A Comprehensive Review on Solitary Fibrous Tumor: New Insights for New Horizons

Abstract

Solitary fibrous tumor (SFT) is a rare mesenchymal, ubiquitous tumor, with an incidence of 1 new case/million people/year. In the 2020 WHO classification, risk stratification models were recommended as a better tool to determine prognosis in SFT, to the detriment of "typical" or "malignant" classic terms. The risk for metastasis is up to 35-45%, or even greater, in series with a longer follow-up. Over the last few decades, advances in immunohistochemistry and molecular diagnostics identified STAT6 nuclear protein expression and the NAB2-STAT6 fusion gene as more precise tools for SFT diagnosis. Recent evidence taken from retrospective series and from two prospective phase II clinical trials showed that antiangiogenics are active and their sequential use from first line should be considered, except for dedifferentiated SFT for which chemotherapy is the best option. Since the fusion transcript driver's first description in 2013, new insights have been brought on key molecular events in SFT. This comprehensive review mainly focuses on the superior efficacy of antiangiogenics over chemotherapeutic agents in SFT, provides the current knowledge of key molecules that could co-drive the SFT behavior, and suggests new target candidates that deserve to be explored in preclinical and clinical research in SFT.

Keywords: anti-angiogenics; solitary fibrous tumor; therapy; tumor biology.

Figure 1

Histopathological features of solitary fibrous tumor (SFT). (A) Low-grade SFT showing a patternless pattern, with spindle cells, low number of mitosis (or lack of) and vessels with “staghorn” appearance (Magnification 40×). (B) High-grade SFT showing hypercellularity with nuclear pleomorphism, high number of mitotic figures (Magnification 200×). (C) Dedifferentiated SFT with an abrupt transition from conventional SFT to high-grade sarcoma (Magnification 10×). (D) STAT6 positive nuclear immunostaining (Magnification 400×).

Figure 2

Most common NAB2–STAT6 fusion variants. NCD: NAB-conserved domain; CID: CHD4-interacting domain; CCD1: Coiled-coil domain 1; DBD: DNA-binding domain; SH2: Src homology 2 and TAD: transcriptional activator domain.

Figure 3

Choi responses to antiangiogenic agents in solitary fibrous tumor (SFT). (A) CT scan of an SFT patient showing a characteristic Choi partial response to pazopanib treatment in one hepatic lesion: decrease in density of 56%. (B) CT scan of an SFT patient showing a characteristic Choi partial response to pazopanib treatment in one hepatic lesion: decrease in density of 33%.