CR-23CLINIOPATHOLOGICAL AND MOLECULAR CHARACTERISTICS OF PAEDIATRIC MENINGIOMAS

Abstract

BACKGROUND: Pediatric meningiomas (pMNG) are distinctly uncommon. Their molecular features are poorly defined. Hence, this study was undertaken to determine the genetic and molecular alterations occurring in pMNG. METHODS: Cases were analyzed for 1p36, 14q32 and 22q deletion by FISH and AKT1E17K and SMOW535L mutations by direct sequencing. Immunohistochemistry was done for MIB1, Merlin, progesterone receptor (PR), p53, GAB1 and Stathmin. RESULT: Of the 34 pMNG cases analyzed, the mean age was 12.3 years with male preponderance. Non skull base and skull base meningiomas comprised of equal proportion of the cases (44% vs45%). On histopathology, 84.5%, 14% and 3% were WHO grade I, grade II and grade III, respectively. MIB1-LI was slightly higher in high grade pMNG (5.17% Vs1.5%). The difference in frequency of combined 1p/14q deletion in low and high grade tumours was not significant (7%vs33%,p = 0.07). 22q deletion was frequent in both low and high grade pMNGs(82%vs67%). A concordance rate of 76% was observed between 22q deletion and Merlin expression. PR immunoreactivity was higher in lower grade pMNG(64%vs33%). Majority(94%) of pMNGs were immunonegative for p53. Surprisingly, AKT1E17K and SMOW535L gene showed no mutation. However, majority of the cases (61.7%) showed co-expression GAB1 and Stathmin. CONCLUSION: Absence of AKT1E17K and SMOW535L mutations suggest a different molecular genetics profile of pMNGs as compared to their adult counterparts. Presence of 1p/14q co-deletion even in low grade pMNGs and possible activation of PI3/AKT and SHH pathways (presence of GAB and stathmin) suggests that pMNGs are inherently aggressive. However, absence of large series precludes any definite conclusion.