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Diagnosis and Discussion: Case 1139

Initial Morphologic Diagnosis: 

Neuroepithelial Neoplasm with High-grade Morphologic Features

Molecular studies return with the following results:

Next-Generation Sequencing
MN1::BEND2 fusion
17p region (TP53) copy number LOSS
Xp/Xq region copy number LOSS

DNA Methylation Array Classification (Heidelberg classifiers)
Methylation Class (v11b4): CNS high-grade neuroepithelial tumor with MN1 alteration (calibrated score - 0.99)
Methylation Class (v12.5): Astroblastoma, MN1-altered (calibrated score – 0.94)
Methylation Subclass: N/A

Final Integrated Morphologic-Molecular Diagnosis: 

Astroblastoma, MN1-Altered

Discussion

We present a rare case of a primary pediatric spinal cord astroblastoma, MN1-altered.

Primary central nervous system tumors are the second most prevalent tumor type found in the pediatric population. Among these, spinal cord tumors account for approximately 10%, with 90-95% of them being glial in origin. Before the advent of molecular classification, the 4th edition of the WHO placed astroblastoma under the classification of Glial Neoplasm of Uncertain Origin due to the unique nature of these tumors having shared features with ependymoma and astrocytoma. Astroblastoma frequently occur in children and young adults (3 months-40 years; median 15yo) with a marked female predominance and are generally supratentorial, however rare intraventricular, brainstem, and spinal cord examples have been documented1-3.

Morphologically, astroblastoma are described as round, cuboidal, or columnar cells with variable pseudopapillary or perivascular growth, vascular/pericellular hyalinization, and perivascular anucleate zones. As a rule, they are circumscribed tumors with pushing borders or minimal infiltrative growth without diffuse infiltration4. Histological variability leads astroblastomas to frequently be described as mimickers, such as our case with the histology mimicking an embryonal tumor, and the hallmark features (astroblastic pseudorosettes and vascular hyalinization) are not entity specific.

Circumscribed gliomas with structural rearrangements of the MN1 gene (22q12.1) that result in fusion are considered diagnostic of astroblastoma, MN1-altered.  Molecular studies identified a MN1::BEND2 fusion in this patient, an alteration that is highly prevalent in astroblastoma. Additional methylation array testing using the University of Heidelberg 12.5 version classifier, matched the tumor to “astroblastoma, MN1 altered” with a high calibrated score (0.94)5. 

Astroblastomas are currently not assigned a WHO grade as variable clinical outcomes have been reported6. The spinal location of this tumor is particularly rare, precluding predicting an accurate prognosis in this case. Since no molecular target was identified and drop lesions were identified on MRI, the patient underwent adjuvant radiation therapy.

References

  1. Fu L, Lao IW, Huang L, Ou L, Yuan L, Li Z, Li S, Hu W, Xi S: Spinal Cord Astroblastoma With EWSR1-BEND2 Fusion in Female Patients : A Report of Four Cases From China and a Comprehensive Literature Review. Am J Surg Pathol 2024, 48:1372-80.
  2. Shin SA, Ahn B, Kim SK, Kang HJ, Nobusawa S, Komori T, Park SH: Brainstem astroblastoma with MN1 translocation. Neuropathology 2018, 38:631-7.
  3. Chen W, Soon YY, Pratiseyo PD, Sutanto R, Hendriansyah L, Kuick CH, Chang KTE, Tan CL: Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases. Brain Tumor Pathol 2020, 37:145-53.
  4. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P: The 2007 WHO classification of tumours of the central nervous system. Acta neuropathologica 2007, 114:97-109.
  5. Capper D, Stichel D, Sahm F, Jones DTW, Schrimpf D, Sill M, Schmid S, Hovestadt V, Reuss DE, Koelsche C, Reinhardt A, Wefers AK, Huang K, Sievers P, Ebrahimi A, Scholer A, Teichmann D, Koch A, Hanggi D, Unterberg A, Platten M, Wick W, Witt O, Milde T, Korshunov A, Pfister SM, von Deimling A: Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol 2018, 136:181-210.
  6. Tauziede-Espariat A, Pages M, Roux A, Siegfried A, Uro-Coste E, Nicaise Y, Sevely A, Gambart M, Boetto S, Dupuy M, Richard P, Perbet R, Vinchon M, Caron S, Andreiuolo F, Gareton A, Lechapt E, Chretien F, Puget S, Grill J, Boddaert N, Varlet P, Renoclip LOC: Pediatric methylation class HGNET-MN1: unresolved issues with terminology and grading. Acta Neuropathol Commun 2019, 7:176.