The clinical diagnostic value of contrast-enhanced ultrasound in patients with ovarian yolk sac tumor: a case description

Ovarian yolk sac tumor (OYST), a rare, highly malignant ovarian germ cell tumor, accounts for approximately 10% of ovarian germ cell tumors and fewer than 2% of all ovarian malignancies. OYST has an incidence of approximately 1.8–3.4 per million people and involves significant demographic and gender disparities, predominantly affecting adolescent and reproductive-aged women. Clinically, it is characterized by rapid growth and early propensity for intra-abdominal metastasis, posing a serious threat to the fertility of young patients (1,2). Although the optimization of combined chemotherapy regimens in recent years has significantly improved the prognosis of patients with OYST, early and accurate diagnosis remains a key prerequisite for improving 5-year survival rates and formulating individualized surgical strategies. However, the imaging manifestations of OYST often overlap with those of benign and malignant lesions such as ovarian teratoma, epithelial carcinoma, and dysgerminoma, and traditional diagnostic modalities have significant limitations. Two-dimensional ultrasound only provides morphological information of the lesion and has insufficient sensitivity for the qualitative differentiation of cystic-solid lesions and difficulty in detecting microvascular abnormalities. Meanwhile, color Doppler ultrasound provides an unsatisfactory detection rate for blood flow signals in deep-seated lesions and cannot reflect microcirculatory perfusion characteristics. Moreover, although computed tomography (CT) and magnetic resonance imaging (MRI) offer high soft tissue resolution, issues such as radiation exposure, high cost, and dependence on renal function render them unsuitable for early screening or dynamic follow-up in young patients.

Contrast-enhanced ultrasound (CEUS), through the intravenous injection of microbubble contrast agents, enables real-time, dynamic tracking of the entire perfusion process of tumor microvasculature under a low mechanical index, representing a leap from morphological observation to functional assessment (3). This technique not only compensates for the insufficiency of traditional ultrasound in observing microcirculation but also avoids the potential risks of CT and MRI. It has demonstrated high sensitivity and specificity in early diagnosis, benign-malignant differentiation, and staging evaluation in fields such as hepatocellular carcinoma, small liver cancer, and breast tumors (4). Given the highly vascularized pathological characteristics of OYST, CEUS holds promise in providing crucial evidence for its differentiation from other ovarian space-occupying lesions by delineating tumor hemodynamic parameters. However, due to the low incidence of OYST, clinical evidence regarding the application of multimodal ultrasound in its diagnosis remains scarce. In this report, we describe a case of ovarian OYST confirmed by surgical pathology; systematically analyze its two-dimensional ultrasound, CEUS, and pelvic MRI features; and discuss the clinical value of multimodal ultrasound in the early diagnosis and benign-malignant differentiation of OYST in conjunction with serum tumor markers and pathological findings. It is hoped this report can provide a reference for the precise diagnosis of such rare tumors in clinical practice.

Case presentation

A 26-year-old female patient was admitted to Gansu Maternal and Child Health Hospital in May 2024 due to the discovery of a pelvic mass 1 month previously. The patient had menarche at the age of 15 years, with regular menstrual cycles of (menstrual cycle length: 28 days; menses duration: 5 days), scant menstrual flow of dark red color, accompanied by severe dysmenorrhea. Her last menstrual period was January 15, 2024. In November 2023, the patient sought medical attention for dysmenorrhea and was clinically diagnosed with uterine adenomyosis. She subsequently received leuprolide acetate injections on November 20, 2023, December 20, 2023, and January 15, 2024, which was followed by maintenance therapy with oral dienogest. In April 2024, a follow-up ultrasound at an external hospital revealed a cystic mass superior to the uterus, measuring approximately 101 mm × 100 mm × 64 mm (Figure 1). The patient experienced abdominal distension and fatigue during menstruation but received no specific treatment. In May 2024, she was admitted to our hospital for further diagnosis and treatment. The patient denied any history of other systemic diseases, surgery, trauma, or infectious diseases. The auxiliary examinations were as follows: on CEUS, the solid components and intracystic septa began enhancing in the early arterial phase (approximately 20 s postinjection), with a rise time (RT) of about 16.2 s and a time to peak (TTP) of about 30.5 s. The peak intensity of the solid component [corresponding to region of interest (ROI) 1] reached 42.59 dB, approximately 11.7% higher than the surrounding normal ovarian tissue (corresponding to ROI2, 38.12 dB). The area under the curve (AUC) was 128.3. The enhancement pattern was characterized as fast-in and fast-out, with rapid washout of the signal after peak enhancement. The cystic areas showed no contrast agent perfusion, and no contrast agent echoes were detected in the pelvic fluid (Figure 2), which suggested malignancy. MRI confirmed multiple cystic lesions in the left ovary with stromal edema and uterine posterior wall adenomyoma combined with anterior wall leiomyoma. Serum tumor marker tests on May 15, 2024 showed a significant elevation in alpha-fetoprotein (AFP) level (2,768.00 ng/mL; reference range, <7.00 ng/mL). The patient underwent exploratory laparotomy in May 2024. During surgery, a left ovarian tumor was identified, and the patient’s clinical stage was determined to be International Federation of Gynecology and Obstetrics (FIGO) stage IC2. The patient ultimately underwent surgery. The findings from postoperative pathological examination indicated left OYST. The immunohistochemical staining results were as follows: AFP(+), pan-cytokeratin(+), PLAP(+), SALL4(+), glypican-3(+), and CD30(+). The final diagnosis was left OYST (Figure 3). All procedures in this case were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Conventional ultrasound characteristics of pelvic cystic-solid masses in a patient with ovarian yolk sac tumor. (A) Conventional ultrasound revealed a complex cystic-solid pelvic mass with an irregular shape and numerous internal septa, presenting a honeycomb-like appearance—a feature indicative of a complex tumor architecture. (B) Color Doppler ultrasound revealed concentrated blood flow signals distributed along the tumor capsule and internal septa, with no flow detected in cystic regions. This finding aligned with the typical blood supply pattern of malignant tumors, in which vascularity is confined to solid components. (C) Spectral Doppler measurements yielded a SPV of 12.60 cm/s and a RI of 0.39 (<0.5), reflecting the malignant hemodynamic characteristic of low resistance and high flow. (D) Elastography exhibited a heterogeneous texture of the lesion: hyperelastic (red) areas corresponded to solid septa, while hypoelastic (blue/green) areas matched cystic/necrotic regions. The quantitative average elasticity value was 29.42 kPa, which was highly consistent with the pathological feature of tumors with dense solid components accompanied by necrosis and cystic degeneration. ED, end diastolic velocity; HR, heart rate; PI, pulsatility index; PS, peak systolic velocity; RI, resistive index; S/D, systolic/diastolic ratio; SPV, systolic peak velocity; TAMAX, time to absolute maximum.

Figure 2 CEUS findings of pelvic cystic-solid masses in a patient with ovarian yolk sac tumor. (A) CEUS revealed a cystic-solid lesion, with rapid, marked enhancement in solid septa and capsule (red circles) and no enhancement in cystic/necrotic regions (yellow circles). (B) The TIC exhibited a steep rising-peak pattern with a short RT and rapid TTP, consistent with hypervascularity and a heterogeneous cystic-solid composition. AP, arterial phase; AS, acceleration slope; AT, acceleration time; AUC, area under the curve; CEUS, contrast-enhanced ultrasound; MI, mechanical index; PKI, peak intensity; ROI, region of interest; RT, rise time; TIC, time-intensity curve; TIS, time to initial signal; TTP, time to peak; WiAUC, weighted area under the curve; WoAUC, wash-out area under the curve.

