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CASE REPORT  
Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 535-537
Primary intraspinal ganglioneuroblastoma of the thoracic spine: A rare case report


1 Department of Pathology, S.C.B. Medical College, Cuttack, Orissa, India
2 Department of Neurosurgery, S.C.B. Medical College, Cuttack, Orissa, India

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Date of Web Publication4-Mar-2013
 

   Abstract 

Cerebral ganglioneuroblastoma is an embryonal tumor of the central nervous system, which has been rarely encountered into the spinal cord. The standard treatment for ganglioneuroblastoma is complete surgical excision. A 15-year old boy was presented with cord compression. Magnetic resonance imaging revealed an intradural and intramedullar enhancing lesion over T2 spine. A histomorphological diagnosis was made in the presence of immature small round cells admixed with a good number of ganglion cells. The morphological diagnosis was verified by immunohistochemistry. This is the first reported case of compressive myelopathy in the thoracic region of the spine.

Keywords: Ganglioneuroblastoma, ganglionic cells, spinal tumor, undifferentiated cell

How to cite this article:
Tripathy K, Misra A, Gouda AK, Das S, Das B. Primary intraspinal ganglioneuroblastoma of the thoracic spine: A rare case report. Indian J Pathol Microbiol 2012;55:535-7

How to cite this URL:
Tripathy K, Misra A, Gouda AK, Das S, Das B. Primary intraspinal ganglioneuroblastoma of the thoracic spine: A rare case report. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Sep 19];55:535-7. Available from: http://www.ijpmonline.org/text.asp?2012/55/4/535/107805



   Introduction Top


Neural tumors of the central nervous system (CNS) are rare. They are classified as ganglioma, ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. These related tumors have a common origin from primordial neural crest cells and reflect different maturation patterns of a common neoplasm. Neuroblastoma is the least differentiated tumor containing primitive neuroblasts, ganglioneuroblastoma possesses both primitive neuroblasts and ganglion cells, while ganglioneuroma is a fully differentiated form containing mature Schwann cells and ganglion cells. Cerebral ganglioneuroblastoma is an embryonal tumor consisting of poorly differentiated neuroepithelial cells, which undergo neuronal differentiation to ganglion cells. [1] This tumor is usually found in the cerebellum, cerebrum, and suprasellar region. The tumor is rarely found in the spinal cord, and only some cases have been documented in conus medullaris of the spine. [2] The authors present here the first case of primary intraspinal ganglioneuroblastoma of the thoracic spine. Histopathological study supported by immunohistochemistry helped the authors to establish the diagnosis. Surgical excision is the treatment of choice for both cerebral and spinal ganglion cell tumors. Radiotherapy is given for residual disease, recurrence, or progression. Since adjuvant chemotherapy was applied for ganglioneuroblastoma treatment with various results, there is no report of chemotherapy as the sole method. We report a 15-year old boy who achieved substantial improvement after surgical excision followed by radiotherapy.


   Case Report Top


A 15-year-old boy was presented with a Lhermitte's symptom (an electric shock-like sensation from lower back to both legs) and urinary retention of 15 days duration. This was followed by sudden paralysis of both lower limbs of 7 days duration. Neurological examination revealed all modalities of sensory loss below T2 vertebra and muscle power was 0-5 around the joints. The patient had no diabetic anamnesis, hypertension, tuberculosis, trauma, and fever. Ultrasonography (USG) of the abdomen showed no abnormalities in any other organs. A computed tomography (CT) scan of the chest showed no tumor in the mediastinum. A magnetic resonance imaging (MRI) of the spine showed a large inhomogenous enhancing lesion spreading into the intramedullary space at the T2 level [Figure 1] and [Figure 2]. A T1 and T2 laminectomy was done. Operative findings were of a soft elastic, moderately vascularized exophytic intramedullary tumor extending into the extramedullar and intradural region of the spine. The tumor had extradural growth. The biopsy sample was received piecemeal and sent for histopathological (HP) study.
Figure 1: Sagittal MRI with contrast of the thoracic spine showing an intradural and intramedullar homogenously enhancing lesion

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Figure 2: Axial MRI with contrast of the thoracic spine showing the tumor

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Microsections revealed a tumor consisting of cells with a round normal nuclei and high nuclear cytoplasmic (N:C) ratio, arranged in a lobular pattern over a delicate fibrous stroma. At places, cells were arranged in a rosette-like pattern. There were large areas showing differentiating neuroblasts and ganglion cells [Figure 3] and [Figure 4]. Areas of calcification were seen. An immunohistochemical study (IHC) showed neurofilament positivity for neuroblastic component [[Figure 3], inset] and synaptophysin positivity for cells with ganglionic differentiation [[Figure 4], inset]. IHC on CD99 and epithelial membrane antigen (EMA) did not reveal the possibility of ependymoma and pPNET, respectively. A cytogenetic study showed nMyc positivity by fluorescence in situ hybridization (FISH) [Figure 5]. Final diagnosis of ganglioneuroblastoma was made, and the patient was assigned to prolonged adjuvant radiotherapy. After 1 month, neurological examination showed an improvement of power of all the joints of the lower limbs to a grade of 2/5. The patient returned 4 months later with progressive sensory-motor paraparesis with 0/5 power in both the lower limbs. Repeat magnetic resonance imaging (MRI) revealed a large recurrent tumor mass in the same region. The patient was referred for radiotherapy.
Figure 3: Pictomicrograph showing undifferentiated cells in nests with rosettes with (inset) neurofilament positivity (H and E, ×200)

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Figure 4 : Pictomicrograph showing neuroblastic cells with rosette and ganglionic differentiation with (inset) synaptophysin positivity (H and E, ×200)

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Figure 5: Findings obtained by FISH analysis of nMyc genes amplified as double minutes (DMs)

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   Discussion Top


Cerebral ganglioneuroblastoma is a term used for tumors, which histologically consist of undifferentiated small round cells in all stages of neuronal differentiation. [1],[2] These are grouped as primitive neuroectodermal tumors (PNETs): (1) "peripheral" or "pPNET"-those that arise from the sympathetic nervous system and (2) "central" or "cPNETs"-those that arise within the CNS. [3] The World Health Organization (WHO) (2007) distinguishes three types of embryonal tumors of the CNS, namely, the medulloblastomas, the PNETs, and the atypical rhabdoid/teratoid tumors. All three types histologically correspond to malignant grade IV tumors. The PNETs include the (ICD-O code 9490/3), medulloepithelioma, and ependymoblastoma. [1],[3] CNS neuroblastomas and ganglioneuroblastomas, which were earlier classified as both neuronal and embryonal tumors by WHO, are now classified only as embryonal tumors. [4] These tumors are usually found in the cerebrum, cerebellum, and suprasellar region. The other common location of these tumors is posterior mediastinum. It is quite possible that tumor is located intraspinally due to extension from the mediastinum. In the reported case, the MRI of the chest revealed no tumors, thus ruling out the possibility written above. Spine is a very rare site for their occurrence. In the spinal canal, this aggressive tumor typically presents as a dumbbell-shaped extradural lesion. Previously, the intramedullary occurrence of the spinal ganglioneuroblastoma has been reported only thrice, most of them in conus areas. [2],[5],[6] The authors present the first case of ganglioneuroblastoma occurring in the thoracic spine involving the intramedullary region. The illustrative case is significant because of the fact that most thoracic spine lesions are low-grade ependymomas or astrocytomas.

The age range of ganglioneuroblastoma is from 4 weeks to 20 years. Clinical symptoms are related to the site of origin. In our case, we presented the patient with compressive myelopathy at the T2 level. [1],[4] Several tumors including astrocytomas, medulloblastomas, schwannomas, and secondaries can clinically lead to compressive myelopathy. [7] A definite histomorphology showing both round cells and ganglionic cells supported by immunohistochemistry for neurofilament and synaptophysin can lead to a final diagnosis.

The prognosis of patients with this tumor is relatively unfavorable. [1],[7] Approximately 25% of neuroblastomas have amplification of nMyc oncogene. Amplification of nMyc gene by FISH is usually done to assess the prognosis of the tumor. Amplification of the nMyc oncogene correlates with an unfavorable prognosis and aggressive disease. Cytogenetic findings in neuroblastomas include double-minute chromosomes (DMs) and homogeneous staining regions (HSRs). DMs appear on mitotic spreads as numerous small doublets that create an illusion of karyotypic "dirt." HSRs consist of chromosomal elongations, often striking in length and having a smooth, light gray, nonbanded quality. Neuroblastomas that possess these cytogenetic features can be easily propagated in vitro and are associated with aggressive clinical behavior. DMs and HSRs consist of amplified segments of nMyc, a proto-oncogene that encodes a helix-loop-helix transcription factor inducing cell proliferation. Amplification of nMyc can best be demonstrated by FISH, which highlights either DMs or HSRs. Paradoxically, hyperdiploidy, a frequent predictor of aggressive clinical outcome in adult cancers, portends good behavior in neuroblastoma. In the case reported, FISH showed amplification visible as myriad dispersed fluorescent dots, indicating the presence of DMs.

The reported case is the first case of primary ganglioneuroblastoma occurring in the thoracic spine involving the intramedullary region. This also justifies the WHO grading as malignant grade IV tumor. Thus, neuroblastic embryonal tumors may be considered in the differential diagnosis of intramedullary thoracic spinal tumors.

 
   References Top

1.Kleihues P. Pathology and genetics of tumors of the nervous system. In: Kleihues P. Editor. World Health Organization Classification of Tumors. Lyon: IARC Press; 2000. p. 141-4.  Back to cited text no. 1
    
2.Singh SK, Srivastava C, Ojha BK, Chandra A, Hussain N. Ganglioneuroblastoma of the conus: A rare and aggressive tumor. Neurol India 2010;58:966-8.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.Ozdemir N, Usta G, Minoglu M, Erbay AM, Berziciglu H, Tunakan M. Primary primitive neuroectodermal tumor extradural space. J Neurosurg Pediatr 2008;2:215-21.  Back to cited text no. 3
    
4.Kikuchi K, Saito M. Ganglion-cell tumor of the filum terminale; Immunohistochemical characterization. Tohoku J Exp Med1999;188:245-56.  Back to cited text no. 4
[PUBMED]    
5.Miele WR, Pfann lR, Kryzanski JT. Primary holocord ganglioneuroblastoma: Case report. J Neurosurg Spine2011;15:457-63.  Back to cited text no. 5
    
6.Sibilla L, Martelli A, Farina L, Uggetti C, Zappoli F, Sessa F, et al. Ganglioneuroblastoma of the spinal cord. AJNR Am J Neuroradiol1995;16:875-7.  Back to cited text no. 6
[PUBMED]    
7.Power JM, Horuopian DS. Ch 77. Central nervous system. In: DamjanovI, LinderJ, editors. Anderson's Pathology. 10 th ed. Vol II. Missouri: Mosby: Elsevier Inc;2009. p. 2693-798.  Back to cited text no. 7
    

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Correspondence Address:
Kalpalata Tripathy
Department of Pathology, S.C.B. Medical College, Cuttack, Orissa
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.107805

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

This article has been cited by
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[Pubmed] | [DOI]



 

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