Search

Unlike patients with World Health Organization (WHO) grade I meningiomas, which are considered benign, patients with WHO grade III meningiomas have very high mortality rates. The principles underlying tumor progression in meningioma are largely unknown, yet a detailed understanding of these mechanisms will be required for effective management of patients with these high grade lethal tumors. We present a case of an intraventricular meningioma that at first presentation displayed remarkable morphologic heterogeneity—composed of distinct regions independently fulfilling histopathologic criteria for WHO grade I, II, and III designations. The lowest grade regions had classic meningothelial features, while the highest grade regions were markedly dedifferentiated. Whereas progression in meningiomas is generally observed during recurrence following radiation and systemic medical therapies, the current case offers us a snapshot of histologic progression and intratumoral heterogeneity in a native pretreatment context. Using whole exome sequencing and high resolution array-based comparative genomic hybridization, we observed marked genetic heterogeneity between the various areas. Notably, in the higher grade regions we found increased aneuploidy with progressive loss of heterozygosity, the emergence of mutations in the TERT promoter, and compromise of ARID1A . These findings provide new insights into intratumoral heterogeneity in the evolution of malignant phenotypes in anaplastic meningiomas and potential pathways of malignant progression. [ABSTRACT FROM AUTHOR]

PURPOSE: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas. DESIGN: Retrospective clinicohistopathologic and immunohistochemical study. METHODS: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins. RESULTS: Three infants (aged 1, 6, and 8 months) had iris neovascularization, 2 had anterior ciliary body tumors, and 1 a posterior tumor associated with a retinochoroidal coloboma. Each tumor displayed a premedullary monolayer of cuboidal epithelium that was S100+, NeuN-, and CRX- and that transitioned into a multilaminar medullary epithelium forming neurotubules with adluminal cells that were CRX+. NeuN first appeared in ablumenal neurotubular cells in 1 tumor and was also discovered among neuroblast-appearing cells in another. The third tumor associated with a coloboma was CRX- and NeuN-. CONCLUSIONS: A simple premedullary epithelial monolayer appears to be the fundamental source for the tumor and its multilaminar medullary epithelium. CRX+ and NeuN- cells within the multilayered medullary layer approximate expression patterns similar to those found in retinal development and differentiation. Discovery of these biomarkers in the neoplastic ciliary epithelium in a small number of tumors indicates preliminarily that the most anterior layers of the optic cup have a retained retinal and neuroglial differentiation potentiality. The third case was CRX- and NeuN- and possibly arose from embryonic pigment epithelium at the edge of the retinochoroidal coloboma. These immunohistochemical findings offer histogenetic and potential diagnostic insights. [ABSTRACT FROM AUTHOR]