Evidence for molecular heterogeneity in human ganglioneuroblastoma

Ganglioneuroblastomas are tumors of sympathetic cell origin that contain both primitive neuroblastomatous and mature ganglioneuromatous elements. It is thought that these tumors arise from a single cellular clone and that the morphologically distinct components of ganglioneuroblastomas represent cells in different stages of differentiation. Two pathologic variants of this tumor, composite and diffuse, have been described; metastasis is more commonly seen with composite ganglioneuroblastomas. We analyzed a composite ganglioneuroblastoma for N-myc copy number at initial resection and 2 years later after progressive disease. In the second sample the more differentiated portion of the tumor was analyzed separately from the neuroblastic foci for N-myc copy number and DNA ploidy. The DNA content and N-myc copy number differed in the two morphologically discrete areas of the tumor, suggesting that at least two clones were present. More composite ganglioneuroblastomas need to be examined to determine whether these tumors are largely composed of tumor cell populations with molecular heterogeneity.