Cerebrospinal fluid dissemination of an intracranial malignant peripheral nerve sheath tumor in the sellar region: illustrative case

Abstract

BACKGROUND

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon types of soft tissue sarcomas. The occurrence of intracranial MPNSTs in the sellar region is exceedingly rare.

OBSERVATIONS

A 37-year-old female, who had undergone transnasal surgery for a pituitary adenoma followed by adjuvant stereotactic radiotherapy 10 years earlier, was diagnosed with an intracranial MPNST in the sellar region. A second transnasal procedure successfully removed the lesion and was followed by proton therapy. Three months postoperatively, spontaneous cerebrospinal fluid (CSF) rhinorrhea occurred and was repaired through a third transnasal surgery. A CSF test revealed the presence of suspicious tumor cells. Subsequently, acute hydrocephalus developed and was urgently managed with a ventriculoperitoneal shunt. About 2 months later, the patient died due to intraspinal metastasis.

LESSONS

Pathologically ambiguous lesions in the sellar region require meticulous observation, as MPNST can be erroneously diagnosed as a pituitary adenoma. Prompt surgical intervention provides the best opportunity for achieving complete resection, which remains the most effective treatment for MPNST. In addition to hematogenous metastasis, MPNST can also disseminate and implant via CSF, leading to recurrence. Acute hydrocephalus or intraspinal metastasis can significantly reduce overall survival.

https://thejns.org/doi/10.3171/CASE24437

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas originating from peripheral nerve sheath cells, typically found in the extremities and torso rather than the head and neck region.¹ MPNSTs occurring in the sellar region are exceptionally rare, with only 6 cases documented to date (Table 1). All previously reported cases were diagnosed postoperatively through histopathological examination due to their atypical clinical presentation and imaging characteristics. MPNST is associated with a poor prognosis due to its invasive nature.

TABLE 1.

Summary of published cases of intracranial MPNST in the sellar region

Authors & Year	Age (yrs)	Sex	Location	Hx	Sxs	Pathological Dx	NF1	Outcome
Kim et al., 200712	72	M	Rt-sided sellar mass	Observed mass for 9 mos	Ptosis of lt eye, diplopia	MTT	NA	Died
Krayenbühl et al., 20077	NA	NA	Intra- & suprasellar	Fractionated conventional radiation therapy	HA, blurred vision, & rapidly progressing visual field deficits	MPNST	No	Ok at 3-mo FU
Guo et al., 20145	68	F	Sellar lesion	Resection of pituitary adenoma & adjuvant radiotherapy 19 yrs earlier	Dizziness, vomiting, blindness in lt eye, reduced mobility of rt eye	MPNST	No	Ok at 4-mo FU
Abushamat et al., 201911	24	M	Pituitary mass extended down to sphenoid sinus	NA	HA, blurred vision, fatigue, decreased sexual drive, weight gain, nausea & vomiting	MPNST	No	NA
Thakkar et al., 202010	60	F	Sellar & suprasellar	NA	HA, bitemporal hemianopia	MPNST	No	Died in early postop period of bleeding complication
Wang et al., 20226	71	M	Sellar & suprasellar	Resection of pituitary adenoma & adjuvant radiotherapy 10 yrs earlier	Vision loss, intermittent nausea & vomiting	MTT	NA	Died 64 days after op to remove MTT

Dx = diagnosis; FU = follow-up; HA = headache; Hx = history; NA = not available; Sx = symptom.

Illustrative Case

A 37-year-old female presented with a history of growth hormone (GH)–secreting pituitary adenoma (Supplementary Figs. 1 and 2), with GH levels exceeding the measurable maximum value. The condition had been managed through an endoscopic endonasal transsphenoidal operation in 2013. As postoperative GH levels continued to exceed the measurable maximum, including GH levels recorded 1 month postoperatively (Table 2), the patient underwent stereotactic radiosurgery (SRS). Following these treatments, the patient recovered well, and no further tests were conducted for several years.

TABLE 2.

Pre- and postoperative GH and IGF-1 in 2013 and in 2023

	Lab Value (reference range)
	GH in µg/L (0.05–8.00)	IGF-1 in ng/mL (115.00–538.00)	IGF-1 in ng/mL (63.00–223.00)
Initial disease
Preop 6/5/2013	>120.00	1331.79
Postop 6/9/2013	>120.00	2284.18
Postop 6/13/2013	>120.00	2007.12
Postop 7/20/2013	>120.00	NA
Recurrence
Preop 8/28/2023	0.41		107
Postop 2/20/2024	0.2		65.8
Postop 2/23/2024	0.16		65

NA = not available.

Ten days prior to her hospital admission in August 2023, the patient experienced headache with vomiting, left ptosis, a fixed left eye, a dilated left pupil unresponsive to light, and no facial numbness. Preoperative levels of GH and insulin-like growth factor–1 (IGF-1) were within normal limits (Table 2). Computed tomography (CT) angiography excluded the presence of an intracranial aneurysm. Magnetic resonance imaging (MRI) revealed a mass occupying the intrasellar, suprasellar, and left parasellar regions, extending into the left cavernous sinus and encasing the internal carotid artery (ICA). The lesion demonstrated low signal intensity on T1-weighted imaging, strong signal on T2-weighted imaging, mixed signal on fluid-attenuated inversion recovery, isointense signal on diffusion-weighted imaging, and significant heterogeneous enhancement (Fig. 1). The optic chiasm was compressed and displaced upward by the mass. Based on these findings, a preliminary diagnosis of recurrent pituitary adenoma was made. The patient underwent an endoscopic endonasal transsphenoidal procedure, achieving gross-total resection with the sellar septa intact and no cerebrospinal fluid (CSF) leakage. Postoperatively, the headache, left eye movement dysfunction, and the absence of light reflex in the left pupil resolved completely. Pathological examination confirmed the diagnosis of MPNST rather than pituitary adenoma, characterized by negative H3K27Me3 and SOX10, positive MyoD1 and SATB2, and a Ki-67 proliferation index exceeding 30% (Fig. 2). No clinical features of neurofibromatosis type 1 (NF1) or NF2 were observed.

FIG. 1.

Preoperative images from August 2023. Sagittal contrast-enhanced MRI scan (A) showing heterogeneously strengthened irregular masses in the sellar and suprasellar regions. Axial (B) and coronal (C) contrast-enhanced MRI scans showing a heterogeneously strengthened irregular mass invading the left cavernous sinus and wrapping the ICA. Sagittal T2-weighted MRI scan (D) showing an irregular mass in the sellar and suprasellar regions, primarily with isointense signals. Axial T1-weighted (E) and T2-weighted (F) MRI scans showing the isointense signal irregular mass invading the left cavernous sinus.

FIG. 2.

The pathological diagnosis in 2023 was an MPNST. Tumor cells were unevenly distributed, and the surrounding blood vessels were rich in cells (A). Under high magnification (B), the cytoplasm of the tumor cells was lightly stained and eosinophilic. The nuclei were deeply stained and irregular (red arrow), with obvious mitotic images and focal necrosis (yellow arrow). Focal heterologous bone differentiation (black arrow, C) is shown. Tumor cells were focally positive for S100 (D). SOX10 was negative (E). H3K27Me3 was deficient in tumor cells (F). Some regions were positive for MyoD1 (G) and SATB2 (H). The Ki-67 proliferation index was 40% (I). Hematoxylin and eosin (A–C), original magnification ×100 (A) and ×200 (B–I).

In the fall of 2023, the patient underwent proton therapy targeting the sellar region, optic chiasm, visual pathway, lens, brainstem, and spinal cord. Imaging studies conducted before and after the therapy showed no evidence of local recurrence in the sellar region (Supplementary Fig. 3). The patient remained in good condition until February 2024, when she developed spontaneous CSF rhinorrhea. A third transsphenoidal operation was performed to repair the CSF leak using fat and femoral fascia, accompanied by lumbar drainage. During the 10-day lumbar drainage period, 1 CSF test identified suspicious tumor cells. The day after lumbar drainage was removed, the patient experienced a decline in consciousness, vomiting, and urinary incontinence. A head CT scan revealed acute hydrocephalus, necessitating an emergency ventriculoperitoneal shunt procedure. The patient recovered well and was discharged shortly thereafter.

However, within 1 week of returning home, the patient began experiencing progressive numbness starting in the feet and advancing to the legs, waist, and chest, accompanied by reduced lower-extremity muscle strength and difficulty with defecation. In April 2024, a physical examination revealed a positive Babinski sign on both sides, muscle strength of 0 in both lower limbs, and complete sensory loss below the T10 sensory level. Thoracolumbar MRI in early May showed extensive abnormal enhancement of lesions in the thoracolumbar pia mater and marked edema of the thoracolumbar spinal cord (Fig. 3). These findings strongly suggested that MPNST had metastasized into the spinal canal via CSF. Given the poor prognosis, the patient and her family declined further treatments, such as radiation therapy, chemotherapy, or targeted therapy, opting instead for hospice care. The patient’s condition deteriorated to generalized paralysis, and she died at the end of May.

