title: High-level expression of divergent endodermal lineage markers in gonadal and extra-gonadal yolk sac tumors.
abstract: Yolk sac tumors occur at both gonadal and extra-gonadal sites. A recent case of ovarian endometrioid-pattern yolk sac tumor with strong diffuse expression of TTF-1 illustrated the potential for misdiagnosis due to divergent expression of endodermal lineage markers. The aim of this study was to investigate the expression of four divergent endodermal lineage markers, TTF-1, CDX2, Hep Par 1, and Napsin A, in gonadal and extra-gonadal yolk sac tumors of differing age, sex, and location (excluding foci of overt hepatoid differentiation). We identified 26 cases (5 ovarian, 15 testicular, and 6 extra-gonadal) containing yolk sac tumor as identified by typical histology and confirmed by positive immunohistochemical staining for alpha-fetoprotein and glypican-3. Mixed or ambiguous foci were confirmed by immunohistochemistry (SALL4 positive and Oct-4 negative). The relative proportion of three histologic patterns: reticular/cystic, solid/myxoid, and glandular was estimated. Percent positivity for the four divergent endodermal lineage markers was compared within yolk sac tumor areas according to site, age group, and histologic pattern. High-level (>25%) staining for one or more divergent endodermal lineage markers was seen in eleven cases: Hep Par 1 in seven cases, all post-pubertal, TTF-1 in four cases, two ovarian and two extra-gonadal, and CDX2 in three cases, with no age or site predilection. No case highly expressed all three divergent endodermal lineage markers, but four co-expressed high levels of two markers: two ovarian yolk sac tumors with TTF-1 and Hep Par 1, one testicular yolk sac tumor with CDX2 and Hep Par 1, and one extra-gonadal yolk sac tumors with TTF-1 and CDX2. While no absolute correlation of high-level divergent endodermal lineage marker expression with histologic subtype was observed, TTF-1 and CDX2 expression was predominantly seen in reticular/cystic and glandular areas while Hep Par 1 was most frequent in myxoid/solid and glandular areas.
authors.affiliation: Pathology Resident, Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Hadi
authors.initials: H
authors.lastname: Shojaei
authors.affiliation: Pathology Resident, Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Hong
authors.affiliation: Departments of Pathology and Reproductive Biology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Redline
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D018240:Endodermal Sinus Tumor / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000473:pathology; D009669:Nose Neoplasms / Q000473:pathology; D010051:Ovarian Neoplasms / Q000473:pathology; D012445:Sacrococcygeal Region / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000473:pathology; D013736:Testicular Neoplasms / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor