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Vaginal yolk sac tumors in infants and children: A case report and literature review

  • Authors:
    • Zhongli Ma
    • Canyu Li
  • View Affiliations

  • Published online on: February 8, 2023
  • Article Number: 120
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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A vaginal yolk sac tumor (YST) is a rare malignant germ cell tumor for infants and children, and it has been >50 years since the first case was reported. The treatment strategy has changed markedly in the past 50 years, from radical surgical treatment to conservative surgery combined with chemotherapy, and then to combined chemotherapy alone. The present study reports the case of a primary vaginal YST in a 13‑month‑old girl that was successfully treated by tumor resection combined with chemotherapy. The clinical symptoms, imaging features and treatment characteristics are described in detail, as well as the postoperative treatment. There was no local recurrence or metastasis for the 2 years of follow‑up to date. A literature review was also conducted to investigate the clinicopathological features, treatment and prognosis of this tumor. Overall, surgery combined with bleomycin, etoposide and carboplatin combination chemotherapy can be an effective option for vaginal YST.


A yolk sac tumor (YST), also known as an endodermal sinus tumor, is a rare and highly malignant germ cell tumor (MGCT) (1), which usually occurs in children. Most of the tumors originate from the gonads (testis and ovaries), with only 20% originating from other locations, including the mediastinum, vagina, cervix, vulva, pelvic cavity, liver, prostate and diaphragm, among others (24). In post-pubertal women, the most common location of extragonadal YSTs (EGYST) is the mediastinum (5). Primary pelvic EGYSTs are extremely rare in post-pubertal women (6). A YST was first described in rats by Teilum in 1959 (7). YST is the most observed histology for vaginal GCTs. Primary YSTs of the vagina are very rare and only constitute 3–8% of all GCTs (1,8); they have been reported to occur in young girls, typically under the age of 3 years (1,8), with a presentation of painless vagina bleeding. Assays of serum α-fetoprotein (AFP) can potentially aid in the diagnosis, monitor the effectiveness of treatment and detect recurrences (9). Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) are common inspection methods. The final diagnosis is based on pathological results (9,10). Over time, the treatment strategy has changed from radical surgical treatment to conservative surgery with adjuvant chemotherapy (11,12). Due to the rarity of the tumors, most of the literature regarding vaginal YSTs consists of case reports, and there is no published standardized clinical practice guideline for vaginal YSTs in children. The reported cases each provide a limited view of the diagnosis and treatment of the tumor. The present study reports the case of a 13-month-old girl with a vaginal YST that was treated with minimally invasive surgery and adjuvant chemotherapy, and reviews the relevant literature to outline the clinical management of diagnosis, treatment and survival.

Case report

A 13-month-old girl was referred to The Third Affiliated Hospital of Zhengzhou University (Zhengzhou, China) due to vaginal bleeding that had persisted for >20 days. The patient was born at full term with a birth weight of 3,700 g, without gestational or neonatal complications. The recorded Apgar score was 10 for both 1 and 5 min after delivery. On presentation, the patient was 80 cm tall (84% for age) and weighed 13 kg (99% for age), without a history of weight loss. The familial history was unremarkable. On physical examination, the patient's abdomen was soft and there was no hepatosplenomegaly. There were no obvious abnormalities in the appearance of the vulva. A small amount of blood was found in the vaginal orifices, and a small amount of bloody discharge and a partial tumor were visible from the vaginal opening. No more obvious abnormalities were discovered in the results. The blood routine examination, coagulation function and biochemical indicators were normal. The serum carcinoma embryonic antigen (CEA) level [chemiluminescence immunoassay; CEA assay kit; cat. no. 00937450(110761); Siemens Centaur xp] was 0.17 µg/l (normal range, 0–5 µg/l) and the carbohydrate antigen 125 (CA125) level [chemiluminescence immunoassay; CA125 assay kit; no. 01678114(128533); Siemens Centaur xp] (Siemens Healthineers) was 11.7 U/ml (normal range, 0–35 U/ml). The serum AFP level (chemiluminescence immunoassay; AFP determination kit; cat. no. 03305838(110764); Siemens Centaur xp; Siemens Healthineers) reached a markedly high value of 2,695 IU/ml (normal range, 0–6.723 IU/ml). Ultrasonography results showed a solid tumor with a diameter of ~3 cm and with high vascularity in the vagina. The vascularization of the tumor on color Doppler displayed abundant blood flow, scoring 3 according to the International Ovarian Tumor Analysis (IOTA) color score (13). The results of plain and contrast-enhanced MRI showed a heterogeneously enhanced tumor (28.8×16.5 mm) in the vagina, without vulva or bladder invasion (Fig. 1). There were no ascites in the peritoneal and pelvic cavities. No abnormality was observed in other parts of the pelvic and abdominal cavities. Imaging findings also showed no distant metastasis. Under general anesthesia, hysteroscopy results showed a tumor with a wide pedicle on the left side of the vagina (Video S1). Transvaginal resections of the tumor and 0.5 cm of the vaginal mucosa around the tumor were performed with no local tissue adhesion and little blood loss. During the operation, it was confirmed that the tumor was confined to the left vaginal mucosa and did not invade the cervix or rectum. The tumor had a dark red surface and was friable. The cross-section of the excised tumor was grayish-white and grayish-yellow (Fig. 2). Sections (4-µm thick) from 10% formalin-fixed (12 h at room temperature), paraffin-embedded blocks were cut for routine hematoxylin and eosin staining. The pathologist used a light microscope for observation (magnification, ×40 or ×15). Histopathological examination results showed numerous intracellular and extracellular periodic acid-Schiff-positive diastases and papillary elements with a Schiller-Duval body cellular structure (Fig. 3). The cells had large, vesicular nuclei and prominent nucleoli. The results of immunohistochemical staining (14) showed positive results for AFP (Fig. 4A), cytokeratin (CK; Fig. 4B), glypican-3 (Fig. S1), β-human chorionic gonadotropin (β-hCG; Fig. S2) and Sal-like protein 4 (SALL-4; Fig. S3), and negative results for of CD-30 (Fig. 4C) and organic cation/carnitine transporter 4 (OCT-4; Fig. 4D). The differential diagnosis included clear cell carcinoma, rhabdomyosarcoma and dysgerminoma. Based on the pathological and immunohistochemical findings, these diagnoses were excluded. The vaginal wall margin was negative. Preoperative imaging assessments showed no abnormalities in other sites, so the tumor was considered to originate in the vagina. As a result, the patient was diagnosed with a primary vaginal YST.

