Intramedullary epithelioid malignant peripheral nerve sheath tumour arising from sporadic schwannoma in the thoracic spine: first case report and review of the literature

Introduction

Intramedullary schwannomas are exceptionally rare due to the absence of Schwann cells in the central nervous system, comprising only 1.1% of all spinal schwannomas (1). The malignant transformation of a schwannoma in a patient without neurofibromatosis type 1 (NF1) is an especially unusual phenomenon (2). Of note, epithelioid malignant peripheral nerve sheath tumours (EMPNSTs) are a rare variant of MPNST with distinctive morphology and immunophenotype. Whilst EMPNSTs are less likely overall to arise from a benign peripheral nerve sheath tumour (BPNST) compared to a conventional MPNST, there is a predisposition if the primary tumour is a schwannoma and if the patient does not have NF1 (3,4).

Here, we report a unique case of a 56-year-old male with no history of NF1 who developed an intramedullary EMPNST secondary to an intramedullary schwannoma. To the best of our knowledge, this is the first report of an intramedullary spinal MPNST arising from an intramedullary schwannoma, the first report of an intramedullary EMPNST and only the fourth report of an intramedullary spinal MPNST (5). We present this case in accordance with the CARE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-24-143/rc).

Case presentation

A 53-year-old man presented with 5 months of progressive neuropathic pain in the right anterior thigh and leg. He had no other neurological symptoms and no NF1. Neurological examination revealed an antalgic gait and diminished knee and ankle reflexes bilaterally with intact power in the lower limbs. Magnetic resonance imaging (MRI) revealed an 8 mm × 4 mm right sided intradural extramedullary oval structure at the T11/12 level with enhancement.

A T11–L1 laminectomy and subtotal resection of the T11/T12 intradural lesion was performed. The intradural extramedullary portion attached to the nerve root was fully resected. The intramedullary portion was left intact to avoid the risk of iatrogenic spinal cord injury. The patient was discharged home with complete symptomatic resolution. A histopathological diagnosis of schwannoma was made. With the exception of the removed extramedullary component, MRI 2 months post-surgery showed an appearance similar to the pre-operative MRI, with expansion and lobulated T2 hyperintensity within T10–T12 and the conus medullaris (Figure 1).

Figure 1 MRI of the thoracolumbar spine demonstrating postoperative changes from T10 to L1 laminectomy. (A) Sagittal T2-weighted image showing expansion and lobulated hyperintensity across T10–T12 and conus medullaris. (B) Sagittal T1-weighted image with contrast showing associated enhancement of the lesion. (C) Axial T2-weighted image. (D) Axial T1-weighted image with contrast. MRI, magnetic resonance imaging.

Three years following the first operation and one year after the last stable surveillance MRI (Figure 2), the patient re-presented with thoracic myelopathy, reporting one month of lower back pain, bilateral posterior thigh pain and weakness, double incontinence and erectile dysfunction. Examination revealed bilateral T11 sensory level with mild weakness in the right lower limb. MRI spine revealed a new 1 cm intramedullary enhancing T1 isointense, T2 hyperintense lesion at the level of T11, causing expansion of the conus (Figure 3). Resection of the conus intramedullary tumour was performed with the aid of neuromonitoring. Intra-operatively, a redo thoracic laminectomy was performed, followed by a midline durotomy and midline myelotomy. Central debulking of the intramedullary tumour with an ultrasonic aspirator followed by gentle circumferential dissection was carried out without significant cord manipulation until gross total resection was achieved. The tumour was reddish-grey in colour and soft in consistency with scattered areas of rubbery and fibrous regions throughout (Figure 4). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Helsinki Declaration and its subsequent amendments. Verbal informed consent was obtained from the patient for publication of this case report and accompanying images.

Figure 2 Surveillance MRI of the thoracolumbar spine 2 months post initial surgery demonstrating persistent lobulated expansion of the spinal cord extending from the base of T10 to the T12 vertebral body. (A) Sagittal T2-weighted image with increased T2 signal intensity suggestive of oedema involving the right hemicord at the T11 level. (B) Sagittal T1-weighted image with contrast showing focal enhancement. (C) Axial T2-weighted image highlighting right hemicord expansion with hyperintensity. (D) Axial T1-weighted image with contrast. MRI, magnetic resonance imaging.

Figure 3 MRI of the thoracolumbar spine. (A) Sagittal T2-weighted image. (B) Sagittal T1-weighted image with contrast showing focal enhancement. (C) Axial T2-weighted image. (D) Axial T1-weighted image with contrast. MRI, magnetic resonance imaging.

Figure 4 Dorsal intra-operative review of the intramedullary MPNST following a dorsal midline myelotomy. MPNST, malignant peripheral nerve sheath tumour.

Immediately following the surgery, the patient was paraplegic. Catheter tug remained intact. Left lower limb power returned to pre-operative baseline over the course of a few days, while the right lower limb had persistent weakness. Post-operative MRI demonstrates complete resection of the enhancing intramedullary tumour. The patient is planned for post-operative radiation therapy (RT).

The pathology of the previously resected schwannoma was reviewed in light of the patient’s unusual clinical progression. Predominant spindle cell morphology with elongated cells in a myxoid background and strong S100 positivity reaffirmed the initial diagnosis of a schwannoma. Histopathological analysis of the present biopsy was performed (Figure 5). The specimen showed a loosely arranged spindle cell lesion with areas of increased cellularity (Figure 5A). Epithelioid cells with moderate amounts of eosinophilic cytoplasm and eccentrically located nuclei produced a rhabdoid appearance (Figure 5B). Immunoperoxidase stains showed variable S100 expression, supporting a neuromelanocytic lineage (Figure 5F). However, lack of Melan-A is more consistent with a neural lineage tumour (Figure 5H). The molecular profile and loss of integrase interactor 1 (INI-1) expression further supported a diagnosis of epithelioid MPNST (Figure 5I).

Figure 5 Histopathology images of the EMPNST using H&E staining (A,B) and immunohistochemical staining (C-J). Numbers in parentheses indicate magnification. (A) H&E stained section under low power demonstrating variable cellularity (×20). (B) H&E stained section showing atypical, dispersed hyperchromatic cells with rhabdoid/plasmacytoid appearance (×200). (C) CD138 non-specific background staining negative in tumour cells (×100). (D) Desmin-negativity in tumour cells, with staining only positive in vessels (×100). (E) AE1/3 negativity (×40). (F) Variable staining of S100 (×20). (G) Patchy SOX10 staining (×40). (H) Melan-A negativity (×40). (I) INI-1 lost in tumour cells, with internal positive control demonstrated in background endothelial and inflammatory cells (×100). (J) High Ki-67 index of 70% (×20). EMPNST, epithelioid malignant peripheral nerve sheath tumour; H&E, haematoxylin and eosin.

Discussion

Three cases of spinal intramedullary MPNSTs are described in the literature. Unlike our patient, all are of cervical spine location with no pre-existing BPNST. Paolini et al. reported the first case at C4–C5 levels in a 50-year-old man with a history of RT for childhood tonsillitis (6). Similarly, Newell et al. described a 35-year-old female with NF1 and past RT for an optic glioma and trigeminal MPNST subsequently diagnosed with a C7 intramedullary MPNST (4). Excluding our current case, only Marton et al. describe an intramedullary MPNST with no underlying risk factors such as prior RT or NF-1 (3). Nevertheless, none of the MPNSTs in the aforementioned cases are described as epithelioid.

Most spinal schwannomas are intradural extramedullary in location. Intramedullary schwannomas are extremely rare, especially in the thoracic region as observed in our patient (7). The pathogenesis of this seemingly paradoxical diagnosis remains unclear given the absence of Schwann cells in the central nervous system (4). One plausible explanation involves the presence of ectopic Schwann cells or embryologic remnants along the spinal cord, which may have given rise to the original intramedullary schwannoma (7). Notably, the concurrent presence of both intramedullary and extramedullary components in our patient’s tumour supports this hypothesis. Although the initial diagnosis of schwannoma was based on histopathological analysis of only the biopsied extramedullary component, extrapolating this diagnosis to the intramedullary lesion could be done with confidence given the consistent clinical and radiological findings, and retrospectively reaffirmed with the benefit of retrospect (i.e., malignant transformation).

The malignant transformation of BPNSTs, particularly schwannomas, remains a rare and poorly understood phenomenon. NF1 and prior radiation are the main established risk factors, associated with worse prognosis and increased risk of mortality if MPNST is developed (8,9). The sporadic nature of our patient’s case suggests that additional underlying genetic and immunological factors may drive tumour progression. This is particularly pertinent given that EMPNSTs, unlike conventional MPNSTs, are rarely associated with NF1 (10). Tumour suppressor genes such as INI-1, which showed loss of expression in our case, aligns with prior research identifying recurrent INI-1 inactivation as a defining molecular feature of EMPNST (11). This loss plays a crucial role in promoting uncontrolled cell proliferation and survival. Additionally, changes in the local tumour microenvironment may catalyse the malignant transformation of a BPNST. Chronic inflammation, hypoxia and mechanical stress from tumour growth are potential contributors. In the intramedullary spinal cord, where space is restricted, persistent mechanical pressure and hypoxic conditions could create an environment conducive to genetic instability and tumour progression.

To the best of our knowledge, intramedullary EMPNSTs are unreported in the literature. The distinct morphology and immunophenotype of EMPNST, characterised histologically by diffuse S100 protein positivity (11) combined with a rare location such as the intramedullary spine, poses a significant diagnostic and management challenge (10). In addition to their rare association with NF1 (10), interestingly the majority of MPNSTs arising from schwannoma display epithelioid cytomorphology despite EMPNSTs comprising only 5% of all MPNSTs (1). These factors align with our patient’s history, highlighting a potentially unique relationship between sporadic schwannomas and EMPNST.

Despite the extraordinary rarity of malignant transformation of BPNST, the present case highlights the importance of close postoperative radiological and clinical surveillance, especially in patients with sporadic spinal schwannoma with intramedullary extension. Further research into the genetic and environmental factors driving these transformations is essential to improve diagnostic accuracy and therapeutic strategies.

Conclusions

We have presented the case of a patient with an intramedullary sporadic schwannoma in the thoracic spine which underwent malignant transformation to become an EMPNST. This represents the first case of an intramedullary spinal MPNST arising from an intramedullary schwannoma, the first report of an intramedullary EMPNST and only the fourth report of an intramedullary spinal MPNST. This case highlights the importance of close clinical and radiological observation in spinal schwannomas with intramedullary extension to ensure timely recognition of malignant transformation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-24-143/rc

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-24-143/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-24-143/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Helsinki Declaration and its subsequent amendments. Verbal informed consent was obtained from the patient for publication of this case report and accompanying images.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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