Undifferentiated Small Round Cell Sarcoma With t(4;19)(q35;q13.1) CIC-DUX4 Fusion A Novel Highly Aggressive Soft Tissue Tumor With Distinctive Histopathology
Undifferentiated Small Round Cell Sarcoma With t(4;19)(q35;q13.1) CIC-DUX4 Fusion A Novel Highly Aggressive Soft Tissue Tumor With Distinctive Histopathology
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DOI：
10.1097/pas.0b013e318297a57d
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发表时间：
2013-09-01
影响因子：
5.6
通讯作者：
Lucas, David R.
中科院分区：
文献类型：
--
作者：
Choi, Eun-Young Karen;Thomas, Dafydd G.;Lucas, David R.
小圆形细胞肉瘤的一个子集仍然难以分类。其中，一种罕见的肿瘤含有带有 CIC-DUX4 融合的 t(4;19)(q35;q13.1)。本研究的目的是更好地了解其临床病理特征。使用常规细胞遗传学、逆转录聚合酶链反应 (RT-PCR) 和荧光原位杂交 (FISH) 方法鉴定了 4 例 CIC-DUX4 肉瘤，全部发生于成人（3 名女性，1 名男性，年龄 20 至 43 岁）。所有 4 个肿瘤均通过 RT-PCR 和 FISH 证实了 CIC-DUX4 融合转录物，并通过 FISH 证实了 CIC 重排。 2 个肿瘤的细胞遗传学结果显示 t(4;19)(q35;q13.1) 在 1 个肿瘤中作为简单核型的一部分出现，在另一个肿瘤中作为复杂核型的一部分出现，后者来自化疗后标本。这两种肿瘤都含有 8 三体性，并且缺乏任何其他已知的与肉瘤相关的易位。 RT-PCR 或 FISH 未检测到 EWS 或 SYT 重排。肿瘤具有小圆形细胞形态，具有独特的组织学特征，包括广泛的地理坏死、轻度核多形性（染色质粗糙和核仁突出）、透明细胞区域和局灶性粘液样基质。每个肿瘤中仅存在 CD99 的局部染色。其中两个具有非常集中的细胞角蛋白染色。所有肿瘤的结蛋白、肌生成素、TLE-1 和 S100 蛋白均为阴性，而核 INI-1 染色保留。肿瘤具有高度侵袭性，所有患者均在 16.8 个月内死于播散性疾病。 CIC-DUX4肉瘤代表了一种新型的易位相关肉瘤，具有独特的组织病理学特征和快速的疾病进展。
A subset of small round cell sarcomas remains difficult to classify. Among these, a rare tumor harboring a t(4;19)(q35;q13.1) with CIC-DUX4 fusion has been described. The aim of this study is to better understand its clinicopathologic features. Four cases of CIC-DUX4 sarcoma, all arising in adults (3 women, 1 man, aged 20 to 43 y), were identified using conventional cytogenetic, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methods. All 4 tumors demonstrated CIC-DUX4 fusion transcript by both RT-PCR and FISH and CIC rearrangement by FISH. Cytogenetic results from 2 tumors showed t(4;19)(q35;q13.1) occurring as part of a simple karyotype in 1 tumor and as part of a complex karyotype in the other, the latter from a postchemotherapy specimen. Both tumors harbored trisomy 8 and lacked any other known sarcoma-associated translocation. No EWS or SYT rearrangements were detected by RT-PCR or FISH. The tumors had small round cell morphology with a distinctive constellation of histologic features including extensive geographic necrosis, mild nuclear pleomorphism with coarse chromatin and prominent nucleoli, clear cell areas, and focal myxoid matrix. Only focal staining for CD99 was present in each tumor. Two had very focal cytokeratin staining. All tumors were negative for desmin, myogenin, TLE-1, and S100 protein, whereas nuclear INI-1 staining was retained. The tumors were highly aggressive, and all patients died of disseminated disease within 16.8 months. CIC-DUX4 sarcoma represents a novel translocation-associated sarcoma with distinctive histopathologic features and rapid disease progression.