Int J Gynecol Pathol. 2022 Nov 1;41(6):642-648. doi: 10.1097/PGP.0000000000000834. Epub 2021 Oct 29.
NTRK1/2/3 rearrangements have been identified as oncogenic drivers in a variety of tumors including those in the uterine cervix, and rarely, the uterine corpus. We report 2 cases of cervical sarcoma with NTRK gene rearrangements. Case 1 was a 54-yr-old woman who presented with postmenopausal bleeding and a 5.4 cm friable mass in the cervix. Microscopic examination of the tumor revealed proliferation of epithelioid and spindle cells arranged in alternating hypercellular and hypocellular areas, with subtle fibrosarcoma-like features. Coagulative tumor cell necrosis and readily recognizable mitoses (up to 40 mitotic figures per 10 high-power fields) were identified. Case 2 was a 52-yr-old woman who presented with abnormal vaginal bleeding and a 1.3 cm cervical mass. The resected cervical tumor showed proliferation of spindled cells with fascicular and storiform growth pattern, infiltrating into the smooth muscle with entrapment of normal endocervical glands. The tumor cells displayed mild cytologic atypia and low mitotic activity (1 mitotic figure per 10 high-power fields). The mixed inflammatory infiltrate was seen throughout the lesion, mimicking morphology of inflammatory myofibroblastic tumor. Immunohistochemical staining for S100 and CD34 demonstrated variable expression in case 1 and uniformly diffuse positivity in case 2. The tumor cells in both cases were focally positive for CD10, Cyclin D1, ER, and PR, and negative for AE1/AE3, desmin, SOX10, HMB-45. RNA fusion analysis identified SPECC1L-NTRK3 gene rearrangements in case 1 and TPM3-NTRK1 in case 2; DNA-based mutational analysis also revealed CDKN2A/B homozygous deletion in case 1. Despite accumulating literature on NTRK fusion mesenchymal tumors in gynecologic pathology, these tumors are still rare and lack well-established morphologic diagnostic criteria. Diagnostic and clinical recognition of these tumors is critical given the potential patient benefit from targeted therapy.
NTRK1/2/3 重排已被确定为多种肿瘤的致癌驱动因素，包括宫颈癌，以及罕见的子宫体癌。我们报告了 2 例伴有 NTRK 基因重排的宫颈肉瘤病例。病例 1 为 54 岁女性，绝经后阴道出血，宫颈有 5.4cm 易碎肿块。肿瘤的显微镜检查显示上皮样和梭形细胞增生，呈交替性细胞丰富区和细胞稀少区，具有微妙的纤维肉瘤样特征。可见凝固性肿瘤细胞坏死和易于识别的有丝分裂（每 10 个高倍视野多达 40 个有丝分裂象）。病例 2 为 52 岁女性，因异常阴道出血和 1.3cm 宫颈肿块就诊。切除的宫颈肿瘤显示梭形细胞增生，呈束状和席纹状生长模式，浸润平滑肌并包绕正常宫颈腺。肿瘤细胞显示轻度细胞异型性和低有丝分裂活性（每 10 个高倍视野 1 个有丝分裂象）。整个病变可见混合性炎症浸润，类似于炎症性肌纤维母细胞瘤的形态。病例 1 的 S100 和 CD34 免疫组化染色显示可变表达，病例 2 则表现为均匀弥漫阳性。两例肿瘤细胞均局灶性 CD10、Cyclin D1、ER 和 PR 阳性，AE1/AE3、结蛋白、SOX10、HMB-45 阴性。RNA 融合分析显示病例 1 存在 SPECC1L-NTRK3 基因重排，病例 2 存在 TPM3-NTRK1 基因重排；基于 DNA 的突变分析还显示病例 1 存在 CDKN2A/B 纯合缺失。尽管妇科病理学中关于 NTRK 融合间充质肿瘤的文献不断增加，但这些肿瘤仍然很少见，缺乏成熟的形态学诊断标准。鉴于这些肿瘤可能对靶向治疗有益，因此对其进行诊断和临床识别至关重要。
