Michal Michael, Kuruc Josef, Hájková Veronika, Michalová Květoslava, Klubíčková Natálie
Bioptical Laboratory, Ltd., Pilsen, Czech Republic.
Department of Pathology, Medical Faculty and Charles University Hospital Plzen, Charles University, Alej Svobody 80, 323 00, Pilsen, Czech Republic.
Virchows Arch. 2024 Oct 10. doi: 10.1007/s00428-024-03936-z.
NTRK-rearranged spindle cell neoplasm represents an emerging entity included in the latest 5th edition of WHO classification of both soft tissue and female genital tumors. By immunohistochemistry, they are commonly positive for CD34, S100 protein, and CD30 and typically harbor fusions of kinase genes such as NTRK1/2/3, RET, and BRAF. In the gynecological tract, they typically affect the uterine cervix or uterine body. Most of the reported cases had fibrosarcoma-like morphology, occasionally showing perivascular and stromal hyalinization with only a few cases showing a less cellular spindle cell proliferation. Except for one case with RET fusion, all other gynecological cases harbored exclusively NTRK1/2/3 fusions. Besides kinase gene fusions, the analogous tumors in soft tissues may also harbor activating EGFR or BRAF point mutations, but no such case has been described in the uterus. Herein we are reporting two cases from the uterine cervix showing morphology and molecular features previously unreported at this anatomic site. The patients were 46 and 34 years old and clinically presented with unremarkable cervical polyps each measuring 8 mm in diameter. Histologically, both cases had a rounded polypoid outline and were composed of hypocellular proliferation of bland spindle cells lacking mitotic activity and growing in a fibrotic stroma which was punctuated by prominent small vessels with thick hyalinized walls. Immunohistochemically, both showed a diffuse expression of CD34, CD30, and S100 protein, whereas SOX10 was negative. Both cases harbored exon 20 EGFR mutation and did not reveal any fusions or significant copy number changes. The patient in case 1 was treated by hysterectomy with salpingectomy with no other residual tumor detected, and she was alive and well 27 months after the diagnosis. The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of "NTRK-rearranged spindle cell neoplasms" of the uterine cervix with novel EGFR mutations.
NTRK重排的梭形细胞肿瘤是一种新出现的实体，被纳入最新的第5版世界卫生组织软组织和女性生殖器官肿瘤分类中。通过免疫组织化学检测，它们通常CD34、S100蛋白和CD30呈阳性，并且通常具有激酶基因融合，如NTRK1/2/3、RET和BRAF。在生殖道中，它们通常累及子宫颈或子宫体。大多数报道的病例具有纤维肉瘤样形态，偶尔可见血管周围和间质透明变性，只有少数病例表现为细胞较少的梭形细胞增殖。除1例有RET融合外，所有其他妇科病例均仅存在NTRK1/2/3融合。除激酶基因融合外，软组织中的类似肿瘤也可能存在激活的EGFR或BRAF点突变，但子宫中尚未有此类病例报道。在此，我们报告2例来自子宫颈的病例，其形态和分子特征在该解剖部位此前未见报道。患者分别为46岁和34岁，临床上均表现为直径8毫米、无明显异常的宫颈息肉。组织学上，两例均有圆形息肉样外形，由缺乏有丝分裂活性的淡染梭形细胞的低细胞增殖组成，生长于纤维化间质中，间质中有突出的、壁增厚透明变性的小血管。免疫组织化学检测显示，两例均弥漫性表达CD34、CD30和S100蛋白，而SOX10为阴性。两例均存在外显子20 EGFR突变，未发现任何融合或显著的拷贝数变化。病例1的患者接受了子宫切除术加输卵管切除术，未检测到其他残留肿瘤，诊断后27个月仍存活且状况良好。病例2的患者在诊断时无其他已知肿瘤，但无后续随访信息。我们认为，所报道的病例代表了子宫颈“NTRK重排的梭形细胞肿瘤”一种迄今未被认识的变异型，具有新的EGFR突变。
