Primary cutaneous Ewing sarcoma with diffuse S100/SOX10 positivity and pseudoalveolar pattern: An extraordinarily rare case highlighting a potential pitfall with significant repercussions

Abstract

Primary cutaneous Ewing sarcoma is a very rare entity with less than 100 cases reported in the literature, sharing the same morphological and immunohistochemical characteristics as their osseous counterparts. Herein, to the best of our knowledge, we report the first case in English literature of a molecularly confirmed Ewing sarcoma with diffuse and strong SOX10 immunoreactivity. This exceedingly rare immunohistochemical finding along with the rarity of this tumor could easily lead to a misdiagnosis with significant repercussions. Our case highlights the difficulty in diagnosing primary cutaneous Ewing sarcoma as well as the pivotal role molecular diagnostics can play in specific scenarios.

Primary Cutaneous Ewing Sarcoma of the Scalp With Metastasis to the Lung: An Unusual Manifestation During Pregnancy

“…Although focal S100 positivity has been described widely in ES, diffuse S100 positivity is exceedingly rare and has only been documented in 4 cases to date. 5,12 S100 positivity raises a concern regarding melanoma in the differential diagnosis of cutaneous tumors, although additional melanocytic differentiation markers were negative in this case. The use of NKX2.2 and PAX7 has emerged as a valuable and potential IHC target for diagnosing ES 5,13–15 ; NKX2.2, a homeodomain-containing transcription factor, is a downstream target EWSR1-FLI1 , which plays a role in neuroendocrine glial differentiation.…”

Adding Perplexity to Rarity: Diffuse S100-Protein and SOX10 Expression in a Molecularly Confirmed PAX7-Positive Primary Cutaneous Ewing Sarcoma

“…9 This reflects the hypothesis that EWS is derived from a primitive mesenchymal cell with neural differentiation capacity. 15 Nevertheless diffuse S100-protein is exceedingly rare with only 3 cases reported in the literature (Table 1). [13][14][15] SOX10, a transcription factor for neural crest cell function, has been reported as diffusely positive only in a single case.…”

“…15 Nevertheless diffuse S100-protein is exceedingly rare with only 3 cases reported in the literature (Table 1). [13][14][15] SOX10, a transcription factor for neural crest cell function, has been reported as diffusely positive only in a single case. 15 In 2 studies by Karamchandani et al and Miettinen et al, 14 and 32 cases respectively were negative for SOX10.…”

“…[13][14][15] SOX10, a transcription factor for neural crest cell function, has been reported as diffusely positive only in a single case. 15 In 2 studies by Karamchandani et al and Miettinen et al, 14 and 32 cases respectively were negative for SOX10. 13,21 For dermatopathologists, a SOX10 and S100-protein positive cutaneous malignant round cell neoplasm raises concern for melanoma.…”

A rapidly enlarging shoulder lump

“…Evangelou et al . highlighted a case of scES with strong S100‐protein and SOX10 expression, which may be mistaken for a melanoma 6 . Another diagnostic pitfall is ERG expression, 7 which is also present in vascular tumors, prostatic adenocarcinoma, and some leukemias.…”