Comparative Ultrasonographic Evaluation of Morphology and Vascularization in Endometriomas and Ovarian Mature Cystic Teratomas

This retrospective study included patients who underwent surgical treatment for benign adnexal masses at the Obstetrics and Gynecology Clinic Narodni Front from 1 January 2020 to 1 January 2022. Ethical review and approval were waived for this study by the ethics committee due to its retrospective design, which involved the analysis of anonymized pre-existing clinical data obtained as part of standard diagnostic care. This waiver is in accordance with national regulations and the institution’s policy on retrospective studies. Surgical intervention was indicated based on the following factors: the size of the adnexal mass (an institutional threshold for surgery in asymptomatic patients), persistent pelvic pain attributable to the mass, or an inconclusive sonographic examination where the features were ambiguous and did not allow for a definitive diagnosis of a classic benign lesion. The inclusion criteria for the study were as follows: (1) preoperative transvaginal ultrasonography performed at our clinic, and (2) a confirmed histopathological diagnosis of either ovarian endometrioma or mature cystic teratoma. The exclusion criteria were as follows: (1) insufficient ultrasound image quality for retrospective analysis, (2) pregnancy at the time of the scan, (3) a final histological diagnosis other than endometrioma or MCT, or (4) medical treatment (e.g., hormonal therapy) in the 3 months preceding the ultrasound. All TVUS examinations were performed by experienced gynecologists using a Voluson E10 system (GE Healthcare, Boston, MA, USA) with a high-resolution intracavitary probe (RIC5-9-D, 5–9 MHz). For this study, stored ultrasound images and cine loops were retrospectively and independently analyzed by two experienced sonographers (E.Đ. and A.J.). To minimize assessment bias, the reviewers were blinded to the patients’ final histological diagnosis and clinical symptoms during the offline analysis. The sonographic features of all masses were described according to the terminology and definitions established by the International Ovarian Tumor Analysis (IOTA) group [ 5 ]. Two types of features were analyzed: 1. Morphological Parameters: The morphological assessment included the largest tumor diameter, volume (calculated using the prolate ellipsoid formula: length × height × width × 0.523), laterality, capsule thickness, and internal echogenicity (categorized as anechoic, homogeneous low-level “ground-glass”, hyperechoic, or mixed/heterogeneous). The presence of septa, papillary projections, solid components, acoustic shadowing, free fluid in the pouch of Douglas, and signs of tumor fixation were also recorded. 2. Hemodynamic Parameters: Assessed using color and pulsed Doppler techniques. The location of blood flow (pericystic, intracystic, in septa) was noted. The peak systolic velocity (Vmax), end-diastolic velocity (Vmin), and Resistance Index (RI) were measured from spectral Doppler waveforms. Measurements were also taken from the ipsilateral uterine artery to obtain its Resistance Index (AURI). Morphological Parameters: The morphological assessment included the largest tumor diameter, volume (calculated using the prolate ellipsoid formula: length × height × width × 0.523), laterality, capsule thickness, and internal echogenicity (categorized as anechoic, homogeneous low-level “ground-glass”, hyperechoic, or mixed/heterogeneous). The presence of septa, papillary projections, solid components, acoustic shadowing, free fluid in the pouch of Douglas, and signs of tumor fixation were also recorded. Hemodynamic Parameters: Assessed using color and pulsed Doppler techniques. The location of blood flow (pericystic, intracystic, in septa) was noted. The peak systolic velocity (Vmax), end-diastolic velocity (Vmin), and Resistance Index (RI) were measured from spectral Doppler waveforms. Measurements were also taken from the ipsilateral uterine artery to obtain its Resistance Index (AURI). The definitive diagnosis was established by histopathological examination of the surgical specimens, which served as the gold standard. Descriptive statistics were reported as mean values accompanied by standard deviations (SDs) for numerical variables, or as absolute counts with percentages for categorical variables. The distinctions between the two groups were presented as mean differences accompanied by 95% confidence intervals and analyzed using Student’s t -test for numerical data and chi-squared tests for categorical data. In all assessments, a p -value of less than 0.05 indicated statistical significance. Statistical analysis was conducted using IBM SPSS statistical software (SPSS for Windows, release 25.0, SPSS, Chicago, IL, USA).

