Int J Gynecol Pathol. 2024 Nov 1;43(6):631-636. doi: 10.1097/PGP.0000000000001024. Epub 2024 Feb 19.
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.
成人颗粒细胞瘤是最常见的恶性卵巢性索-间质肿瘤，约 90%至 95%的病例中存在 FOXL2 基因特征性突变 c.402C>G(p.C134W)。迄今为止，在这些肿瘤中尚未发现其他 FOXL2 突变变体。在这里，我们报告了首例 FOXL2 点突变 c.398C>T(p.A133V)的成人颗粒细胞瘤病例，该病例发生于 1 名 64 岁绝经后女性，患者因非典型子宫内膜增生接受了全子宫切除术和双侧输卵管卵巢切除术，大体检查显示右侧卵巢有 3.2cm 大小的偶然发现的肿块，切面呈实性、亮黄色、均匀。镜下，约 30%的肿瘤呈巢状生长模式，由具有圆形核和中等量淡染胞质的均匀肿瘤细胞组成，而其余区域由良性的梭形纤维母细胞瘤基质组成。网状纤维染色显示在巢状区域内个体细胞周网络丢失，而背景间质成分保留细胞周染色模式。对两个成分均进行 FOXL2 测序分析，发现巢状成分中存在 c.398C>T(p.A133V)突变，而纤维母细胞瘤基质中存在野生型 FOXL2 序列。子宫切片显示低级别子宫内膜样腺癌伴浅肌层浸润。患者因子宫内膜癌接受了阴道残端近距离放疗辅助治疗，目前随访 8 个月时仍存活且情况良好。该病例说明，随着常规分子检测的应用越来越广泛，可能会在卵巢性索-间质肿瘤中检测到新的 FOXL2 突变，这增加了病理诊断的复杂性。在正确的形态学和临床背景下，即使 FOXL2 突变与优势热点突变 c.402C>G(p.C134W)不同，也可以支持成人颗粒细胞瘤的诊断。
