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

Abstract

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.

Epithelial marker expression does not rule out a diagnosis of Ewing’s sarcoma family of tumours

“…ESFT appears to have the potential for differentiating toward mesenchymal, neural, and epithelial lineages. The immunohistochemical (IHC) study in a large series of ESFT previously described by Llombart-Bosch et al [2] confirmed the diagnostic value of CD99, HNK1, Fli1, and CAV1, which together cover more than 99% of ESFT and substantiated the mesenchymal and neural differentiation of this neoplasm [2][3][4].…”

“…Other gene fusions have been described in ESFT, including FUS/ERG, FUS/FEV, EWSR1/PATZ1, EWSR1/SP3, EWSR1/NFATc2, BRD4/NUT, CIC/DUX4 [5,6], and EWSR1/SMARCA5 [7]. The histopathology includes three larger categories according to their predominant morphological criteria: conventional Ewing's sarcoma (ES), peripheral neuroectodermal tumors (PNET), and atypical ES comprising all subtypes distinct from the other two types [2,3]. ESFT appears to have the potential for differentiating toward mesenchymal, neural, and epithelial lineages.…”

“…Particular attention must be paid to the atypical ESFT in which an epithelial differentiation may be present, especially when expressing epithelial membrane antigen (EMA) [2,3]. In these cases, the histology might not be diagnostic, making the differential diagnosis with other SRCT more challenging [2,3,6,14].…”

“…Ewing's sarcoma family of tumors (ESFT) is formed by a group of small round cell tumors (SRCT) genetically defined by specific chromosomal translocations which result in a fusion of the EWSR1 gene, mainly with a member of the ETS family of transcription factors: FLI1 (11q24), ERG (21q22), FEV (2q33), ETV1 (7p22), and ETV4 (17q12) [1][2][3][4][5][6]. Other gene fusions have been described in ESFT, including FUS/ERG, FUS/FEV, EWSR1/PATZ1, EWSR1/SP3, EWSR1/NFATc2, BRD4/NUT, CIC/DUX4 [5,6], and EWSR1/SMARCA5 [7].…”

Ewing’s Sarcoma/Pnet Presenting as Breast Mass

“…The term ESFT includes typical Ewing's Sarcoma, the Peripheral Neuro ectodermal tumour (PNET) or Askin'stumor of the chest wall [1]. It is the second most malignant tumour in the 10-20 year age group [2].…”