Endodermal sinus tumors (EST) have also been referred to as yolk sac carcinomas, because they are derived from the primitive yolk sac. These lesions are the third most frequent malignant germ cell tumor of the ovary. Endodermal sinus tumors occur at a median age of 18 years, and about one third of the patients are premenarchal at the time of presentation. Like the other nondysgerminomatous ovarian malignancies, abdominal or pelvic pain is the most frequent presenting symptom, occurring in about 75% of patients. An asymptomatic pelvic mass is documented in about 10% of patients.

Most EST lesions secrete AFP and rarely they may produce detectable AAT. There is a good correlation with the extent of disease and the AFP level, although discordance has been observed. The serum level of AFP is particularly useful in monitoring the patient during and after treatment.

Surgery
The treatment of EST includes a surgical exploration, a unilateral oophorectomy, and a frozen section for diagnosis. Any gross metastases should be removed if possible, but a thorough surgical staging is not necessary because all patients need chemotherapy. The tumors tend to be solid and large, ranging in size from 7 to 28 cm (median is 15 cm). The EST is thought never to be bilateral, and the other ovary will have metastasis only when there are other metastases in the peritoneal cavity. Most patients have early-stage disease: 71% have stage I, 6% have stage II, and 23% have stage III. The performance of a hysterectomy and contralateral salpingo-oophorectomy does not alter outcome.

Chemotherapy
Endodermal sinus tumors are treated in all patients, regardless of stage, with either adjuvant or therapeutic chemotherapy. Prior to the routine use of combination chemotherapy for this disease, the 2-year survival was only about 25%. After the introduction of the VAC regimen, this rate improved to 60% to 70%, indicating the chemosensitivity of the majority of these tumors. Furthermore, with conservative surgery and adjuvant chemotherapy, fertility can be preserved as with other germ cell tumors.

As with other nondysgerminomatous germ-cell tumors, a cisplatin-containing combination chemotherapy regimen, either BEP or VBP, is most effective in the treatment of EST, particularly in the treatment of measurable or incompletely resected tumors. In the GOG series, only about 20% of patients with residual metastatic disease responded completely to the VAC regimen, whereas about 60% of those treated with VBP had a complete response. In addition, this regimen may salvage some failures of V therapy. As with patients with immature teratomas, BEP probably is the best current primary chemotherapy for this disease. The optimal number of treatment cycles has not been established. The GOG protocols have used nine treatment cycles of VBP given every 4 weeks. but four to six cycles may be equally effective.

Second-Look Procedure
It is unclear whether a second look has any value in patients with EST, and it may be reasonable to omit the operation in those with pure lesions that are of low stage and in those whose AFP values return to normal and remain normal for the rest of their treatment. In patients with advanced-stage disease or in those with measurable or incompletely resected lesions whose AFP levels do not return to normal, persistent disease can be assumed and alternative chemotherapy offered.