Emerging soft tissue tumors with kinase fusions: An overview of the recent literature with an emphasis on diagnostic criteria.

A recent breakthrough in the classification of soft tissue tumors (STT) has been a significant expansion in the number of neoplasms associated with NTRK and other kinase related fusions. This is important not only for diagnostic purposes, but also because it opens new avenues for targeted therapy. Indeed, recent clincal trials have shown significant benefit across multiple tumor-types, prompting approval of NTRK inhibitors for clinical use in the setting of advanced/metastatic NTRK-rearranged neoplasms. Despite these therapeutic oportunities, diagnostic challenges have transpired in recognizing these emerging new histologic subtypes of kinase fusions positive-STT prospectively. This, in part, is attributable to their wide morphologic spectrum, variable risk of malignancy, and non-specific immunoprofile. As such, recommendations for pathologic criteria and immunohistochemical testing are needed to improve classification and streamline the small subset of potential candidates for further molecular validation. This overview summarizes the key histologic features of various STT associated with NTRK and other kinase fusions, which appear to share a similar morphologic spectrum. Immunohistochemically, many of these tumors, regardless of the kinase fusion type, notably show co-expression of S100 and CD34; issues related to the utility of pan-NTRK and NTRK1 immunostaining are therefore summarized. Finally, I discuss the role of confirmatory molecular testing and how, in some instances, this may also be of prognostic value. This review is intended as a critical summary of the current literature to emphasize pathologic criteria for improving recognition of this emerging and complex group of kinase fusion associated STT.
(© 2020 Wiley Periodicals, Inc.)