FIG. 3.

Thoracolumbar MRI scans from May 2024. Thoracic (A) and lumbar (D) T2-weighted MRI scans showing that the spinal cord was compressed and uneven in thickness. Thoracic (B) and lumbar (E) T1-weighted MRI scans revealed that the extramedullary and subdural spinal cavities were filled with abnormal isointense signal masses. Thoracic (C) and lumbar (F) MRI scans with contrast agent showing that extramedullary subdural lesions were extensive. After enhancement, the pia, terminalis, cauda equina, and cisterna terminalis showed multiple bands and nodules with enhanced shadows, and the boundaries were not clear. The arrows in the figure indicate some of the lesions.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

MPNST is a relatively uncommon malignant mesenchymal lesion, constituting 5%–10% of all soft tissue sarcomas.² It refers to malignant tumors originating from peripheral nerves or their sheath cells, excluding epineurium or nerve vasculature. The subtypes include epithelioid MPNST, malignant triton tumor (MTT), and glandular MPNST.³ Its prevalence in the general population is about 1 in 100,000, with equal incidence in both sexes. The tumor primarily affects the proximal limbs, followed by the trunk, head, and neck regions. NF1 is present in 50% of cases, 10% have a history of radiation exposure, and the remainder are predominantly sporadic.⁴ MPNST in the sellar region is exceptionally rare, with only 6 cases reported to date (Table 1). Among these, 2 cases were similar to the present one, occurring years after pituitary adenoma resection and radiation therapy, with no history of NF1.^5,6 Another case was initially misdiagnosed as a relapsed lesion 10 months after sellar neurofibroma resection. Subsequent pathological diagnosis confirmed MPNST, leading to adjuvant radiation therapy. A relapse with increased malignancy occurred a decade later.⁷ About 10%–13% of MPNST patients report a history of therapeutic irradiation, with a mean latency period of 13.5 ± 7.8 years following radiotherapy,⁸,⁹ Sporadic sellar region MPNST cases have also been documented without any history of NF1 or prior radiation exposure.^10–12

Our case satisfies the Cahan criteria for true malignant transformation secondary to radiation therapy: 1) a histological diagnosis of a benign condition prior to irradiation, 2) malignancy developing within the radiation field, 3) a latency period of more than 5 years before malignancy appears, and 4) histological confirmation of malignancy.¹³ The association between radiation therapy and the development of MPNSTs is well documented. Ionizing radiation induces chromosomal damage and promotes cytological atypia in Schwann cells, which likely accelerates the formation of malignant nerve sheath tumors, particularly in predisposed individuals.¹⁴

SRS has been widely used to treat benign tumors such as pituitary adenomas, meningiomas, and schwannomas. SRS, delivered using the Gamma Knife (GK), CyberKnife, or linear accelerator (LINAC), is an established treatment to minimize radiation effects on surrounding structures.¹⁵ Muracciole and Régis reported that, 20 years after radiotherapy, the risk of malignant transformation was less than 0.1% for patients treated with SRS, compared to a 10% risk with conventional external radiotherapy.¹⁶

The malignant transformation did take place in the reported case of vestibular schwannoma after GK radiosurgery, which was with extensive cerebrospinal dissemination. MPNST is the most common malignancy arising from a vestibular schwannoma treated with SRS.¹⁷ While SRS carries a minimal but significant risk of tumor transformation, such events typically occur 8–10 years after treatment. The overall incidence of radiosurgery-associated malignancies has been reported as 6.8 per 100,000 patient-years, corresponding to a cumulative incidence of 0.045% over 10 years. The risk of neoplastic transformation or the development of a new radiation-induced intracranial malignancy following SRS is low and comparable to the annual incidence of primary central nervous system (CNS) tumors in the general population, even with long-term follow-up extending beyond 10 years.¹⁸ Because of the low incidence of vestibular schwannoma transformation to an MPNST after radiotherapy in patients without neurofibromatosis, discontinuing treatment is not recommended.¹⁵ In 2018, the Congress of Neurological Surgeons presented a level 3 evidence-based recommendation that patients should be informed that the risk of a malignant transformation of vestibular schwannoma after SRS is minimal.¹⁹

