Superficial Neurocristic EWSR1::FLI1 Fusion Tumor: A Distinctive, Clinically Indolent, S100 Protein/SOX10-Positive Neoplasm

IF 7.1 1区 医学 Q1 PATHOLOGY
Andrew L. Folpe , Michael T. Tetzlaff , Steven D. Billings , Jorge Torres-Mora , Alexander David Borowsky , Teresa C. Santiago , Baptiste Ameline , Daniel Baumhoer
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引用次数: 0

Abstract

It is now understood that identical gene fusions may be shared by different entities. We report a distinctive neoplasm of the skin and subcutis, harboring the Ewing sarcoma-associated EWSR1::FLI1 fusion but differing otherwise from Ewing sarcoma. Slides and blocks for 5 cutaneous neoplasms coded as other than Ewing sarcoma and harboring EWSR1::FLI1 were retrieved. Immunohistochemical and molecular genetic results were abstracted from reports. Methylation profiling was performed. Clinical information was obtained. The tumors occurred in 4 men and 1 woman (median: 25 years of age; range: 19-69 years) and involved the skin/subcutis of the back (2), thigh, buttock, and chest wall (median: 2.4 cm; range: 1-11 cm). Two tumors were present “years” before coming to clinical attention. The lesions were multinodular and circumscribed and consisted of nests of bland, round cells admixed with hyalinized collagenous bands containing spindled cells. Hemorrhage and cystic change were often present; necrosis was absent. All were diffusely S100 protein/SOX10-positive; 4 of 5 were CD99-negative. One tested case was strongly positive for NKX2.2. A variety of other tested markers were either focally positive (glial fibrillary acidic protein, p63) or negative. Molecular genetic results were as follows: EWSR1 exon 7::FLI1 exon 8, EWSR1 exon 11::FLI1 exon 5, EWSR1 exon 11::FLI1 exon 6, EWSR1 exon 7::FLI1 exon 6, and EWSR1 exon 10::FLI1 exon 6. Methylation profiling (3 cases) showed these to form a unique cluster, distinct from Ewing sarcoma. All patients underwent excision with negative margins; one received 1 cycle of chemotherapy. Clinical follow-up showed all patients to be alive without disease (median: 17 months; range: 11-62 months). Despite similar gene fusions, the morphologic, immunohistochemical, epigenetic, and clinical features of these unique EWSR1::FLI1-fused neoplasms of the skin and subcutis differ substantially from Ewing sarcoma. Interestingly, EWSR1 rearrangements involved exons 10 or 11, only rarely seen in Ewing sarcoma, in a majority of cases. Superficial neurocristic EWSR1::FLI1 fusion tumors should be rigorously distinguished from true cutaneous Ewing sarcomas.

浅表神经嵴EWSR1::FLI1融合瘤:一种独特的、临床症状不明显的 S100 蛋白/SOX10 阳性肿瘤。
现在人们知道,不同的实体可能共享相同的基因融合。我们报告了一种独特的皮肤和皮下肿瘤,它携带尤文肉瘤相关的 EWSR1::FLI1 融合基因,但在其他方面与尤文肉瘤不同。检索了 5 例非尤文肉瘤且携带 EWSR1::FLI1 的皮肤肿瘤的切片和切块。从报告中摘录了免疫组化和分子遗传结果。进行甲基化分析。获得了临床信息。肿瘤发生于 4 名男性和 1 名女性(中位年龄 25 岁;范围 19-69 岁),累及背部(2 例)、大腿、臀部和胸壁的皮肤/皮下组织(中位 2.4 厘米;范围 1-11 厘米)。有两个肿瘤在引起临床注意前已存在 "多年"。病变呈多结节、环状,由平滑的圆形细胞巢组成,巢内混有含棘细胞的透明胶原带。经常出现出血和囊变,但没有坏死。所有病例均呈弥漫性 S100 蛋白/SOX10 阳性;5 例中有 4 例为 CD99 阴性。一个受检病例的 NKX2.2 强阳性。其他多种检测标记物要么呈局部阳性(GFAP、p63),要么呈阴性。分子遗传学结果如下EWSR1外显子7::FLI1外显子8、EWSR1外显子11::FLI1外显子5、EWSR1外显子11::FLI1外显子6、EWSR1外显子7::FLI1外显子6,以及EWSR1外显子10::FLI1外显子6。甲基化分析(3 个病例)显示,这些病例形成了一个独特的群集,有别于尤文肉瘤。所有患者均接受了边缘阴性的切除术;其中一名患者接受了一个周期的化疗。临床随访显示,所有患者均无病存活(中位数17个月;范围11-62个月)。尽管基因融合相似,但这些独特的皮肤和皮下 EWSR1::FLI1 融合瘤的形态学、免疫组化、表观遗传学和临床特征却与尤文肉瘤大相径庭。有趣的是,大多数病例中的 EWSR1 重排涉及第 10 或第 11 号外显子,而这在尤文肉瘤中很少见。应将浅表神经性 EWSR1::FLI1 融合肿瘤与真正的皮肤型尤文肉瘤严格区分开来。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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