The many faces of atypical Ewing's sarcoma. A true entity mimicking sarcomas, carcinomas and lymphomas

Ewing's sarcoma family of tumours (ESFT) comprises a group of small round cell tumours (SRCT) genetically defined by specific chromosomal translocations resulting in a fusion of the EWSR1 gene with a member of the ETS family of transcription factors. Atypical ESFT are the most challenging of the ESFT subtypes, and the differential diagnosis with other SRCT of bone and soft tissue is difficult since these subtypes can resemble other neoplasms. The present article describes nine cases of genetically confirmed, atypical ESFT, having unusual alterations at morphological and immunohistochemical (IHC) levels associated with atypical clinical presentation mimicking sarcomas, carcinomas and lymphomas. Present results demonstrate that ESFT showing overlapping morphological and immunohistochemical features with other SRCT of soft tissue and bone, or even with carcinomas or lymphoma, can be differentiated using molecular techniques. In SRCT with EWSR1 translocation demonstrated by FISH, the RT-PCR analysis of specific sarcoma-related gene fusion can offer important clues for the diagnosis of specific entities, especially in tumours with unusual histopathology and/or IHC findings. Thus, we confirm that the integration of clinical, histopathological, IHC and genetic data becomes decisive in the diagnosis of bone and soft tissue sarcomas.