Unusual Neuroendocrine Differentiation in a Small Round Cell Angiosarcoma: A Potential Histologic Mimicker of Superficial Ewing Sarcoma

Abstract: Neuroendocrine differentiation or aberrant expression of neuroendocrine markers is very uncommon in angiosarcomas (AS) and creates a challenging differential diagnosis with other superficial or soft tissue tumors. Herein, we report a new case of superficial AS presenting as a tumor lesion on the little finger of the right hand of a 52-year-old man. The tumor displayed CD56, chromogranin-A, and synaptophysin immunoreactivity. Tumor cells were positive for vascular markers (CD31, FLI1, ERG, D2-40, VE-cadherin, VEGR1,2, and 3), CD99, and EMA, but were negative for S100, CK (AE1/AE3), CK20, polyomavirus, and myogenic (desmin and myogenin) and melanocyte markers (melan-A and HMB45). Ki67 immunostains indicated high proliferative activity (>50%). The whole-body computed tomography did not reveal distant disease. The initial assessment considered several tumor subtypes as possible histological diagnoses, including Ewing sarcoma, Ewing-like sarcoma, Merkel cell carcinoma, and undifferentiated “small round cell sarcoma”. Fluorescence in situ hybridization analysis was negative for EWSR1 translocation and molecular analysis failed to detect any EWSR1 , CIC , SYT or BCOR rearrangement. As a follow-up investigation, we tested 17 cutaneous/superficial AS for neuroendocrine markers; however, only one of these showed focal CD56 and synaptophysin expression. In conclusion, the present findings indicate that neuroendocrine differentiation is a very infrequent feature in AS. We report an AS of the finger with an uncommon histological appearance and immunohistochemical profile: predominant round cell tumor proliferation and neuroendocrine differentiation. Pathologists should be aware of these potential histological and immunohistochemical pitfalls in AS.