Primary malignant peripheral nerve sheath tumor of the spine with ...

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Jun 13, 2014 - MALIGNANT peripheral nerve sheath tumors. (MPNSTs) are uncommon types of soft tissue sarcomas that usually arise from peripheral.

J Neurosurg Spine 21:367–371, 2014 ©AANS, 2014

Primary malignant peripheral nerve sheath tumor of the spine with acute hydrocephalus: a rare clinical entity Case report Yaxiong Li, M.M.,1 Fengshi Fan, M.D.,1 Jianguo Xu, M.D., Ph.D., 3 Jie An, M.D., 2 and Weining Zhang, M.D.1 Departments of 1Neurosurgery and 2Pathology, Bethune International Peace Hospital, Shijiazhuang, Hebei; and 3Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point. The authors report their experience with 1 new case of a primary MPNST. A 33-year-old woman presented with low-back pain radiating to the right calf that progressed over 1 year. Magnetic resonance imaging of the spine revealed an intradural extramedullary lesion at the T12–L1 level. The patient was diagnosed with primary MPNST, underwent two surgical excisions and radiation therapy, and developed leptomeningeal metastases as well as brain metastases. The patient revisited the emergency room with sudden loss of consciousness. A brain CT scan displayed bilateral lateral ventricle enlargement, for which a ventriculoperitoneal shunt was inserted. These symptoms have not been described in any previous report. Primary spinal MPNST is an exceedingly rare entity, and the overall prognosis is very poor. To the authors’ knowledge, no standard of care for primary spinal MPNSTs has yet been established. All 19 cases of primary spinal MPNSTs are reviewed, and the authors discuss their clinical, radiological, and therapeutic features and outcomes. (http://thejns.org/doi/abs/10.3171/2014.4.SPINE13739)

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Key Words      •      primary malignant peripheral nerve sheath tumor      •      spinal tumor      • metastases      •      hydrocephalus      •      oncology

alignant peripheral nerve sheath tumors (MPNSTs) are uncommon types of soft tissue sarcomas that usually arise from peripheral nerve sheaths and rarely involve the spinal roots. These tumors are believed to originate from Schwann cells or pluripotent cells of the neural crest. The estimated incidence of MPNSTs in patients without a history of neurofibromatosis is very low, approximately 0.001%.7 Malignant peripheral nerve sheath tumors tend to recur locally at the original sites and metastasize to the lungs, liver, lymph nodes, and bones.10 In this report, we present a case of a primary MPNST at the T-12 and L-1 vertebrae with metastasis to the brain leading to acute hydrocephalus, and provide a detailed clinical and pathological analysis in conjunction with a brief literature review. Ethics approval for this study was provided by the Ethics Committee of Hebei University, and consent to publish the details of this case was obtained from the patient’s relatives.

Case Report History and Examination. A 33-year-old woman with a 1-year history of low-back pain and calf pain on the right Abbreviations used in this paper: GFAP = glial fibrillary acidic protein; MPNST = malignant peripheral nerve sheath tumor.

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side was admitted to the Department of Neurosurgery at Bethune International Peace Hospital. Her radicular pain had increased gradually until she was unable to walk. On physical examination, neither sensory abnormality nor muscle weakness was noted in her upper or lower extremities. The patient’s skin demonstrated no superficial stigmata of neurofibromatosis, including café-au-lait spots or terminal nerve twigs. Laboratory examination data were normal. She had no previous medical history or family history of neoplastic disease or neurofibromatosis. Magnetic resonance imaging revealed a mass approximately 3.4 cm long in the spinal canal from T-12 to L-1 that presented as isointense on a T1-weighted image and slightly hyperintense on a T2-weighted image, which enhanced after Gd administration (Fig. 1). The tumor had a well-defined contour. It was believed to be a benign tumor, and we decided to remove it surgically.