Four cycles of vincristine (1 mg/m2 from days 1 to 5), cyclophosphamide (60 mg/m2 from days 1 to 5) and actinomycin D (0.2 mg/m2 from days 1 to 5) were administered every 4 weeks from day 13 after surgery. On day 12 after surgery, the serum AFP level dropped to 106.5 IU/ml before the first cycle of chemotherapy, and then decreased to 2.70 IU/ml (within the normal range) after the second cycle of chemotherapy. The serum AFP level remained normal during the third and fourth cycles of chemotherapy. Pelvic ultrasound examination and a second-look hysteroscopic examination were performed and no positive results were found 6 months after the first surgery (Video S2). Pelvic CT and MRI scans were not suggested, as the results of the CT examination performed recently in a local hospital were negative. The surgical scar was almost invisible, with little influence on sexual and reproductive functions. The serum AFP level increased to 22.4 IU/ml within nearly 1 year of the surgery. The imaging result was negative, and no abnormal vaginal bleeding was found. Due to the COVID-19 situation in the area where the patient lived, the patient received chemotherapy treatment 4 months after the blood AFP level was found to be elevated. Combined chemotherapy was administered for the second time using a belomycin, etoposide and carboplatin (BEP) regimen, which consisted of 80 mg/m2 etoposide from days 1 to 3, 200 mg/m2 carboplatin on day 2 and 8 mg/m2 bleomycin on day 3, every 4 weeks for 4 cycles. The serum AFP level decreased to 2.04 IU/ml after the second cycle of chemotherapy (Fig. 5). The side effects of the chemotherapy were tolerable. To date, the patient has been followed up for 2 years, and the AFP is at a normal level, without any sign of recurrence. A perfect score was recorded for the Activities of Daily Living scale (15). Regular medical check-ups, including abdominal and rectal examinations, serum AFP analysis, and ultrasonography of the pelvis and abdomen, were performed as follow-up. Future follow-up examinations will occur once every 1 month for the first year, once every 2 months for the second year, once every 3 months for the third and fourth years, and then once every 6 months for the fifth year and afterwards. A complete blood analysis, and renal and liver function tests will be performed every year (16).

