Images in Pediatric Neurosurgery Pediatr Neurosurg 2013;49:119–120 DOI: 10.1159/000356932
Received: July 7, 2013 Accepted after revision: October 29, 2013 Published online: December 24, 2013
Spinal Dumbbell-Shaped Peripheral Primitive Neuroectodermal Tumor in a Child George A. Alexiou a George Sfakianos a Efthymios Dimitriadis d Kalliopi Stefanaki b John Anastasopoulos c Georgios Matsinos c Neofytos Prodromou a Departments of a Neurosurgery and b Pathology and c 2nd Orthopaedic Department, Children’s Hospital ‘Agia Sofia’, and d Department of Genetics, Saint Savvas Hospital, Athens, Greece
A 9-year-old boy presented with a 1-month history of progressive bilateral leg weakness. Neurological examination showed paraparesis and decreased deep tendon reflexes of the lower extremities. No skin lesion was noted in the lumbosacral region. For further investigation a spinal MRI was performed which showed a dumbbellshaped lesion extending from L1 to L3 (fig. 1, 2). The patient was operated on and the lesion was subtotally excised via an L2–L3 laminectomy. Histology revealed a malignant small round blue cell tumor composed of uniform small round cells with a limited rim of clear or eosinophilic cytoplasm and dusty nuclei with mild nuclear atypia and a moderate/brisk mitotic activity (12–35 mitoses/10hpfX40). Considerable apoptotic necrosis of the neoplasm was also observed. In the neoplastic cells, immunohistochemistry revealed a diffuse membranous expression of CD99/MIC2 (clones 12E7 and O-13), heterogeneous nuclear expression of Fli-1, focal expression of neurofilaments 2F11 (15–20%) and Bcl-2 protein (>90%). There was no expression of CD56/NCAM, synaptophysin, GFAP, S-100, desmin, myogenin/Myf-4, keratin AE1/AE3, keratins 7, 19, EMA, TdT, CD34, CD10, CD79a, CD20/L-26, CD3, or myeloperoxidase. The Ki67/MIB-1 proliferation index was 30% and the p-53 pro© 2013 S. Karger AG, Basel 1016–2291/13/0492–0119$38.00/0 E-Mail [email protected] www.karger.com/pne
tein was detected in 40% of the nuclei. The diagnosis was Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (pPNET). Molecular investigation by RT-PCR on fresh tissue revealed the EWSR1/FLI-1 fusion transcript (rearrangement between exon 7 EWS and exon 6 FLI-1, fusion type 1) derived from the t(11;22)(q24;q12) chromosomal translocation, which is specific for Ewing’s sarcoma/pPNET tumor family. Postoperatively, the patient recovered from paraparesis and was referred to the Oncological Department for further treatment. Spinal pPNET are exceedingly rare and represent less than 1% of primary spinal tumors [1, 2]. They typically present in patients in the third decade of life and have a male predominance [3]. They usually cause backache and have features of myelopathy and/or radiculopathy [4]. Spinal pPNET arise from all levels of the spinal region, although the commonest location is the cauda equina. They can be intramedullary, extramedullary/intradural or extradural [3, 5, 6]. A dumbbell-shaped appearance is exceedingly rare. To our knowledge 2 previous cases have been reported in adults, thus our patient is the first pediatric case of a dumbbell-shaped spinal pPNET reported in the literature [1, 7]. The presence of the characteristic translocation (11;22)(q24;q12) in more than 90% of cases George Alexiou, MD Aetideon 52 Holargos, Attikis GR–11561 Athens (Greece) E-Mail alexiougrg @ yahoo.gr
1
2
Fig. 1. T2-weighted MRI of the lumbar
spine revealing the tumor. Fig. 2. T2-weighted MRI – coronal view re-
vealing the dumbbell-type extension of the lesion from the spinal canal through the right intervertebral foramens.
is the strongest diagnostic tool. Expression of MIC2 glycoprotein by immunocytochemical staining (CD99) is another useful diagnostic indicator [3]. In the present case the neoplastic cells expressed CD99 and RT-PCR revealed the characteristic chromosome rearrangement. Spinal pPNET are aggressive tumors and they evolve rapidly [5]. The goal of surgery should be the decompression
of the neural elements, prevention of further deterioration of function, obtainment of tissue for diagnosis and excision of as much tumor as possible [3]. Chemotherapy and radiotherapy, ranging from 30 to 60 Gy, are currently used after tumor excision. Nevertheless, despite treatment the prognosis remains poor, with a median patient survival of 1–2 years [3, 8].
