Diagnosis -- Astroblastoma, MN1-Altered

FINAL DIAGNOSIS

Astroblastoma, MN1-Altered

DISCUSSION

MN1-altered astroblastomas occur most often in the cerebral hemispheres of young adults and children with strong female predominance [1]. MRI imaging typically shows a well-circumscribed mass with low T1, high T2, contrast enhancement and peripheral edema. Histologic features include pushing borders with limited tumor CNS infiltration. Astroblastic pseudorosettes are a characteristic finding, demonstrating neoplastic cells radially arranged in a perivascular pattern. The processes of these neoplastic cells tend to be shorter and broader than those typically encountered in ependymoma. Prominent vascular sclerosis and hyalinization are common [2]. While MN1 altered CNS tumors commonly demonstrate an astroblastic morphology [3], these morphologic features are not entirely specific to MN1-altered astroblastomas, with entities such as ZFTA-altered ependymomas, epithelioid glioblastomas, and pleomorphic xanthoastrocytomas being some of the entities in morphologic differential diagnosis [4]. Thus, differentiating MN1-altered astroblastomas from the aforementioned neoplasms is important as MN1-altered astroblastomas have been reported to have a better prognosis than other tumors with astroblastoma morphology [1,2], although a definitive WHO grade for MN-1 altered astroblastomas has yet to be defined.

The recently released 5th edition of the WHO classification of tumors of the central nervous system has revised the name of astroblastomas to reflect the underlying molecular alternation that characterizes this entity, namely alterations involving the MN1 gene (22q12.1). While this most commonly involves an in-frame fusion with the BEND2 gene (Xp22.13), other partners have been observed [3]. As in this case, alteration in MN1 frequently occur in isolation, although copy number variations, including monosomy 16, partial loss of 22q and X have been reported [3].DNA methylation array studies have reported that MN1-altered astroblastomas show a distinctive pattern from other tumors with astroblastic morphology and a specific methylation class (astroblastoma, MN1-altered, MN1:BEND2 fused) in the brain tumor classifier version 12.5 from the University of Heidelberg [5].

In summary, the demographic, radiologic, morphologic and immunohistochemical features present in the current case were compatible with a diagnosis of MN1-altered astroblastoma, a finding confirmed by molecular studies which demonstrated a MN1::BEND2 fusion. While the best match on methylation studies performed at the time of diagnosis was to high grade neuroepithelial tumor with MN1 alteration, the result demonstrated a low calibration score, most likely reflecting the lack of the more appropriate methylation class astroblastoma, MN1-altered, MN1:BEND2-fused in the version 11b4 of the brain tumor classifier that is now present in the more recent version 12.5 the brain tumor classifier from the University of Heidelberg.

REFERENCES

1. Chen, W., Soon, Y. Y., Pratiseyo, P. D., Sutanto, R., Hendriansyah, L., Kuick, C. H., Chang, K., & Tan, C. L. (2020). Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases. Brain tumor pathology, 37(4), 145-153.
2. Lehman, N. L., Usubalieva, A., Lin, T., Allen, S. J., Tran, Q. T., Mobley, B. C., ... & Orr, B. A. (2019). Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis. Acta neuropathologica communications, 7(1), 1-11.
3. Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., Soffietti, R., von Deimling, A., & Ellison, D. W. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-oncology, 23(8), 1231-1251.
4. Tauziède-Espariat A, Pagès M, Roux A, et al. Pediatric methylation class HGNET-MN1: unresolved issues with terminology and grading. Acta Neuropathol Commun. 2019;7(1):176.
5. Capper, D., Stichel, D., Sahm, F. et al. Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol 136, 181-210 (2018).

Contributed by Aofei Li, MD and Scott Kulich, MD, PhD