Figure 3 Gross and microscopic findings from the ovarian yolk sac tumor. (A) Surgical specimen of the yolk sac tumor. (B) Corresponding pathological section (hematoxylin and eosin staining; magnification, ×100).

Discussion

Yolk sac tumor is a malignant tumor originating from primitive germ cells, histologically exhibiting yolk sac differentiation. It is one of the most common malignant ovarian germ cell tumors in children and adolescent females. The age of onset for yolk sac tumor is concentrated in childhood and adolescence (5). Yolk sac tumor is highly malignant and, without timely intervention, progresses rapidly and entails a poor prognosis (6). The ultrasound manifestations of yolk sac tumor are classified into three types: (I) cystic type, presenting as a large cystic mass with regular morphology and clear boundaries; (II) cystic-solid mixed type, showing mixed cystic and solid echoes on two-dimensional ultrasound; and (III) solid type, presenting as a solid heterogeneous echo with clear boundaries and internally exhibiting a “cleft sign” (4). The solid type is the most common, which is consistent with the highly malignant nature of the tumor (5). Furthermore, most yolk sac tumors feature characteristic irregular, finely textured, and slightly hyperechoic solid tissue, which can aid in differential diagnosis (6). The “cleft sign” observed on ultrasound is attributed to ischemic band-like necrosis in fragile areas due to immature vascular development and a limited blood supply resulting from rapid tumor growth.

Doppler ultrasound can assess the blood flow characteristics of yolk sac tumors, providing evidence for benign-malignant differentiation (7). Color Doppler ultrasound shows abundant blood flow signals within the solid parts and septa of yolk sac tumors, and pulse Doppler reveals arterial flow with a low-to-moderate resistive index (RI) (0.21–0.63) (3). In our case, the peak systolic velocity of the yolk sac tumor was 12.6 cm/s, and the RI was 0.39, indicating low-resistance blood flow within the tumor vasculature. These characteristic Doppler ultrasound findings are consistent with the pathological feature of abundant neovascularization within yolk sac tumors. Compared with conventional ultrasound, CEUS offers significant advantages in the diagnosis of OYSTs. Conventional ultrasound primarily provides morphological information, whereas CEUS generates information related to function and blood perfusion, allowing for a more comprehensive assessment of the tumor’s vascular characteristics (8).

OYSTs exhibit characteristic enhancement patterns on CEUS (9). In a study by Chen et al., CEUS examinations in patients with yolk sac tumor showed rapid and marked enhancement of solid components and cystic septa, consistent with the rapid enhancement of solid components/tumoral septa observed in our case. Another CEUS feature of OYST is its characteristic vascular distribution pattern. Chen et al. (7) further reported that color Doppler reveals abundant blood flow in solid parts, with CEUS showing faster and more intense enhancement in yolk sac tumors as compared to benign ovarian tumors, reflecting the former’s rich blood supply. This vascular distribution aligns with the pathological features of the tumor, specifically, the abundant neovascularization and highly vascularized solid components. Anfelter et al. (10) reported that 95% of OYSTs show marked vascularization. CEUS can more clearly display the internal vascular distribution of yolk sac tumors, including vessel morphology, density, and distribution patterns, which may aid in differentiation from other ovarian tumors. Regarding contrast agent safety, studies indicate that sulfur hexafluoride microbubble contrast agents are inert, and minimal residual amounts in the body show no significant toxicity. The incidence of adverse reactions is below 1%, with cases being mostly mild allergic reactions (11). In our case, the patient undergoing CEUS received saline flush to minimize contrast residue and ensure safety and experienced no adverse reactions.

