Adrenal gland and paraganglia
Neuroblastic tumors
Prognostic factors for neuroblastic tumors

Author: Nat Pernick, M.D. (see Authors page)

Revised: 25 January 2016, last major update February 2005

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

Definition / General
  • Poor prognostic indicators: 1p36.33 deletion (subtelomeric region, may be site of differentiation associated genes); N-myc amplification (> 10 copies, is associated with 1p36 deletion), 14p deletion, diploidy, low expression of TrkA gene (maturation factor), undifferentiated morphology, high mitotic rate-karyorrhexis index and age 1 year old or more; this group has a 5% cure rate; also 17q+, elevated serum ferritin (> 150 ng/mL)
  • Intermediate prognostic indicators: near-diploid / tetraploid, no N-myc amplification, no 1p deletions and low levels of TrkA; older patients; this group has a 25-50% cure rate
  • Favorable prognostic indicators: age < 1 year regardless of stage, hyperdiploid / near-triploid, high levels of TrkA gene (associated with lack of N-myc amplification), stages 1, 2 or 4S versus stages 3 or 4
  • Note: the more copies of N-myc, the greater the number of double minutes and homogenously staining regions, and the worse the prognosis
Classification

Shimada classification
  • Features include age, degree of neuroblast differentiation, presence or absence of Schwannian stromal development (stroma-rich or stroma-poor), mitosis-karyorrhexis index (MKI) and nodular pattern
  • Stroma rich: significant number of Schwann cells in association with neuroblastoma cells - corresponds to ganglioneuroblastoma
  • Stroma poor: undifferentiated or differentiated neuroblastoma
  • Mitosis-karyorrhexis index (MKI): count of cells undergoing mitosis or karyorrhexis, based on count of 5000 cells; either low (< 100 cells), intermediate (100-199 cells) or high (200 or more cells)
  • Note: the unfavorable histologic features are reported inconsistently by various sources

    Favorable histology group:
    • Patients of any age with stroma-rich tumors without a nodular pattern
    • Patients younger than 18 months, with stroma-poor tumors, an MKI less than 200/5000 (200 karyorrhectic cells per 5000 cells scanned) or
    • Patients 18-60 months with stroma-poor tumors, an MKI less than 100/5000 and well-differentiated tumor cells

    Unfavorable histology group:
    • Patients of any age with stroma-rich tumors and a nodular pattern
    • Patients of any age with stroma-poor tumors and an MKI more than 200/5000
    • Patients 18-60 months with stroma-poor tumors, differentiated neuroblasts and an MKI of 100-200/5000
    • Patients 18-60 months with stroma-poor tumors, undifferentiated neuroblasts
    • Patients older than 60 months with stroma-poor tumors

Joshi classification of neuroblastoma
  • Grade 1: < 10 MF/10 HPF and calcification - good prognosis (5 year survival of 89%)
  • Grade 2: < 10 MF/10 HPF or calcification, but not both - intermediate prognosis (5 year survival of 77%)
  • Grade 3: > 10 MF/10 HPF and no calcification, any age - poor prognosis (5 year survival of 33%)

International Neuroblastoma Pathology Committee (INPC)
  • Four major categories: (1) neuroblastoma (schwannian stroma-poor neuroblastic tumor), (2) ganglioneuroblastoma, nodular (composite schwannian stroma-rich / stroma-dominant and stroma-poor neuroblastic tumor), (3) ganglioneuroblastoma, intermixed (schwannian stroma-rich neuroblastic tumor) and (4) ganglioneuroma (schwannian stroma-dominant neuroblastic tumor)

  • Favorable histology categories for neuroblastoma include: poorly differentiated, low or intermediate MKI and age < 1.5 years; or differentiating, low MKI and age 5 years or less; or differentiating, intermediate MKI and age < 1.5 years
  • All other neuroblastomas are unfavorable histology
  • Overall 5 year survival was 97.8% for favorable versus 35.6% for unfavorable histology groups for neuroblastoma
  • Ganglioneuroblastoma-intermixed and ganglioneuroma were considered to have favorable histology and had 100% overall 5 year survival
  • Ganglioneuroblastoma-nodular was considered to have unfavorable histology and had 59% overall 5 year survival