Solitary fibrous tumor: An evolving and unifying entity with unsettled issues

Abstract

Solitary fibrous tumor (SFT) is a distinct fibroblastic neoplasm of intermediate biological potential, prototypically presenting as a pleuraassociated tumor characterized by patternless proliferation of generally banal oval to spindle cells with hemangiopericytoma-like staghorn vessels in fibrocollagenous stroma. Over the past decades, the clinicopathological spectrum of SFT has been everexpanding with the incorporation of cases exhibiting myxoid, giant cell-containing, and fat-forming histology, as well as those from extrathoracic sites, including the meninx. Atypical, frankly malignant and even dedifferentiated variants have also been recognized in a subset of SFTs. Notably, the recent groundbreaking discovery of the disease-defining NAB2-STAT6 gene fusion, resulting from intrachromosomal inversion involving 12q13.3, has largely unified tumors with the aforementioned variations. The derived immunohistochemical detection of nuclear STAT6 expression has high diagnostic value in distinguishing SFTs from histologic mimics, although some relevant pitfalls have been proposed as a precaution. NAB2-STAT6 fusions yield numerous transcript subtypes associated with the clinicopathological variations. Despite mostly following a favorable course, SFT is notoriously difficult for prognostication because of the propensity for late relapse or even metastases in 10-40% of cases, which prompts several proposed schemes incorporating age, size, mitosis, and/or necrosis as factors for risk stratification. Mitotic figures >4/10 HPFs, TERT promoter and/or TP53 mutations have been considered as variables that are better correlated with aggressiveness. Although radiotherapy and chemotherapy provide unsatisfactory responses, a better understanding of SFT tumorigenesis may pave the way for new treatment modalities. In this review, we comprehensively discuss the recent advances of SFTs in diagnostic and molecular pathology.