Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern
Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern
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DOI：
10.1002/path.4701
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发表时间：
2016-04-01
影响因子：
7.3
通讯作者：
Agaimy, Abbas
中科院分区：
文献类型：
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作者：
Haller, Florian;Knopf, Jasmin;Agaimy, Abbas
具有肌外皮细胞瘤样模式的新生物代表了病变的形态学谱，包括皮肤和软组织的肌外皮细胞瘤、血管平滑肌瘤、肌纤维瘤病/婴儿血管外皮细胞瘤和报告为恶性肌外皮细胞瘤的推定肿瘤。恶性肌周细胞肉瘤缺乏可重复的表型和遗传特征，阻碍了肌周细胞肉瘤作为可接受的诊断类别的建立。在通过全基因组和RNA测序检测到一例儿童血管外皮细胞瘤样肉瘤的LMNA-NTRK 1基因融合后，我们确定了另外三例携带NTRK 1基因融合的肉瘤，称为“梭形细胞肉瘤，NOS伴肌/血管外皮细胞生长模式”。患者为两名11个月和2岁的儿童以及两名51岁和80岁的成人。虽然成人的肿瘤是惊人的肌外皮细胞瘤样，但具有明确的非典型特征，儿科病例更类似于婴儿肌纤维瘤病/血管外皮细胞瘤。所有病例均含有大量厚壁发育不良样血管，伴节段性或弥漫性结节性粘液透明平滑肌肌动蛋白阳性细胞内膜增生，偶尔伴有血栓形成。免疫组化显示平滑肌肌动蛋白和CD 34的表达变化，但其他间充质标志物，包括STAT 6，是阴性的。这项研究显示了一种新的变种肌/血管外皮细胞肉瘤复发NTRK 1基因融合。鉴于最近引入了一种针对NTRK融合阳性肿瘤的新型治疗方法，强烈鼓励认识这种罕见但可能报告不足的肉瘤变体。版权所有（c）2016大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Neoplasms with a myopericytomatous pattern represent a morphological spectrum of lesions encompassing myopericytoma of the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma and putative neoplasms reported as malignant myopericytoma. Lack of reproducible phenotypic and genetic features of malignant myopericytic neoplasms have prevented the establishment of myopericytic sarcoma as an acceptable diagnostic category. Following detection of a LMNA-NTRK1 gene fusion in an index case of paediatric haemangiopericytoma-like sarcoma by combined whole-genome and RNA sequencing, we identified three additional sarcomas harbouring NTRK1 gene fusions, termed 'spindle cell sarcoma, NOS with myo/haemangiopericytic growth pattern'. The patients were two children aged 11 months and 2 years and two adults aged 51 and 80 years. While the tumours of the adults were strikingly myopericytoma-like, but with clear-cut atypical features, the paediatric cases were more akin to infantile myofibromatosis/haemangiopericytoma. All cases contained numerous thick-walled dysplastic-like vessels with segmental or diffuse nodular myxohyaline myo-intimal proliferations of smooth muscle actin-positive cells, occasionally associated with thrombosis. Immunohistochemistry showed variable expression of smooth muscle actin and CD34, but other mesenchymal markers, including STAT6, were negative. This study showed a novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. Given the recent introduction of a novel therapeutic approach targeting NTRK fusion-positive neoplasms, recognition of this rare but likely under-reported sarcoma variant is strongly encouraged. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.