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Background <p>Spinal ependymomas (SE) account for 10% of ependymomas and are the most frequent spinal glial tumors. <i>NF2</i>-related Schwannomatosis (<i>NF2-</i>SWN) patients are predisposed to multiple SE in addition to other tumors, schwannomas and meningiomas. Surgery remains the main treatment option, but mays lead to severe morbidity. In many cases, it is the&#xa0;cystic rather than the solid component&#xa0;of the tumor that drives neurological symptoms and ultimately necessitates surgical intervention. Understanding tumor and associated cyst formation is therefore important to develop new therapeutic approaches.</p> Methods <p>This clinical and radiological study includes 33 <i>NF2</i>-SWN with a long-term follow-up and 11 sporadic SE patients. Tumor and cyst characteristics were assessed, and histopathological analyses performed, including multiplex immunohistochemistry and RNA sequencing.</p> Results <p>Radiological analysis revealed that peritumoral edema frequently precedes cystic formation. Histological analysis showed that macrophage infiltration, particularly by SPP1-positive macrophages, was associated with cystic growth in <i>NF2-</i>SWN SE. RNAseq analysis identified distinct immune microenvironments differentiating <i>NF2</i>-SWN from sporadic SE, including differences in <i>VEGF-C</i> expression. Consistent with these results, AXITINIB, a selective inhibitor of VEGFR and VEGFR3 which acts as the receptor for VEGF-C, was proposed to a <i>NF2</i>-SWN patient with a progressing cystic SE and resulted in clinical improvement accompanied by a reduction in the peritumoral cyst.</p> Conclusion <p>These results support a role for VEGF signaling and macrophage-mediated microenvironmental changes in edema and cystic growth of <i>NF2</i>-SWN SE. The observed clinical response to AXITINIB in an index patient suggests that new combinations of anti-angiogenic therapies may represent a promising early targeted approach.</p>

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Comprehensive characterization of spinal ependymomas in NF2-Schwannomatosis

  • 期刊论文

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  • 发表日期：

    2026年5月28日

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  • Pauline Marijon,
  • Yu Teranishi,
  • Franck Bielle,
  • Marc Sanson,
  • Matthieu Peyre,
  • Michel Kalamarides

摘要

Background

Spinal ependymomas (SE) account for 10% of ependymomas and are the most frequent spinal glial tumors. NF2-related Schwannomatosis (NF2-SWN) patients are predisposed to multiple SE in addition to other tumors, schwannomas and meningiomas. Surgery remains the main treatment option, but mays lead to severe morbidity. In many cases, it is the cystic rather than the solid component of the tumor that drives neurological symptoms and ultimately necessitates surgical intervention. Understanding tumor and associated cyst formation is therefore important to develop new therapeutic approaches.

Methods

This clinical and radiological study includes 33 NF2-SWN with a long-term follow-up and 11 sporadic SE patients. Tumor and cyst characteristics were assessed, and histopathological analyses performed, including multiplex immunohistochemistry and RNA sequencing.

Results

Radiological analysis revealed that peritumoral edema frequently precedes cystic formation. Histological analysis showed that macrophage infiltration, particularly by SPP1-positive macrophages, was associated with cystic growth in NF2-SWN SE. RNAseq analysis identified distinct immune microenvironments differentiating NF2-SWN from sporadic SE, including differences in VEGF-C expression. Consistent with these results, AXITINIB, a selective inhibitor of VEGFR and VEGFR3 which acts as the receptor for VEGF-C, was proposed to a NF2-SWN patient with a progressing cystic SE and resulted in clinical improvement accompanied by a reduction in the peritumoral cyst.

Conclusion

These results support a role for VEGF signaling and macrophage-mediated microenvironmental changes in edema and cystic growth of NF2-SWN SE. The observed clinical response to AXITINIB in an index patient suggests that new combinations of anti-angiogenic therapies may represent a promising early targeted approach.