecular profiles with IDH1 mutation being the only shared feature. Although the presence of a common progenitor population with only IDH1 mutation cannot be entirely excluded, we do not have clear evidence of such a population, and we favor the random synchronous development of two independent IDH-mutant glial neoplasms. Whether this could be influenced in the current case by a risk allele predisposing to IDH-mutant tumors has not been tested.

REFERENCES

1. Di Russo P, Perrini P, Pasqualetti F, Meola A, Vannozzi R. Management and outcome of high-grade multicentric gliomas: a contemporary single-institution series and review of the literature. Acta Neurochir (Wien). 2013 Dec;155(12):2245-51.
2. Terakawa Y, Yordanova YN, Tate MC, Duffau H. Surgical management of multicentric diffuse low-grade gliomas: functional and oncological outcomes: clinical article. J Neurosurg. 2013 Jun;118(6):1169-75.
3. Vaubel RA, Kollmeyer TM, Caron AA, Barr Fritcher EG, Voss JS, Liang H, Jenkins RB, Giannini C, Kipp BR. Synchronous gemistocytic astrocytoma IDH-mutant and oligodendroglioma IDH-mutant and 1p/19q-codeleted in a patient with CCDC26 polymorphism. Acta Neuropathol. 2017 Aug;134(2):317-319.
4. Oktay Y, Ülgen E, Can Ö, Akyerli CB, Yüksel ?, Erdemgil Y, Duras? IM, Henegariu OI, Nanni EP, Selevsek N, Grossmann J, Erson-Omay EZ, Bai H, Gupta M, Lee W, Turcan ?, Özp?nar A, Huse JT, Sav MA, Flanagan A, Günel M, Sezerman OU, Yak?c?er MC, Pamir MN, Özduman K. IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation. Sci Rep. 2016 Jun 10;6:27569.
5. González-Castro TB, Juárez-Rojop IE, López-Narváez ML, Tovilla-Zárate CA, Genis-Mendoza AD, Pérez-Hernández N, Martínez-Magańa JJ, Rodríguez-Pérez JM. Genetic Polymorphisms of CCDC26 rs891835, rs6470745, and rs55705857 in Glioma Risk: A Systematic Review and Meta-analysis. Biochem Genet. 2019 Aug;57(4):583-605.
6. Huse JT, Diamond EL, Wang L, Rosenblum MK. Mixed glioma with molecular features of composite oligodendroglioma and astrocytoma: a true "oligoastrocytoma"? Acta Neuropathol. 2015 Jan;129(1):151-3.
7. Wilcox P, Li CC, Lee M, Shivalingam B, Brennan J, Suter CM, Kaufman K, Lum T, Buckland ME. Oligoastrocytomas: throwing the baby out with the bathwater? Acta Neuropathol. 2015 Jan;129(1):147-9.

Contributed by Wen Zhong, MD and Tom Pearce, MD, PhD