Operative Course. Complete removal of the tumor was intended. After laminectomy of T-12 and L-1, a longitudinal incision was made at the center of the exposed dura. A dark red, soft, vascular mass, 3.4 cm in length and 2.0 cm in diameter, protruded over the entire area. The spinal cord was severely compressed by the lesion. Following partial resection inside the capsule, the upper and lower boundaries of the tumor were found. The spinal cord and some nerve roots could not be separated from the mass, 367

Y. Li et al. (Dako), epithelial membrane antigen (Dako), smooth muscle actin (Dako), glial fibrillary acidic protein (GFAP), neurofilament protein, and CD34. Microscopic examination of the surgical specimen revealed a spindle-shaped cell tumor composed of tumor cells arranged in short intersecting fascicles with hypercellularity (Fig. 2A). Some cells had increased mitotic activity. Immunohistochemical staining showed tumor cells positive for S100, GFAP, vimentin, and CD34 (Fig. 2B–E), but negative for neurofilament protein, smooth muscle actin, and epithelial membrane antigen. These findings were compatible with those of an MPNST.

Fig. 1.  Magnetic resonance images of the lumbar spine before the first operation.  A and B: Sagittal T1-weighted (A) and T2-weighted (B) views reveal an isolated intradural tumor from T-12 to L-1. C: Enhanced sagittal image reveals enhancement of the mass (arrow).  D and E: Coronal (D) and axial (E) T1-weighted views with Gd show a tumor with a nonuniform signal, representing the necrotic tissue.

so partial excision was performed for decompression and diagnosis.

Histopathology and Immunohistochemistry. The excised specimens were subjected to thorough histopathological examination, including H & E staining and immunohistochemistry for S100 protein (Dako), vimentin

Postoperative Course. A few days after surgery, the pain had almost completely disappeared, so the patient was not treated with radiation therapy. Four months after the operation, the patient again began to complain of lowback pain radiating to the right calf, increasing muscle weakness in both lower extremities, and urinary dysfunction. Brain MRI demonstrated an intradural lesion from T-12 to L-1 that was slightly larger in size than the previous mass. Removal of the recurrent tumor was attempted. Partial resection was performed because the lesion was strongly adherent to the spinal cord and nerve root. Histopathological examination of operative specimens again resulted in findings compatible with those of an MPNST. After surgery, the patient’s lower extremity muscle strength did not improve. She was treated with radiation therapy (19 fractions of 2800 cGy) for the residual tumor. However, nearly 2 weeks after the second operation, the patient became symptomatic and presented to the emergency department with complaints of visual disturbances. Magnetic resonance imaging revealed that the MPNST had metastasized to all spinal segments, as well as the brain (Fig. 3). One week later, the patient revisited our

Fig. 2.  Photomicrographs of the surgical specimen. A: Slide stained using H & E shows a tumor composed of spindle cells.  B–E: Immunohistochemical stain for vimentin (B), diffuse positivity of tumor cells and S100 (C), and positivity of GFAP (D) and CD34 (E). Original magnification ×10.

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Leptomeningeal metastasis of an MPNST with acute hydrocephalus

Fig. 4.  Axial CT scan (A) and T2-weighted MR image (B) show communicating hydrocephalus and periventricular edema.

Fig. 3.  Magnetic resonance images 1 year after the first operation. A–C: Sagittal T1-weighted views of the spine with Gd demonstrate that the mass spread to all spinal segments and the brain. D: Enhanced axial view reveals a well-demarcated mass around the left midbrain (arrow). E: Axial T1-weighted view reveals that the ventricles are not enlarged.

emergency room and had been in a coma for 1 hour when she arrived. There was a history of episodic headache accompanied by vomiting preceding this urgent situation. Her right pupil had dilated to 5 mm, and the left pupil had dilated to 2 mm, without any light reflex. A subsequent cranial CT scan showed a communicating hydrocephalus causing dilation of the third and lateral ventricles (Fig. 4). We administered mannitol 250 ml intravenously guttae and dexamethasone 10 mg intravenously to lower her intracranial pressure, and her consciousness gradually recovered. On the following day in the hospital, the patient had continual seizures. Based on a lumbar puncture, pressure in the CSF was increased, so she underwent ventriculoperitoneal shunt insertion. A Medtronic pump (medium pressure), attached to the peritoneal tubing, was placed during surgery. Surgery was uneventful, and the patient had a benign postoperative course. The patient died 2 years and 5 months after the initial surgery.

