A nulliparous, obese, diabetic 68-year-old woman with a history of pelvic endometriosis presented with an International Federation of Gynecology and Obstetrics stage III 17-cm ovarian mass. Histology showed endometriotic cysts with an intracystic growth of well-differentiated endometrioid adenocarcinoma with squamous morular change. This coexisted with a second papillary epithelial pattern corresponding to a glandular yolk sac tumor (YST) that merged with the endometrioid adenocarcinoma. Immunohistochemistry discriminated between endometrioid adenocarcinoma and glandular YST phenotypes. The expression of traditional YST markers, such as α-fetoprotein and glypican 3, was heterogeneous and irregular, failing to demarcate the YST from the endometrioid carcinoma. However, the coexpression of SALL4 and villin clearly differentiated the positive YST from the negative endometrioid adenocarcinoma.
Müllerian epithelial markers, such as epithelial membrane antigen, cytokeratin 7, and PAX8, highlighted endometrioid carcinoma areas but were consistently negative in both glandular and classic variants of YST.
Germ cell tumors arising from somatic Müllerian tumors in the female genital tract are aggressive, high clinical stage nondysgerminomatous tumors of both the ovary and endometrium; the most frequent association is endometrioid adenocarcinoma and YST. They likely originate from tumor stem cells. Their endometrioid adenocarcinoma component is usually high grade, although a minority arises from low-grade neoplasms with morular differentiation. The germ cell component is always YST with a predominance of glandular and hepatoid variants. Immunohistochemical differentiation between both patterns should be accomplished using a broad panel including SALL4, villin, GATA3, α-fetoprotein, and glypican 3. However, a reduced panel using just SALL4 and villin is often sufficient for the diagnosis of the majority of YST. Müllerian antibodies against epithelial membrane antigen, cytokeratin 7, and PAX8 are usually negative in YST but positive in Müllerian tumors.