OPINION article

Front. Oncol., 23 May 2023

Sec. Gynecological Oncology

Volume 13 - 2023 | https://doi.org/10.3389/fonc.2023.1193123

At what age endometriosis-associated ovarian cancer is diagnosed? The implications for women in the reproductive age

  • 1. Reproductive Medicine, Department of Obstetrics and Gynecology, Baruch-Padeh Medical Center, Poriya, Israel

  • 2. Azrieili Faculty of Medicine, Bar-Ilan University, Safed, Israel

  • 3. Department of Evolutionary and Environmental Biology, University of Haifa, Haifa, Israel

Introduction

Endometriosis-associated ovarian cancer (EAOC) is an evolving distinct clinical entity and challenge considered to develop from endometrioma (). Several systematic reviews and meta-analyses corroborated the association between endometriosis and ovarian cancer (–). In the most recent and comprehensive, the summary relative risk of EAOC was estimated as 1.93 compared to women with no endometriosis (). Furthermore, contemporary state-of-the-art methodologies have provided evidence of genetic correlation and causal relationship between endometriosis and EAOC ().

Clear-cell and endometrioid ovarian epithelial carcinomas are the most intensely and reproducibly associated malignancies with endometriosis. While endometriosis may also be associated with low-grade serous ovarian carcinoma, this linkage is not well documented (). Coexistence with endometriosis is observed in about 20%–50% of all women with clear-cell and endometrioid ovarian carcinomas (–). The increased risk of developing clear-cell and endometrioid ovarian carcinomas in women with endometriosis is 3.4 and 2.3-fold, respectively ().

The rationale for the current opinion

Endometriosis is a widespread, chronic, inflammatory, and estrogen-dependent condition, and endometrioma is the most pathognomonic and diagnosed form of the disease. Their estimated prevalence is 1 in 10 and 1 in 18, respectively, in women of reproductive age (). Therefore, the diagnosis of EAOC in women with endometriosis, particularly with an intact endometrioma, may raise much concern. Furthermore, the link and its translation into clinical practice regarding information to patients and early cancer detection still need to be clarified ().

Overall, ovarian cancer is a postmenopausal disease, although, in about 12% of cases, it may develop in women < 44 years of age (). This estimate includes numerous women with borderline and non-epithelial tumors, typically presenting at a young age (, ). Overall, women with EAOC are older than those with benign endometrioma but younger than women with non-EAOC ovarian carcinomas, such as high-grade serous ovarian carcinoma. Additionally, although there are several case reports of EAOC at a young age (–), the exact age distribution of EAOC diagnosis is still not well-expounded.

Furthermore, although age was suggested as a risk factor in cases with EAOC, many discrepancies exist between reports (–). For example, previous publications reported a wide range of EAOC premenopausal diagnosis rates between 30 and 70% of cases (, –). Moreover, due to the disease’s infrequency, publications exploring EAOC in the last decade were retrospective in design and included a modest number of women, the largest including 163 women ().

Collectively, the age at EAOC diagnosis is still not well delineated. Although endometrioma is a prevalent manifestation in the reproductive age, EAOC may seem exceptional. A methodical assessment of age at EAOC diagnosis may have numerous implications on the clinical management of women with intact endometrioma, especially in planning future pregnancies. It may clarify the chance of EAOC diagnosis stratified by age and direct physicians on advising, following, and treating their patients relying on relevant medical evidence. Moreover, it may supplement essential information to reproductive endocrinologists and gynecological surgeons in their counseling for the best treatment approach, especially when atypical features of an endometrioma appear on transvaginal ultrasound (TVUS).

Methods

To reach the objective of this opinion paper, a search for cohort studies published in the English literature was performed on Pubmed.com from January 2011 to October 2022, addressing EAOC, clear-cell ovarian cancer, and endometrioid ovarian cancer. Cohort studies that targeted women with EAOC elaborating on the mean age ± standard deviation (SD) or median and interquartile range (IQR) or range (minimum and maximum) were included in the quantitative assessment. The diagnosis of EAOC should have been performed surgically and approved by pathology.

The keywords ‘endometriosis’, ‘endometrioma’, ‘ovarian endometriosis’, ‘endometriosis-associated ovarian cancer’, ‘clear-cell ovarian carcinoma’, ‘endometrioid ovarian carcinoma’, ‘age’, and ‘reproductive age’ were included. The relevance of reached publications was evaluated following reading the abstract. Case reports and reviews were excluded. Furthermore, publications that assessed only a specific age group of women were omitted from the evaluation. Articles with an inappropriate design were also excluded.

Statistical evaluation

We assumed normal distribution for the statistical analyses of women’s age since this information was not specified in the 25 studies included in our analysis. The mean and standard deviation of women’s age were reported in 17 studies. For the other studies where only median and IQR or median and minimum/maximum were given, mean and SD were approximated using the method of Wan et al. (). The weighted mean and SD were calculated with the number of participants in each study as the weighting factor, using the formulas of N.I.S.T () for each of the four studied groups (all eligible studies combined, studies that targeted EAOC originating from ovarian endometriosis, studies that were conducted in countries with a high incidence of EAOC and studies that included women solely with clear-cell ovarian carcinoma). Using z-scores, we calculated the percentage of women in the four groups below 50, 45, 40, and 35 years.

Results

Twenty-five studies (27 cohorts) were eligible for the quantitative age evaluation at EAOC diagnosis, including 1082 cases (Table 1). The diagnosis of EAOC was performed surgically and examined by experienced pathologists in all studies (–, –, –).

Table 1

StudyNo. of womenCountryStudy methodologyStudy period
(years)		Age (years) Mean +/- SDAge range
(years)		NotesCancer arising from ovarian endometriosis
Hernández et al., 2022 17SpainRetrospective observational3Median 50Interquartile 43-63All with EAOCYes
Huang et al., 2022 57TaiwanRetrospective cooperative353.1 ± 9.3NDAll with CCOC 47/57 cases associated with endometriosisYes
So et al., 2021 12South KoreaRetrospective1736.3 ± 5.229-56All with EAOCYes
Zhang et al., 2021 14ChinaRetrospective comparative947.1 ± 11.0NDAll with EAOCYes
Zhou et al., 2021 114ChinaRetrospective2151.1 ± 9.024–79All with EAOCND
Zhu et al., 2021 16ChinaRetrospective1045.5 ± 6.235-54All with CCOC associated with endometriosisYes
Udomsinkul et al., 2020 79ThailandRetrospective case-control16Median 49Interquartile 44-54All with EAOCYes
Li et al., 2019 34ChinaRetrospective comparative1748.7 ± 9.032-63All with EAOCYes
Son et al., 2019 35South KoreaRetrospective comparative17Median 4733-60All with CCOC associated with endometriosisYes
Bassiouny et al., 2018 168CanadaRetrospective comparative1356.6 ± 11.5NDAll with EAOCYes
Yamamoto et al., 2018 28JapanRetrospective comparative453.1 ± 14.5NDAll with EAOCYes
Moro et al., 2018 49European countriesRetrospective multicenter17Median 5326-86All with EOC associated with endometriosisYes
Muangtan et al., 2018 32ThailandRetrospective comparative551.4 ± 10.1NDAll with EAOCYes
Pozzati et al., 2018 24
10
20		European countriesRetrospective multicenter17Median 47.5
Median 55.0
Median 55.0		32-72
37-80
35-70		All with CCOC associated with endometriosisYes
Yes
No
Paik et al., 2018 41South KoreaRetrospective comparative1545.1 ± 7.0NDAll with EAOCYes
Park et al., 2018 78South KoreaRetrospective comparative22Median 4829-69All with CCOC associated with endometriosisYes
Tanase et al., 2018 40JapanRetrospective comparative854.3 ± 8.939-75All with EAOCYes
Kuo et al., 2017 11ThailandRetrospective1044.7 ± 3.240-52All with EAOCYes
Bounus et al., 201645ItalyRetrospective comparative1059.0 ± 9.6NDAll with EAOCNo
34/45 of cases had extra-gonadal endometriosis
Dinkelspiel et al., 2016 49USARetrospective comparative14Mean 52
Median 52		47-57All with EAOCYes
Acién et al., 2015 20SpainRetrospective comparative2048.8 ± 11.632-72All with EAOCNo
Akbarzadeh-Jahromi et al., 2015 28IranRetrospective multi-center649.9± 9.429-72All with EAOCNo
Included cases with extra-gonadal endometriosis
Scarfone et al., 2014 27ItalyRetrospective comparative2251.4 ± 10.030-71All with CCOC associated with endometriosisYes
Wang et al., 2013 17ChinaRetrospective comparative146.1 ± 10.133-66All with EAOCNo
Included cases with extra-gonadal endometriosis
Kondi-Pafiti et al., 201217GreeceRetrospective10Median 5826-76All with EAOCYes

Age at diagnosis of endometriosis-associated ovarian cancer – a summary of cohort studies.

