Review ArticlesEpithelioid Sarcoma Diagnostic Features and GeneticsThway, Khin MD, FRCPath; Jones, Robin L. MD, MRCP; Noujaim, Jonathan MD; Fisher, Cyril MD, DSc, FRCPath Author Information Sarcoma Unit, The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, London, UK Supported by the NIHR Royal Marsden/ICR Biomedical Research Centre. The authors have no funding or conflicts of interest to disclose. Reprints: Khin Thway, MD, FRCPath, Sarcoma Unit, The Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK (e-mail: [email protected]). All figures can be viewed online in color at http://www.anatomicpathology.com. Advances In Anatomic Pathology 23(1):p 41-49, January 2016. | DOI: 10.1097/PAP.0000000000000102 Buy Metrics Abstract Epithelioid sarcoma (ES) is a rare, aggressive soft-tissue neoplasm of uncertain differentiation, characterized by nodular aggregates of epithelioid cells, which are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen, and often for CD34. It has a propensity for multifocal disease at presentation, local recurrence, and regional metastasis. These are aggressive neoplasms with particularly poor prognosis after regional or distant metastatic disease, for which surgical resection is still the mainstay of treatment, and options for patients with metastatic disease remain undefined. There are 2 distinct variants: classic ES, which typically presents as a subcutaneous or deep dermal mass in the distal extremities of young adults and comprises nodular distributions of relatively uniform epithelioid cells with central necrosis, and the proximal variant, which has a predilection for proximal limbs and limb girdles and the midline of the trunk, which is composed of sheets of larger, more atypical cells with variable rhabdoid morphology. Both classic and proximal-type ESs are associated with the loss of SMARCB1/INI1 protein expression, but appear otherwise molecularly relatively heterogeneous. We review classic and proximal-type ES, discussing morphology, immunohistochemical and genetic findings, the differential diagnosis, and the future potential for targeted therapies. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.