Discussion

Malignant peripheral nerve sheath tumors are uncommon malignant neoplasms that originate from diverse cells in the peripheral nerve sheath. Malignant peripheral nerve sheath tumors represent 5% of all malignant softtissue tumors, and only 2%–3% of all MPNSTs originate in the spinal nerves.8 The reported cases of primary spinal MPNSTs are summarized in Table 1. To the best of our J Neurosurg: Spine / Volume 21 / September 2014

knowledge, only 18 cases have been found in the English literature (PubMed). In this paper, we aimed to establish the clinical behavior of this rare entity. Malignant peripheral nerve sheath tumors appear to occur mostly in young patients. Table 1 shows all 18 spinal MPNSTs that have been published in the literature between 1981 and 2012. The mean age of patients with tumors at diagnosis was 35.05 ± 18.90 years (range 4–70 years), and both sexes were equally involved. Our review of intradural MPNSTs found that 5 (26.32%) were located in the cervical vertebrae, 6 (31.58%) in the thoracic vertebrae, 7 (36.84%) in the lumbar vertebrae, the sacrum, or the cauda equina, and 1 (5.26%) in the spinal accessory. In our case, the MPNST had disseminated throughout the entire spinal cord and metastasized to the brain, which may have occurred via leptomeningeal invasion and metastasis or via CSF circulation. The most frequently presented complaints were painful radiculopathy (47.37%) and weakness (42.11%). However, our case presented with some atypical symptoms, such as coma and seizures, which were related to the communicating hydrocephalus (Fig. 4). The primary causes of hydrocephalus could have been obstruction of ependymal cell malfunction or altered production or reabsorption of the CSF, leading to impaired CSF transport and increased intracranial pressure. The imaging features of the MPNSTs in our case were different from conventional neurilemmomas. The tumors invaded the entire spinal cord, and on MRI, the lesions exhibited enhancement of a “string-of-beads” pattern on T1-weighted imaging (Fig. 3A–C), which was not described in any previous report. The clinical and neurological status of the patient worsened due to the aggressiveness of the tumor and the brainstem invasion, leading to an increase in CSF pressure and impaired brainstem function. Histologically, according to the description of the pathological characteristics by Valdueza et al.,12 the most reliable criteria of intracranial MPNSTs are high cellularity, nuclear atypia, and increased mitotic rate, necrosis, and endothelial proliferation. In our patient, some isolated areas had high cellularity with spindle-shaped cells. The mitotic activity was high, and pathological mitotic figures were also detected. The mass was associated with the L-1 spinal and nerve roots. 369

Y. Li et al. The best treatment for spinal MPNSTs remains poorly defined due to the rarity of the tumor and the lack of prospective trials. Surgery is currently the mainstay of treatment for MPNSTs, and radical resection has been recommended for spinal MPNSTs prior to tumor metastasis. Improved prognosis has been observed after complete removal of the lesions.7,8 Surgical removal is useful to not only relieve the complications but also to elucidate the histopathological features of the tumor. In the narrow spinal canal, radical excision of a mass with a margin of normal

tissue is hardly ever possible without causing neurological injury. Total excision was achieved in 68.42% of the patients in previous studies (Table 1). Several studies have recommended the use of en bloc resection of the tumor to improve patient outcome.11,14 However, local recurrence and intradural metastases were found postoperatively in these studies. Insufficient removal of the tumor and release of highly malignant cells may be the cause of recurrence and metastases. The Oncology Consensus Group recommends ad-

TABLE 1: Clinical summary of 19 cases of primary spinal MPNST without neurofibromatosis* Authors & Year Thomeer et   al., 1981 Valdueza et   al., 1991

Seppälä &  Haltia,   1993

Yone et al.,  2004 Celli et al.,   1995

Chamoun et   al., 2009 Amin et al.,  2004 Adamson et   al., 2004 Xu et al., 2012 Sheikh et al.,  2012 present study

