CASE REPORT CD99-positive undifferentiated round cell sarcoma diagnosed on fine needle aspiration cytology, later found to harbour a CIC-DUX4 translocation: a recently described entity B. Kajt ar*, T. Torn oczky*, E. K alm an*, J. Kuzsner † , P. C. W. Hogendoorn ‡ and K. Szuhai § *Department of Pathology and † Department of Orthopaedics, University of P ecs, Hungary ‡ Department of Pathology and § Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands Accepted for publication 4 May 2013 Introduction Poorly differentiated, small round cell sarcomas often represent a serious differential diagnostic prob- lem. CD99 expression was initially considered to be specific for Ewing sarcoma (ES); however, it may also be seen in many histologically similar neo- plasms. The differential diagnosis of these tumours includes mesenchymal chondrosarcoma, poorly dif- ferentiated synovial sarcoma and lymphoblastic lym- phoma. However, rarely, CD99 expression may appear in other neoplasms of a similar morphology such as the blastemal component of Wilms’ tumour, small cell osteosarcoma, rhabdomyosarcoma, small cell carcinomas, etc., further expanding the list of differentials. 1 Here we describe a case of CD99-posi- tive, EWSR1-translocation negative undifferentiated small round cell sarcoma with plasmacytoid mor- phology, which was initially diagnosed on fine nee- dle aspiration (FNA) cytology and subsequently found on molecular analysis of a resection specimen to harbour the CIC-DUX4 translocation. Correct recognition of these entities is facilitated by cytogenetic or molecular genetic studies. Some of the above neoplasms are characterized by specific cytogenetic abnormalities; primary examples are synovial sarcoma characterized by SYT-translocations and ES harbouring EWSR1-translocations in the majority of cases. 1 Recently, a BCOR–CCNB3 gene fusion described in undifferentiated sarcoma of the bone has been added to the list of such cytogenetic abnormalities. 2 A proportion of small blue round cell tumours (SBRCT) lack a characteristic phenotype and geno- type, and cannot be diagnosed with confidence on morphological grounds alone and are often labelled as undifferentiated sarcoma. It is likely that several of these will be reclassified based on genetic changes associated in recently described cases. Next to the TET/ETS fusions cases of ‘Ewing-like sarcomas’ have been identified with fusions between EWSR1 and other non TET-proteins such as NFATc2, ZSG, POU5F1 and others. 3,4 Moreover cases have been identified without similarities to EWSR1-based fusions. Such an example is a recently described recurrent translocation t(4;19)(q35;q13) in a propor- tion of undifferentiated sarcomas. 5–10 The transloca- tion results in the fusion of the CIC gene to the C-terminal part of the DUX4 gene located at 19q13 or 4q35 regions, respectively. 10 Case history A 62-year-old woman detected a small nodule in her right inguinal region in 2010, which showed rapid progression within 3 months. FNA was performed, followed by the resection of a 110 9 85 9 80-mm necrotic tumour. No association with the peripheral nerves was seen. No lymph node or distant metasta- ses were detected. The patient received radiotherapy and chemotherapy. Another resection was performed 4 months after the first because of local recurrence. Significant progression was seen in 3 months with the appearance of multiple pulmonary metastases and an additional mass in the left thigh. Radiother- Correspondence: B. Kajt ar, Department of Pathology, University of P ecs, Pf.: 99, P ecs 7602, Hungary. Tel.: +36-72-526-282; Fax: +36-72-526-281; E-mail: bela. kajtar@kk.pte.hu DOI:10.1111/cyt.12079 1 © 2013 John Wiley & Sons Ltd Cytopathology 2013