Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome--a new clinical perspective.

PURPOSE: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). EXPERIMENTAL
DESIGN: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004.
RESULTS: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages <or=3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages <or=3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001).
CONCLUSIONS: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages <or=3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.