Literature review

In November 2022, the PubMed (, Medline ( and Embase ( databases were searched for relevant studies published since January 2000. The keywords ‘vaginal’ and ‘yolk sac tumor’ or ‘endodermal sinus tumor’ were used in the search. Studies were included if they met the following criteria: i) Referring to vaginal YST or endodermal sinus tumor; ii) concerning patients with a diagnosis of histologically confirmed YST or endodermal sinus tumor; iii) containing relevant information on clinical course, treatments, outcomes and follow-up; iv) written in English; v) containing one or multiple clinical case reports or letters; and vi) patients were <12 years old. The exclusion criteria were as follows: i) An origin outside of the vagina and extension or metastases to the vagina; ii) mixed tumors; iii) incomplete data on diagnosis, treatment or follow-up; and iv) repeated case reports (Fig. 6). Reviewers resolved all discrepancies by discussion during the study identification process. All included cases were reviewed to consider the age at the time of diagnosis, symptoms, tumor size, serum AFP level, treatment and follow-up. Table I summarizes 12 typical and representative studies on vaginal YSTs, and describes the therapeutic strategies used in the literature.

Table I.

Review of primary vaginal yolk sac tumors in 12 representative cases from the literature.

Table I.

Review of primary vaginal yolk sac tumors in 12 representative cases from the literature.

First authorYear of publicationReported cases, nAge at diagnosis, monthsAFP, ng/mlTumor size (max diameter), cmBiopsySurgeryBrachytherapyChemotherapy (no. of cycles)Follow-up result (months)(Refs.)
Neels et al2004110393246YesNoNoPEI (5)CR (36)(43)
Kumar et al200511293314NoSvNoPEB (5)CR (12)(30)
Lacy et al20061723644.7YesNoNoPEB (5)CR (21)(41)
Terenziani et al2007Case 1/26/243006/1043403.7/10Yes/YesNoNoPEB (6)/PEB (4)CR (168)/CR (35)(42)
Watanabe et al2010Case 1/212/4634247/4.45/2Yes/NoSel/StrNoPEB (3) + JEB (3)/JEB (4)CR (19)/CR (14)(24)
Tang et al2014Case 11381275NoSpvNoPEB (8)CR (27)(47)
Case 21222552No (DT)NoNoBIP (1) + IP (4)CR (57)
Case 37236504.5YesNoNoPEB (6) + VIP (6)AWR (27)
Case 47205924No (DT)NoNoJEB + A (6) + PEB (6)PR (29)
Rajagopal et al2015Cases 1/2/617/18/2380892/2139/6.7/3.3/4.8YesNoNoPEB (6/4/12)CR (60)/CR(11)
>10000a (156)/CR (300)
Case 32387680a7YesNoNoPEB (6) + JEB (6) + VAC (2)CR (240)
Case 41610580a3YesNoNoPVB (8) + PEB (3) + VAC (4)Lost to follow-up (17)
Case 532180a3YesStrYesPEB (10) + JEB (7) + VAC (2)CR (288)
Bhatt et al20151655653.7NoStrNoPEB (6)CR (24)(9)
Lightfoot et al201811413863.6YesNoNoPEB (4)CR (12)(18)
Mayhew et al2021111116365YesNoNoPEB (4)CR (12)(46)
Meng et al20221414b6002c3.9cYesNoNoPEB (6.4c)CR (98.2c)(19)
(1 case DOD)
521b12605c3.7cNoStrNoPEB (6.4c)CR (107c)
(1 case local relapse after 6 months)
11321003.4YesNoNoPV (4) + PVB (8)CR (95)
Yin et al20221311b78403.6cYesNoNoPEB (4.5)CR (94c)(12)
(1 case DOD)
Cases 1/2/820/44/1015100/646/87543.7cYesNoNoPEB (3.7c) + PEV (2.3c) + VAC (1)CR (281)/CR (278)/CR (96)
Cases 13/209/3219766/331476/9YesNoNoPEB (5) + PE (1)/CEB (6) + PEV (2) + PEB (2)CR (69)/CR (10)
Cases 18/19/2136/15/10 54000/1000/69777/5/4NoStvrNoPEB (10)/NVEB (1) + PEB (2)/VPEB(2) + CEB (1) + PEB (2)CR (122)/CR (62)/CR (51)

a IU/ml;

b mean;

c average; C, chemotherapy; AFP, α-fetoprotein; Stvr, transabdominal vaginal lesion resection; Sv, vaginohysterectomy; B, brachytherapy; Str, tumor resection; Spv, partial vaginectomy; Sel, exploratory laparotomy; DT, discharged tumor fragment; CR, complete remission; PR, partial response; AWR, alive with relapse; DOD, died of disease; PEB, cisplatin, etoposide and bleomycin; PEV, cisplatin, etoposide and vincristine; VAC, vincristine, dactinomycin and cyclophosphamide; PE, cisplatin and etoposide; NVEB, nedaplatin, vindesine, etoposide and bleomycin; CEB, carboplatin, etoposide and bleomycin; VPEB, vincristine, cisplatin, etoposide and bleomycin; VI, vincristine, irinotecan; IE, ifosfamide, etoposide; VDC, vincristine, adriamycin, cyclophosphamide; PEI, cisplatin, etoposide and ifosfamide; JEB+A, carboplatin, etoposide, bleomycin and tetrahydropyranyl Adriamycin.


