Histopathology defines prognostic subsets of ganglioneuroblastoma, nodular- A report from the Children's Cancer Group

BACKGROUND, Ganglioneuroblastoma, nodular (GNBn) is a rare subtype of the f amily of neuroblastic tumors (neuroblastoma, ganglioneuroblastoma, and gang lioneuroma) that are classified in the unfavorable histology group accordin g to the International Neuroblastoma Pathology Classification (Shimada syst em). Tumors of this subtype have been considered to represent a prototypic example of biologically and clinically nonaggressive (Schwannian stroma-ric h and stroma-dominant) components combined with biologically and clinically aggressive nodular (Schwannian stroma-poor) components. However, detailed histopathologic analysis as well as thorough prognostic evaluation of patie nts with this subtype has not been reported. METHODS. Pathology slides and reports from a total of 70 GNBn patients from the Children's Cancer Group (CCG)-3881 and CCG-3891 studies were reviewed. Sixty-eight tumors were classified in the favorable subset (FS) or the unf avorable subset (US) based on the evaluation of nodular components by apply ing the same histopathologic criteria (patient age, grade of neuroblastic d ifferentiation, mitosis-karyorrhexis index] that are used for neuroblastoma s in the International Neuroblastoma Pathology Classification. Patient prog nosis as well as clinical and biologic characteristics within the subsets w ere analyzed, and the results were compared with those from 654 non-GNBn pa tients who were enrolled in the same CCG studies during the same period. RESULTS. Patients with GNBn tumors, usually diagnosed at age > 1 year, had a significantly lower overall 5-year event free survival (EFS) rate than pa tients with non-GNBn subtypes (44.7% EFS vs. 65.0% EFS; P = 0.0073). A sign ificant difference in the outcome of the patients between the FS (22 patien ts; 86.1% EFS; 95.0% survival rate) and the US (46 patients; 29.0% EFS; 40. 7% survival rate) of the GNBn subtype (P < 0.0005) was shown. When the coho rt of patients with GNBn tumors was subdivided into FS and US, the outcomes were similar to those of patients with tumors of favorable histology (397 patients; 90.5% EFS; 97.6% survival rate) and with tumors of unfavorable hi stology (257 patients; 27.0% EFS; 35.7% survival rate) of the non-GNBn type . The patients with US tumors frequently (63.0%) presented with distant met astasis. CONCLUSIONS. The current study demonstrates that the nodular components in GNBn tumors are not always aggressive. The prognosis of these patients can be determined by the analysis of age-linked histopathologic features. (C) 2 000 American Cancer Society.