Member of the International Neuroblastoma Pathology Committee.
Article first published online: 28 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 3, pages 363–370, March 2013
How to Cite
Suganuma, R., Wang, L. L., Sano, H., Naranjo, A., London, W. B., Seeger, R. C., Hogarty, M. D., Gastier-Foster, J. M., Look, A. T., Park, J. R., Maris, J. M., Cohn, S. L., Amann, G., Beiske, K., Cullinane, C. J., d'Amore, E. S.G., Gambini, C., Jarzembowski, J. A., Joshi, V. V., Navarro, S., Peuchmaur, M. and Shimada, H. (2013), Peripheral neuroblastic tumors with genotype–phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr. Blood Cancer, 60: 363–370. doi: 10.1002/pbc.24238
Rie Suganuma and Larry L. Wang contributed equally to this article.
Conflicts of interest: Nothing to declare.
Presented in part at the Advances in Neuroblastoma Research 2006 Conference in Los Angeles, California, May 17–20, 2006 and at the Society for Pediatric Pathology Fall Meeting 2011 in Milwaukee, Wisconsin, September 29–October 2, 2011.
- Issue published online: 15 JAN 2013
- Article first published online: 28 JUN 2012
- Manuscript Accepted: 29 MAY 2012
- Manuscript Received: 5 APR 2012
- National Institutes of Health. Grant Numbers: U10 CA98413, U10 CA98543
- genotype–phenotype correlation;
- International Neuroblastoma Pathology Classification;
Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children's Cancer Group and Children's Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype–phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis).
To distinguish prognostic subgroups in the genotype–phenotype discordant pNTs, two subgroups, “conventional” and “bull's eye,” were identified based on the nuclear morphology. The “conventional” tumors (35 cases) included: Neuroblastoma, poorly differentiated subtype (NB-PD, 26 cases) with “salt-and-pepper” nuclei; neuroblastoma, differentiating subtype (4 cases); ganglioneuroblastoma, intermixed (3 cases); and ganglioneuroma, maturing subtype (2 cases). The “bull's eye” tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors.
No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11q LOH. However, prognosis of the patients with “conventional” tumors (5-year EFS 85.7 ± 12.2%; OS 89.3 ± 10.3%) was significantly better than those with “bull's eye” tumors (EFS 31.3 ± 13.0%; OS 42.9 ± 16.2%; P = 0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested “conventional” tumors were negative, and 10/11 tested “bull's eye” tumors were positive for N-myc protein expression.
Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, “conventional” with a better prognosis and “bull's eye” with a poor prognosis, were distinguished among the genotype–phenotype discordant pNTs. Pediatr Blood Cancer 2013; 60: 363–370. © 2012 Wiley Periodicals, Inc.