Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France.
Unité INSERM U1218, Bordeaux, France.
Mod Pathol. 2019 Jul;32(7):1008-1022. doi: 10.1038/s41379-018-0184-6. Epub 2019 Mar 16.
Mesenchymal neoplasms of the uterus (corpus and cervix) encompass a heterogeneous group of tumors with differing morphologies, immunophenotypes and molecular alterations. With the advent of modern molecular techniques, such as next generation sequencing, newly defined genetic abnormalities are being reported in this group of neoplasms. Herein we report the clinicopathological and molecular features of a series of 13 spindle cell sarcomas of the uterus and vagina (10 cervix, 2 uterine corpus, 1 vagina) with morphology resembling fibrosarcoma. After targeted RNA-sequencing, dual FISH fusion and array-CGH analysis, 7 of 13 tumors exhibited NTRK rearrangements (6 TPM3-NTRK1 and 1 EML4-NTRK3) and 3 a COL1A1-PDGFB fusion; in the other 3 neoplasms, all of which were positive with S100 (2 diffuse, 1 focal), we identified no rearrangement. All the NTRK fusion-positive sarcomas were located in the cervix and exhibited diffuse staining with Trk while all the other neoplasms were negative. CD34 was diffusely positive in all 3 of the COL1A1-PDGFB fusion sarcomas. The latter molecular abnormality is identical to that commonly found in dermatofibrosarcoma protuberans and has not been reported previously in uterine mesenchymal neoplasms. We suggest that uterine sarcomas with a morphology resembling fibrosarcoma (and in which leiomyosarcoma and the known molecularly confirmed high-grade endometrial stromal sarcomas have been excluded) can be divided into 3 groups:- an NTRK fusion group, a COL1A1-PDGFB fusion group and a group containing neither of these molecular abnormalities which, on the basis of positive staining with S100, could be tentatively classified as malignant peripheral nerve sheath tumor, although additional molecular studies may identify specific genetic alterations necessitating a nomenclature change. We suggest a diagnostic algorithm when reporting such neoplasms. Identification of these newly described fusion-associated sarcomas is important given the potential for targeted treatments.
子宫（体和颈）间叶性肿瘤包含一组具有不同形态、免疫表型和分子改变的异质性肿瘤。随着现代分子技术（如下一代测序）的出现，在这组肿瘤中不断报道新定义的遗传异常。在此，我们报告了 13 例子宫和阴道梭形细胞肉瘤（10 例宫颈、2 例子宫体、1 例阴道）的临床病理和分子特征，其形态类似于纤维肉瘤。经过靶向 RNA 测序、双重 FISH 融合和 array-CGH 分析，13 例肿瘤中有 7 例存在 NTRK 重排（6 例 TPM3-NTRK1 和 1 例 EML4-NTRK3），3 例存在 COL1A1-PDGFB 融合；在另外 3 例肿瘤中，所有肿瘤均为 S100 阳性（2 例弥漫性，1 例局灶性），我们未发现重排。所有 NTRK 融合阳性肉瘤均位于宫颈，Trk 弥漫性染色阳性，而所有其他肿瘤均为阴性。CD34 在所有 3 例 COL1A1-PDGFB 融合肉瘤中均弥漫阳性。后一种分子异常与常见于隆突性皮肤纤维肉瘤中的异常相同，以前尚未在子宫间叶性肿瘤中报道过。我们建议，形态类似于纤维肉瘤的子宫肉瘤（排除平滑肌肉瘤和已知的分子上已证实的高级别子宫内膜间质肉瘤）可以分为 3 组：-NTRK 融合组、COL1A1-PDGFB 融合组和既没有这些分子异常的一组，根据 S100 阳性染色，这一组可以暂定为恶性外周神经鞘瘤，尽管进一步的分子研究可能会发现需要改变命名的特定遗传改变。我们建议在报告此类肿瘤时使用诊断算法。识别这些新描述的融合相关肉瘤很重要，因为它们可能有针对性的治疗。
