Neuroblastomas with discordant genotype-phenotype relationships: Report of four cases with MYCN amplification and favorable histology

Atsuko Nakagawa, Kentaro Matsuoka, Hajime Okita, Hideto Iwafuchi, Hisanari Hori, Masaaki Kumagai

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


MYCN amplification prevents cellular differentiation and promotes mitotic and karyorrhectic activities in neuroblastomas. Hence, MYCN-amplified tumors typically show an appearance of neuroblastoma of either an undifferentiated or a poorly differentiated subtype with a high mitosis-karyorrhexis index. In addition, they are classified as part of the unfavorable histology group, according to the International Neuroblastoma Pathology Classification. Large cell type and/or presence of prominent nucleoli is also reported to be an additional hallmark of MYCN amplification. However, there are few neuroblastomas having MYCN amplification and favorable histology. Four cases of MYCN amplification and favorable histology were identified in our file of 63 cases of neuroblastoma. The patients (M:F = 3:1) were diagnosed between 6 and 13 months of age, and all had adrenal primary tumors and were treated with high-dose therapy and autologous stem cell rescue. Three patients (stages 1, 3, and 4) are alive and well 7 years, 26 months, and 19 months after diagnosis, respectively. One patient with stage 4 disease died 8 months after diagnosis. Their tumors showed the same histologic feature of neuroblastoma: poorly differentiated subtype with a low mitosiskaryorrhexis index; they were not qualified as large cell type and had no prominent nucleoli. MYCN amplification of those tumors was confirmed by fluorescence in situ hybridization in all 4 cases, but MYCN protein expressionwas not demonstrated by immunohistochemistry (4 cases) and MYCN mRNA was not detected by reverse transcriptase polymerase chain reaction (1 case). Those cases showed a discrepant genotype-phenotype that was not simply a laboratory observation but could indicate the concept that that MYCN amplification did not automatically equate to a poor prognosis in this group of patients.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalPediatric and Developmental Pathology
Issue number2
Publication statusPublished - 2011 Mar
Externally publishedYes


  • Favorable histology
  • MYCN amplification
  • Neuroblastoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine


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