ND - not disclosed; EAOC - endometriosis-associated ovarian cancer; CCOC - clear-cell ovarian cancer; EOC - endometrioid ovarian cancer.

Eleven studies were excluded from the quantitative evaluation. Five studies did not disclose EAOC patients’ age, SD, or range (–). Two studies assessed only EAOC women above 45 or below 40 years (, ). One study targeted women following endometrioma resection (55), and one more study evaluated only EAOC cases resistant to platinum (56). Other studies did not meet the inclusion criteria (57, 58).

The characteristics of eligible 25 studies are précised in Table 1. All studies were retrospective in design. The studies originated from countries around the globe in Asia, Europe, and North America. Most studies (19/25) summarized an extended institutional clinical experience of more than seven years. In all studies, the mean ( ± SD) duration invested in EAOC institutional evaluation was 12.26 ± 6.39 years.

Eighteen studies assessed all cases of EAOC combined (–, , , , –, –, –), six evaluated only patients with clear-cell ovarian cancer associated with endometriosis (, , , , , ), and one study endometrioid ovarian cancer associated with endometriosis (). In addition, six eligible studies were performed in countries with a higher prevalence of EAOC, in Japan, Thailand, and Taiwan (, , , , , ). Nineteen eligible studies included EAOC cases arising within the endometrioma following Sampson and Scott’s criteria (59, 60). In contrast, six studies included patients with extra-gonadal endometriosis (61), or the subtype of endometriosis was not disclosed (Table 1).

Assessing all eligible studies conjointly, the mean age of the 1082 women at EAOC diagnosis was 51.64 ± 3.24 years. Among these women, 30.68% and 2.10% were below 50 and 45 years, respectively, equivalent to 31:100 and 2:100 among all women assessed. On the other hand, EAOC diagnosis in women below 40 and 35 years resulted in much lower estimates corresponding to 0.017% and <0.001%, equivalent to 2:10,000 and <1:100,000, respectively.

Nineteen studies targeted EAOC originating from ovarian endometriosis and included 838 cases with a mean age of 51.51 ± 3.29 years. Among these women, 32.26% and 2.38% were below 50 and 45 years of age, equivalent to 32:100 and 2:100, respectively. However, EAOC diagnosis in this group of women below 40 and 35 years resulted in much lower estimates corresponding to 0.023% and <0.001%, equivalent to 2:10,000 and <1:100,000, respectively.

Six studies were conducted in countries with a high incidence of EAOC and included 247 cases with a mean age of 51.39 ± 3.30 years. Of these women, 33.71%, 2.66%, 0.028%, and <0.001% were below 50, 45, 40, and 35 years, equivalent to 34:100, 3:100, 3:10,000, and <1:100,000, respectively.

Six studies included women solely with clear-cell ovarian carcinoma and involved 267 cases with a mean age of 50.27 ± 3.58 years. Of these women, 46.95%, 7.02%, 0.20%, and 0.001% were below 50, 45, 40, and 35 years, equivalent to 47:100, 7:100, 2:1000, and 1:100,000, respectively.

Discussion

Our methodical assessment, summarizing 25 carefully chosen studies (27 cohorts) and including 1082 EAOC cases, shows that EAOC diagnosis is a disease of the menopausal age. These global results rely on an extended experience of 12.26 ± 6.39 years invested among various institutional practices. In our analysis of all eligible studies, the mean age of women with EAOC was 51.64 ± 3.24 years. Nonetheless, 31% of women were < 50 years of age, most probably peri- or premenopausal, and only 2% of patients were <45 years of age, apparently diagnosed during the reproductive period. Furthermore, the diagnosis of EAOC in young women <40 and <35 years of age was sporadic, equivalent to 1:5,000 and <1:100,000, respectively. These estimates did not change when EAOC cases in women with extra-gonadal endometriosis were excluded from the evaluation.

Estimates of premenopausal EAOC diagnosis in countries with a higher disease prevalence, Japan, Thailand, and Taiwan, seem to increase slightly. Almost 34:100, and 3:100, of women developing EAOC in those countries, were <50 and <45 years, respectively. However, only 3:10,000 and <1:100,000 were below <40 and <35 years, respectively.

Furthermore, studies that evaluated only clear-cell ovarian cancer associated with endometriosis showed a further increase in premenopausal diagnosis. Almost 47:100 and 7:100 of women with this type of cancer were diagnosed <50 and <45 years, respectively. However, no significant clinical change in this group was diagnosed in young women <40 and <35 years. Therefore, it is plausible that the slight increase in the premenopausal diagnosis of EAOC in Japan, Thailand, and Taiwan is caused by the predominance of clear-cell ovarian carcinoma in these countries (62).

Taken together, our results demonstrate that a malignant transformation of a benign endometrioma to EAOC in the reproductive age is a sporadic event, notably in women <40 years of age. In women of late reproductive age, between 40-45 years, EAOC is diagnosed in almost 2-3% of cases. In cases with clear-cell ovarian carcinoma associated with endometriosis, our results imply that up to 7% of cases are diagnosed in this age group. These estimates are clinically significant since endometriosis and endometrioma are prevalent at young ages, estimated at 1 in 10 and 1 in 18, respectively. They may be beneficial to ease the concerns of these patients and their attending practitioners. Furthermore, these estimates may be employed for proper guidance and counseling of women of reproductive age with an intact endometrioma planning for a future pregnancy.

Our results, assessing a total of 1082 cases, demonstrates the age diversity at diagnosis between patients with EAOC and non-EAOC, specifically high-grade serous ovarian cancer (HGSOC). The mean age of women with HGSOC, the most common and lethal type of ovarian cancer, is 63 years (63), almost 12 years older than EAOC.

Furthermore, our analyses substantiate previous studies, counting on modest numbers, indicating that age is an independent risk factor in cases of EAOC (–); and translating these risks into informatics that may be introduced into the clinical setting. Our calculations also imply that EAOC should not be an argument for surgical treatment of an intact endometrioma in the reproductive age, particularly in cases planning a future pregnancy. It is well recognized today that endometriotic cystectomy significantly reduces ovarian reserve (64, 65), estimated by 39% and 57%, in uni- and bilateral cases, 9-12 months following surgery, suggesting a long-standing impact on women’s reproductive life span (65).

Although EAOC diagnosis at the reproductive is infrequent and even sporadic in women <40 years, the index of suspicion should be directed into distinct clinical situations. Cases with relapsing or worsening pelvic pain, the rapid growth of an endometrioma, or alternately larger-sized endometrioma, particularly >9 cm, should be perused to investigate EAOC (). In this setting, serum cancer antigen 125 has no added benefit (66, 67).

Clinically, imaging is vital in evaluating and differential diagnosing an endometrioma transformation to an EAOC, noticeably in reproductive age. Pelvic transvaginal ultrasound (TVUS) is the first-line imaging mode, while computerized tomography scan performs poorly. Magnetic resonance imaging (MRI) is a valuable adjunct for ovarian findings described as intermediate or atypical by TVUS (68, 69).

On TVUS, benign endometrioma appears as an ovarian mass with a homogenous ‘ground glass’ appearance, uni- or bilateral, without solid parts or papillations. However, as age increases, papillations and other solid parts become more frequent, and the ‘ground glass’ appearance becomes less common, while cyst diameter seems to stay the same (70). Conversely, EAOC, specifically clear-cell and endometrioid ovarian carcinomas, are large, above 9 cm, with a mean size of 11-13 cm, unilateral tumors with solid components, papillary projections, and vascularization (, 71).

In clinical practice, about 5–25% of cases will have indeterminate or atypical adnexal findings by TVUS (72). Since most of these cases may be benign, MRI performance is crucial in managing and counseling these cases. In addition, MRI-supportive performance in such situations may reduce patient anxiety, repeat imaging, unnecessary follow-up, and avoid surgery. On MRI, benign endometriomas typically display features of T2-weighted image shading (72). A larger cyst and an enhanced solid portion of the endometrioma may suggest a malignant transformation (73). Shading disappearance within the endometrioma on T2-weighted images may also mean malignant transformation ().

