Faculty Collaboration Database

Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer 2013 Mar;60(3):363-70

Date

06/30/2012

Pubmed ID

22744966

Pubmed Central ID

PMC3397468

DOI

10.1002/pbc.24238

Scopus ID

2-s2.0-84872472525 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

BACKGROUND: 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).

PROCEDURE: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Author List

Suganuma R, Wang LL, Sano H, Naranjo A, London WB, Seeger RC, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Amann G, Beiske K, Cullinane CJ, d'Amore ES, Gambini C, Jarzembowski JA, Joshi VV, Navarro S, Peuchmaur M, Shimada H

Author

Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Female
Genetic Association Studies
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Infant
Kaplan-Meier Estimate
Male
N-Myc Proto-Oncogene Protein
Neuroblastoma
Nuclear Proteins
Oncogene Proteins
Prognosis
Research Report