MGCTs account for 3% of all childhood malignant tumors (17). Vaginal MGCTs can cause vaginal bleeding. YSTs originating in the vagina account for 3–8% of all reported GCT cases, and patients in most GCT cases are under the age of 3 years (1,8). Rhabdomyosarcoma (RMS) is considered the most common pathological type of vaginal tumor in prepubertal females, followed by YST (18). However, Meng et al (19) found that YST may be the most common pathological type of vaginal tumor in Chinese children, followed by RMS. Vaginal YST should be considered for a young girl with vaginal bleeding. Any vaginal bleeding in children >10 days should be considered abnormal, and further investigation is necessary to eliminate vaginal malignant tumors in prepubertal females (20).

The clinical presentation of vaginal YST includes vaginal bleeding, blood-tinged vaginal discharge or a friable mass. A rectal examination helps to assess the extent of the tumor and rule out the possibility of invasion. Ultrasonography is usually used as the first choice for diagnosis and follow-up. CT and MRI are non-invasive methods for estimating the primary site, extravaginal invasion and possible distant metastasis (10,21). According to previous studies, vaginal YST is uniformly isointense on T1-weighted imaging (T1WI), heterogeneously hyperintense on T2WI and heterogeneously enhanced after administrating contrast agents, which is different from vaginal RMS. Diffusion-weighted MRI may also be useful for differentiating vaginal YST and RMS (10). Serum AFP is a sensitive and reliable YST marker and plays an important role in evaluating the treatment efficacy, remission status or disease progression (22). It is useful to examine the lectin affinity fractionation of AFP, which can improve the specificity and sensitivity of the final diagnosis (23). However, not all vaginal YSTs are AFP-positive (24). A biopsy or complete pathological examination of the tumor and an elevated serum AFP level confirm the final diagnosis (18). Pathological examination typically shows a loose reticular pattern of cells. Papillary structures with a vascular core lined by a single layer of cells (Schiller-Duval bodies) may be seen in yolk sac tumors from any site and are pathognomonic when present (17). Further histological patterns have been proposed by some studies (8,25), including festoon, reticular, solid and polyvesicular. Most tumors exhibit more than one of these patterns. Immunohistochemically, CK AE1/AE3, CD117, AFP, glypican-3, SALL-4, OCT-4, CD30 and β-hCG are usually assessed to provide an accurate diagnosis. YSTs are characterized by the positive expression of AFP (variable, focal), glypican-3 (patchy), CK AE1/AE3, SALL4 and LIN28, and the lack of expression of OCT-4, CD-30 and phospholipase A-2-activating protein, and have variability in the expression of CK7, CK20 and β-hCG (2).

Due to the rarity of such tumors, there are no clinical practice guidelines, expert consensus or standard treatment principles or protocols for treating vaginal YSTs. Before 1965, radical surgery and radiotherapy were the main methods to treat vaginal YSTs (26). Radical surgery guaranteed complete tumor removal, but the prognosis was very poor with a survival rate of 56.3% (27). Meanwhile, the sexual and reproductive functions of patients were severely damaged, and even the functions of the bladder and rectum were adversely affected (2830). Therefore, treatment effects on sexual and reproductive functions should be considered in the long-term treatment process, especially when deciding the scope of surgical resection.

Improvements to surgery and the application of adjuvant chemotherapy have since allowed young patients to receive relatively conservative surgical regimens that can preserve their reproductive and sexual functions (31,32). Moreover, diversified treatment options contribute to a higher cure rate (32). Numerous published reports on a combination of chemotherapy and less invasive surgery have confirmed the usefulness of this combined method (24,33,34), including the report by Mauz-Korholz et al (35) about nationwide multicenter clinical trials in Germany. Therefore, it is necessary and valuable to perform early surgical resection of vaginal YSTs for patients, without tumor residue or organ invasion or metastasis. Complete resection of the tumor can provide a complete tissue specimen for pathological examination to rule out mixed germ cell tumors, which is critical to treatment plans. However, this regimen should still be carefully evaluated, as there are risks and complications associated with any type of surgery. Furthermore, it is not clear whether the best time to operate is before or after chemotherapy. After reviewing treatment options published over the past 20 years, it was found that conservative treatment is showing a growing trend (2,11,18,19,36,37). A number of studies tended to adopt a biopsy combined with chemotherapy or chemotherapy combined with conservative surgery (38,39). Local tumor resection followed by chemotherapy can also be an effective option (9,39,40).

