Marani Carla, Akaev Iolia, Yeoh Chit Cheng, Walsh Elizabeth, Rahimi Siavash
Histopathology Division, San Carlo di Nancy Hospital, Rome 00165, Italy.
School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UK.
Exp Ther Med. 2021 Apr;21(4):394. doi: 10.3892/etm.2021.9825. Epub 2021 Feb 24.
Malignant mixed mesonephric tumours (MMMsT) of the female genital tract are extremely rare, and the majority are located in the wall of the cervix uteri. At present, there are no reports of the molecular characterisation of MMMsT of the female genital tract. Herein, we report the morphological, immunohistochemical and molecular features of this rare malignancy using next-generation sequencing (NGS) analysis. A 58-year-old woman presented with vaginal bleeding. In 2013, she had been diagnosed with a cervical carcinosarcoma of probable mesonephric origin and International Federation of Gynaecology and Obstetrics (FIGO) stage IB that had been treated by total hysterosalpingo-oopherectomy without adjuvant chemo-radiotherapy. Ultrasonography showed a vaginal mass measuring 25 mm in the maximum dimension. Biopsy was performed and showed a biphasic neoplasm composed of adenocarcinoma and sarcoma. Immunohistochemistry showed positive staining for epithelial membrane antigen (EMA), pancytokeratin (MNF116), paired box 8 (PAX-8), β-catenin, cytokeratin 7, cyclin D1, GATA3 and CD10. Androgen receptor positivity was detected in very limited areas. Cytokeratin 20, carcinoembryonic antigen (CEA), oestrogen receptor (ER), progesterone receptor (PR), transcription termination factor 1 (TTF1), Wilm's tumour antigen-1 (WT-1), calretinin and p16 were negative. The immunohistochemical profile was consistent with mesonephric origin. NGS analysis identified a variant of the ataxia-telangiectasia mutated () gene (p.Phe858Leu; c.2572 T>C; COSM21826). The number of detected allele frequency reads of mutation following clinical relapse was higher, compared to its baseline: 65 vs. 96%. The differential diagnosis of MMMsT includes mesonephric hyperplasia, malignant mixed Mullerian tumour (carcinosarcoma), endometrioid adenocarcinoma and endometrial stromal sarcoma. The clinical significance of the observed variant in the case reported herein is unknown. The present findings need further verification, as the mutation in may result in chemotherapy resistance or conversely, may be exploited for targeted therapies.
女性生殖道恶性混合性中肾瘤（MMMsT）极为罕见，大多数位于子宫颈壁。目前，尚无关于女性生殖道MMMsT分子特征的报道。在此，我们使用二代测序（NGS）分析报告了这种罕见恶性肿瘤的形态学、免疫组化和分子特征。一名58岁女性出现阴道出血。2013年，她被诊断为可能起源于中肾的宫颈癌肉瘤，国际妇产科联盟（FIGO）分期为IB期，接受了全子宫输卵管卵巢切除术，未进行辅助放化疗。超声检查显示阴道有一最大径为25mm的肿块。进行了活检，显示为一种由腺癌和肉瘤组成的双相性肿瘤。免疫组化显示上皮膜抗原（EMA）、全细胞角蛋白（MNF116）、配对盒8（PAX - 8）、β - 连环蛋白、细胞角蛋白7、细胞周期蛋白D1、GATA3和CD10呈阳性染色。在非常有限的区域检测到雄激素受体阳性。细胞角蛋白20、癌胚抗原（CEA）、雌激素受体（ER）、孕激素受体（PR）、转录终止因子1（TTF1）、肾母细胞瘤抗原 - 1（WT - 1）、钙视网膜蛋白和p16均为阴性。免疫组化结果与中肾起源一致。NGS分析鉴定出共济失调毛细血管扩张突变（）基因的一个变体（p.Phe858Leu；c.2572 T>C；COSM21826）。临床复发后检测到的该突变等位基因频率读数数量高于基线：分别为65%和96%。MMMsT的鉴别诊断包括中肾增生、恶性混合性苗勒管肿瘤（癌肉瘤）、子宫内膜样腺癌和子宫内膜间质肉瘤。本文报道病例中观察到的该变体的临床意义尚不清楚。目前的发现需要进一步验证，因为该突变可能导致化疗耐药，或者相反，可用于靶向治疗。
