title: Modified histologic grading of neuroblastomas by replacement of mitotic rate with mitosis karyorrhexis index. A clinicopathologic study of 223 cases from the Pediatric Oncology Group.
abstract: BACKGROUND
  Histologic grading (HG) of neuroblastomas (NB) of prognostic significance is based on the presence of absence of calcification and low mitotic rate ( < or = 10/10 high power fields). Mitosis karyorrhexis Index (MKI) is the main feature used for prognostic categorization in Shimada classification and can be determined more readily than mitotic rate (MR). The purpose of this study is to test whether MKI can be used instead of MR for histologic grading.
  
  
  METHODS
  Low and intermediate MKI were lumped together as low MKI. We replaced MR with the modified MKI categories. Histologic grades for 223 NBs registered with the Pediatric Oncology Group protocols 8104 and 8441, were defined ad follows: HG 1 = calcification + low MKI, HG 2 = calcification or low MKI, HG 3 = high MKI and absence of calcification. Shimada classification was also determined for comparison or modified HGs with favorable histology (FH) and unfavorable histology (UH), HGs were linked with age: low risk (LR) = HG 1 in all age groups + HG 2 in patients age younger than 1 year; high risk (HR) = HG 2 in patients age 1 year of older + HG 3 in all age groups.
  
  
  RESULTS
  Statistically significant differences in 5-year survival were seen in the NBs of different modified HG (1: 92.7%, 2: 74.9%, and 3: 18.2%) and risk groups (LR 93.0% and HR 47.9%) (P < 0.0001 and P = 0.0001, respectively).
  
  
  CONCLUSIONS
  Pathologists may readily adapt to the modified HG described here. Advantages of modified HGs include: (1) familiarity and reproducibility of MKI; (2) no need for linkage with age; and (3) a combination of features used in original HGs and Shimada classification.
authors.affiliation: East Carolina University, School of Medicine, Greensville, North Carolina, USA.
authors.forename: V V
authors.initials: VV
authors.lastname: Joshi
authors.forename: P V
authors.initials: PV
authors.lastname: Rao
authors.forename: A B
authors.initials: AB
authors.lastname: Cantor
authors.forename: G
authors.initials: G
authors.lastname: Altshuler
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: R P
authors.initials: RP
authors.lastname: Castleberry
mesh_terms: D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008940:Mitotic Index; D009447:Neuroblastoma / Q000145:classification / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis