Problems of mass screening for neuroblastoma: Analysis of false-negative cases

Abstract The Japanese mass screening (MS) system for neuroblastoma at 6 months of age has resulted in the earlier diagnosis of the tumor with excellent therapeutic results. However, some problems are involved in the present MS system. We present six false-negative cases, ages ranging from 1 year 11 months to 3 years 11 months. Neuroblastoma cells taken from four of these patients were studied biologically. These patients had advanced disease (one was stage III; five were stage IV). Three of the patients have died and one is terminally ill despite undergoing surgery combined with intensive chemotherapy. Cytogenetic analysis performed in three cases showed that all the cases had diploid chromosome mode associated with 1P-, double minutes (DMs), or marker chromosomes. N-myc oncogene analysis, performed in four cases, showed amplification in two; one patient had diploid chromosomes, but the other was not examined cytogenetically. These findings were strikingly different biologically from those of cases found by MS. The majority of neuroblastomas detected by MS were found to be triploid tumors without N-myc amplification. These findings suggest that the main reason for the false-negative results in the patients we examined is that they were tumor-free or the tumors were so small in size that they were unable to produce urinary vanillylmandelic acid and or homovanillic acid levels high enough to be detected at the time of MS. Therefore, we conclude that MS at 6 months of age is too early to detect neuroblastoma with a diploid chromosome mode and/or amplified N-myc oncogene. We propose that MS at the age of 1 year 6 months would be more effective to pick up these cases, because treatment strategies depend on the different biological characteristics of tumor cells.