References 1 Hrabálek L, Kalita O, Svebisova H, Ehrmann J Jr, Hajduch M, Trojanec R, Kala M: Dumbbell-shaped peripheral primitive neuroectodermal tumor of the spine – case report and review of the literature. J Neurooncol 2009;92: 211–217. 2 Engelhard HH, Villano JL, Porter KR, Stewart AK, Barua M, Barker FG, Newton HB: Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine 2010;13:67–77.
120
3 Ellis JA, Rothrock RJ, Moise G, McCormick PC 2nd, Tanji K, Canoll P, Kaiser MG, McCormick PC: Primitive neuroectodermal tumors of the spine: a comprehensive review with illustrative clinical cases. Neurosurg Focus 2011;30:E1. 4 Prabu R, Thulkar S, Chand Sharma M, Mohanti BK, Dhawan D, Bakhshi S: PNET spine: morbid and mortal, but ignored till late. J Pediatr Hematol Oncol 2012;34:e164–e169. 5 Fabre E, Guillevin R, Chretien F, Le Guerinel C, Duffau H: Peripheral primitive neuroectodermal tumor of the cauda equina in an elderly patient. Case report. J Neurosurg Spine 2006;5:68–71. 6 Kumar R, Reddy SJ, Wani AA, Pal L: Primary spinal primitive neuroectodermal tumor: case series and review of the literature. Pediatr Neurosurg 2007;43:1.
Pediatr Neurosurg 2013;49:119–120 DOI: 10.1159/000356932
7 Liu HM, Yang WC, Garcia RL, Noh JM, Malhotra V, Leeds NE: Intraspinal primitive neuroectodermal tumor arising from the sacral spinal nerve root. J Comput Tomogr 1987;11: 350–354. 8 Kampman WA, Kros JM, De Jong TH, Lequin MH: Primitive neuroectodermal tumours (PNETs) located in the spinal canal; the relevance of classification as central or peripheral PNET: case report of a primary spinal PNET occurrence with a critical literature review. J Neurooncol 2006;77:65–72.
Alexiou/Sfakianos/Dimitriadis/Stefanaki/ Anastasopoulos/Matsinos/Prodromou
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Received: July 7, 2013 Accepted after revision: October 29, 2013 Published online: December 24, 2013
Spinal Dumbbell-Shaped Peripheral Primitive Neuroectodermal Tumor in a Child George A. Alexiou a George Sfakianos a Efthymios Dimitriadis d Kalliopi Stefanaki b John Anastasopoulos c Georgios Matsinos c Neofytos Prodromou a Departments of a Neurosurgery and b Pathology and c 2nd Orthopaedic Department, Children’s Hospital ‘Agia Sofia’, and d Department of Genetics, Saint Savvas Hospital, Athens, Greece
A 9-year-old boy presented with a 1-month history of progressive bilateral leg weakness. Neurological examination showed paraparesis and decreased deep tendon reflexes of the lower extremities. No skin lesion was noted in the lumbosacral region. For further investigation a spinal MRI was performed which showed a dumbbellshaped lesion extending from L1 to L3 (fig. 1, 2). The patient was operated on and the lesion was subtotally excised via an L2–L3 laminectomy. Histology revealed a malignant small round blue cell tumor composed of uniform small round cells with a limited rim of clear or eosinophilic cytoplasm and dusty nuclei with mild nuclear atypia and a moderate/brisk mitotic activity (12–35 mitoses/10hpfX40). Considerable apoptotic necrosis of the neoplasm was also observed. In the neoplastic cells, immunohistochemistry revealed a diffuse membranous expression of CD99/MIC2 (clones 12E7 and O-13), heterogeneous nuclear expression of Fli-1, focal expression of neurofilaments 2F11 (15–20%) and Bcl-2 protein (>90%). There was no expression of CD56/NCAM, synaptophysin, GFAP, S-100, desmin, myogenin/Myf-4, keratin AE1/AE3, keratins 7, 19, EMA, TdT, CD34, CD10, CD79a, CD20/L-26, CD3, or myeloperoxidase. The Ki67/MIB-1 proliferation index was 30% and the p-53 pro© 2013 S. Karger AG, Basel 1016–2291/13/0492–0119$38.00/0 E-Mail [email protected] www.karger.com/pne