Adnexal masses are a common clinical finding in routine gynecological practice, with prevalence and incidence rates demonstrating significant variation by age and reproductive status. In the general premenopausal female population, these masses are frequently encountered, with an estimated 6–8% of women affected [ 1 ]. The incidence among women of reproductive age rises dramatically from childhood, increasing from a minimal rate in young girls to a peak of approximately 152 per 100,000 women by the age of 35 [ 2 ]. Moreover, they are identified in up to 8.8% of pregnancies [ 3 ]. There is also a substantial lifetime surgical burden, as up to 10% of all women will undergo surgery for an adnexal mass [ 4 ]. Further factors associated with the prevalence of adnexal masses include the characteristics of the masses and the presence of symptoms associated with these masses. Transvaginal ultrasonography (TVUS) is the preferred imaging modality for assessing adnexal masses in size and complexity [ 4 ]. Many investigations have attempted to identify ultrasonographic characteristics that enhance diagnostic precision and guide surgical choices regarding malignancy risk. This effort has led to the development of highly accurate evidence-based risk stratification systems, such as the International Ovarian Tumor Analysis (IOTA) group’s Simple Rules, the ADNEX model, and the Ovarian-Adnexal Reporting and Data System (O-RADS) [ 5 , 6 ]. These models demonstrate impressive accuracy in preoperative differentiation between benign and malignant adnexal masses [ 5 , 6 ], but they are not specifically designed to discriminate between different types of benign tumors. Consequently, there has been a notable lack of focus on comparative studies concerning benign adnexal tumors. In most clinical situations, the combination of IOTA-based models and expert pattern recognition provides sufficient diagnostic accuracy. Endometriomas, for example, are typically recognized as unilocular cysts with ground-glass echogenicity and without solid components, while mature cystic teratomas (dermoid cysts) are usually identified by the presence of Rokitansky nodules, echogenic sebaceous material, or hair–fluid levels [ 7 , 8 , 9 ]. However, clinical practice also frequently presents cases in which the distinction between these two common benign tumors is not straightforward. Endometriomas may sometimes appear multilocular, heterogeneous, or with solid-appearing papillary structures, whereas dermoid cysts may lack their classical echogenic features or mimic hemorrhagic corpus luteum cysts [ 10 , 11 ]. Such atypical presentations are not uncommon and can cause diagnostic difficulties, especially among less experienced sonographers. Importantly, existing IOTA and O-RADS frameworks are not specifically designed to address differentiation between benign subtypes, but rather to stratify the risk of malignancy. This leaves a gap in standardized guidance for cases where the main diagnostic challenge lies between two benign entities. On the other hand, knowledge of the role of vascularization in the ultrasonographic assessment of benign adnexal tumors remains limited. Vascular indices, such as the Resistance Index (RI) or the uterine artery Resistance Index (AURI), have been evaluated in attempts to differentiate malignant from benign masses. The role of these indices in distinguishing between different benign subtypes remains limited [ 12 , 13 ]. Hemodynamic parameters could potentially reflect different biological behaviors and features of endometriomas and dermoids, resulting in different Doppler patterns. While these indices are not included in the existing malignancy prediction models, exploring them in benign scenarios might provide additional insights and may be especially beneficial in atypical cases, where morphology alone is unreliable. Therefore, the primary aim of this study was to perform a direct, detailed comparison of the morphological and, more importantly, hemodynamic characteristics of ovarian endometriomas and mature cystic teratomas, as assessed by TVUS. We sought to determine whether Doppler parameters, specifically RI and AURI, could provide objective criteria to supplement morphological assessment and improve diagnostic confidence in differentiating these two common benign conditions.

This study included a total of 93 patients. Based on histopathological examination, 47 patients were diagnosed with endometriomas, and 47 patients were diagnosed with MCTs. One patient was diagnosed with both tumors synchronously. The demographic and reproductive characteristics of the patients are presented in Table 1 . There were no significant differences in age between the two groups (37.8 ± 10.2 vs. 38.4 ± 13.3 years, p = 0.8). However, the teratoma group had a significantly higher parity rate (median 1 vs. 0, p = 0.02). The cohort included 16 postmenopausal women (12.8% of the endometrioma group and 23.4% of the teratoma group, p = 0.2). There were no significant differences between the groups in tumor size, volume, capsule thickness, septal thickness, the presence of free fluid, or tumor fixation ( Table 2 ). There was a significant difference in tumor laterality, with endometriomas being more frequently bilateral than teratomas (17.0% vs. 4.3%, p = 0.042). There were significant differences in the ultrasonographic morphological appearance between the two groups classified according to the IOTA terminology ( p < 0.001, Table 3 ). MCTs most frequently presented as multilocular solid cysts (51.0%) or unilocular solid cysts with hyperechoic content (20.4%). On the other hand, the majority of endometriomas were classified as unilocular cysts with ground-glass echogenicity (45.5%). Other morphological types were observed less frequently in both groups. The most common morphological types of endometriomas and ovarian teratomas are presented in Figure 1 and Figure 2 , respectively. The overall vascularization pattern did not differ significantly between the groups. The total number of blood vessels was slightly higher in endometriomas (n = 168) compared to MCTs (n = 149), but the mean number of blood vessels was comparable (3.03 ± 1.67 vs. 3.00 ± 2.30, p = 0.5). The most frequent localization of blood vessels in both groups was pericystic, followed by vessels in septa, solid regions, or multiple locations, with no statistically significant differences ( p = 0.5). Vascularization patterns, along with blood vessel features, are presented in Table 4 . Examples of blood vessel localizations are presented in Figure 3 . A significant difference was identified in the Resistance Index (RI) and AURI of the impacted side, with endometriomas presenting elevated RI values (0.57 vs. 0.54, p = 0.04) and reduced AURI (0.81 vs. 0.83, p = 0.02) when compared with teratomas. Additional Doppler parameters, such as Vmax, Vmin, and vascular asymmetry indices (ΔAURI and ΔVmaxAU), exhibited no significant differences between the two groups ( Table 5 ).

The results of our study revealed significant differences in both morphological and hemodynamic characteristics between endometriomas and MCTs. Morphologically, endometriomas more frequently appeared as unilocular cysts with homogeneous low-level echogenicity, while MCTs typically manifested as cystic lesions with solid components or heterogeneous echogenicity. More importantly, our Doppler analysis further identified hemodynamic differences: a significant difference was observed in the RI and AURI of the impacted side, with endometriomas presenting elevated RI values (0.57 vs. 0.54, p = 0.04) and reduced AURI (0.81 vs. 0.83, p = 0.02) compared to MCTs. Additional Doppler parameters showed no significant differences between the two groups. Our findings strongly support the established sonographic patterns associated with endometriomas and MCTs. MCTs typically present with distinctive ultrasonographic characteristics, often including “dots and/or lines” and an “echogenic white ball” [ 14 , 15 ]. Conversely, an endometrioma is generally unilocular, with low-level “ground-glass” echogenicity [ 7 ]. Although endometriotic implants may show cyclical changes, ovarian endometriomas typically retain a stable sonographic appearance throughout the menstrual cycle. This stability is useful in clinical differentiation from hemorrhagic corpus luteum cysts, which may undergo rapid morphological changes over short intervals [ 16 ]. The vascularization of adnexal masses represents a cornerstone of sonographic assessment, primarily utilized in established models like the IOTA Simple Rules to stratify malignancy risk by distinguishing avascular (Score 1) from highly vascularized lesions (Score 4) [ 5 , 17 ]. This paradigm is grounded in the understanding that malignant tumors provoke intense neovascularization to facilitate their rapid growth. This leads to the formation of vessels that are both structurally and functionally compromised, as shown by high density yet low impedance. This is evident sonographically as low RI values [ 18 , 19 , 20 , 21 ]. Our study confirms that both endometriomas and MCTs align with benign vascular patterns, exhibiting primarily pericystic vascularization without the marked neovascularization characteristic of malignancies. Our findings demonstrate that within the benign spectrum, there are notable and mechanistically informative hemodynamic differences. The higher intratumoral RI in endometriomas presents a vascular paradox. While endometriosis is a state of heightened angiogenic activity, it results in chaotic and dysfunctional vasculature. Endometriotic lesions are characterized by estrogen-dependent angiogenesis and a profound inflammatory microenvironment, marked by elevated TNF-α and interleukins, which promote persistent endothelial cell activation and neovascularization [ 22 ]. Crucially, ovarian endometriomas exhibit elevated HIF-1α levels compared to normal endometrium. Chronic bleeding, iron deposition, and subsequent tissue hypoxia drive