Pathology and Biology of Human Germ Cell Tumors by Francisco F. Nogales & Rafael E. Jimenez

Author:Francisco F. Nogales & Rafael E. Jimenez
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

Alpha-fetoprotein (AFP) has been considered a gold standard for the diagnosis of YST, although it is known that this embryonal protein can be expressed, among others, in ovarian clear cell carcinoma [108] and in ovarian metastases of gastric carcinoma. In the normal yolk sac, AFP is present as early as the 5th week showing a granular cytoplasmic positivity, which is concentrated in the intra- and intercellular lumina and tubular surfaces that constitute a complex transfer system. In classic YST patterns, AFP expression is constant but heterogeneous in the epithelium, (Fig. 6.7b) where it also delineates occasional cellular lumina. In somatic glandular or solid [95] patterns, however, its distribution tends to be focal or absent [109]. Thus, it can be said that AFP negativity does not necessarily preclude a diagnosis of YST.

Glypican-3 (GPC3). In the normal yolk sac, GPC3 displays a cytoplasmic or membranous expression (Fig. 6.7c) that also highlights inter- and intracellular tubules. GPC3 is also extensively or patchily expressed in YST [110]. GPC3 is diffusely expressed in classical YST patterns but has a heterogeneous distribution, and it is even absent in somatic glandular variants. Similar in distribution to AFP, it is a more sensitive antibody, although not as specific as AFP [111], being also expressed in tumors of the female genital tract such as the primitive neural tubules of immature teratoma, hepatocellular carcinoma, squamous cell carcinomas, carcinosarcomas, and placental site trophoblastic tumors, among many others. Some clear cell carcinomas may also express GPC3, and consequently its demonstration may not be that useful in the differential diagnosis [112] of YST originating from somatic tumors.

Hepatocyte paraffin-I (HepPar-1) is expressed throughout the lifespan of the human yolk sac, reflecting its vicarious hepatic role. HepPar-1 positivity has been reported in both the hepatoid areas of YST and in hepatoid carcinomas [113]. Our study suggests that the frequent, but focal, HepPar-1 positivity in YST does not necessarily mean that it identifies a hepatic tissue, but that it can also reflect a HYS differentiation. Well-differentiated glandular YST of intestinal type show an intense and diffuse HepPar-1 expression (Fig. 6.7d) similar to that found in the small intestine [114].

CDX2 expression is consistently present in the human yolk sac [107]. In classical patterns, CDX2 expression is focal [115, 116] (Fig. 6.7e), but in somatic glandular patterns, it displays a stronger, diffusely positive, staining [96]. Therefore, it would seem that CDX2 positivity will highlight both areas of HYS and intestinal differentiation, the latter being more evident in somatic glandular patterns, especially those with vacuolated epithelia resembling the embryonal gut.

Villin is consistently expressed during early embryogenesis in both HYS and early endoderm [107] and is a highly sensitive endodermal epithelial component marker in all cases of YST, both in classical and somatic glandular patterns (Fig. 6.7f), being absent in pure embryonal carcinoma and seminoma/dysgerminoma. Its diffuse cytoplasmic expression parallels that of the HYS [107] and intestinal adenocarcinomas, where both diffuse and apical staining patterns occur [117]. We believe that villin is an excellent marker of both primitive and differentiated YST variants.

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