Buza Natalia, Wong Serena, Hui Pei
Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
Int J Gynecol Pathol. 2018 Jul;37(4):305-315. doi: 10.1097/PGP.0000000000000426.
Correlation of FOXL2 mutation status with morphologic features and reticulin staining patterns was performed in a comprehensive single-institutional cohort of ovarian sex cord-stromal tumors. Fifty-one cases were included, 35 of which were morphologically diagnosed as adult granulosa cell tumor, 4 as Sertoli-Leydig cell tumor, 11 as fibroma/fibrothecoma and 1 as a thecoma. Of the adult granulosa cell tumors, 31 (88.6%) harbored FOXL2 mutation. Abundant pale cytoplasm was seen in 51.6% (16/31) of FOXL2 mutated tumors, compared with 6.7% (1/15) among FOXL2 wild type tumors (P=0.003). Nearly half of FOXL2 negative tumors showed individual pericellular reticulin staining pattern, while none of the FOXL2 positive cases demonstrated this feature (P=0.0001). Nested reticulin pattern was observed in 67.7% of FOXL2 positive tumors, compared with 20% of FOXL2 negative cases (P=0.004). Indeterminate reticulin staining pattern was seen in nearly one third of cases in both groups. Nested reticulin pattern was 87.5% specific and 67.7% sensitive for FOXL2 mutation, while individual reticulin pattern was 100% specific for absence of FOXL2 mutation. No statistical significance was observed between the 2 groups in tumor size, mitotic activity, nuclear atypia, and nuclear grooves. Follow-up was available for 44 patients ranging from 0.3 to 259 months (mean: 67.5 mo). Two patients developed recurrence, both of them harbored FOXL2 mutation. In conclusion, the pathology diagnosis of sex cord-stromal tumors continues to be difficult, and reticulin staining remains a valuable tool as an initial step in the diagnostic work-up. Individual pericellular reticulin pattern essentially rules out adult granulosa cell tumor, while cases with indeterminate or nested patterns can be subjected to FOXL2 mutation testing to aid the diagnosis.
在一个综合性单机构队列的卵巢性索间质肿瘤中，对FOXL2突变状态与形态学特征及网硬蛋白染色模式进行了相关性研究。纳入51例病例，其中35例形态学诊断为成人颗粒细胞瘤，4例为支持-间质细胞瘤，11例为纤维瘤/纤维卵泡膜瘤，1例为卵泡膜瘤。在成人颗粒细胞瘤中，31例（88.6%）存在FOXL2突变。FOXL2突变肿瘤中51.6%（16/31）可见丰富的淡染细胞质，而FOXL2野生型肿瘤中这一比例为6.7%（1/15）（P = 0.003）。近一半的FOXL2阴性肿瘤显示单个细胞周围网硬蛋白染色模式，而FOXL2阳性病例均未表现出这一特征（P = 0.0001）。67.7%的FOXL2阳性肿瘤观察到巢状网硬蛋白模式，而FOXL2阴性病例中这一比例为20%（P = 0.004）。两组中近三分之一的病例可见不确定的网硬蛋白染色模式。巢状网硬蛋白模式对FOXL2突变的特异性为87.5%，敏感性为67.7%，而单个网硬蛋白模式对FOXL2突变缺失的特异性为100%。两组在肿瘤大小、有丝分裂活性、核异型性和核沟方面未观察到统计学差异。44例患者获得随访，随访时间为0.3至259个月（平均：67.5个月）。2例患者复发，均存在FOXL2突变。总之，性索间质肿瘤的病理诊断仍然困难，网硬蛋白染色作为诊断检查的第一步仍然是一个有价值的工具。单个细胞周围网硬蛋白模式基本可排除成人颗粒细胞瘤，而不确定或巢状模式的病例可进行FOXL2突变检测以辅助诊断。
