AGE-LINKED PROGNOSTIC CATEGORIZATION BASED ON A NEW HISTOLOGIC GRADING SYSTEM OF NEUROBLASTOMAS - A CLINICOPATHOLOGICAL STUDY OF 211 CASES FROM THE PEDIATRIC-ONCOLOGY-GROUP

UNIV TEXAS,HLTH SCI CTR,SW MED SCH DALLAS TX 75235 UNIV ALABAMA,SCH ME D BIRMINGHAM AL 35233 Histologic sections (minimum of four sections pe r patient) from 211 patients with neuroblastoma were reviewed. The tum ors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (less-than-or-equal-to ten per te n high-power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log-rank t ests (P < 0.0001 and P = 0.0065, respectively). Histologic Grades 1, 2 , and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had abse nce of low MR, i.e., these tumors had high MR [> ten per ten high-powe r fields]). Statistically significant differences in survival were obs erved in the grades after adjusting for age and stage (P < 0.001). The degree of differentiation, although significant by itself, was no lon ger significant after adjusting for the grades. Age groups (less-than- or-equal-to 1 versus > 1 year of age), which also emerged as an indepe ndent prognostic feature (P < 0.001), were linked with the grades to d efined two risk groups as follows: (1) a low-risk (LR) group consistin g of patients in both age groups with Grade 1 tumors and patients 1 ye ar of age or younger with Grade 2 tumors and (2) a high-risk (HR) grou p consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statisti cally significant (P < 0.001). Concordance between these LR and HR gro ups and the Shimada classification was observed in 84% of cases. The n ew histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested o n a new data set with an appropriate histologic sample of similar size to confirm these results.