Astroblastoma is a rare tumor with diversified forms in the central nervous system, and the pseudorosettes and blood vessel hyaloplasm are its important characteristics. Most astroblastomas occur in the cerebral hemisphere. Two lesions were discovered on T5-7 and T12-L1, which were benign lesions observed under radiography.

Rhabdoid cell and radial cell were observed from the perspective of morphology. Due to unique cellular structure (high level of mitotic count and porous morphological structure), this tumor is classified as high-grade tumor.

IHC: Diffuse expression GFAP, Olig-2 and S-100.

FISH: MN1 rearrangement and 1p chromosome deletion detected.

NGS and Sanger sequencing: To further determine that the partner gene of MN1 is BEND2.

MN1 mutation plays an important role in the diagnosis and prognosis of rare astroblastoma. Astroblastoma in the spinal cord may have a high recurrence rate, because the residual lesions are in a unique position and at a high grade, and the relationship with gene mutation is unclear. It is necessary to follow up patients regularly and further research and evidence-based medical evidence are needed to determine the diagnosis, prognosis and treatment of astroblastoma with molecular characteristics.

Astroblastoma is a rare brain tumor, which was first discovered and reported by Bailey and Bucy in 1930. This tumor can occur at any age, but it most commonly happens in infants and adolescents, especially in females. The site of occurrence is common in the cerebral hemispheres and rarely in the spinal cord. The tumor morphology can be seen in almost all cases with a cellular pseudorosette-like mass and distinct hyalinization in the blood vessels.

With the rapid development of molecular pathology, researchers have found that there are more and more molecular genetic changes in astroblastomas, including the acquisition of chromosomes 20q and 19, the deletion of chromosome 10 and sex chromosome X, the BRAF V600E mutation and the loss of heterozygosity of 9p. Strum et al. has defined astroblastomas as CNS solid tumors with changes in MN1 (CNS HGNET- MN1). RNA sequencing revealed two different fusion genes: MN1-BEND2 and MN1-CXXC5. Most tumors histologically identified as astroblastomas in the current database belong to this class of molecular grade tumors. Hirose et al. determined astroblastomas as a separate class of solid tumors with different clinical, radiological, and pathological features from ependymomas and other diffuse gliomas. X chromosome aberrations and MN1 rearrangement appear to be the characteristics of astroblastomas.

This article describes 1 case of recurrent astroblastoma in the spinal cord on a female aged 26. MN1-BEND2 fusion was detected with NGS.

Case reporting

The patient, female, 26Y, complained numbness and weakness of her lower limbs lasting for 1 year, with difficult defecation for 1 week. According to diagnosis, a mass was found on T5-T6 under MRI. (1A) She was treated in other hospitals in 2019. After operation, she was pathologically diagnosed as astroblastoma.

In 2021, the patient developed hypertension below the head, urinary incontinence, and occasional ambulatory instability. The patient was treated in our hospital with MRI showing 2×1.2×1.2cm and 0.9×0.8×0.7cm masses in the spinal cord at on T5-7 (1B) and T12-L1 (1C). The masses were well circumscribed and considered to be a recurrent tumor.

After the second operation, some mixed signals were found in the spinal cord through MRI, which was worrying because there were few residual lesions.

After excision of the original lesion, the patient did not undergo new adjuvant therapy. After resection of the recurrent tumor, the patient underwent radiation therapy as well as chemotherapy with temozolomide and erlotinib. Due to the unique location, the lesions were not completely removed in the two surgeries.

Six months later, MRI scan showed pseudorosette-like mass or nodular lesions on T6-7 and T9. The possibility of recurrence will not be ruled out in 2022.

Morphology: The histopathological features of astroblastoma reveal that the protrusions of intermediate fibroblasts are formed in parallel or radial arrangement and terminated in the vascular basilar membrane to form astrocyte pseudorosettes. The cross-sections are radial and the longitudinal sections are zonal (2A, B, C). Another important point in the diagnostic process is the lack of fibrous background in the tumor area. Tumor cells with striated muscle-like or signet-ring-like characteristics could be observed. (2D, E) The present case can be diagnosed a high-grade astroblastoma (2F) based on cellular structure, high mitotic count (more than 5 per 10 high-power fields), and heterogeneity. Stromal mucoid degeneration was focal (2G, h). In this case, there was bleeding in the focal area (2I).

IHC: The tumor cells were diffuse and strongly positive for the expressions of GFAP, Olig2, Vimentin, SSTR2, INI-1 and S-100 (3A, B, C and I). SYN and PR were diffusely positive (3D, h). IDH1, CAM5.2, BRAF V600E, H3 K27M, CD34, and NSE were all negative. CK-pan, EMA, CD57, EGFR, and CD44 were all focally positive (3E, G). P53 was weak positive. The Ki67 PI was less than 15% (3F).

Molecular detection: FISH was used to detect 98% (4A) of the isolated signals of MN1 gene. No EWSR1 gene rearrangement was detected (4B); and the detection of a 1p/19q co-deletion state revealed only the deletion of 1p (4C, D).

Tips: From the images of the MN1 separation probe used in this case, it could be seen that the signal types of multi-red-one fusion were common, and this type of atypical separation signal indicated positive separation. It is recommended to use a third-party platform for verification.

Furthermore, methylation mutation of BRAF gene, IDH1 gene, IDH2 gene, TERT promoter, or MGMT promoter was not detected.

To confirm the fusion type of the MN1 gene, NGS was used to detect the total RNA of tumor cells. MN1-Exon1 (22q12.1, red) and BEND2-Exon2 (Xp22.13, blue) were matched on the UCSC Genome Browser Human Feb. 2009 website (5A). According to the results of transcriptome sequencing, the relevant primers for MN1-BEND2 fusion were designed (5A). The predicted size of the PCR product was 300bp (5B). Sanger sequencing was performed using the above fragments and the result covered the breakpoint area. The sequence before and after the breakpoint was consistent with the transcription analysis, further confirming the existence of MN1-BEND2 fusion (5C).

In addition, about 1,267 cancer-related genes and immune-related markers for precise treatment were detected, but the results of the immune markers did not support immunotherapy.

Conclusion: These recurrent high-grade astroblastomas have multiple lesions, which are rare in the spinal cord, and are complicated with rhabdomyoid features, signet-ring cells, and mucoid degeneration. NGS and Sanger sequencing was used to confirm the MN1-BEND2 fusion. Obviously, researchers have found MNI mutations in many astroblastomas and announced the findings of other genes. This is very significant for the diagnosis and prognosis of rare astroblastomas, but requires more evidence-based data to support these findings.

Note: This case is published on Clinical Neuropathology

Spinal astroblastomas may have a poor prognosis. Complete surgical excision of the tumor within a few years is complex and may be a factor contributing to its recurrence. In particular, high-grade astroblastomas require regular follow-up to patients.