For infants and young children with vaginal YSTs, chemotherapy alone can also eliminate tumor tissue and restore serum AFP to a normal level according to some reports (9,18,19,36,41,42), which may avoid damaging vaginal or pelvic structures. Neels et al (43) suggested that vaginal YST with distant metastases and good response to chemotherapy could be cured with intensive chemotherapy without surgery after their study. By analyzing the reported cases, Bhatt et al (9) found that the efficacy of platinum chemotherapy alone was equivalent to that of surgery combined with platinum chemotherapy, and the recurrence rates of the two methods were 14 and 13%, respectively. Cisplatin-based multiagent chemotherapy has been playing an important role in improving outcomes in children with malignant GCTs since the 1970s (26). The most frequently used chemotherapeutic drugs nowadays include etoposide, cisplatin, cyclophosphamide and bleomycin. Despite their effectiveness for inhibiting tumor growth, they have some significant and long-term toxic effects, such as hearing impairment, secondary malignancy, pulmonary fibrosis and infertility in and after the whole course of treatment. The longest period of follow-up for a patient receiving chemotherapy was 25 years, and the patient had two spontaneous vaginal deliveries (11). However, it is hard to fully assess the long-term consequences of these toxic effects, as such a case is still in the minority. The PEB chemotherapy regimen is currently considered to be the most effective regimen with minimal side effects (19,44). Yuan et al (15) suggested that PEB chemotherapy should be adopted for patients who experienced early stage disease and received non-surgical treatment. Based on the summary and analysis of 12 patients with vaginal YST, Han et al (45) suggested that standardized PEB chemotherapy could be used for patients diagnosed with vaginal YSTs by pathology before surgery. The study found that most patients could achieve complete responses with a good prognosis after chemotherapy. According to existing reports, all the patients receiving chemotherapy alone have been treated with over 4 cycles of chemotherapy (18,19,36,44,46). However, due to the scarcity of case reports and serial reports, there is limited evidence of the effectiveness of chemotherapy alone and a lack of critical information on the dosage and duration of chemotherapy used for patients.

In the present case, based on the systemic preoperative evaluation and hysteroscopy, the tumor was considered to be localized at the vaginal wall. Therefore, a complete tumor resection was performed without affecting the vaginal structure, instead of just a biopsy. This procedure was advisable according to the treatment plan published by the Children's Oncology Group (18,19). Moreover, since mixed germ cell tumors could not be ruled out, a complete resection would help to give a more accurate diagnosis, which is important as the subsequent treatment may vary based on the final pathological results. Mixed component YSTs may exhibit recurrence even after effective chemotherapy (19). Tang et al (47) indicated that chemotherapy alone was more suitable for simple YSTs and that chemotherapy combined with local surgery should be used for tumors with mixed components.

In conclusion, more attention should be paid to vaginal bleeding in infants, and a complete evaluation is essential. Imaging findings from ultrasonography or MRI benefit the diagnosis. The final diagnosis is determined by histological examination and AFP levels, which are also helpful during follow-up. Prospective studies on a larger scale are needed to determine the long-term effectiveness and safety of chemotherapy alone among patients with vaginal YSTs. Thus far, conservative surgery combined with adjuvant chemotherapy has been considered effective, and it may be less toxic than chemotherapy alone potentially in the long term due to the lower number of chemotherapy cycles.

Supplementary Material

Supporting Data
Supporting Data
Supporting Data


Not applicable.


Funding: No funding was received.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

ZM contributed to the study conception, reviewed the literature and drafted the manuscript. CL collected medical images (MRI scans and pathological section scans) and analyzed patient-related data. Both authors read and approved the final manuscript. ZM and CL confirm the authenticity of all the raw data.

Ethics approval and consent to participate

This case report has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Zhengzhou, China; approval no. 2023-031-01).

Patient's consent to publication

The patient's family provided oral consent for the publication of the article. The Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Zhengzhou, China) approved that the oral consent was sufficient for this case report.

Competing interests

The authors declare that they have no competing interests.



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Ma Z and Ma Z: Vaginal yolk sac tumors in infants and children: A case report and literature review. Oncol Lett 25: 120, 2023
Ma, Z., & Ma, Z. (2023). Vaginal yolk sac tumors in infants and children: A case report and literature review. Oncology Letters, 25, 120.
Ma, Z., Li, C."Vaginal yolk sac tumors in infants and children: A case report and literature review". Oncology Letters 25.3 (2023): 120.
Ma, Z., Li, C."Vaginal yolk sac tumors in infants and children: A case report and literature review". Oncology Letters 25, no. 3 (2023): 120.