title: Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee.
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).
  
  
  METHODS
  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.
authors: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
authors: Rie
authors: R
authors: Suganuma
authors: Larry L
authors: LL
authors: Wang
authors: Hideki
authors: H
authors: Sano
authors: Arlene
authors: A
authors: Naranjo
authors: Wendy B
authors: WB
authors: London
authors: Robert C
authors: RC
authors: Seeger
authors: Michael D
authors: MD
authors: Hogarty
authors: Julie M
authors: JM
authors: Gastier-Foster
authors: A Thomas
authors: AT
authors: Look
authors: Julie R
authors: JR
authors: Park
authors: John M
authors: JM
authors: Maris
authors: Susan L
authors: SL
authors: Cohn
authors: Gabriele
authors: G
authors: Amann
authors: Klaus
authors: K
authors: Beiske
authors: Catherine J
authors: CJ
authors: Cullinane
authors: Emanuele S G
authors: ES
authors: d'Amore
authors: Claudio
authors: C
authors: Gambini
authors: Jason A
authors: JA
authors: Jarzembowski
authors: Vijay V
authors: VV
authors: Joshi
authors: Samuel
authors: S
authors: Navarro
authors: Michel
authors: M
authors: Peuchmaur
authors: Hiroyuki
authors: H
authors: Shimada
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D011379:Prognosis; D058028:Research Report
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins