NTRK -Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification.
NTRK -Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification.
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DOI：
10.1097/pas.0000000000001929
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发表时间：
2022-10-01
影响因子：
5.6
通讯作者：
Kolin, David L.
中科院分区：
文献类型：
--
作者：
Costigan, Danielle C.;Nucci, Marisa R.;Dickson, Brendan C.;Chang, Martin C.;Song, Sharon;Sholl, Lynette M.;Hornick, Jason L.;Fletcher, Christopher D. M.;Kolin, David L.
NTRK重排的子宫肉瘤是一种罕见的梭形细胞肿瘤，通常发生在年轻女性的子宫颈。一些肿瘤复发或转移，但迄今尚未确定预测行为的特征。将这些肿瘤与形态学模拟物区分开是重要的，因为患有晚期疾病的患者可以用TRK抑制剂治疗。在此，我们提出了15例NTRK重排的子宫肉瘤，迄今为止最大的系列。中位患者年龄为35岁（范围16 - 61岁）。大多数发生在子宫颈（n = 14），除2例外，所有患者在诊断时均局限于器官。肿瘤由浸润性、束状增生的梭形细胞组成，大多数表现为轻度至中度的细胞学异常。免疫组化结果显示13例全TRK阳性，S100（11/13）和CD34（6/10）常阳性。RNA或DNA测序发现NTRK1（10/13）和NTRK3（3/13）与伴侣TPR、TPM3、EML 4、TFG、SPECC1L、C16orf72和IRF2BP2融合。在两个最初被诊断为不可分类的子宫肉瘤的肿瘤中观察到不寻常的形态，其中一个也含有TP53突变。对9名患者进行了随访，其中3人死于疾病。通过合并既往报告的肿瘤结局数据，确定了不良预后特征，包括有丝分裂指数≥ 8/10高倍视野、淋巴血管浸润、坏死和NTRK3融合。缺乏这四个特征中任何一个的肿瘤患者预后良好。本研究扩展了NTRK重排的子宫肉瘤的形态学谱，并确定了可用于危险分层的特征。
NTRK-rearranged uterine sarcomas are rare spindle-cell neoplasms that typically arise in the uterine cervix of young women. Some tumors recur or metastasize, but features which predict behavior have not been identified to date. Distinguishing these tumors from morphologic mimics is significant because patients with advanced stage disease may be treated with TRK inhibitors. Herein, we present fifteen cases of NTRK-rearranged uterine sarcomas, the largest series to date. Median patient age was 35 years (range 16–61). The majority arose in the uterine cervix (n=14) and all but two were organ-confined at diagnosis. Tumors were composed of an infiltrative, fascicular proliferation of spindle cells and most showed mild-to-moderate cytologic atypia. All were pan-TRK positive by immunohistochemistry (13/13); S100 (11/13) and CD34 (6/10) were usually positive. RNA or DNA sequencing found NTRK1 (10/13) and NTRK3 (3/13) fusions with partners TPR, TPM3, EML4, TFG, SPECC1L, C16orf72, and IRF2BP2. Unusual morphology was seen in two tumors which were originally diagnosed as unclassifiable uterine sarcomas, one of which also harbored TP53 mutations. Follow up was available for nine patients, of whom three died of disease. By incorporating outcome data of previously reported tumors, adverse prognostic features were identified, including a mitotic index ≥8 per 10 high power fields, lymphovascular invasion, necrosis, and NTRK3 fusion. Patients with tumors which lacked any of these four features had an excellent prognosis. This study expands the morphologic spectrum of NTRK-rearranged uterine sarcomas and identifies features which can be used for risk stratification.