Agnes Nagy, Na Niu, Elena Ratner, Pei Hui, Natalia Buza
{"title":"卵巢成人颗粒细胞瘤中的新型 FOXL2 基因突变:病例报告及诊断和临床病理学意义。","authors":"Agnes Nagy, Na Niu, Elena Ratner, Pei Hui, Natalia Buza","doi":"10.1097/PGP.0000000000001024","DOIUrl":null,"url":null,"abstract":"<p><p>Adult granulosa cell tumor, the most common malignant ovarian sex cord-stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases. To date, no other variants of FOXL2 mutations have been identified in these tumors. Here we report the first case of an adult granulosa cell tumor with a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia and gross examination revealed an incidental 3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically, ~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the individual pericellular network within the nested areas, while the pericellular staining pattern was retained in the background stromal component. FOXL2 sequencing analysis was performed in both components and revealed a c.398C>T (p.A133V) mutation in the nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up. This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord-stromal tumors with increasing use of routine molecular testing, adding to the complexity of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2 mutation-even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)-can support the diagnosis of adult granulosa cell tumor.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"631-636"},"PeriodicalIF":1.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications.\",\"authors\":\"Agnes Nagy, Na Niu, Elena Ratner, Pei Hui, Natalia Buza\",\"doi\":\"10.1097/PGP.0000000000001024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Adult granulosa cell tumor, the most common malignant ovarian sex cord-stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases. To date, no other variants of FOXL2 mutations have been identified in these tumors. Here we report the first case of an adult granulosa cell tumor with a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia and gross examination revealed an incidental 3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically, ~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the individual pericellular network within the nested areas, while the pericellular staining pattern was retained in the background stromal component. FOXL2 sequencing analysis was performed in both components and revealed a c.398C>T (p.A133V) mutation in the nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up. This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord-stromal tumors with increasing use of routine molecular testing, adding to the complexity of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2 mutation-even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)-can support the diagnosis of adult granulosa cell tumor.</p>\",\"PeriodicalId\":14001,\"journal\":{\"name\":\"International Journal of Gynecological Pathology\",\"volume\":\" \",\"pages\":\"631-636\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Gynecological Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/PGP.0000000000001024\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Gynecological Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PGP.0000000000001024","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications.
Adult granulosa cell tumor, the most common malignant ovarian sex cord-stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases. To date, no other variants of FOXL2 mutations have been identified in these tumors. Here we report the first case of an adult granulosa cell tumor with a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy for atypical endometrial hyperplasia and gross examination revealed an incidental 3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically, ~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the individual pericellular network within the nested areas, while the pericellular staining pattern was retained in the background stromal component. FOXL2 sequencing analysis was performed in both components and revealed a c.398C>T (p.A133V) mutation in the nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up. This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord-stromal tumors with increasing use of routine molecular testing, adding to the complexity of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2 mutation-even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)-can support the diagnosis of adult granulosa cell tumor.
期刊介绍:
International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.