Neuroblastoma may develop at any site of sympathetic nervous system tissue. Tumors originating from different sties might have different clinical and biological characteristics. Indeed, a few studies have reported that the tumor site was prognostically important in neuroblastoma (14
). However, most studies addressing the prognostic significance of the tumor site of origin compared thoracic neuroblastomas and others, and found that thoracic neuroblastomas were associated with more favorable clinical features than neuroblastomas originating from other sites, including the abdomen (14
). The investigators suggested that the clinical features of rare neuroblastomas, originating from both extra-thoracic and extra-abdominal sites, might be similar with those of thoracic neuroblastomas. Therefore, the present study was designed to determine the differences in the clinical and biological features between extra-abdominal and abdominal neuroblastomas.
We have shown that the biology of extra-abdominal neuroblastomas is indeed different from that of abdominal neuroblastomas. The results of the present study revealed that the extra-abdominal neuroblastomas were associated with more favorable prognostic factors than were the abdominal neuroblastomas. Frequencies of disseminated tumors, N-myc amplified tumors and tumors with unfavorable Shimada pathology were lower in patients with extra-abdominal tumors compared to those with abdominal tumors. In addition, levels of the serum LDH, ferritin, NSE and urine VMA were lower in the extra-abdominal tumors than in the abdominal tumors. When the analysis was confined to only the patients older than 1 yr of age at diagnosis, patients with stage 4 tumors or with high-risk tumors, the levels of LDH and NSE were significantly lower in patients with extra-abdominal tumors compared to those with abdominal tumors (data not shown). The characteristics of both extra-thoracic and extra-abdominal tumors were very similar to those of thoracic tumors. In addition, the results of this study demonstrated that patients with extra-abdominal neuroblastomas had a more favorable long-term outcome than did the patients with abdominal neuroblastomas. All patients with both extra-thoracic and extra-abdominal tumors are currently event free.
It is not clear whether the more favorable outcome with extra-abdominal tumors could be attributed to their association with favorable clinical and biological features, or whether the extra-abdominal site is an independent favorable prognostic factor; this is because a multivariate Cox analysis was not possible in the present study because of the small number of patients. However, the long-term outcome was better in the patients with extra-abdominal tumors than in patients with abdominal tumors even when the data was corrected for age at diagnosis, stage or risk-group.
Prior studies on thoracic neuroblastomas have reported a female prevalence (2
); however, there was no female prevalence in the extra-abdominal group in the present study. When the analysis was confined to only the patients with thoracic neuroblastomas, there was no female prevalence. According to the study reported by Morris et al. (14
), patients with thoracic neuroblastomas were younger than patients with other sites of origin. However, there was no difference in the age at diagnosis between the extra-abdominal and abdominal neuroblastomas in the present study. In addition, when the analysis was confined to 21 patients with thoracic neuroblastomas, there was no difference in the age at diagnosis when compared with other neuroblastomas. In the report by Suita et al. (15
), there was also no difference in age between thoracic and nonthoracic patients. Adams et al. (16
) confirmed that children with thoracic neuroblastomas have a more favorable outcome, and this was not because of earlier clinical presentation or earlier expression of symptoms.
During the last decade, HDCT/ASCR has improved the survival of patients with high-risk neuroblastoma (24
). Most patients with high-risk tumors in the present study received tandem HDCT/ASCR and the probability of 5-yr EFS among the high-risk patients was over 60%. However, despite the remarkable improvement in the survival rate in the present study compared to previous studies addressing the prognostic significance of tumor site in neuroblastoma, there is still a significant difference in survival between patients with extra-abdominal neuroblastomas and those with an abdominal origin. This finding suggests that the tumor site of origin is a prognostic factor even with the most current treatment protocols.
This is the first study to investigate the differences in the clinical and biological characteristics between extra-abdominal and abdominal neuroblastomas. The results of the present study show that neuroblastomas originating from extra-abdominal sites are associated with better clinical and biological characteristics and they are associated with a better outcome than those originating from the abdomen. Further study is needed to explain these findings and to determine whether an extra-abdominal site is an independent favorable prognostic factor.