Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: A clinicopathologic study of 53 cases

Pediatric and NF2-associated meningiomas are uncommon and poorly characteri zed in comparison to sporadic adult cases. In order to elucidate their mole cular features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL-1 protein, and chromosomal arms 1p and 14q in 53 meningiomas fr om 40 pediatric/NF2 patients using immunohistochemistry and dual-color fluo rescence in situ hybridization (FISH). Fourteen pediatric (42%) patients, i ncluding 5 previously undiagnosed patients, had NF2. The remaining 19 (58%) did not qualify. All 7 of the adult patients had NF2. Meningioma grading r evealed 21 benign (40%), 26 atypical (49%), and 6 anaplastic (11%) examples . Other aggressive findings included high mitotic index (32%), high MIB-1 L I (37%), aggressive variant histology (e.g. papillary, clear cell) (25%), b rain invasion (17%), recurrence (39%), and patient death (17%). FISH analys is demonstrated deletions of NF2 in 82%, DAL-1 in 82%, Lp in 60%, and 14q i n 66%. NF2-associated meningiomas did not differ from sporadic pediatric tu mors except for a higher frequency of merlin loss in the former (p=0.020) a nd a higher frequency of brain invasion in the latter (p=0.007). Thus, alth ough pediatric and NF2-associated meningiomas share the common molecular al terations of their adult, sporadic counterparts, a higher fraction are geno typically and phenotypically aggressive. Given the high frequency of undiag nosed NF2 in the pediatric cases, a careful search for other features of th is disease is warranted in any child presenting with a meningioma.