Cytologic diagnosis of round cell sarcomas in the era of ancillary testing: an updated review

Round cell sarcomas constitute a large proportion of “small round blue cell tumors,” which encompass a broad differential diagnosis and can be difficult to distinguish on cytomorphologic grounds alone. Numerous pathogenetic insights and advances in ancillary testing in soft tissue pathology over the last several decades have made accurate classification of soft tissue neoplasms increasingly feasible. Immunohistochemistry and genetic/molecular testing can now be performed on all cytologic preparations, including unstained smears, needle rinses, cell blocks, and liquid-based preparations, and this has greatly increased our diagnostic abilities. Nevertheless, there remain numerous diagnostic challenges, including variable sensitivity and specificity of available immunohistochemical markers, overlapping immunophenotypes between entities, and “promiscuity” of genetic alterations such as EWSR1 rearrangements, present in a multitude of tumor types. Herein we provide a review on the cytologic, immunohistochemical, and genetic features of the more frequently encountered round cell sarcomas, as well as recently described entities, with an emphasis on diagnostic pitfalls and judicious use of ancillary studies.