HETEROGENEITY OF MYCN AMPLIFICATION IN A CHILD WITH STROMA-RICH NEUROBLASTOMA (GANGLIONEUROBLASTOMA)

Amplification of MYCN portends rapid tumor progression and poor progno sis in neuroblastoma. MYCN copy number has been described as homogeneo us within a tumor and congruent in primary tumor and metastasis. We re port a child with stage III favorable histology stroma-rich neuroblast oma (ganglioneuroblastoma) and a poor outcome with an apparent change in MYCN gene amplification by Southern blot. Initial biopsy revealed a ganglioneuroblastoma with predominance of differentiating cells desig nated as neuroblastoma, stroma-rich, intermixed (Shimada). Southern bl ot failed to demonstrate MYCN gene amplification. After front-line che motherapy failed, a total resection was performed. IN this specimen, S outhern blot demonstrated MYCN amplification (15-20 copies) in the und ifferentiated component and no amplification in the differentiated. Fl uorescence in situ hybridization (FISH) analysis performed retrospecti vely on both tumor biopsies demonstrated MYCN amplification in the und ifferentiated sections of both tumor specimens but not in the differen tiated ones. This is the first well-documented case report of heteroge neous MYCN amplification in a child with neuroblastoma. Because key th erapeutic decisions are based on the presence of MYCN amplification, p hysicians diagnosing and treating children with neuroblastoma need to be aware of the possibility that MYCN amplification may be heterogeneo us within a tumor and may be missed using techniques based on pooled D NA such as Southern blotting. FISH may be a preferable method for dete rmining MYCN amplification.