MPNST in the sellar region presents significant challenges for accurate preoperative diagnosis due to the absence of specific symptoms or radiological markers. In 1 reported case, an MPNST in the sellar region was initially observed for 9 months under the assumption that it was a “nonfunctioning pituitary adenoma” with no neurological symptoms, until the development of left-sided ptosis and diplopia resulting from left oculomotor nerve palsy. Postoperative pathological examination confirmed the diagnosis of MTT, a subtype of MPNST characterized by rhabdomyolysis differentiation.¹² This underscores the importance of continuous and cautious observation of sellar region masses. In this reported case, the patient’s normal circulating levels of GH and IGF-1 in 2023 provided a clue that the mass was distinct from a GH-secreting pituitary adenoma, which typically elevates these markers. The origin of the MPNST was likely the cranial nerve in the left cavernous sinus, possibly involving the left oculomotor nerve. Following the initial surgery in 2013, a residual tumor in the left cavernous sinus was targeted with SRS. The patient’s symptoms in 2023, specifically left oculomotor nerve palsy, were consistent with the progression of the tumor in this region. This highlights the need for vigilant monitoring and consideration of differential diagnoses when assessing masses in the sellar region.

Metastatic recurrences of MPNST, including brain and leptomeningeal metastases, have been documented and are attributed to their potential for hematogenous spread.²⁰ Our case represents the first reported instance of primary intracranial MPNST in the sellar region metastasizing to the spinal canal via CSF dissemination. Tumor cells, likely enterocytes, were detected in the CSF, and acute hydrocephalus developed shortly thereafter, necessitating emergency ventriculoperitoneal shunt placement. About 2 months later, intradural lesions in the spinal canal emerged and progressively worsened, strongly suggesting CSF-mediated metastasis. Reports exist of acute hydrocephalus,²¹,²² brain metastasis,²³ or leptomeningeal metastasis associated with primary intradural extramedullary MPNST.²⁴ Seven intracranial nerve MPNST cases have been reported to result in drop metastases to the spine.²⁵ Intradural extension of paraspinal MPNSTs has been linked to higher rates of CNS metastases and poorer survival outcomes, potentially due to malignant cell seeding in the CSF.²⁶ Once CSF dissemination occurs, survival is typically short, as demonstrated in our case.

Among the limited treatments for MPNST, complete resection with negative margins is considered the most effective.³,²⁷ Chemotherapy is an alternative for unresectable or metastatic cases, although its efficacy remains debated.²⁸ Targeted therapies are under phase II clinical trials,³ and radiation therapy remains controversial. Repeated SRS has shown success in local tumor control of spinal MPNST,²⁹ and LINAC-based SRS has been deemed safe and effective for brain metastases.³⁰ In our case, gross-total resection was followed by proton therapy as adjuvant treatment, which potentially offered a low toxicity rate.³¹ Despite these interventions, rapid CSF dissemination led to the patient’s death within a short time, emphasizing the aggressive nature of MPNST with CSF spread.

Lessons

Pathologically unidentified lesions in the sellar region require cautious and continuous observation, as MPNST can closely mimic pituitary adenomas. Early identification and surgical intervention increase the likelihood of achieving complete resection, which remains the most effective treatment for MPNST.

Radiotherapy, a known risk factor for the development of MPNST, should be recommended with prudence as an adjuvant therapy for patients with pituitary adenomas. Given the poor prognosis associated with MPNSTs in the sellar region, the risks of radiotherapy must be carefully weighed against its potential benefits.

MPNST recurrence and metastasis occur not only through hematogenous spread but also via CSF dissemination and implantation. Once metastasis through CSF occurs, manifesting as acute hydrocephalus or intraspinal metastasis, the prognosis is extremely poor, with survival times often being very short.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Yong Wang, Li, Wu, Yibao Wang. Acquisition of data: Yong Wang, Li, Xiao, Wu, Guo, Xing. Analysis and interpretation of data: Yong Wang, Li, Xiao, Sun, Wu, Guo, Xing. Drafting the article: Yong Wang, Li, Sun. Critically revising the article: Yong Wang, Li, Wu, He. Reviewed submitted version of manuscript: Yong Wang, Li. Approved the final version of the manuscript on behalf of all authors: Yong Wang. Statistical analysis: Li, Xing. Administrative/technical/material support: Yong Wang, Li, Xiao, Guo, Xing. Study supervision: Yong Wang, Wu.

Supplemental Information

Online-Only Content

Supplementary Figs. 1–3. https://thejns.org/doi/suppl/10.3171/CASE24437.

Correspondence

Yong Wang: The First Hospital of China Medical University, Shenyang, Liaoning Province, China. wangyongdl@126.com.