Clinicopathological and molecular characteristics of pediatric meningiomas

Abstract

Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Therefore, we analyzed clinical, morphological and molecular profiles of pediatric meningiomas. Forty pediatric meningiomas from January 2002 to June 2015 were studied. 1p36, 14q32 and 22q-deletion were assessed by fluorescent in situ hybridization and mutations of most relevant exons of AKT, SMO, KLF4, TRAF and pTERT using sequencing. Expression of GAB1, stathmin, progesterone receptor (PR), p53 along with MIB-1 LI was examined using immunohistochemistry. There were 36 sporadic and four NF2 associated meningiomas. Among sporadic meningiomas, the majority (72.2%) of cases harbored 22q-deletion. Difference in frequency of combined 1p/14q deletion in Grade-I versus Grade-II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade-I and 14.2% of Grade-II/III tumors (P = 0.03). The majority (97.2%) of meningiomas were immunonegative for p53. Stathmin and GAB co-expression was observed in 58.3% of cases. Notably, AKT, SMO, KLF4, TRAF7 (exon 17) and pTERT mutations were seen in none of the cases analyzed. 1p/14q codeletion was frequent in skull base as compared to non-skull base meningiomas (23% vs 11.1%, P = 0.37). All NF2 meningiomas harbored 22q-deletion and showed GAB and stathmin co-expression while none showed 1p/14q loss. Pediatric meningiomas share certain phenotypic and cytogenetic characteristics with adult counterparts, but GAB and stathmin co-expression in the majority of cases and non-significant difference in frequency of 1p/14q co-deletion between low- and high-grade meningiomas indicate an inherently aggressive nature. Characteristic AKT/SMO, KLF4/TRAF7 and pTERT genetic alterations seen in adults are distinctly absent in pediatric meningiomas.

Pediatric meningioma: a clinicopathologic and molecular study with potential grading implications

“…We did not see any loss of chromosome 10, which is a notable feature of high‐grade meningioma in adults (39). Likewise, we did not identify any chromosome 1p and 14q codeletion events, which were reported in 28.5% of high grade tumors in previous study (total n = 7 pediatric tumors graded as II and III) (7). This discrepancy could be due to methodological differences or due to differences in the patient population (eg, prevalence of NF2 patients in the current study as compared to the predominance of sporadic meningiomas in the previous study).…”

“…Copy number variants were less frequent in our cohort compared to adult meningioma (39) and previous pediatric studies (7). We did not see any loss of chromosome 10, which is a notable feature of high‐grade meningioma in adults (39).…”

“…), higher mitotic and proliferation indices, more frequent brain invasion, higher recurrence rates and a predilection for atypical sites (particularly the spinal cord) (13, 15, 17, 19, 28, 34, 38, 44). They also lack the female sex bias seen in adult tumors (17), are more often associated with inherited genetic syndromes (eg, Neurofibromatosis type II (5, 27, 34, 43, 50) and Gorlin's syndrome (3, 31)), have increased sensitivity to environmental risk factors (such as exposure to ionizing radiation) (18, 20, 21, 46) and show a unique mutational profile (7). The dissimilarities in tumor characteristics and behavior may reflect distinct molecular and cytogenetic mechanisms in adult vs. pediatric meningiomas (44).…”

Molecular and translational advances in meningiomas

“…89 An exploratory study using targeted Sanger sequencing did not identify the typical mutations found in adult meningiomas, such as mutations in SMO, AKT, KLF4, TRAF7 (exon 17), and TERT promoter. 90 Of the 40 cases studied in this series, NF2 deletions were observed in 30 patients (75%). Future studies focusing on meningiomas should attempt to discover novel non-NF2 alterations, which may help explain both the predominance of specific histological subtypes as well as the lack of common non-NF2-associated mutations.…”

The Loss of 1p as a Reliable Marker of Progression in a Child with Aggressive Meningioma: A 16-Year Follow-Up Case Report

“…Cases of pediatric meningioma present in parts similar characteristics according to Battu et al [23]. Pediatric meningiomas can be associated with NF-gene mutations.…”