Abstract: Primary Cutaneous Ewing Sarcoma (PCES) is exceptionally rare and represent a notorious diagnostic mimicker of Merkel cell carcinoma (MCC), particularly when it aberrantly expresses neuroendocrine markers. This pitfall can lead to significant diagnostic error and inappropriate management. A 73-year-old woman presented with a progressive, FDG-avid nodule on the left upper arm. An initial punch biopsy revealed a malignant small round cell tumor with a classic neuroendocrine immunophenotype, including dot-like positivity for CK20 and Neurofilament, which did not allow distinction between PCES and MCC. Subsequently, wide local excision was performed. Histological and extensive immunohistochemical analyses were conducted on the excision specimen, and fluorescence in situ hybridization (FISH) was employed for molecular confirmation. Examination of the resectate showed a multinodular dermal tumor composed of uniform round cells. Immunohistochemistry revealed diffuse positivity for CD99 and NKX2.2, whereas S100 and SOX10 were negative. Crucially, FISH analysis confirmed an EWSR1::FLI1 gene fusion. The sentinel lymph node was negative for metastasis. This case exemplifies a profound diagnostic pitfall in which PCES closely mimicked the immunoprofile of MCC. It underscores that dot-like CK20 and Neurofilament staining are not entirely pathognomonic for MCC diagnosis. In the differential diagnosis of cutaneous round cell tumors, which includes metastases, melanoma, and several sarcoma types, the present case reveals the diagnostic challenges of cutaneous sarcomas and highlights the necessity of a multimodal approach for accurate diagnosis.
Haiduk et al. (2026) studied this question.