Genetic profiling by single-nucleotide polymorphism-based array analysis defines three distinct subtypes of orbital meningioma

Abstract

Orbital meningiomas can be classified as primary optic nerve sheath (ON) meningiomas, primary intraorbital ectopic (Ob) meningiomas and spheno-orbital (Sph-Ob) meningiomas based on anatomic site. Single-nucleotide polymorphism (SNP)-based array analysis with the Illumina 300K platform was performed on formalin-fixed, paraffin-embedded tissue from 19 orbital meningiomas (5 ON, 4 Ob and 10 Sph-Ob meningiomas). Tumors were World Health Organization (WHO) grade I except for two grade II meningiomas, and one was NF2-associated. We found genomic alterations in 68% (13 of 19) of orbital meningiomas. Sph-Ob tumors frequently exhibited monosomy 22/22q loss (70%; 7/10) and deletion of chromosome 1p, 6q and 19p (50% each; 5/10). Among genetic alterations, loss of chromosome 1p and 6q were more frequent in clinically progressive tumors. Chromosome 22q loss also was detected in the majority of Ob meningiomas (75%; 3/4) but was infrequent in ON meningiomas (20%; 1/5). In general, Ob tumors had fewer chromosome alterations than Sph-Ob and ON tumors. Unlike Sph-Ob meningiomas, most of the Ob and ON meningiomas did not progress even after incomplete excision, although follow-up was limited in some cases. Our study suggests that ON, Ob and Sph-Ob meningiomas are three molecularly distinct entities. Our results also suggest that molecular subclassification may have prognostic implications.

Keywords: NF2; SNP array; chromosome 22; cytogenetics; optic nerve sheath; orbital meningioma.

Figure 1

Three subtypes of orbital meningiomas. A. Optic nerve sheath meningiomas form intraorbital masses in close relation to optic nerve (arrows) (axial T1‐weighted MRI post‐contrast). B. Intimate association with optic nerve may be demonstrated on histologic sections (H&E). Intraorbital ectopic meningiomas are unassociated with nerve. A small focus of ossification was present in this example on (C) CT scan (arrow) and (D) H&E. E. Spheno‐orbital meningiomas are characterized by intracranial (arrow) and intraorbital (arrowhead) components. Hyperostosis of the posterior lateral wall and lateral sphenoid, and tumor extension to the subtemporal area is also present (asterisk) (F). This example infiltrated surrounding soft tissues, including skeletal muscle.

Figure 2

Chromosome map summarizing the genomic alterations in orbital meningiomas by case. Abnormalities are listed sequentially by case number to the left of the respective chromosomes. Only cases with abnormalities are illustrated (2, 3, 5, 6, 7, 8, 10, 11, 13, 14, 16, 17, 19). Gains are illustrated in green, deletions in red and copy neutral loss of heterozygosity (LOH) in gray.

Figure 3

Orbital meningioma subtypes have different cytogenetic abnormalities. Chromosome 22 loss was frequent in ectopic orbital meningiomas (A) but rare in meningiomas of the optic nerve proper which usually had no alterations in Ch 22 (B). Conversely, optic nerve meningiomas contained other less frequent abnormalities. In this example alterations in chromosome 2 (del 2pter‐p16.3, del 2q22.1‐qter) are shown (C).

Figure 4

Graphic illustrating the three subtypes of orbital meningiomas at different anatomic sites. Optic nerve sheath (ON) meningioma; intraorbital ectopic (Ob) meningioma; spheno‐orbital (Sph‐Ob) meningioma.