Xuechao Ji
Zian Zheng3
Guoliang Li
Xiangyu Liu- 1Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- 2Department of Gynecology, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, China
- 3Department of Medical Administration, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- 4Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Background: Approximately 95% of ovarian teratomas are classified as benign, with only about 5% being malignant. Nevertheless, no research has previously explored the connection between primary tumor laterality and prognostic outcomes among malignant ovarian teratoma (MOT) patients. Our aim was to investigate the association of primary tumor laterality with prognosis in MOT.
Methods: This retrospective study enrolled patients with MOT from The Affiliated Hospital of Qingdao University from January 2012 to December 2021. The primary outcome was progression-free survival (PFS) and overall survival (OS). The prognostic difference between left-sided, right-sided and bilateral groups was investigated using Kaplan-Meier analyses and Cox proportional hazards regression analyses.
Results: A total of 51 eligible patients with MOT were included with a median age of 52 years. Among the patients with MOT, the multivariate Cox regression analyses showed that right-sided (hazard ratio [HR]=0.01; 95% confidence interval [CI]=0.00-0.04; P = 0.01) MOT was associated with better PFS, compared with left-sided MOT (HR = 1.00). Kaplan-Meier analyses also showed that the primary tumor laterality had a significant prognostic effect in MOT.
Conclusion: Among patients with MOT, those with unilateral tumors, particularly right-sided ones, had a significantly better prognosis than those with bilateral tumors. Gynecologic oncologists might account for the prognostic impact of primary tumor laterality in MOT and tailor treatment and surveillance accordingly.
1 Background
Ovarian teratomas originate from the primitive germ cells found in the embryonic ovary. This type of tumor represents the most prevalent category of ovarian germ cell tumors, accounting for 36% to 69% of cases (1, 2). Approximately 95% of ovarian teratomas are classified as benign, with only about 5% being malignant (3). Mature cystic teratomas are the most common type of ovarian tumor in individuals of reproductive age, comprising tissues derived from the ectoderm, mesoderm, and endoderm (4). Although malignant ovarian teratomas (MOT) are infrequent in clinical settings, their incidence ranges from 0.2 to 0.5 per 100,000 (5). The clinical signs of MOT are often indistinguishable from those of benign teratomas (6, 7). Only a limited number of MOT cases can be identified prior to surgery, creating challenges for gynecologists and oncologists in determining the appropriate treatment approach.
MOT contains immature teratomas (IT) as well as malignant transformation of mature cystic teratomas (MT-MCT) (6, 8). Nevertheless, no research has previously explored the connection between primary tumor laterality and prognostic outcomes among MOT patients. As such, further studies are warranted to examine how the primary tumor laterality influences the prognosis of MOT, to advance the development of personalized treatment approaches.
In this retrospective analysis, we examined MOT patients over a decade to explore the relationship between the primary tumor site and patient prognosis, both within the overall MOT population and when classified by histopathological subtypes.
2 Methods
2.1 Study population
In this retrospective study, patients with MOT were enrolled from The Affiliated Hospital of Qingdao University from January 2012 to December 2021. Patients with any of the following characteristics were excluded: 1) not diagnosed by the histopathological pathology; 2) with overlapping primary tumor sites or missing data on the primary tumor site; 3) with missing data on follow-up time or survival status. All patients provided written informed consent under the approval of the ethics committee of The Affiliated Hospital of Qingdao University (QYFY WZLL28449). All ethical standards, including ethics committee approval and the informed consent process, adhered to international guidelines.
2.2 Data collection
Part of the data collection process is similar to that of an article previously published (9). Clinical data for MOT cases were retrospectively obtained from the institutional Hospital Information System (HIS) system. Cases demonstrating IT or MT-MCT on histopathological review underwent expanded data collection, including patients’ information, clinical presentation, pathological characteristics, surgical outcomes, adjuvant therapies and survival outcomes. All histological specimens underwent blinded dual review by board-certified gynecologic pathologists, with concordance assessment through hematoxylin-eosin (HE) staining and immunohistochemistry for all included patients. A third reviewer participated in discussions to resolve any discrepancies. The standard tumor stage was defined by the International Federation of Gynecology and Obstetrics (FIGO) staging system in 2014. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Progression-free survival (PFS) was defined as the time between the date of the first diagnosis and the date of ovarian cancer progression. Overall survival (OS) was defined as the time between the date of the first diagnosis and the date of death.
2.3 Statistical analysis
The groups’ baseline characteristics were compared using Chi-squared tests. To estimate survival curves for PFS and overall survival OS, Kaplan–Meier analysis was employed, and differences were evaluated using the log-rank test. Both univariate and multivariate Cox proportional hazards regression analyses were used to discern independent prognostic factors. Significant variables identified in the univariate analysis were incorporated into the multivariate analysis. The findings are expressed as hazard ratios (HRs) accompanied by 95% confidence intervals (CIs). Analyses were also conducted based on histopathological subtypes. All statistical evaluations were carried out with SPSS (version 28.0), and a two-sided P-value of less than 0.05 was deemed statistically significant.
3 Results
A total of 53 women were diagnosed as MOT between 2012–2021 at The Affiliated Hospital of Qingdao University. Two patients were excluded because of missing data on follow-up time or survival status (Figure 1). Patient characteristics are summarized in Table 1. Thirty-two women were diagnosed with MT-MCT and nineteen were diagnosed with IT. The tumors in 19 women were located in the left ovary, 20 in the right ovary. The tumors of twelve women involved both ovaries. Patients’ age ranged from 10 to 78. The mean age of IT patients was 26, and the mean age of MT-MCT patients was 60. The median age of the total patients was 52 years. The mean diameter of all the tumors is 15 cm. MT-MCT predominated in bilateral cases (75.0%), while IT was more common in left-sided tumors (47.4%). Patients aged ≥52 years constituted 54.9% overall but were particularly prevalent in right-sided (55.0%) and bilateral tumors (75.0%); younger patients (<52 years) were more frequent in left-sided tumors (57.9%). Larger tumors (≥15 cm) were more common in left-sided (57.9%), while smaller tumors (<15 cm) predominated right-sided cases (70.0%). Bilateral tumors showed aggressive features: 75.0% were poorly differentiated (G3) and presented as FIGO Stage III. Abdominal pain/bloating was the most frequent symptom overall (56.9%) and universal in bilateral cases; 27.5% were asymptomatic, primarily right-sided tumors (45.0%). Fertility-sparing surgery was performed more often in left-sided tumors (68.4%). Normal serum AFP (≤20 ng/ml) was observed in 66.7% of patients overall, with elevated levels (>20 ng/ml) in 19.6%.
Figure 1. Flowchart of the study. MOT, malignant ovarian teratoma; MT-MCT, malignant transformation of mature ovarian teratoma; IT, immature teratoma.
Table 1. Baseline characteristics of patients with MOT according to primary tumor laterality.
With a median overall survival of 66.5 months, the 5-year OS rates in left, right-sided and bilateral groups were 84.2%, 85.0%, and 25%, respectively. The median PFS was 52 months. In the Kaplan-Meier analysis, OS was significantly poorer in the bilateral MOT group compared with the left-sided MOT group (P = 0.005) and the right-sided MOT group (P = 0.002). No significant difference in OS was observed between the left-sided and right-sided groups (P = 0.954) (Figure 2A). For PFS, the bilateral MOT group also showed significantly worse outcomes than both the left-sided MOT group (P < 0.001) and the right-sided MOT group (P < 0.001) (Figure 2B). However, among patients diagnosed with IT, no significant difference in OS was found between these three groups (Figure 3A). Notably, both the right-sided group (P = 0.003) and the left-sided group demonstrated significantly improved PFS (Figure 3B). In the MT-MCT group, no significant differences in OS or PFS were observed between the left-sided and right-sided groups. Bilateral MT-MCT patients had worse PFS and OS than left and right-sided groups patients (Figures 4A, B).
Figure 2. Kaplan-Meier analysis of OS and PFS in total MOT patients. OS curves in total patients (A), PFS curves in total patients (B). PFS, progression-free survival; IT, immature teratoma; MOT, malignant ovarian teratoma.
Figure 3. Kaplan-Meier analysis of OS and PFS in IT patients. OS curves in IT patients (A), PFS curves in IT patients (B). OS, overall survival; PFS, progression-free survival; IT, immature teratoma.
Figure 4. Kaplan-Meier analysis of OS and PFS in MT-MCT patients. OS curves in MT-MCT patients (A), PFS curves in MT-MCT patients (B). OS, overall survival; PFS, progression-free survival; MT-MCT, malignant transformation of mature ovarian teratoma.
The univariate and multivariate Cox regression analyses showed that right-sided tumors (HR = 0.01; 95% CI, 0.01-0.04; P = 0.03) were associated with better PFS, compared to left-sided disease and bilateral disease. However, histopathological subtypes, grade, age, tumor size, chemotherapy and surgery methods were not independent prognostic factors (P > 0.05) (Table 2).
Table 2. Univariate and multivariate analysis of prognostic factors in MOT.
4 Discussion
In this study, patients with right-sided MOT exhibited significantly better prognosis than those with left-sided tumors, particularly among patients with MT-MCT. Additionally, patients with unilateral ovarian tumors appeared to have a more favorable prognosis compared to those with bilateral disease. Tumor laterality was associated with disease progression in MOT patients. However, no significant difference in overall survival (OS) was observed across the IT cohort.
Due to the different anatomical locations of tumors, the prognosis of malignant tumors originating from the same organ can vary, as observed in many solid tumors. However, data on the prognostic value of primary tumor laterality in MOT remain limited. In 1977, data from the National Cancer Institute indicated that women with bilateral ovarian cancer had lower survival rates than those with unilateral ovarian cancer (10). In 2011, a retrospective study by Mahdi et al. enrolled 1,529 patients with ovarian germ cell tumors, including 665 with MOT (11). They reported that bilateral MOT was also associated with poorer survival outcomes. In 2021, a cross-sectional study by He et al. examined the lateral distribution and related clinical characteristics of Chinese patients with benign ovarian teratomas (12). Their findings showed that recurrent ovarian teratomas occurred more frequently on the left side than on the right.
MOT patients showed varied PFS. Specifically, patients in the right-sided group had a 99% decreased risk of recurrence, compared to those in the left-sided group. These findings are consistent with the results of Zhang et al., who reported the impact of laterality on the prognosis of epithelial ovarian cancer (11). Cox regression analysis showed no significant difference between left-sided, right-sided and bilateral groups in both MT-MCT and IT patients, respectively. Due to the rarity of MOT, identifying prognostic factors has proven challenging, and relevant data remain scarce. Our findings provide new insights into the prognostic factors of MOT, which are crucial for understanding this rare malignancy in clinical practice.
The pathophysiological mechanisms underlying the different prognostic effects of laterality in MOT remain unclear. Anatomical disparities between the left and right hemipelvis may contribute to this phenomenon through their influence on metastasis patterns. Specifically, hematogenous dissemination represents a key route for distant spread in ovarian cancer. The distinct venous drainage pathways—where the right ovarian vein drains directly into the inferior vena cava, while the left drains into the left renal vein (13)—could facilitate more efficient systemic circulation of tumor cells from right-sided lesions. Conversely, the close anatomical proximity between the sigmoid colon and the left adnexa (14, 15) might promote direct tumor spread and local implantation on the left side. These asymmetric anatomical factors potentially explain the observed poorer prognosis associated with left-sided MOT.
In our study, tumor laterality was the only dependent prognostic factor. However, factors such as FIGO stage, age, histopathological subtypes and differentiated grade, have been regarded as significant prognostic factors for ovarian cancer in previous studies (16). Ovarian germ cell tumors frequently occur in children, particularly in cases of mature and immature teratomas (17), whereas MT-MCT typically arises in older women. This study included both younger and adult women, with the mean age of patients with IM being lower than that of those with MT-MCT. The prognosis for IT was also more favorable compared to MT-MCT. However, due to the small sample size, it remains unclear whether patient age at onset is an independent prognostic factor. Studies with larger sample size are needed to further assess the association between these factors and prognosis in patients with MOT.
This study’s primary strength lies in the novel exploration of the relationship between primary tumor laterality and prognosis in MOT. Using both Kaplan–Meier and Cox regression analyses, complemented by in-depth subgroup analyses, we were able to enhance the robustness and reliability of our findings. These results suggest potential clinical implications that merit further investigation. To our knowledge, we are the first to highlight the prognostic value of primary tumor laterality in MOT, offering a new perspective that could eventually help gynecological oncologists refine risk stratification for MOT patients pending validation in larger cohorts. This finding, if confirmed, could inform the future development of more personalized treatment strategies and follow-up plans.
Given the observed poorer prognosis in patients with left-sided or bilateral MOT in this study, future research could explore whether more intensive therapeutic approaches might be beneficial to reduce recurrence and improve survival outcomes. Conversely, the more favorable prognosis associated with right-sided MOT raises the question of whether less intensive treatment regimens and monitoring could be sufficient, potentially reducing the burden on both patients and healthcare systems. However, these treatment considerations are currently hypothetical and require robust clinical validation. Moreover, exploring the treatment response differences between MOT patients with different tumor laterality could offer valuable insights for developing more targeted and personalized therapeutic approaches.
Our study has several limitations. First, as a single-institution, retrospective study, it is prone to inherent selection bias. Second, the MOT group included a heterogeneous mix of histopathological subtypes, which may have distinct prognostic outcomes. Additionally, due to the rarity of MOT, the sample size was insufficient to thoroughly examine the relationship between primary tumor laterality and prognosis. Larger-scale prospective studies are needed to confirm these findings and explore the underlying biological mechanisms.
5 Conclusion
This retrospective study identified primary tumor laterality as an independent prognostic factor in MOT. Patients with right-sided MOT had the most favorable outcomes, while those with bilateral MOT experienced the poorest prognosis. Left-sided MOT patients exhibited an intermediate prognosis. Gynecologic oncologists could consider primary tumor laterality as a potential factor when assessing prognosis in MOT, and future studies should investigate whether incorporating laterality can optimize treatment and surveillance strategies.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by The Affiliated Hospital of Qingdao University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.
Author contributions
XJ: Conceptualization, Data curation, Investigation, Methodology, Software, Writing – original draft. ZZ: Data curation, Resources, Writing – review & editing. JY: Data curation, Resources, Writing – review & editing. GL: Writing – review & editing. XL: Data curation, Resources, Writing – review & editing.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Conflict of interest
The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Abbreviations
MOT, Malignant Ovarian Teratomas; IT, Immature Teratomas; MT-MCT, Malignant Transformation of Mature Cystic Teratomas; HIS, Hospital Information System; HE, Hematoxylin-eosin; FIGO, International Federation of Gynecology and Obstetrics; PFS, Progression-free Survival; OS, Overall Survival; HR, Hazard ratio; CI, Confidence Intervals.
References
1. Park M, Lim J, Lee JA, Park HJ, Park BK, Lim MC, et al. Incidence and outcomes of Malignant ovarian germ cell tumors in Korea, 1999-2017. Gynecol Oncol. (2021) 163:79–84. doi: 10.1016/j.ygyno.2021.07.037
2. Cong L, Wang S, Yeung SY, Lee JHS, Chung JPW, and Chan DYL. Mature cystic teratoma: an integrated review. Int J Mol Sci. (2023) 24:6141. doi: 10.3390/ijms24076141
3. Smith HO, Berwick M, Verschraegen CF, Wiggins C, Lansing L, Muller CY, et al. Incidence and survival rates for female Malignant germ cell tumors. Obstet Gynecol. (2006) 107:1075–85. doi: 10.1097/01.AOG.0000216004.22588.ce
4. Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, and Correa CN. Pathology and classification of ovarian tumors. Cancer. (2003) 97:2631–42. doi: 10.1002/cncr.11345
5. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. (2018) 68:284–96. doi: 10.3322/caac.21456
6. Saleh M, Bhosale P, Menias CO, Ramalingam P, Jensen C, Iyer R, et al. Ovarian teratomas: clinical features, imaging findings and management. Abdom Radiol (NY). (2021) 46:2293–307. doi: 10.1007/s00261-020-02873-0
7. Ayhan A, Bukulmez O, Genc C, Karamursel BS, and Ayhan A. Mature cystic teratomas of the ovary: case series from one institution over 34 years. Eur J Obstet Gynecol Reprod Biol. (2000) 88:153–7. doi: 10.1016/s0301-2115(99)00141-4
8. Outwater EK, Siegelman ES, and Hunt JL. Ovarian teratomas: tumor types and imaging characteristics. Radiographics. (2001) 21:475–90. doi: 10.1148/radiographics.21.2.g01mr09475
9. Li Y, Qin M, Shan Y, Wu HW, Liu XD, Yin J, et al. 30-year experience with 22 cases of Malignant transformation arising from ovarian mature cystic teratoma: A rare disease. Front Oncol. (2022) 12:842703. doi: 10.3389/fonc.2022.842703
10. Weiss NS and Silverman DT. Laterality and prognosis in ovarian cancer. Obstet Gynecol. (1977) 49:421–3.
11. Mahdi H, Kumar S, Seward S, Semaan A, Batchu R, Lockhart D, et al. Prognostic impact of laterality in Malignant ovarian germ cell tumors. Int J Gynecol Cancer. (2011) 21:257–62. doi: 10.1097/IGC.0b013e31820581e5
12. He X, Zhao X, Wang X, Liang G, Qi H, Zhu C, et al. Distinctive pattern of left-right asymmetry of ovarian benign teratomas in Chinese population: a 12-year-long cross-sectional study. Arch Gynecol Obstet. (2021) 303:729–37. doi: 10.1007/s00404-020-05864-0
13. Karaosmanoglu D, Karcaaltincaba M, Karcaaltincaba D, Akata D, and Ozmen M. MDCT of the ovarian vein: normal anatomy and pathology. AJR Am J Roentgenol. (2009) 192:295–9. doi: 10.2214/AJR.08.1015
14. Chapron C, Chopin N, Borghese B, Foulot H, Dousset B, Vacher-Lavenu MC, et al. Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution. Hum Reprod. (2006) 21:1839–45. doi: 10.1093/humrep/del079
15. Warschkow R, Sulz MC, Marti L, Tarantino I, Schmied BM, Cerny T, et al. Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer. (2016) 16:554. doi: 10.1186/s12885-016-2412-0
16. Xiang H, Xiao Y, Li F, Li C, Liu L, Deng T, et al. Development and validation of an interpretable model integrating multimodal information for improving ovarian cancer diagnosis. Nat Commun. (2024) 15:2681. doi: 10.1038/s41467-024-46700-2
Keywords: immature teratoma, malignant ovarian teratoma, malignant transformation of mature cystic teratoma, primary tumor laterality, prognosis
Citation: Ji X, Zheng Z, Yang J, Li G and Liu X (2026) The prognostic significance of primary tumor laterality in malignant ovarian teratomas: a 10-year experience at a single institution. Front. Immunol. 16:1700779. doi: 10.3389/fimmu.2025.1700779
Received: 07 September 2025; Accepted: 15 December 2025; Revised: 04 December 2025;
Published: 09 January 2026.
Edited by:
Kanjoormana Aryan Manu, Amala Cancer Research Centre, IndiaReviewed by:
Przemyslaw Karol Wolak, Jan Kochanowski University, PolandOmar Hamdy, Mansoura University, Egypt
Copyright © 2026 Ji, Zheng, Yang, Li and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xiangyu Liu, bGl1eGlhbmd5dUBxZHUuZWR1LmNu