Time-intensity curve (TIC) analysis is an important quantitative assessment method in CEUS, providing objective parameters of tumor hemodynamics. For OYSTs, TIC typically exhibits a steep rising slope, high peak intensity, and relatively fast TTP, reflecting their rich blood supply and rapid perfusion characteristics (12). During dynamic CEUS observation, yolk sac lesions typically show marked enhancement in the early arterial phase, a high AUC, and rapid washout. Anfelter et al. (10) reviewed ultrasound images of 21 pure yolk sac tumor cases and found that the arterial phase featured large areas of hyperechoic filling in solid tissue, with low echo and clear boundaries in cystic areas, representing typical CEUS signs of pure yolk sac tumors. Chen et al. (7) reviewed 16 pelvic pure yolk sac cases and noted that both solid-cystic mixed and purely solid types could exhibit rapid and pronounced high enhancement signals, with earlier and stronger peak enhancement times compared to the those of the myometrium. Maxim et al. (13) observed that in 6 cases of indeterminate ovarian tumors, the RT of yolk sac lesions was significantly shorter than that of benign tumors, and the TTP was earlier, suggesting high vascularization. A synthesis of these research findings suggests that the CEUS features of OYST mainly include the following: (I) diffuse high AUC in the early arterial phase; (II) a significantly high peak intensity; (III) a relatively high AUC; (IV) rapid but incomplete washout reflecting rich intratumoral capillaries; and (V) the presence or absence of contrast perfusion in cystic cavities that can aid in tumor infiltration assessment. Although this study did not directly apply artificial intelligence (AI) technology, research indicates that AI diagnostic models based on CEUS TIC parameters (e.g., RT, TTP, and AUC) can increase the diagnostic sensitivity for ovarian malignancies to 91%, significantly improving diagnostic efficiency. Future studies could incorporate AI algorithms, in combination with features observed in this reports including differences in cystic cavity perfusion, to optimize CEUS parameter analysis for OYST, further enhancing the speed and accuracy of early diagnosis (14).

In this case, the patient underwent conventional ultrasound, CEUS, and pelvic MRI. Each method has its advantages and disadvantages: MRI offers high soft tissue resolution but is costly and time-consuming, being more suitable for supplementary evaluation of complex cases. In contrast, conventional ultrasound and CEUS offer the advantages of convenience, speed, low cost, and absence of radiation risk, making them more suitable as first-line screening and diagnostic methods for ovarian masses in women of reproductive age. This further confirms the safety of CEUS in clinical application and is particularly suitable for young patients with contraindications to radiation exposure.

Regarding differential diagnosis, it is crucial to distinguish OYST from other common malignant germ cell tumors such as ovarian dysgerminoma and immature teratoma. The key differentiating points in terms of ultrasound features, tumor markers, and hemodynamic manifestations are as follows: (I) for ovarian dysgerminoma, which predominantly affects adolescent females, an important feature is the bilateral occurrence which occurs in approximately 10–20% of cases. Conventional ultrasound typically shows a well-defined, regularly shaped, homogeneous solid mass with fine, uniform internal echoes (similar to normal ovarian parenchyma), with almost no cystic components and a lack of the characteristic “cleft sign” of yolk sac tumor (15). Color Doppler shows abundant blood flow signals within the lesion, mostly Adler grade 2–3, but the RI is generally higher and often stabilizes between 0.50 and 0.60 (whereas the RI of OYST typically falls within the 0.21–0.63 range, suggesting low resistance) (15). Tumor markers are specific: AFP level remains normal throughout, while that of beta-human chorionic gonadotropin (β-hCG) is usually not elevated (and only mildly elevated in rare cases with syncytiotrophoblastic differentiation) (15). This helps form a clear distinction from the typical significant AFP elevation seen in yolk sac tumor (the AFP value in this study was 2,768.00 ng/mL; values from the literature are often >1,000 ng/mL). CEUS typically shows homogeneous rapid enhancement with slow washout and significantly more uniform enhancement than in yolk sac tumor, does not have the characteristic lack of perfusion in cystic cavities or contrast retention in cystic cavities, and has a post-peak washout rate that is markedly lower than that of yolk sac tumor. (II) For immature teratoma, onset age is slightly younger than that of yolk sac tumor. The core ultrasound feature is mixed cystic-solid echoes, with calcifications (hyperechoic with posterior acoustic shadowing) being the decisive differentiating point (16). Cystic parts often contain fat, hair, or keratin, frequently showing typical teratoma signs such as “fat-fluid level” or “dermoid plug” signs. Solid parts consist of immature embryonic tissue with chaotic, heterogeneous echoes, lacking the fine-textured solid component and “cleft sign” of yolk sac tumor (17). Tumor markers are characterized by mild AFP elevation (often <5,000 ng/mL, which is related to the presence of small yolk sac-like differentiation components within the tumor) and are often accompanied by mild cancer antigen 125 (CA125) elevation (often <200 kU/L), differing from the significant AFP elevation and typically normal CA125 levels in yolk sac tumor (18). CEUS shows heterogeneous enhancement of solid parts, with lower enhancement intensity than that in yolk sac tumor, along with clear boundaries between enhancing areas, calcifications, and cystic regions. Calcifications and pure necrotic areas show no contrast perfusion, significantly differing from the pattern of yolk sac tumor, namely, the consistent rapid enhancement of the solid component and tumoral septa. Combining calcification features and the degree of AFP elevation allows for definitive differentiation.

