目的:卵黄囊瘤青春期后型(YSTpt)表现出广泛的组织学模式,诊断具有挑战性。最近,叉头框转录因子A2(FoxA2)作为YSTpt形成的驱动因子和诊断YSTpt的有希望的标记物出现。然而,FoxA2尚未在YSTpt的不同模式中进行测试。本研究旨在评估不同模式的YSTpt和其他睾丸生殖细胞肿瘤(GCTT)中FoxA2的染色模式,将其与磷脂酰肌醇蛋白聚糖-3(GPC3)和甲胎蛋白(AFP)进行比较。
结果:在24YSTpt(24个微囊/网状,10粘液样,两个大囊性的,五个腺体/肺泡,两个内胚层窦/血管周围,四个固体,两个多胚瘤/胚状体和两个多囊卵黄)和81个其他GCTT。阳性细胞百分比(0,1+,2+,3)和强度(0、1、2、3)的评估与每个YSTpt模式无关。FoxA2在所有YSTpt(24个中的24个)中均呈阳性,除1个(24个中的23个)外,均表现出2/3染色,强度[中位数(mv):2.6]高于AFP(1.8)和GPC3(2.5)。FoxA2和GPC3在所有微囊/网状中均呈阳性(24个中的24个),粘液样(10个中的10个),大囊性(两个中的两个),内胚层窦/血管周(四个中的四个)和多胚瘤/胚体(两个中的两个)模式。然而,只有FoxA2在所有腺体/肺泡(五个中的五个)中呈阳性,固体(四个中的四个)和多囊卵黄(两个中的两个)模式。在几乎所有YST模式中,FoxA2的强度均高于AFP和GPC3。在另一个GCTT,FoxA2仅在青春期后畸胎瘤(Tpt)中呈阳性[20个中的13个(65%)],染色几乎完全局限于成熟的胃肠道/呼吸道上皮。
结论:FoxA2是一种高度敏感和特异性的生物标志物,支持YSTpt的诊断。FoxA2优于GPC3和AFP,特别是在罕见且难以诊断的YSTpt组织学模式中,但是Tpt的成熟腺体可能代表一个潜在的诊断缺陷。
OBJECTIVE: Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2 (FoxA2) emerged as a driver of YSTpt formation and a promising marker for diagnosing YSTpt. However, FoxA2 has not been tested in the different patterns of YSTpt. This study aimed to assess the staining pattern of FoxA2 in te different patterns of YSTpt and other germ cell tumours of the testis (GCTT), comparing it with glypican-3 (GPC3) and α-fetoprotein (AFP).
RESULTS: FOXA2, GPC3 and AFP immunohistochemistry was performed on 24 YSTpt (24 microcystic/reticular, 10 myxoid, two macrocystic, five glandular/alveolar, two endodermal sinus/perivascular, four solid, two polyembryoma/embryoid body and two polyvesicular vitelline) and 81 other GCTT. The percentage of positive cells (0, 1+, 2+, 3+) and the intensity (0, 1, 2, 3) were evaluated regardless of and within each YSTpt pattern. FoxA2 was positive in all YSTpt (24 of 24) and all but one (23 of 24) exhibited 2+/3+ stain, with higher intensity [median value (mv): 2.6] than AFP (1.8) and GPC3 (2.5). Both FoxA2 and GPC3 were positive in all microcystic/reticular (24 of 24), myxoid (10 of 10), macrocystic (two of two), endodermal sinus/perivascular (four of four) and polyembryoma/embryoid body (two of two) patterns. Nevertheless, only FoxA2 was positive in all glandular/alveolar (five of five), solid (four of four) and polyvesicular vitelline (two of two) patterns. The intensity of FoxA2 was higher than AFP and GPC3 in almost all YST patterns. In the other GCTT, FoxA2 was positive only in teratoma postpubertal-type (Tpt) [13 of 20 (65%)], with staining almost exclusively confined to the mature gastrointestinal/respiratory tract epithelium.
CONCLUSIONS: FoxA2 is a highly sensitive and specific biomarker that supports the diagnosis of YSTpt. FoxA2 is superior to GPC3 and AFP, especially in rare and difficult-to-diagnose histological patterns of YSTpt, but mature glands of Tpt could represent a potential diagnostic pitfall.