The International Neuroblastoma Pathology classification (the Shimada system)

BACKGROUND. The International Neuroblastoma Pathology Committee, which is c omprised of six member pathologists, was convened with the objective of pro posing a prognostically significant and biologically relevant classificatio n based on morphologic features of neuroblastic tumors (NTs) (i.e., neurobl astoma, ganglioneuroblastoma, and ganglioneuroma). METHODS. A total of 227 cases were reviewed. Consensus diagnoses from morph ologic features (criteria described separately) based on five of six or six of six agreements by the reviewer pathologists were used for prognostic an alysis. Prognostic effects of morphology, both individual and in combinatio n, 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 fo r categorization: neuroblastoma (Schwannian stroma-poor), 190 cases; gangli oneuroblastoma, intermixed (Schwannian stroma-rich), 5 cases; ganglioneurom a (Schwannian stroma-dominant) maturing, 1 case; ganglioneuroblastoma, nodu lar (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 different iated, 15 cases), mitosis-karyorrhexis index (90% consensus: low 94 cases; intermediate, 40 cases; and high, 37 cases), mitotic rate (75% consensus: l ow, 89 cases; high, 50 cases; and not determined, 4 cases), and calcificati on (100% consensus: yes, 110 cases and no, 80 cases) were recorded. Statist ical analysis demonstrated that the Shimada classification system (90% cons ensus; 3-year event Free survival: 85% for the group with favorable histolo gy and 41% for the group with unfavorable histology; P = 0.31 x 10(-9)) had a significantly stronger prognostic effect than individual features and ot her combinations. CONCLUSIONS. The International Neuroblastoma Pathology Classification, a sy stem based on a framework of the Shimada classification with minor modifica tions, is proposed for international use in assessing NTs. Cancer 1999;86:3 64-72. (C) 1999 American Cancer Society.