AFP, as a specific tumor marker for yolk sac tumor, closely correlates with tumor burden, treatment efficacy, and recurrence risk. In clinical practice, preoperative AFP levels in patients with OYST are often significantly elevated (sensitivity >90%). Postoperatively, if AFP levels begin to decline within 1–2 weeks and normalize within 4–6 weeks, this suggests effective treatment. A slow decline or sustained elevation warrants vigilance for residual tumor or recurrence. Multimodal ultrasound is critical for postoperative follow-up: conventional ultrasound can dynamically monitor changes in lesion size, morphology, and internal echoes, while CEUS can accurately determine the nature of the residual tissue (tumor recurrence vs. postoperative fibrosis/inflammatory reaction) based on blood perfusion characteristics. For example, if a pelvic hypoechoic nodule is found on postoperative conventional ultrasound and CEUS shows characteristic OYST features (e.g., fast-in and fast-out early arterial rapid enhancement) in combination with elevated AFP level, recurrence can be diagnosed early. Meanwhile, no significant enhancement on CEUS likely indicates benign scar tissue, and awareness of this feature can reduce overtreatment. This combined follow-up model offers noninvasiveness, real-time capability, and cost-effectiveness and thus may serve as a first-line option for long-term postoperative monitoring, providing crucial support for fertility preservation and prognosis improvement in young patients.

This report describes a case of surgically and pathologically confirmed OYST and discusses the clinical diagnostic value of multimodal ultrasound. Traditional imaging is limited in its ability to diagnose OYST due to it being a rare, high-risk germ cell tumor. Meanwhile, CEUS, through the observation of characteristic blood perfusion manifestations such as fast-in and fast-out early arterial rapid enhancement combined with significantly elevated serum AFP level, can effectively differentiate OYST from similar lesions such as ovarian dysgerminoma and immature teratoma. CEUS offers the advantages of convenience, noninvasiveness, and absence of radiation, meeting the needs of young patients. When combined with conventional ultrasound, it can not only enhance the precision of early OYST diagnosis but also accurately determine the nature of residual tissue during postoperative follow-up, providing crucial support for treatment planning and fertility preservation. Overall, multimodal ultrasound is an important tool throughout the OYST diagnosis and treatment process.

Conclusions

CEUS exhibits characteristic perfusion patterns in OYST, which, when considered in combination with significantly elevated serum AFP level, facilitates early diagnosis and differentiation from other ovarian malignancies. As a noninvasive, radiation-free approach, multimodal ultrasound (conventional ultrasound + CEUS) serves as a valuable first-line screening and diagnostic tool for young, reproductive-aged patients with OYST and can reliably support postoperative follow-up and fertility preservation.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2147/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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