Atypical Presentation of an Ovarian Yolk Sac Tumor in an 80-Year-Old Woman: A Case Report and Review of the Literature

Yolk sac tumors, also known as endodermal sinus tumors, are malignant primitive germ cell tumors commonly arising in the gonads and are rare and rapidly growing neoplasms. In pediatric ages, yolk sac tumors in the testes or ovary are found in a pure form and have a good prognosis in this age group, whereas yolk sac tumors in adults are often found in combination with other types of germ cell tumors [1‒3]. In females, ovarian germ cell tumors usually present in the adolescence and in young women in fertile age, with a prevalence of approximately 1–3% of all malignant ovarian neoplasms and poor prognosis [4]. Given that malignant germ cell tumors occur rarely compared to epithelial ovarian tumors, greater focus is required in their diagnosis and treatment. Suggestive diagnostic findings including an enhanced large solid cystic mass with intertumoral hemorrhage in radioimaging studies and increased serum alpha-fetoprotein (AFP) levels should be confirmed by microscopic examination of biopsy or surgical specimens [5, 6].

The present-day treatment for yolk sac tumors is surgery (fertility-sparing procedures) and adjuvant chemotherapy, achieving high complete remission rates and prolonged overall survival [7‒9]. Ovarian yolk sac tumors occur very rarely after menopause. We here report an atypical case of yolk sac tumor in an older woman. This case is unique because it occurred in an octogenarian patient and showed a favorable clinical course without signs of tumor recurrence after 1 year of follow-up.

An 80-year-old woman was admitted to the hospital because of anasarca, ascites, toxic syndrome, and an abdominal mass. Family history was unrevealing. Gynecological history showed menarche at 14 years of age, menopause at 44 years, 1 eutocic delivery, and 1 spontaneous abortion. A thoracoabdominal computed tomography (CT) scanning revealed an abdominopelvic mass, 18.5 cm in diameter, probably originated from the right uterine appendages, abundant ascites with trabeculation of the anterior peritoneal fat, hepatic steatosis, a possible small pathological focus in segment II, and focal and partial thrombosis in the intrahepatic inferior vena cava (Fig. 1, 2). Bowel involvement was not detected in the CT scan. Thrombosis of the inferior vena cava was treated with anticoagulation at prophylactic doses due to the patient’s general condition. Laboratory studies were unrevealing except for an increased serum AFP level (246,720 ng/mL; normal range up to 40 ng/mL for adults). A diagnostic paracentesis was performed, disclosing the presence of malignant cells with AFP immunocytochemical expression. A tentative diagnosis of primary hepatic tumor or germ cell tumor (yolk sac) with hepatoid differentiation was established. The case was evaluated by the Gynecologic Oncology Tumor Committee, and given that the diagnosis of hepatocellular carcinoma could not be excluded and a primary yolk sac tumor appeared improbable on imaging findings, magnetic resonance imaging of the liver and a position emission tomography-CT were indicated, which could not be finally performed due to claustrophobia and patient’s refusal. Clinical staging according to the International Federation of Gynecology and Obstetrics (FIGO) [10] was IIA.

During hospital admission, the patient’s clinical status deteriorated due to progressive tumor growth, and on June 13, 2023, she was operated on undergoing a subtotal hysterectomy with bilateral adnexectomy. There was an adherence of the tumor mass to the sigma (without malignant cell infiltration), but a diverting colostomy was necessary due to intraoperative inadvertent bowel perforation. Total hysterectomy was not performed due to technical difficulties. Postoperatively, she presented hypovolemic shock with rectosigmoid perforation requiring intestinal resection and pararectal colostomy. She was admitted to the intensive care unit, presented a favorable clinical course, and was discharged home.

The histopathological examination of the surgical specimen confirmed a yolk sac tumor (175 × 120 × 105 mm) with multiple tumor foci in the ovary surface and invasion of the fat tissue involving the fallopian tube and the uterine serosa, without evidence of lymphovascular or perineural invasion. Immunohistochemical analysis showed positive expression of AFP, glypican 3, cytokeratin AE1/AE3, and focal SALL4, CK7, PAX8, and WT1 expression (Fig. 3). Other immunohistochemical markers, such as inhibin, calretinin, PLAP, BHCG, CD30, OCT3/4, CK7, CK20, and Ber-Ep4, gave negative results. The definite diagnosis of malignant ovarian primitive germ cell tumor was established, and chemotherapy with bleomycin, etoposide, and cisplatin (BEP) was proposed, but it was refused by the patient. She was aware of the risks associated with expectant management. Postoperatively, serum levels of AFP decreased progressively to 186 ng/mL at 8 weeks of surgery, 32 ng/mL at 12 weeks, and 2.68 ng/mL at 6 months. Monthly clinical and analytical controls were scheduled, and at present, in June 2024, the patient’s general condition is excellent with good quality of life and the level of AFP is 2.0 ng/mL.