tein was detected in 40% of the nuclei. The diagnosis was Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (pPNET). Molecular investigation by RT-PCR on fresh tissue revealed the EWSR1/FLI-1 fusion transcript (rearrangement between exon 7 EWS and exon 6 FLI-1, fusion type 1) derived from the t(11;22)(q24;q12) chromosomal translocation, which is specific for Ewing’s sarcoma/pPNET tumor family. Postoperatively, the patient recovered from paraparesis and was referred to the Oncological Department for further treatment. Spinal pPNET are exceedingly rare and represent less than 1% of primary spinal tumors [1, 2]. They typically present in patients in the third decade of life and have a male predominance [3]. They usually cause backache and have features of myelopathy and/or radiculopathy [4]. Spinal pPNET arise from all levels of the spinal region, although the commonest location is the cauda equina. They can be intramedullary, extramedullary/intradural or extradural [3, 5, 6]. A dumbbell-shaped appearance is exceedingly rare. To our knowledge 2 previous cases have been reported in adults, thus our patient is the first pediatric case of a dumbbell-shaped spinal pPNET reported in the literature [1, 7]. The presence of the characteristic translocation (11;22)(q24;q12) in more than 90% of cases George Alexiou, MD Aetideon 52 Holargos, Attikis GR–11561 Athens (Greece) E-Mail alexiougrg @ yahoo.gr
1
2
Fig. 1. T2-weighted MRI of the lumbar
spine revealing the tumor. Fig. 2. T2-weighted MRI – coronal view re-
vealing the dumbbell-type extension of the lesion from the spinal canal through the right intervertebral foramens.
is the strongest diagnostic tool. Expression of MIC2 glycoprotein by immunocytochemical staining (CD99) is another useful diagnostic indicator [3]. In the present case the neoplastic cells expressed CD99 and RT-PCR revealed the characteristic chromosome rearrangement. Spinal pPNET are aggressive tumors and they evolve rapidly [5]. The goal of surgery should be the decompression
of the neural elements, prevention of further deterioration of function, obtainment of tissue for diagnosis and excision of as much tumor as possible [3]. Chemotherapy and radiotherapy, ranging from 30 to 60 Gy, are currently used after tumor excision. Nevertheless, despite treatment the prognosis remains poor, with a median patient survival of 1–2 years [3, 8].
References 1 Hrabálek L, Kalita O, Svebisova H, Ehrmann J Jr, Hajduch M, Trojanec R, Kala M: Dumbbell-shaped peripheral primitive neuroectodermal tumor of the spine – case report and review of the literature. J Neurooncol 2009;92: 211–217. 2 Engelhard HH, Villano JL, Porter KR, Stewart AK, Barua M, Barker FG, Newton HB: Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine 2010;13:67–77.
120
3 Ellis JA, Rothrock RJ, Moise G, McCormick PC 2nd, Tanji K, Canoll P, Kaiser MG, McCormick PC: Primitive neuroectodermal tumors of the spine: a comprehensive review with illustrative clinical cases. Neurosurg Focus 2011;30:E1. 4 Prabu R, Thulkar S, Chand Sharma M, Mohanti BK, Dhawan D, Bakhshi S: PNET spine: morbid and mortal, but ignored till late. J Pediatr Hematol Oncol 2012;34:e164–e169. 5 Fabre E, Guillevin R, Chretien F, Le Guerinel C, Duffau H: Peripheral primitive neuroectodermal tumor of the cauda equina in an elderly patient. Case report. J Neurosurg Spine 2006;5:68–71. 6 Kumar R, Reddy SJ, Wani AA, Pal L: Primary spinal primitive neuroectodermal tumor: case series and review of the literature. Pediatr Neurosurg 2007;43:1.
Pediatr Neurosurg 2013;49:119–120 DOI: 10.1159/000356932
7 Liu HM, Yang WC, Garcia RL, Noh JM, Malhotra V, Leeds NE: Intraspinal primitive neuroectodermal tumor arising from the sacral spinal nerve root. J Comput Tomogr 1987;11: 350–354. 8 Kampman WA, Kros JM, De Jong TH, Lequin MH: Primitive neuroectodermal tumours (PNETs) located in the spinal canal; the relevance of classification as central or peripheral PNET: case report of a primary spinal PNET occurrence with a critical literature review. J Neurooncol 2006;77:65–72.
Alexiou/Sfakianos/Dimitriadis/Stefanaki/ Anastasopoulos/Matsinos/Prodromou
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