Age (yrs), Sex

Spinal Level

Presenting Symptom

Resection

Adjuvant Therapy

Recurrence

Metastasis

Outcome

42, M cauda equina low-back pain, RD, weak ness 43, F T10–12 low-back pain, weakness

complete

RT, chemo

yes

no

alive at 3 yrs w/ recur rence no alive at 10 yrs w/ re currence no alive, disease-free at   7 mos systemic metas- dead at 7 mos  tases

incomplete

RT

yes

70, F

C4–6

neck pain, RD

complete

no

no

13, M

lumbar

weakness

complete

RT

yes

23, F

T1–4

RD

complete

RT

yes

37, F

C5–8

paraparesis

complete

RT

yes

4, M

L3–5

RT, chemo

yes

52, F

T–2

low-back pain, RD, urinary complete  dysfunction pain, weakness complete

systemic metas- dead at 8 mos  tases systemic metas- dead at 6 yrs  tases brain dead at 21 mos

no

no

no

68, F

L–4

pain, weakness

complete

no

no

no

43, M

L–3

pain

complete

no

no

no

36, F

T–11

pain

complete

RT

yes

no

30, M 5, F

T–7 C4–5

pain, weakness abdominal pain, vomiting,   gait difficulty

complete incomplete

RT RT, chemo

yes yes

38, M

L3–S1

biopsy

chemo

NM

37, M

C5–6

RD, weakness, sphincter  dysfunction RD

lung brain, thoracic   spine, cauda  equina NM

incomplete

RT

yes

no

30, F 8, M

C5–6 L3–5

RD, Horner’s syndrome pain, RD

incomplete complete

no RT

yes yes

complete

RT

NM

incomplete

RT

yes

54, M spinal acces- headache, visual distur sory   bances, loss of short  term memory, ataxic  gait 33, F T12–L1 low-back pain, RD, weak  ness, hydrocephalus  symptom

alive, disease-free at   72 mos alive, disease-free at   24 mos alive, disease-free at   72 mos alive, disease-free at   48 mos dead at 14 mos alive at 4 mos NM

dead after 1 yr & a   few mos no dead after 1 yr brain, lumbar, & dead at 16 mos  sacral brain, lung NM

brain, spinal  cord

dead at 2 yrs & 5 mos

*  chemo = chemotherapy; NM = not mentioned; RD = radiculopathy; RT = radiation therapy.

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Leptomeningeal metastasis of an MPNST with acute hydrocephalus ministering postoperative radiation therapy as part of a uniform treatment policy for MPNSTs, and some studies have proven that adjuvant radiation therapy may help with local control.1,5,12 However, no significant improvement in survival was observed in a group of patients with MPNSTs located in the trunk and extremities. Acharya et al.1 indicated that postoperative radiation therapy might help eradicate or suppress residual tumor growth. Of the 19 patients with spinal MPNSTs, 13 underwent radiation therapy. Our patient underwent 2 partial resections and accepted a common intraspinal radiation therapy. The lesion relapsed, and there was leptomeningeal metastasis to the spine and intracranial space. The outcome was poor. Our case demonstrated that radiotherapy was ineffective, and the mass was insensitive to radiation therapy. The role of chemotherapy was unclear, and therefore it should be limited to desperate cases of disseminated metastatic disease.5,6 The clinical outcome for patients with spinal MPNSTs has been very poor. The 1-year, 18-month, and 5-year survival rate in this series of primary spinal MPNSTs was 68.42% (13/19), 42.11% (8/19), and 10.53% (2/19), respectively. Even after an apparently complete removal followed by radiation therapy, local recurrence (68.42%, 13/19) and metastases (47.37%, 9/19) were common. The most common sites for metastatic spread were the lungs and the liver, while cerebral metastases were also detected in 4 patients (Table 1). The poorer outcome for spinal MPNSTs is probably due to the surgical challenges posed by their anatomical location, with a greater invasiveness of the tumor, in addition to the rich vascular supply of the spinal canal, which increases the systemic spread. Our patient developed symptomatic recurrence 4 months after the first removal procedure. As the symptoms gradually deteriorated, she underwent reoperation, and the lesion was partially removed. The patient twice received radiation therapy after an operation. She died 1 year after the second operation, with recurrent disease, CNS metastases, and acute hydrocephalus. Primary spinal MPNSTs are extremely rare, with only 18 such cases previously reported in the English literature. They exhibit aggressive behavior, with a very high recurrence rate even after gross-total resection, and they have significant potential for leptomeningeal and systemic metastasis. In our case, the tumor had disseminated to all spinal segments and the brain, with a communicating hydrocephalus, which is the first such case reported. There is no definite consensus regarding treatment of primary intradural MPNSTs. The optimal management of these tumors largely depends on the personal experience of the treating medical team, and we support surgical tumor removal combined with postoperative radiation therapy. The overall prognosis is very poor. Due to the rarity of this tumor, it is impossible to perform randomized trials. We hope to see more research in the future to improve the prognosis of this disease. Disclosure 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 to the study and manuscript preparation

