Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases.
Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases.
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DOI：
10.1111/his.14323
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发表时间：
2021-09
期刊：
影响因子：
6.4
通讯作者：
Antonescu CR
中科院分区：
文献类型：
--
作者：
Xu B;Suurmeijer AJH;Agaram NP;Zhang L;Antonescu CR
原发性骨内横纹肌肉瘤（RMS）是一种罕见的实体定义EWSR 1/FUS-TFCP 2或不太常见的MEIS 1-NCOA 2融合。病变通常表现为混合梭形和上皮样表型，经常共表达肌源性标志物、ALK和细胞角蛋白，并表现出骨盆和颅面骨的显著倾向。我们研究了11例头颈部（HN）RMS的临床病理和分子特征，其特征在于骨内RMS的遗传改变。通过FISH和/或靶向RNA/DNA测序分析分子异常。7例患者存在FUS-TFCP 2融合，4例患者存在EWSR 1-TFCP 2融合，而无MEIS 1-NCOA 2融合。除1例病例外，所有病例均为骨内病变，累及下颌骨（n=4）、上颌骨（n=3）和颅骨（n=3）。1例发生在颈部浅表软组织。中位年龄为29岁（范围：16-74岁），性别分布相等。所有肿瘤表现为混合上皮样和梭形形态。免疫组化染色显示结蛋白、肌细胞生成素、myoD 1、ALK和细胞角蛋白在大多数病例中同时表达。43%的患者检测到基因内ALK缺失。分别有3名和4名患者出现区域性和远处传播。两名患者死于疾病。在此，我们提出了最大的一系列HNRMS窝藏TFCP 2融合。研究结果表明，一个强烈的偏好，骨骼在年轻的成年人，虽然我们也报告了一个骨外的情况。肿瘤的特征是独特的梭形和上皮样表型以及肌源性、上皮性和ALK标志物共表达的特殊免疫特征。它与预后不良有关，包括区域或远处传播和疾病相关死亡。
Primary intraosseous rhabdomyosarcoma (RMS) is a rare entity defined by EWSR1/FUS-TFCP2 or less commonly MEIS1-NCOA2 fusions. The lesions often display a hybrid spindle and epithelioid phenotype, frequently co-express myogenic markers, ALK and cytokeratin, and show a striking propensity for the pelvic and craniofacial bones. We investigated the clinicopathologic and molecular features of 11 head and neck (HN) RMS characterized by the genetic alterations described in intraosseous RMS. The molecular abnormalities were analyzed by FISH and/or targeted RNA/DNA sequencing. Seven cases harbored FUS-TFCP2 fusions, four had EWSR1-TFCP2, while none showed MEIS1-NCOA2 fusions. All except one case were intraosseous, affecting the mandible (n=4), maxilla (n=3), and skull (n=3). One case occurred in the superficial soft tissue of the neck. The median age was 29 (range: 16-74), with equal gender distribution. All tumors demonstrated a mixed epithelioid and spindle morphology. Immunohistochemical coexpression of desmin, myogenin, myoD1, ALK and cytokeratin was seen in most cases. An intragenic ALK deletion was detected in 43%. Regional and distant spread were seen in three and four patients respectively. Two patients died of their disease. We herein present the largest series of HNRMS harboring TFCP2 fusions. The findings show a strong predilection for the skeleton in young adults, although we also report an extraosseous case. The tumors are characterized by a distinctive spindle and epithelioid phenotype and a peculiar immunoprofile with co-expression of myogenic, epithelial and ALK markers. It is associated with a poor prognosis, including regional or distant spread and disease-related death.
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影响因子：
28.4
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影响因子：
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Tirode, Franck
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5.6
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通讯作者：
Antonescu, Cristina R.
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3.8
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