Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors—A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma

IF 1.6 4区医学 Q3 DERMATOLOGY Journal of Cutaneous Pathology Pub Date : 2024-03-31 DOI:10.1111/cup.14610

Carina A. Dehner, Emma F. Johnson, Carrie N. Wieland, Michael J. Camilleri, Andre Kajdacsy-Balla, Andre M. Oliveira, Kevin C. Halling, Sounak Gupta, Ruifeng Guo

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Abstract

Background

While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology.

Aims

Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms.

Materials & Methods

Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained.

Results

Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1–83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1).

Discussion and conclusion

Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

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融合驱动的皮肤和浅表间质及附件肿瘤--15 例临床病理学和分子研究，包括一例新的 ACTB::ZMIZ2 重排附件癌。

背景：尽管融合驱动的软组织肿瘤正在迅速增加，但人们对它们在皮肤和表皮间质及附件肿瘤中的重要性仍然知之甚少。这一挑战在组织病理学不明确、难以根据形态学分类的病例中尤为明显。目的：我们的目标是研究下一代测序在诊断复杂皮肤肿瘤方面的优势：材料与方法：在科室档案中搜索融合驱动的皮肤肿瘤。检索切片并获取包括随访在内的临床信息：15例患者中，8例为女性，7例为男性，确诊时的中位年龄为26岁（范围：1-83岁）。肿瘤累及四肢（9 例）、头皮（5 例）和头颈部（1 例）。主要特征包括肌上皮性（5 例）、巢状纺锤体伴透明胞质（2 例）、非典型附件/鳞状细胞（2 例）、小圆形蓝细胞（2 例）、细胞纺锤体（3 例）和纤维组织细胞形态（1 例）。最常见的融合涉及 EWSR1（6 例）与 ERG（1 例）、FLI1（1 例）、CREB1（2 例）、CREM（1 例）和 PBX3（1 例）融合，其次是 PLAG1（4 例）与 LIFR（2 例）、TRPS1（1 例）和 CHCHD7 融合。此外，还发现了 YAP1::NUTM1、EML4::ALK、SS18::SSX1（2）和一种新型融合：ACTB：：ZMIZ2。综合组织学特征和分子研究结果，最终诊断为原发性皮肤尤文肉瘤（2 例）、软组织肌上皮瘤（4 例）、皮肤滑膜肌上皮瘤（1 例）、皮肤附件癌（1）、孔癌（1）、炎性肌纤维瘤（1）、滑膜肉瘤（2）、透明细胞肉瘤（2）和血管瘤样纤维组织细胞瘤（1）。讨论和结论：我们的研究结果表明，融合检测是一种有用的诊断工具，尤其是在浅表部位出现异常或不常见形态的病例中。此外，在某些情况下，它还能确定潜在的治疗目标。

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来源期刊

Journal of Cutaneous Pathology 医学-病理学

CiteScore

3.20

自引率

5.90%

发文量

174

审稿时长

3-8 weeks

期刊介绍： Journal of Cutaneous Pathology publishes manuscripts broadly relevant to diseases of the skin and mucosae, with the aims of advancing scientific knowledge regarding dermatopathology and enhancing the communication between clinical practitioners and research scientists. Original scientific manuscripts on diagnostic and experimental cutaneous pathology are especially desirable. Timely, pertinent review articles also will be given high priority. Manuscripts based on light, fluorescence, and electron microscopy, histochemistry, immunology, molecular biology, and genetics, as well as allied sciences, are all welcome, provided their principal focus is on cutaneous pathology. Publication time will be kept as short as possible, ensuring that articles will be quickly available to all interested in this speciality.