Recurrent HGNET-MN1 altered (astroblastoma MN1-altered) of the foramen magnum: Case report and molecular classification
- Department of Neurosurgery, Baylor College of Medicine,
- Departments of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sricharan Gopakumar, Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
DOI:10.25259/SNI_1208_2021Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Sricharan Gopakumar1, Malcolm F. McDonald1, Himanshu Sharma1, Claudio E. Tatsui2, Gregory N. Fuller3, Ganesh Rao1. Recurrent HGNET-MN1 altered (astroblastoma MN1-altered) of the foramen magnum: Case report and molecular classification. 15-Apr-2022;13:139
How to cite this URL: Sricharan Gopakumar1, Malcolm F. McDonald1, Himanshu Sharma1, Claudio E. Tatsui2, Gregory N. Fuller3, Ganesh Rao1. Recurrent HGNET-MN1 altered (astroblastoma MN1-altered) of the foramen magnum: Case report and molecular classification. 15-Apr-2022;13:139. Available from: https://surgicalneurologyint.com/surgicalint-articles/11544/
Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.
Case Description: Here, we present the case of a 36-year-old right-handed woman with recurrent low-grade astroblastoma in the cervicomedullary junction. The patient presented with worsening motor and sensory deficits of her upper extremities, pain, ataxia, visual disturbance, and nausea. Due to extensive recurrence and neurological symptoms, the patient underwent reoperation.
Conclusion: We review a rare case of recurrent astroblastoma in the foramen magnum in light of new relevant literature about tumor biology and prognostic significance of the new classification of astroblastoma MN1-altered.
Keywords: Astroblastoma, MN1-altered, Foramen magnum
Astroblastoma located in the cervicomedullary junction is an exceedingly rare entity.[
A 36-year-old right-handed woman with a history of low-grade astroblastoma presented with a 2-month history of worsening left-sided weakness, neck pain, right upper extremity numbness, gait ataxia, blurry vision, nausea, dizziness, and fatigue. She previously underwent gross total surgical resection in 2002 followed by 6 weeks of radiation therapy in 2004 for progressive disease. Tumor progression in 2015 prompted subtotal resection followed by hypofractionated stereotactic radiosurgery for continued progression in 2016 and six cycles of temozolomide in 2017. The patient has a long-standing history of orthostatic hypotension, back pain, spasticity, and left foot drop.
On physical examination, the patient had persistent horizontal nystagmus on bilateral lateral gaze, tongue deviation to the right, and left-sided hemiparesis. Upper and lower extremities were spastic bilaterally but worse on the left side. Lower extremities were deconditioned with 0/5 motor strength in the left ankle, which was hyper-reflexic with nonsustained clonus. Fine touch sensation was diminished in the right upper extremity and proprioception was diminished in the right upper extremity and both lower extremities.
MRI imaging revealed a right paramedian intradural foramen magnum lesion, most likely representing recurrent expansile cervicomedullary astroblastoma given the patient’s history [
MRI of astroblastoma MN1-altered tumor. (a-c) Sagittal, axial, and coronal preoperative T1 MRI revealing an intra-axial, heterogeneously enhancing lesion centered in the cervicomedullary junction with rostral extension into the pontomedullary junction and caudal extension into the C1-C2 spinal cord. (d-f) Sagittal, axial, and coronal postoperative T1 MRI demonstrating successful resection of the lesion.
The patient was considered a candidate for repeat surgical resection using a midline sub-occipital approach with the patient in the prone position to avoid the prior right far lateral craniotomy. A sub-occipital craniotomy, C1 laminectomy, midline durotomy, and subtonsillar approach were used. Neuromonitoring, SSEPs, and MEPs for cranial nerves 9, 10, 11, and 12 were utilized with the goal of maximal safe debulking using ultrasound, the operative microscope, and neuronavigation. Tissue samples were obtained for histological and immunohistochemical analyzes.
The patient tolerated surgery well and was extubated. Postoperatively, she experienced bilateral numbness in all extremities with increased numbness on the right side. Baseline left-sided hemiparesis and bilateral hyper-reflexia remained. Muscle tone in the upper and lower extremities was increased without spasticity and tongue deviation was further to the right. Postoperative MRI demonstrated successful resection of the lesion [
Pathological analysis revealed an epithelioid neoplasm with tumor cells displaying elevated mitotic activity with a Ki67 proliferation index of 19% on average and up to 26% in hotspots, distinct cell borders, and variable sheet-like, pseudopapillary, and trabecular architecture [
Histopathology of astroblastoma MN1-altered tumor. (a-c) Hematoxylin and eosin staining exhibiting epithelioid neoplasm with highly mitotic tumor cells with an average Ki67 proliferation index of 19%, distinct cell borders, variable sheet-like, pseudopapillary, and trabecular architecture, and multiple foci of bland necrosis with hyalinized vessels. (d) Positive for EMA immunoreactivity, (e) positive for Ki67 staining (average index of 19%, hotspots of 26%).
At 15-month follow-up, the patient had completed four cycles of bevacizumab and lomustine but continued to decline with worsening diffuse weakness and quadriplegia due to tumor recurrence. The patient required frequent assistance and medical care with a Karnofsky performance score of 50. Given her progressive decline with worsening weakness and quadriplegia, patient was referred to home hospice.
Astroblastoma is a rarely occurring glioma estimated to account for 0.5–2.8% of diagnosed pediatric gliomas.[
Histologic and genetic characteristics of astroblastoma
Given the rarity of astroblastoma, ependymoma typically needs to be excluded, especially since both tumors frequently occur in younger patients and appear well-circumscribed, solid, and cystic.[
Molecular analysis has allowed for classification of primitive neuroectodermal tumors of the CNS and has given rise to four novel brain tumor groups defined by DNA-methylation, including a new entity termed CNS HGNET-MN1 located at 22q12.3.[
Prognostic factors and new classification
Given this new discovery, a series of cases with either astroblastoma morphology or molecular MN1 alteration were reanalyzed for prognostic significance. In a case series of 73 patients with MN1 altered tumors, astroblastoma morphology was significantly associated with improved overall survival compared to nonastroblastoma tumors, suggesting the value of an integrated molecular and histological diagnosis.[
Interestingly, recent reports of brainstem and spinal cord astroblastoma tumors have a novel fusion between Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) and BEN Domain Containing 2 (BEND2).[
The histologic and clinical features of our patient’s neoplasm are consistent with the newly described astroblastoma MN1-altered, specifically a recurrent HGNET-MN1 altered astroblastoma. In addition, another recent molecular case series which reanalyzed previously diagnosed astroblastomas observed that MN1-altered tumors had a prolonged clinical course with multiple local tumor recurrences, which was also seen in our case.[
Foramen magnum tumors may be challenging to localize due to myriad of symptoms that cause complex clinical presentation. Astroblastomas have characteristics of both astrocytoma and ependymoma, though its origin remains unclear.[
The authors certify that they have obtained all appropriate patient consent.
There are no conflicts of interest.
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