Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor.

ABSTRACT

Intracranial mesenchymal tumor (IMT), FETCREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1CREM fusion and two featuring an EWSR1ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and a slight female predominance (female/male ratio = 1.55). Among the confirmed fusions, 25 (33.8%) featured an EWSR1ATF1 fusion, 24 (32.4%) EWSR1CREB1, 23 (31.1%) EWSR1CREM, one (1.4%) FUSCREM, and one (1.4%) EWSR1CREB3L3. Among 66 patients with follow-up information available (median 17 months; range 1-158 months), 26 (39.4%) experienced progression/recurrences (median 10.5 months; range 0-120 months). Ultimately, three patients died of disease, all of whom underwent a subtotal resection for an EWSR1ATF1 fusion-positive tumor. Outcome analysis revealed subtotal resection as an independent factor associated with a significantly shorter progression free survival (PFS; median 12 months) compared with gross total resection (median 60 months; p < 0.001). A younger age (< 14 years) was associated with a shorter PFS (median 9 months) compared with an older age (median 49 months; p < 0.05). Infratentorial location was associated with a shorter overall survival compared with supratentorial (p < 0.05). In addition, the EWSR1ATF1 fusion appeared to be associated with a shorter overall survival compared with the other fusions (p < 0.05). In conclusion, IMT is a locally aggressive tumor with a high recurrence rate. Potential risk factors include subtotal resection, younger age, infratentorial location, and possibly EWSR1ATF1 fusion. Larger case series are needed to better define prognostic determinants in these tumors.