Spinal ganglioneuroblastoma--complete response to chemotherapy alone.

Ganglioneuroblastoma in the spinal region is rare, the treatment of choice being surgical excision. We present a 21 year old male who was diagnosed to have this condition in the dorsolumbar spinal region. The tumour was extending intraspinally and was unresectable. Combination chemotherapy with Adriamycin (doxorubicin hydrochloride), vincristine, cyclophosphamide, etoposide, ifosfamide and cisplatin resulted in histologically proven complete remission. No radiotherapy or curative resection was done. The patient is alive without evidence of disease 24 months later. Never before has chemotherapy been successfully used as the sole modality of treatment in this condition. Our report raises important questions about the management of this rare condition, particularly in a situation of unresectability.

We report a 21 year old man who achieved complete remission following combination chemotherapy.

Case report
A 21 year old man was referred to the medical oncology department of this hospital in November 1990. He was earlier admitted to the orthopaedics ward for backache, wasting and weakness of his right leg of 3 months duration. He was immobilized because of severe pain, there was wasting and weakness (Power grade 2/5) of hip flexors and extensors. Blood pressure was normal and there was no lymphadenopathy. His haematological and biochemical parameters, chest X-ray and electrocardiography were normal. A computed tomographic (CT) scan of the spine revealed a soft tissue mass 3 cm wide extending from the dorsal 10 to lumbar 4 vertebra. The mass extended intraspinally and up to the chest displacing the right crus of the diaphragm. There was also the destruction of lumbar 2 and 3 vertebral bodies. A True-cut biopsy of the mass revealed ganglioneuroblastoma ( Figure 1). Urinary vanylmandelic acid was elevated marginally to 2.5 ng (normal 2.4 ng). The tumour was considered unresectable by the orthopaedic surgeons and it was therefore decided to try chemotherapy, to be followed by surgical resection in the event of reduction of the size of the tumour. The chemotherapy given was as follows.
Assessment after two courses of chemotherapy revealed complete disappearance of pain and return of good power. The patient was able to walk without help. A repeat CT scan at this stage revealed a partial response (more than 50% reduction) in the tumour mass. In view ofthe fact that the patient tolerated chemotherapy very well and there was a good response, chemotherapy was con- tinued. Drugs were selected based on stray reports of response as seen from the literature. The aim was to give the patient a broad spectrum exposure to anti-cancer drugs. A follow-up CT scan and T1weighted magnetic resonance image revealed nearcomplete clearance ofthe tumour except for a small residual opacity (very good partial response, defined as more than 90% reduction in tumour mass). The patient was surgically explored at the end of the chemotherapy and a small 1 x 1 cm residual lesion completely removed. Histopathology of this revealed fibrous tissue. There was no tumour. The patient remains well 24 months later and a recent follow-up CT scan has not shown any abnormality.

Discussion
Ganglioneuroblastoma is predominantly encountered in older children and adolescents. The commonest site is the adrenal medulla and the most common extra-adrenal site is posterior mediastinum.S The most common site in the brain is the temporoparietal lobe followed by the cerebral hemisphere, the floor of the third ventricle, the brain stem, the cerebellum and the spinal cord.' Ganglion cell tumours of the spinal cord are extremely rare. So far only 16 cases have been reported.6'7 The standard treatment of ganglioneuroblastoma is complete surgical excision.5 Radiotherapy is given in an adjuvant setting if the patient is over 12 years old, if there is incomplete excision, or if the tumour is of a composite pattern. Information regarding the use of chemotherapy as the major mode of treatment of ganglioneuroblastoma is limited. In a large series of 80 patients of posterior mediastinal ganglioneuroblastoma, Adam treated two unresectable ganglioneuroblastoma with chemotherapy and radiotherapy.' A 10 year old patient treated with cyclophosphamide and 1,810 cGy radiation therapy was alive for 5 years post-treatment. Another one year old patient treated with cyclophosphamide and 2,500 cGy radiation therapy achieved complete remission and had no evidence of disease for 16 years. Since both these patients were given both radiotherapy and chemotherapy, it is difficult to pinpoint the source of benefit. Kilton reported two patients, one patient with stage IV disease received cyclophosphamide 15 mg/kg and vincristine 0.025 mg/kg without any response and the other patient with paraspinal ganglioneuroblastoma received three courses of similar chemotherapy following a laminectomy, without any change in the size of the tumour.4 To the best of our knowledge ours is the first ever case of ganglioneuroblastoma in which complete remission has been achieved with chemotherapy alone.
Ganglioneuroblastoma may infiltrate locally as well as metastasize by way of haematogenous and lymphatic channels, as does neuroblastoma. Ganglioneuroblastomas are slow growing tumours and long-term postoperative survivals have been reported in many clinical series.2'3'8 The prognosis is generally favourable with 2 year survival of 92% and 5 year survival of 88% in a large series.' Spontaneous regression of neuroblastoma is well documented and there is evidence in the literature that many of the so-called cures in neuroblastoma are in fact spontaneous regression. In our patient no mature ganglioneuroma was found on excision and response occurred only after chemotherapy, too close a coincidence for spontaneous regression.
Literature regarding the role of chemotherapy in ganglioneuroblastoma is limited and results are conflicting. The excellent response obtained in the present case warrants a closer look at chemotherapy as the first line of treatment. We used a fairly aggressive and broad-spectrum protocol and it is not clear which drug was the most active. The change in drugs after the first three courses of a different protocol were preplanned to reduce the toxicity and to maximize the response. In view of the fact that the tumour is so rare we may not have an answer to these questions for a long time to come. Our experience is particularly relevant to a situation where the tumour is unresectable or surgery is hazardous.

Introduction
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Case report
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