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include the following. Conception and design: Li. Acquisition of data: Fan. Analysis and interpretation of data: Xu. Drafting the article: Li. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Li. Administrative/technical/material support: An. References   1.  Acharya R, Bhalla S, Sehgal AD: Malignant peripheral nerve sheath tumor of the cauda equina. Neurol Sci 22:267–270, 2001   2.  Adamson DC, Cummings TJ, Friedman AH: Malignant peripheral nerve sheath tumor of the spine after radiation therapy for Hodgkin’s lymphoma. Clin Neuropathol 23:245–255, 2004   3.  Amin A, Saifuddin A, Flanagan A, Patterson D, Lehovsky J: Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina. Spine (Phila Pa 1976) 29:E506– E509, 2004   4.  Celli P, Cervoni L, Tarantino R, Fortuna A: Primary spinal malignant schwannomas: clinical and prognostic remarks. Acta Neurochir (Wien) 135:52–55, 1995   5.  Chamoun RB, Whitehead WE, Dauser RC, Luerssen TG, Okcu MF, Adesina AM, et al: Primary disseminated intradural malignant peripheral nerve sheath tumor of the spine in a child: case report and review of the literature. Pediatr Neurosurg 45:230–236, 2009   6.  Goldman RL, Jones SE, Heusinkveld RS: Combination chemotherapy of metastatic malignant schwannoma with vincristine, adriamycin, cyclophosphamide, and imidazole carboxamide: a case report. Cancer 39:1955–1958, 1977   7.  Gupta G, Maniker A: Malignant peripheral nerve sheath tumors. Neurosurg Focus 22(6):E12, 2007   8.  Prieto R, Pascual JM, García-Cabezas MA, López-Barea F, Barrios L, González-Llanos F: Low-grade malignant triton tumor in the lumbar spine: a rare variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Neuropathology 32:180–189, 2012   9.  Seppälä MT, Haltia MJ: Spinal malignant nerve-sheath tumor or cellular schwannoma? A striking difference in prognosis. J Neurosurg 79:528–532, 1993 10.  Sheikh OA, Reaves A, Kralick FA, Brooks A, Musial RE, Gasperino J: Malignant nerve sheath tumor of the spinal accessory nerve: a unique presentation of a rare tumor. J Clin Neurol 8: 75–78, 2012 11.  Thomeer RT, Bots GT, van Dulken H, Luyendijk W, Helle P: Neurofibrosarcoma of the cauda equina. Case report. J Neurosurg 54:409–411, 1981 12.  Valdueza JM, Hagel C, Westphal M, Hänsel M, Herrmann HD: Primary spinal malignant schwannoma: clinical, histological and cytogenetic findings. Neurosurg Rev 14:283–291, 1991 13.  Xu Q, Xing B, Huang X, Wang R, Li Y, Yang Z: Primary malignant peripheral nerve sheath tumor of the cauda equina with metastasis to the brain in a child: case report and literature review. Spine J 12:e7–e13, 2012 14.  Yone K, Ijiri K, Hayashi K, Yokouchi M, Takenouchi T, Manago K, et al: Primary malignant peripheral nerve sheath tumor of the cauda equina in a child case report. Spinal Cord 42: 199–203, 2004 Manuscript submitted August 3, 2013. Accepted April 28, 2014. Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.4.SPINE13739. Address correspondence to: Yaxiong Li, M.M., Department of Neurosurgery, Bethune International Peace Hospital, 398 ZhongShan West Rd., Hebei 050082, China. email: [email protected] com.

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