sustained overexpression of VEGF and lead to pathological angiogenesis [ 23 , 24 ]. However, the process results in immature vessels with incomplete pericyte coverage and significant surrounding fibrosis. This disorganization leads to an increase in vascular impedance and a decrease in diastolic flow, which are sonographically represented by the elevated RI that we noted. Conversely, the lower RI in teratomas reflects a different, more organized vascularization pattern, which could be a result of their developmental origin. Since MCTs are formed by tissues from three germ layers [ 25 ], their heterogeneous but well-differentiated components (neural, adipose, and epithelial) create different microenvironments that promote developmental angiogenesis. This process typically results in more organized vascular networks that reflect the developmental origin of the heterogeneous tissue components [ 26 ]. These characteristics lead to lower resistance to blood flow and the lower RI values that we recorded. The reduced AURI on the side affected by endometriomas indicates a more extensive pelvic hemodynamic influence, potentially representing compensatory vasodilation induced by the inflammatory cascade associated with endometriosis [ 27 , 28 , 29 ]. This indicates a widespread hemodynamic adaptation that is absent in the isolated, non-inflammatory teratomas. While RI and AURI are not incorporated into current IOTA or O-RADS models, which are exclusively focused on malignancy risk stratification, our results suggest that these quantitative Doppler parameters could have significant potential for refining the differentiation between common benign tumors. The combination of a higher intratumoral RI and a lower ipsilateral AURI could form a distinctive “hemodynamic signature” more suggestive of an endometrioma. In practical settings, especially those with restricted access to expert sonography or advanced modeling, this objective hemodynamic assessment could enhance morphological evaluation and facilitate more informed decision-making in clinically ambiguous cases. Moreover, RI and AURI values offer standardized, numerical metrics that minimize dependence on subjective interpretation, ensuring consistent reproducibility across various operators and clinical settings. Objective measurements enhance communication among healthcare providers and promote more consistent reporting. Understanding the various morphological characteristics and vascularization patterns can benefit gynecologists in their everyday clinical work. Furthermore, our findings could have implications for educational applications. They provide a systematic framework for experienced clinicians to instruct inexperienced medical professionals in identifying distinctive sonographic patterns of common benign adnexal tumors. This pattern-based interpretative approach may increase diagnostic confidence in both training and routine practice. On the other hand, this study has several limitations. First of all, the retrospective, single-center design presents an inherent risk of selection bias, as it exclusively included patients who underwent surgical intervention, likely reflecting a group with more symptomatic or complex masses. The small sample size of postmenopausal women (n = 16) in our cohort prevented a robust statistical analysis regarding the possible confounding influence of menopausal status on our Doppler parameters. This is an important factor to consider, as the sonographic features of an atypical appearance of adnexal mass in postmenopausal women require careful evaluation due to the significant risk of malignancy linked to these lesions in this population [ 30 ]. While the analysis was conducted by skilled sonographers, the lack of formal assessment for inter-observer agreement regarding morphological classification presents a notable methodological limitation. Additionally, we were unable to record tumor marker values (e.g., CA-125) for every patient. The incorporation of this data would have offered significant correlative insights and enriched the clinical context surrounding our ultrasonographic findings. Additional potential confounding factors, including the phase of the menstrual cycle, were not examined and require consideration in future research.

The results of our study not only confirm IOTA recognition patterns as the gold standard in the differentiation between endometriomas and mature cystic teratomas but also indicate a significant difference in the vascular pattern between these two benign adnexal masses. Elevated RI within the tumor, with significantly lower AURI on the ipsilateral side in endometriomas, may indicate a different hemodynamic signature between the two tumor types: a more chaotic vascular network fueled by complex inflammatory processes and a more stable and scarce vascularization of the teratoma, most likely as a consequence of a specific embryonic origin. While current risk stratification models focus solely on malignancy, these objective Doppler parameters have a promising potential as a valuable addition to B-mode ultrasound. By providing reproducible numerical data, they might strengthen diagnostic confidence in ambiguous cases and improve differential diagnosis, ultimately facilitating more accurate clinical decision-making. However, for the validation of these results and investigation in order to incorporate specific Doppler parameters into existing predictive models, and to determine how exactly a different vascular pattern would help in differentiating between these two types of benign adnexal tumors, it is necessary to conduct larger, multicenter studies with experienced ultrasonographic experts.