Yolk Sac Tumor in Extragonadal Pelvic Sites: Still a Diagnostic Challenge

We present the clinicopathologic features of 15 cases of extragonadal yolk sac tumor (EGYST) detected in female patients and reviewed at our institution from 1988 to 2016. We recorded: patient age, clinical presentation, tumor location, FIGO stage (where applicable), histologic patterns including presence/absence of Schiller-Duval bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. Patients' ages ranged from 17 to 87 (median, 62) years and presentation included: abnormal uterine bleeding, 12; hematuria, 1; labial mass, 1; abdominal pain, 1. Primary sites were as follows: uterus (11), vagina (1), vulva (1), bladder (1), and peritoneum (1). Seven patients presented at FIGO stage III or IV. The following histologic patterns were observed: microcystic/reticular (7), glandular (8), solid (8), papillary (5), and hepatoid (1). An admixture of histologic patterns was present in 10 cases. Schiller-Duval bodies were seen in only 3 (23%) cases. Eight cases (46%), all uterine primaries, had associated somatic components, and 2 (15%) had a second germ cell component. In 13/14 (93%) cases, the yolk sac tumor component was either missed or misclassified as adenocarcinoma. Immunoperoxidase studies facilitated the diagnosis in all cases as follows: SALL4, 12/12; CDX2, 10/12; α fetoprotein, 7/14; glypican-3, 9/10; cytokeratin 20, 5/9 (rare cells); cytokeratin 7, 3/12 (nondiffuse); PAX8, 2/9 (variable expression). All patients received chemotherapy and all except 1 underwent surgical resection. Follow-up from 5 to 86 months was available for 13 patients: 5 died of disease, 6 are alive with disease, and 2 have no evidence of disease. EGYST arising in the female pelvis of peri/postmenopausal patients may be associated with a somatic component and represent either somatically derived YST or YST differentiation within a somatic carcinoma. EGYST in younger patients is likely a true germ cell neoplasm, and may respond to germ cell appropriate chemotherapy. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST is less clear. Awareness that the presence of glandular or microcystic patterns may lead to under-recognition or misdiagnosis of EGYST in combination with immunomarkers for germ cell and yolk sac differentiation will facilitate the diagnosis.