The International Neuroblastoma Pathology Classification (the Shimada system)

BACKGROUND: The International Neuroblastoma Pathology Committee, which is comprised of six member pathologists, was convened with the objective of proposing a prognostically significant and biologically relevant classification based on morphologic features of neuroblastic tumors (NTs) (i.e., neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: A total of 227 cases were reviewed. Consensus diagnoses from morphologic features (criteria described separately) based on five of six or six of six agreements by the reviewer pathologists were used for prognostic analysis. Prognostic effects of morphology, both individual and in combination, taken in conjunction with age (Shimada classification, histologic grade, and risk group), were analyzed. RESULTS: Approximately 99% of cases (224 of 227) had consensus diagnoses for categorization: neuroblastoma (Schwannian stroma-poor), 190 cases; ganglioneuroblastoma, intermixed (Schwannian stroma-rich), 5 cases; ganglioneuroma (Schwannian stroma-dominant) maturing, 1 case; ganglioneuroblastoma, nodular (composite Schwannian stroma-rich/stroma-dominant and stroma-poor), 19 cases; and NT-unclassifiable, 9 cases. For the NTs, subtype (93% consensus: undifferentiated, 6 cases; poorly differentiated, 155 cases; and differentiated, 15 cases), mitosis-karyorrhexis index (90% consensus: low, 94 cases; intermediate, 40 cases; and high, 37 cases), mitotic rate (75% consensus: low, 89 cases; high, 50 cases; and not determined, 4 cases), and calcification (100% consensus: yes, 110 cases and no, 80 cases) were recorded. Statistical analysis demonstrated that the Shimada classification system (90% consensus; 3-year event free survival: 85% for the group with favorable histology and 41% for the group with unfavorable histology; P = 0.31 x 10(-9)) had a significantly stronger prognostic effect than individual features and other combinations. CONCLUSIONS: The International Neuroblastoma Pathology Classification, a system based on a framework of the Shimada classification with minor modifications, is proposed for international use in assessing NTs.