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neuroblastic tumors present a wide spectrum of tumors , including the benign ganglioneuroma , intermediate ganglioneuroblastoma and undifferentiated neuroblastoma ( nb)38 ) .
ganglioneuromas are benign tumors , which usually arise from the thoracic cavity as mediastinal tumors or abdominal cavity as retroperitoneal mass lesions4,25,30 ) .
ganglioneuroblastomas are tumors with decreased differentiation , which consist of a ganlioneuromatous stroma and a neuroblastomatous component38 ) .
nb is a common malignant tumor in pediatric age group , on contrary to that it is a rare entity in adults 11,19 ) .
we report a case of spinal nb recurrent from a ganglioneuroblastoma after disease free survival of 13 years . to our knowledge
, it is the second spinal case in the literature indicating such a malignant transformation and the only case with further genetic investigations .
a 22-year - old male patient admitted with abdominal pain to the general surgery department .
an abdominal computed tomography scan was obtained and a retroperitoneal mass lesion with spinal involvement was observed . the patient was then referred to neurosurgery department .
magnetic resonance imaging ( mri ) of the thoracolumbar spine showed a retroperitoneal mass lesion at t12-l3 level , extending from the left paraspinal region into the spinal canal . using a combined lateral and posterior approach ,
the tumor was near totally removed with only a small retroperitoneal remnant , which could not be reached with the current approach .
the patient was discharged from the hospital with no neurological deficits . after four years with stable disease , the patient presented with the same complaints .
mri revealed a t11-l3 left paraspinal mass growing towards t11 - 12 neural foramen and spinal canal ( fig .
1 ) . with the same approach tumor was subtotally removed ( except the retroperitoneal extension ) and spinal cord was decompressed .
macroscopic examination revealed a grey coloured , lobulated , soft tumor with a capsule and 87.55 cm in size .
while there was a inconsistency between the previous and current biopsies , the patient 's former biopsy material was reevaluated .
histopathologically , most of the tumor consists of spindle schwannian component and mature ganglion cells . in one section of the first specimen ,
the cells in this section are round blastic in appearance . in between these cells scattered mature ganglion cells were also seen .
the diagnosis of the first tumor was changed and accepted as a ganglioneuroblastoma ( fig .
an anterior approach was planned for the resection of the retroperitoneal rest tumor and oncological treatment afterwards . however , the patient refused to have further treatment and lost to follow - up .
nine years after the second operation , the patient admitted with progressive paraparesis , urinary retention and hypoesthesia .
3 ) . with posterior approach and t10 right hemilaminectomy the extradural part of soft , white - brown coloured tumor tissue within the spinal canal was removed .
the tumor cells showed positive immunoreactivity for cd56 , synaptophysin and negative immunoreactivity for desmin ( fig .
interphase fluorescent in situ hybridisation ( fish ) analysis was used for the evaluation of n - myc ( 2p24 ) status in the tumor cells with the use of " cytocell n - myc amplification fish probe " .
vysis 1p36/1q25 and 19q13/19p13 fish probe " and " vysis 11q23 fish probe " was used and it was shown that the n - myc oncogene was not amplified and there wer no deletions of chromosome 1p and 11q for all of the pathological samples .
ganglioneuroma is a slow growing , benign tumor , which can be rarely associated with neurofibromatosis type i and multiple tumor syndromes like multiple endocrine neoplasia type iib33 ) .
spinal ganglioneuromas represent less than 10% of all ganglioneuromas , usually with the involvement of paraspinal region28 ) .
surgical excision is the treatment of choice in the management of symptomatic ganglioneuromas with very good prognosis36 ) .
ganglioneuroblastoma is one of the neuroblastic tumors and like ganglioneuroma or nb , it is also derived from the primordial neural crest cells .
it contains both spindle schwannian stroma with mature ganglion cells and undifferentiated neuroblastic cells38 ) .
spinal involvement of nb constitues 20 - 30% of all pediatric primary extradural spinal tumors34 ) .
