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 characterized in comparison to sporadic adult cases. In order to elucidate their molecular features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL-1 protein, and chromosomal arms 1p and 14q in 53 meningiomas from 40 pediatric/NF2 patients using immunohistochemistry and dual-color fluorescence in situ hybridization (FISH). Fourteen pediatric (42%) patients, including 5 previously undiagnosed patients, had NF2. The remaining 19 (58%) did not qualify. All 7 of the adult patients had NF2. Meningioma grading revealed 21 benign (40%), 26 atypical (49%), and 6 anaplastic (11%) examples. Other aggressive findings included high mitotic index (32%), high MIB-1 LI (37%), aggressive variant histology (e.g. papillary, clear cell) (25%), brain invasion (17%), recurrence (39%), and patient death (17%). FISH analysis demonstrated deletions of NF2 in 82%, DAL-1 in 82%, 1p in 60%, and 14q in 66%. NF2-associated meningiomas did not differ from sporadic pediatric tumors except for a higher frequency of merlin loss in the former (p = 0.020) and a higher frequency of brain invasion in the latter (p = 0.007). Thus, although pediatric and NF2-associated meningiomas share the common molecular alterations of their adult, sporadic counterparts, a higher fraction are genotypically and phenotypically aggressive. Given the high frequency of undiagnosed NF2 in the pediatric cases, a careful search for other features of this disease is warranted in any child presenting with a meningioma.
Perry
A
A
Divisions of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Giannini
C
C
Raghavan
R
R
Scheithauer
B W
BW
Banerjee
R
R
Margraf
L
L
Bowers
D C
DC
Lytle
R A
RA
Newsham
I F
IF
Gutmann
D H
DH
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000075202:Contraindications; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008840:Microfilament Proteins; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D025521:Tumor Suppressor Proteins
C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins