Journal of Clinical Neuroscience 18 (2011) 601–606
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Review
Intraspinal Ewing’s sarcoma/primitive neuroectodermal tumors Yong Yan , Tao Xu , Juxiang Chen ⇑, Guohan Hu, Yicheng Lu Department of Neurosurgery, Changzheng Hospital, Neurosurgery Research Institution of Shanghai, 415 Fengyang Street, Huangpu District, Shanghai 200003, China
a r t i c l e
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Article history: Received 13 August 2010 Accepted 22 September 2010
Keywords: Ewing’s sarcoma Intradural–extramedullary spinal cord neoplasms Intramedullary spinal cord neoplasms Malignant spinal cord neoplasms Primitive neuroectodermal tumors
a b s t r a c t Intraspinal Ewing’s sarcoma (ES) and primitive neuroectodermal tumors (PNET) are very rare, and the characteristics and prognoses of the disease remain unclear. We present an illustrative patient with an intradural, extramedullary PNET arising within the cervical spinal canal, with clinical and radiological manifestations of leptomeningeal spread, and review the reports of a further 77 patients with intraspinal ES/PNET. Cox regression analyses showed that tumor location (extradural, intradural) (p = 0.002, RR = 4.217, 95% confidence interval [CI] 1.668–10.664) and spinal segment location (cervical, thoracic, lumbar, or sacral) (p = 0.017, RR = 2.040, 95% CI 1.133–3.673) were independent factors in the prognosis of intraspinal ES/PNET. We concluded that a peripheral PNET may originate within the spinal canal and exhibit leptomeningeal spread similar to that seen in central PNET, and that a patient with an intradural ES/PNET high in the spinal canal is more likely to have a poor prognosis. Ó 2010 Published by Elsevier Ltd.
1. Introduction Ewing’s sarcoma (ES) and primitive neuroectodermal tumors (PNET) have been defined as two separate diseases occurring at different sites with different origins. ES was thought to be a malignant tumor originating from marrow mesenchymal stem cells and was predisposed to growing in the extremities, whereas PNET signified all embryonal tumors of the central nervous system (CNS), regardless of their sites of origin.1,2 ES and PNET had similar histologic appearances, consisting of monomorphic, undifferentiated, small, round, hyperchromatic cells. With the finding that ES also occurred in soft tissue (extraskeletal ES), and that tumors outside the CNS were derived from the neural crest (peripheral PNET), the definitions of ES and PNET began to overlap.3 Accordingly, PNET derived in the CNS was named central PNET (cPNET) to differentiate it from peripheral PNET (pPNET).4 Cytogenetic analysis detected the presence of a reciprocal translocation t(11;22)(q24;q12) or t(21;22)(q22;q12) with high frequency (up to 95%) in both pPNET and ES, whereas this translocation was not detected in cPNET.4,5 Fusion genes led to the abnormal expression of a series of polypeptides or proteins, with the most common being CD99. Immunoreactivity to CD99 was present in extraskeletal ES and peripheral PNET, but absent in central PNET. Therefore, ES and pPNET represented two ends of the spectrum of the same tumoral entity, with diverse degrees of histological differentiation. pPNET displayed many properties
⇑ Corresponding author. Tel.: +86 21 81885673.
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[email protected] (J. Chen). The first two authors contributed equally to the article.
0967-5868/$ - see front matter Ó 2010 Published by Elsevier Ltd. doi:10.1016/j.jocn.2010.09.012
of neurogenic tumors, including positive immunoreactivity for neuronal markers (neuron-specific enolase [NSE] and synaptophysin [syn]), light microscopic evidence of Homer-Wright rosettes, and ultrastructural evidence of neuronal differentiation (interdigitating cell processes and neurosecretory granules).6,7 ES did not display such differentiated properties. Therefore, ES was considered to be the least differentiated, and pPNET was the most differentiated member of the ES family.8 Intraspinal ES/PNET is rare, and the characteristics and prognosis of the disease remain unclear. Our literature search revealed reports of 78 patients with ES/PNET located within the spinal canal,3,4,9–58 and we discuss the clinical characteristics, factors affecting prognosis, and treatment choices of the disease. In addition, we present an illustrative patient with an intradural, extramedullary pPNET arising within the cervical spinal canal that was associated with a rapidly deteriorating clinical course and poor prognosis.