familial genetic predisposititon and enviromental causes are thought to be responsible for the etiology of nb , although mechanisms leading to the disease are not fully understood5,12 ) .
nb is an unexpected pathological diagnosis in adults and spinal involvement of this tumor is extremely rare .
the differentiation of nb into ganglioneuroblastoma or ganglioneuroma was first described by cushing and wolbach10 ) in 1927 . also the transformation from ganglioneuroma into malignant nerve sheath tumors
however , the malignant transformation of a ganglioneuroma or a ganglioneuroblastoma into nb was only described by kulkarni et al.22 ) in 1998 . in this particular report malignant transformation from a ganglioneuroma to a nb was occured 11 years after the initial surgery . to our knowledge
kulkarni et al.22 ) proposed whether a malignant transformation of the remnant tumor or a neuroblastomatous component , which remained undiagnosed after the first operation . considering the long survival period in both patients by kulkarni et al . and the present report ,
namely 11 and 13 years , it is not possible to claim the latter proposal is realistic .
however , with careful reevaluation of the former biopsy material , an undiagnosed cellular area with ganglioneuroblastomatous characteristics was found in our case .
four years after the first operation , it was observed that the whole tumor shared the pathological characteristics of this small ganglioblastomatous nodule .
although the biopsy of the first tumor in our case was in consistency with a ganglioneuroma , except this small nodule , it should be accepted as a ganglioneuroblastoma .
after the second operation our patient was lost to follow - up , neither underwent surgery for the resection of the retroperitoneal rest tumor nor get any further oncological treatment .
the total nine year survey after the second operation ( a total of 13-year disease free survival until the neuroblastic transformation ) despite a rest tumor and without any additional therapy is considerably long .
our case demonstrates that the biological behaviour of these tumors varies greatly and it might be more likely related to genetic factors rather than the histopathological characteristics .
the limited number of familial cases limits the pursuit of genetic factors or familial inheritence in nb24 ) .
well known genetic abnormalities in nb are chromosome deletion of 1p , 11q , gain of 17q and amplification of the n - myc oncogene6,27,32 ) .
prior to the current report , there were no cytogenetic work - up has been done for the spinal nb .
the specimens were tested for the amplification of the n - myc oncogene for the deletions of chromosome 1p and 11q .
the prognosis might change in each particular case with regression , maturation , or progression of the tumors5,26 ) .
the variety in clinical behavior was found to be associated with spesific cytogenetic malformations9 ) .
histologic grade , age , tumor differantiation , the status of n - myc oncogene , 11q and dna ploidy are associated with clinical outcome9 ) .
previously reportes cases of adult spinal nb is related with a shorter survival , less than 2 years2,18 ) .
however the present case and the case presented by kulkarni et al.22 ) had similar survival of more than 10 years .
this prolonged survival with stable disease may be related to better prognosis of spinal nb . for pediatric age group
it is known that , spinal - paraspinal nb has a more favorable outcome with less frequent metastases21,29,35 ) .
two genetic abnormalities , which were known to be oncogenic factors in nb , namely n - myc amplification and 1p , 11q deletions , were not found in this case .
the relation between prolonged survival of our case and lack of this genetic abnormalities is debatable , however our patient is still doing well with no neurological deficits or complaints two years after the third operation with no recurrence .
this report demonstrates that ganglioneuroblastomas or even ganlioneuromas can rarely dedifferentiate into nb with a quite long transformation process .
ganglioneuromas are benign tumors . 
 surgical excision is the treatment of choice with very good prognosis . 
 however , neuroblastomatous malignant transformation of ganglioneuromas was previously reported . 
 we report a patient with spinal neuroblastoma recurrent from a ganglioneuroblastoma after disease free survival of 13 years . 
 this is one of the rare examples of spinal neuroblastoma and to our knowledge the second case report with malignant transformation from a ganglioneuroblastoma or a ganglioneuroma . 
 the present case is the only report in the literature with further genetic investigations .