A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes.
A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes.
复制标题
DOI：
10.1002/gcc.22671
复制
发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Antonescu CR
中科院分区：
文献类型：
--
作者：
Suurmeijer AJH;Dickson BC;Swanson D;Zhang L;Sung YS;Cotzia P;Fletcher CDM;Antonescu CR
肿瘤的特征是S100和CD 34的共表达，在没有SOX 10的情况下，仍然难以分类。由少数具有单形细胞形态学和独特的间质和血管周围玻璃样变、S100和CD 34免疫阳性以及RAF 1和NTRK 1融合的指示病例触发，作者对具有相似特征的肿瘤进行了系统综述。大多数病例先前被诊断为低度恶性外周神经鞘瘤，而其他病例被认为是未分类的。用靶向RNA测序和/或FISH研究肿瘤。共鉴定出25例激酶融合病例（15例成人和10例儿童），包括8例涉及RAF 1、2例BRAF、14例NTRK 1和1例NTRK 2基因重排。大多数肿瘤表现为单形梭形细胞增生，间质和血管周围瘢痕疙瘩胶原，在一个无模式的架构，只有偶尔散在的多形性或多核细胞。大多数病例表现为低细胞性、低有丝分裂计数和无坏死。虽然一个子集显示与脂肪纤维瘤样神经肿瘤重叠，但研究组显示出独特的玻璃样变和明显的恶性特征，如高度细胞化的束状生长和原始外观。所有肿瘤均显示S100和CD 34共表达，范围从局灶性到弥漫性。SOX 10均为阴性。NTRK 1免疫组化显示在所有NTRK 1基因重排的肿瘤中高水平表达。保留了在病例子集中进行的H3 K27 me 3表达。这些发现与RAF 1、BRAF和NTRK 1/2激酶中的复发性基因融合一起提示了具有一致的S100和CD 34免疫反应性的不同分子肿瘤亚型。
Tumors characterized by co-expression of S100 and CD34, in the absence of SOX10, remain difficult to classify. Triggered by a few index cases with monomorphic cytomorphology and distinctive stromal and perivascular hyalinization, immunopositivity for S100 and CD34, and RAF1 and NTRK1 fusions, the authors undertook a systematic review of tumors with similar features. Most of the cases selected were previously diagnosed as low-grade malignant peripheral nerve sheath tumors, while others were deemed unclassified. The tumors were studied with targeted RNA sequencing and/or FISH. A total of 25 cases (15 adults and 10 children) with kinase fusions were identified, including 8 cases involving RAF1, 2 BRAF, 14 NTRK1, and 1 NTRK2 gene rearrangements. Most tumors showed a monomorphic spindle cell proliferation with stromal and perivascular keloidal collagen, in a patternless architecture, with only occasional scattered pleomorphic or multinucleated cells. Most cases showed low cellularity, a low mitotic count, and absence of necrosis. Although a subset showed overlap with lipofibromatosis-like neural tumors, the study group showed distinctive hyalinization and overt malignant features, such as highly cellular fascicular growth and primitive appearance. All tumors showed co-expression of S100 and CD34, ranging from focal to diffuse. SOX10 was negative in all cases. NTRK1 immunohistochemistry showed high levels of expression in all tumors with NTRK1 gene rearrangements. H3K27me3 expression performed in a subset of cases was retained. These findings together with the recurrent gene fusions in RAF1, BRAF, and NTRK1/2 kinases suggest a distinct molecular tumor subtype with consistent S100 and CD34 immunoreactivity.
登录
查看更多内容
DOI：
10.1097/pas.0000000000001055
发表时间：
2018-06
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Chiang S;Cotzia P;Hyman DM;Drilon A;Tap WD;Zhang L;Hechtman JF;Frosina D;Jungbluth AA;Murali R;Park KJ;Soslow RA;Oliva E;Iafrate AJ;Benayed R;Ladanyi M;Antonescu CR
通讯作者：
Antonescu CR
影响因子：
16.6
作者：
Stransky, Nicolas;Cerami, Ethan;Schalm, Stefanie;Kim, Joseph L.;Lengauer, Christoph
通讯作者：
Lengauer, Christoph
DOI：
10.1016/s1470-2045(18)30119-0
发表时间：
2018-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Laetsch TW;DuBois SG;Mascarenhas L;Turpin B;Federman N;Albert CM;Nagasubramanian R;Davis JL;Rudzinski E;Feraco AM;Tuch BB;Ebata KT;Reynolds M;Smith S;Cruickshank S;Cox MC;Pappo AS;Hawkins DS
通讯作者：
Hawkins DS
影响因子：
5.6
作者：
Chen, Benjamin J.;Marino-Enriquez, Adrian;Hornick, Jason L.
通讯作者：
Hornick, Jason L.
影响因子：
7.3
作者：
Haller, Florian;Knopf, Jasmin;Agaimy, Abbas
通讯作者：
Agaimy, Abbas