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Problems of mass screening for neuroblastoma: analysis of false-negative cases
K Ishimoto1, N Kiyokawa, H Fujita
1Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Insights
Japanese mass screening for neuroblastoma misses aggressive diploid tumors. Current screening at 6 months is too early for these cases. A later screening at 1 year 6 months is proposed for better detection.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Diagnostic Screening
Background:
- The Japanese mass screening (MS) for neuroblastoma at 6 months has improved early diagnosis and treatment outcomes.
- However, the current MS system has limitations, failing to detect certain neuroblastoma cases.
- This study investigates six false-negative cases missed by the standard 6-month screening.
Purpose of the Study:
- To analyze the biological characteristics of neuroblastoma cases missed by mass screening.
- To identify reasons for false-negative results in the current neuroblastoma screening program.
- To propose an optimized screening schedule for improved detection of aggressive neuroblastoma subtypes.
Main Methods:
- Clinical data review of six false-negative neuroblastoma cases (ages 1 year 11 months to 3 years 11 months).
- Biological analysis of neuroblastoma cells from four patients, including cytogenetic analysis (chromosome mode, 1P-, double minutes, marker chromosomes).
- N-myc oncogene amplification analysis in four patients.
Main Results:
- False-negative cases presented with advanced disease (Stage III/IV) and poor outcomes (3 deaths, 1 terminal).
- Cytogenetic analysis revealed diploid chromosome modes with abnormalities (1P-, DMs, marker chromosomes) in three cases.
- N-myc oncogene amplification was observed in two of the four analyzed cases, contrasting with typical MS-detected tumors (triploid, no N-myc amplification).
Conclusions:
- Neuroblastomas with diploid chromosome mode and/or N-myc amplification may be missed by 6-month mass screening.
- These tumors might not produce sufficient urinary vanillylmandelic acid/homovanillic acid for detection at 6 months.
- Screening at 1 year 6 months is suggested to improve detection of these biologically distinct, aggressive neuroblastoma 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 cell 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.
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