The case here reported of a yolk sac tumor in an 80-year-old woman illustrates the occurrence of ovarian germ cell tumors in a very rare age group. The main clinical manifestations were an abdominal mass and ascites. Timely diagnosis is crucial for improved prognosis in these patients. Our patient, however, refused to undergone diagnostic procedures for tumor staging and required surgery for a final histopathological diagnosis. In the differential diagnosis of a large adnexal mass, other forms of rare tumors should be considered, including a mucinous ovarian cancer, embryonal carcinoma, sex cord tumor, immature teratoma, hepatocellular carcinoma, and dysgerminoma. Fine-needle aspiration biopsy of the mass was not performed due to its large tumor, risk of rupture, and positive cytology suggestive of yolk sac tumor. According to FIGO recommendations [10], patients with ovarian germ cell tumors should undergo surgical staging similar to that established for ovarian epithelial cancer. Tumor stage in our patient was pT1N0MX (there was only an adherence of the tumor mass to the sigma without malignant cell infiltration).

In contrast to initial clinical stage and extension of the disease, age is not a negative prognostic factor, although the presence of comorbid diseases associated with advanced age should be taken into account at the time of surgical resection of the tumor. In a review of the Malignant Germ Cell International Consortium dataset of 251 patients (78 children, 139 adolescents, and 34 adults) followed for a median of 5.8 years, the overall 5-year event-free survival and overall survival was 91% and 96%, respectively, and age did not affect risk of event or death, modeled either as a categorical or continuous variable. Also, analysis failed to identify an age cut point that affected risk [11]. However, other studies have reported that ovarian yolk sac tumors in postmenopausal women are characterized by high malignancy and may have a worse prognosis compared with those in younger patients [12]. Surgery and adjuvant BEP chemotherapy is the recommended approach, but without treatment, the prognosis is poor, although the clinical condition of our patient has been favorable and serum AFP decreased after surgery and remained within normal limits in the last follow-up control, 1 year after surgery.

The experience regarding diagnosis, treatment, and outcome in yolk sac tumors in postmenopausal women is limited, with a total of 11 cases reported in the literature [12‒19]. The characteristics of these patients together with those of the present case are summarized in Table 1. The mean age of the patients was 63.4 years (range 52–82 years). With the exception of 2 cases in which serum AFP levels were not reported, the remaining 9 patients had elevated preoperative serum AFP levels, with the highest values of 273,550 ng/mL in 1 case reported by Wang et al. [12] followed by 246,720 ng/mL in our patient. Also, after surgical treatment of tumors, postoperative AFP levels usually decreased to normal limits. In relation to FIGO staging, stage II was the most frequent (41.7%) followed by stage I (33.3%) and stage III (25%). All patients underwent surgical treatment, with cytoreductive surgery as the most common procedure. Immunohistochemical analysis was performed in all cases, with consistent positivity for distinctive diagnostic markers including p53, AFP, SALL4, glypican 3, AE1/3, and CK7. Moreover, all patients received adjuvant chemotherapy, especially the BEP protocol (bleomycin, etoposide, cisplatin), although in the case reported by Ahn et al. [13], chemotherapy was refused by the patient as occurred in our case. One patient died [14] and another patient developed pelvic peritoneal recurrence and infiltration in a supraclavicular lymph node [13], whereas in the remaining patients, recurrence was not documented. However, it should be noted that the length of follow-up was mainly limited to some months, except for our patient who remained asymptomatic at the time of last control after 1 year of surgery. This illustrates the favorable course of the disease in the case here reported.

We presented a very rare case of yolk sac tumor in an octogenarian patient presenting with an abdominopelvic mass and ascites. Very high preoperative serum AFP levels were documented, and she underwent subtotal hysterectomy, bilateral adnexectomy, and diverting colostomy. The definitive diagnosis was established by histopathological examination of the surgical specimen and immunohistochemical detection of positivity for AFP, glypican 3, cytokeratin AE1/AE3, and focal positivity for SALL4 and CK7. The patient refused adjuvant chemotherapy, and 1 year after surgery, she remains in good clinical condition with normal serum AFP levels and absence of signs of tumor recurrence.

The authors thank Dr. Marta Pulido for editing the manuscript and editorial assistance supported by Institut d’Investigació Sanitària Pere Virgili (IISPV).

Declaration of generative AI in scientific writing: the authors declined the use of artificial intelligence, language models, machine learning, or similar technologies to create content or assist with writing or editing of the manuscript. Ethical approval is not required for this study in accordance with local guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material at https://doi.org/10.1159/000542244.

The authors declare that they have no conflicts of interest.

The study is funded by the authors’ own resources.

Vanessa Maldonado and María Masvidal contributed to the design of the report and drafted the manuscript. Vanessa Morente Laguna, Jacqueline Cimerman, and Salvador Mertinez Soriano contributed to the revision of the medical history and critically revised the manuscript. All authors were involved in the care of the patient and contributed at the pathology revision.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of the research participant but are available from the corresponding author (M.M.).