Intracranial mesenchymal tumor with (novel) COX14::PTEN rearrangement

Figures

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  Fig. 1. Radiological features. A voluminous tumour in the left temporal pole, extending superiorly to fronto-basal and fronto-lateral regions, deeply to the insula and posteriorly till the supramarginal gyrus was discovered (a, b). The tumour was initially interpreted as atypical meningioma with peripheral intratumoral degenerative cysts. The tumour was completely resected with no signs of residue; brain tissue’s compression resolved (c, d). A two months post-surgery MRI control demonstrated a huge left fronto-temporal local tumoral recurrence (e, f). Three months MRI control after a second intervention showed only a small local recurrence on the posterior margin of the surgical cavity but a diffuse leptomeningeal tumoral spread on the inferior surface of cerebellum, around the brainstem and around the spinal cord (g, h)

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  Fig. 2. Histological findings. The tumor showed circumscribed borders with focal areas of irregular tumor-brain interface, suggestive of brain invasion (inset, higher magnification), and tumor nests extending along the Virchow-Robin spaces (a). The hypercellular spindle areas appeared as short irregular fascicles of elongated cells, immersed in a dense collagenous stroma (b). The hypercellular epithelioid areas showed a predominant lobular architecture (c). In other adjacent areas, epithelioid cells were organized in sheet-like and cord-like structures, with clearer cytoplasm and multiple necrotic foci (d). The hypocellular areas were composed of a myxoid stroma with immersed spindle or stellate cells (e), often showing an angiocentric arrangement (f). In some myxoid areas there were more evident cytologic atypia and numerous daisy-like multinucleated elements (indicated by arrows), characterized by intracytoplasmic eosinophilic globules encircled by multiple nuclei (g). A rich vascular component was diffusely present, prevalently composed of small thin-walled vessels (h), and focally of larger vessels with thickened walls (i)

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  Fig. 3. Immunohistochemical results. The tumor resulted diffusely and strongly positive for CD34 (a) and MUC4 (b). The tumor cells were also positive for EMA and SMA, but in a patchier manner (c, d). The H3K27me3 expression was retained in the nuclei of tumor cells (e). Conversely, tumor cells showed PTEN loss of expression, particularly in the nuclei, while appeared retained in endothelial cells (f)

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  Fig. 4. Molecular findings. RNAseq revealed a reading frame unclear transcript between COX14-PTEN, with disruption of the C2 domain of PTEN protein (a). The copy number variation profile obtained from DNA methylation analysis (b)