2. Illustrative patient A 10-year-old Chinese boy presented with a 20-day history of neck pain and worsening muscle weakness, as well as a 1-week history of dysuria. Neurological examination revealed bilateral hypoesthesia in the upper limbs and paralysis of the extremities, with 2/5 strength in the right arm, 3/5 strength in the right leg, and 4/5 strength in the left limbs. The patient was also found to have flaccid muscle tone and reduced tendon reflexes in the right arm. The patient’s MRI scan revealed an extramedullary mass to the right of C2–C3, causing severe compression of the spinal cord. The
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Y. Yan et al. / Journal of Clinical Neuroscience 18 (2011) 601–606
mass measured 3.0 cm by 2.0 cm by 1.5 cm and had long T1weighted and T2-weighted signals on MRI, with homogeneous and intermediate post-contrast enhancement. An unusual feature was pial enhancement, extending above the tumor (Fig. 1). There was no clinical or radiologic evidence of cerebellar medulloblastoma or other intracranial tumors. A laminectomy was performed to decompress the spinal cord and debulk the tumor. A grey-reddish colored, well-circumscribed lesion with moderate blood supply and intact pseudocapsule was found on the opening of the spinal dura (Supplementary Fig. 1). The lesion was closely related to the cervical nerves, with no extension to the dura matter or spinal cord. The tumor was totally removed via bolck resection. Muscle strength in the extremities improved to 5/5 after surgery. The boy had urinary difficulty on the first few days after surgery, but soon recovered to normal. Unfortunately, the child’s condition deteriorated. He developed dizziness and nausea, hearing loss, facial paralysis, oculomotor nerve paralysis, seizures, and limb movement disturbance. Seeding metastasis of the tumor into the cerebrospinal fluid (CSF) was suspected; however, no tumor cells were detected on CSF cytological analysis. There were, however, many lymphocytes. The child was transferred to another hospital to receive radiation treatment; however, he died just before the radiation could be given. It was approximately 30 days after surgery. The tumor had a tough texture and a gray-white cut-surface macroscopically. Microscopically, the tumor was composed of diffuse solid sheets of small cells with scanty cytoplasm, round–oval nuclei, inconspicuous nucleoli, and fine chromatin. Rosettes were present (Supplementary Fig. 2a). The tumor cells were strongly positive for CD99 (Supplementary Fig. 2b), weakly positive for vimentin, and negative for syn, cytokinin, desmin, glial fibrillary acidic protein, leucocyte common antigen, neurofilament protein, NSE, S-100, actin, myogenic differentiation antigen 1, chromogranin A, myeloperoxidase, terminal deoxynucleotidyl transferase, and lymphoid markers (including CD19, CD5, CD10, CD20, CD2, CD117, CD79a, CD3, and CD34). The immunohistochemical characteristics were consistent with pPNET. 3. Review of the literature We found a total of 78 patients with intraspinal PNET (55) and ES (23) in the literature (Table 1). Survival time, and variables
including age (615, 16–30, 31–60, P61 years), sex (male, female), resection extent (biopsy, partial resection, subtotal or total resection), spinal level (lumbar and sacral, thoracic, cervical), tumor location (extradural, intradural), radiotherapy (yes, no), chemotherapy (yes, no), and pathology (PNET, ES) were collected to perform Cox regression analysis on the prognostic factors of these 78 patients with intraspinal ES/PNET. Calculations were done using the Statistical Package for the Social Sciences version 17.0 (SPSS, Chicago, IL, USA). 3.1. Cox regression analysis of prognostic factors From the available data (Table 1), we found that ES/PNET is more likely to occur in males (male/female = 1.8849/26) and young people (age < 25 years/P25 years = 2.052/26). It was more likely to occur in the lower spinal canal than in the upper (cervical [n = 19, 24.7%], thoracic [n = 25, 32.5%], lumbar and sacral [n = 33, 42.9%]). Most tumors (n = 70, 89.7%) occurred in the extradural space (extradural [n = 31, 44.3%], cauda equina [n = 13, 18.6%], extramedullary [n = 12, 17.1%], intra–extramedullary [n = 5, 7.1%], and intramedullary [n = 9, 2.9%]). ES was more common extradurally (n = 17, 85.0%), and PNET was more common intradurally (n = 37, 74.5%). Cervical extramedullary PNET was rare: to our knowledge, only four patients have been reported. Leptomeningeal spread of the tumor was common in cPNET, but rare in pPNET. To our knowledge, ours is the first report of pPNET with leptomeningeal spread. Cox regression analysis showed that tumor location (p = 0.002, RR = 4.217, 95% confidence interval [CI] 1.668–10.664) and spinal cord level (p = 0.017, RR = 2.040, 95% CI 1.133–3.673) were independent factors in the prognosis of spinal ES/PNET patients. Thus, patients with intradural and high spinal cord level ES/PNET have a poor prognosis. 3.2. Clinical features Given the clinical differences seen in cPNET and pPNET, it is necessary to separate the two. Although both cPNET and pPNET are aggressive tumors, pPNET is known to be metastatic and invasive, while cPNET rarely metastasizes outside the CNS.4 An interesting finding in our patient is the unusual pial enhancement. On close examination, the pial enhancement extended inferiorly to the cervical–thoracic junction and posteriorly and superiorly to the ventral medulla and pons (Fig. 1), which suggests that a pPNET
Fig. 1. Post-contrast MRI of a 10-year-old Chinese boy: (a) sagittal T1-weighted MRI showing a moderately enhanced lesion in the intradural and extramedullary space at the C2–C3 level; and (b) coronal T1-weighted MRI showing unusual pial enhancement extending superiorly, involving the ventral medulla and pons, and extending inferiorly as far as the cervicothoracic junction, particularly posteriorly.
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Y. Yan et al. / Journal of Clinical Neuroscience 18 (2011) 601–606 Table 1 Reports of patients with spinal Ewing’s sarcoma (ES)/primitive neuroectodermal tumors (PNET). Yearref 9
1969 197810 197810 197810 198511 198511 198511 198712 198713 198814 198814 198915 199116 199217 199217 199217 199217 199217 199217 199217 199218 199319 199319 199420 199421 199622 199623 199623 199724 199725 199826 199827 199928 199928 199929 199930 200031 200032 200133 200134 200134 200134 200134 200134 200135 200236 200237 200238 200339 200339 20032 20032 20032 20032 200440 200441 200442 200443 200544 200645 20064 200646 200647 200648 200749 200749 200749 200750 200750 200751 200852 200853 200854 200855
Age/sex
Level
Location
Treatment
Survival (m)
Diagnosis
24 y/M