Endometrioma and deep infiltrating endometriosis (DIE) occasionally co-exist in the same women (74, 75). In a recent cross-sectional study of 1,191 women with subfertility aged 25–39 years, undergoing a systematic TVUS evaluation, both disease subtypes were found in almost 22% of women (75). Nevertheless, the available evidence supports EAOC rise mainly from endometrioma (). Malignant transformation of extra-gonadal sites, as in superficial or deep endometriosis, is most unusual (76–78). In a recent narrative review of cases with DIE malignant transformation, only eight patients were collected in ten years (78). Thus, a high level of suspicion should be invested in DIE cases presenting with new clinical manifestations and appearing with a pelvic mass such as on the pelvic wall, pouch of Douglass, and recto-vaginal septum (78). Further studies are essential to explore the association between extra-gonadal endometriosis and malignant transformation.

Figure 1 summarizes in a flow chart our suggested way of clinical management of endometrioma (isolated or joined by DIE) developing manifestations of EAOC, including atypical TVUS endometrioma features. The risk factors for EAOC have been discussed earlier () and are summarized in Figure 1. MRI performance is mandatory in these cases, especially when atypical endometrioma features appear on TVUS. A definite diagnosis of EAOC necessitates surgery, most commonly by endoscopy. Definitive management should consider the patient’s age, the final pathological diagnosis, stage, and grade of disease. Since women with EAOC are diagnosed at an earlier stage and have a more favorable histological grade (), conservative surgical management should be discussed in infertile cases or women of reproductive age desiring a future pregnancy.

Figure 1

The time and intervals of follow-up in cases with isolated endometrioma, with typical or atypical TVUS features, is an intricate but essential demand and need more targeted studies to be addressed. Likewise, follow-up of cases with atypical TVUS features and reassuring MRI results need further investigation. Meanwhile, we recommend a multidisciplinary case-by-case consultation (adjoining a gynecological oncologist and reproductive medicine experts) contemplating, age, desire for future pregnancy, symptomatology, ovarian reserve, physical and TVUS findings, and MRI features.

In summary, this is the first report in the literature delineating and expounding the age at EAOC diagnosis, substantiating that age is an independent risk factor for the disease. Our results analyzing 1082 cases from 25 studies demonstrate that EAOC is a menopausal disease, with a mean age of 51.64 ± 3.24 years at diagnosis. About 30.68% of patients with EAOC are <50 years upon diagnosis, presumably premenopausal, equivalent to 31 in 100 women. However, only 2.1%, 0.017%, and <0.001%, apparently during the reproductive age, comparable to 1 in 50, 1 in 5,000, and < 1 in 10,000, are <45, <40, and <35 years, respectively. In cases with clear-cell ovarian carcinoma associated with endometriosis, 47 in 100 and 7 in 100 are below 50 and 45 years, with no clinically significant changes in women <40 and <35 years. Since endometrioma is widespread in women of reproductive age, these estimates are essential for guidance and counseling, especially in women planning for a future pregnancy. Our results imply that the likelihood of EAOC development during reproductive age is reassuring, and this should be translated into clinical practice regarding information to patients. At the same time, a high index of suspicion should remain in special situations when clinical, TVUS, and MRI features suggest EAOC. Conversely, an extended follow-up should be considered in women with large or atypical endometriomas not retracting following menopause.

Statements

Author contributions

JY conceived the idea of this perspective, contributed to study design and data extraction, performed the analyses and data interpretation, and drafted the manuscript; II contributed to study design and execution, contributed to analyses and interpretation of data, performed the statistical analysis, and revised the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

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References

  • 1

    SaavalainenLLassusHButATiitinenAHärkkiPGisslerMet al. Risk of gynecologic cancer according to the type of endometriosis. Obstet Gynecol (2018) 131:1095–102. doi: 10.1097/AOG.0000000000002624

  • 2

    PearceCLTemplemanCRossingMALeeANearAMWebbPMet al. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol (2012) 13:385–94. doi: 10.1016/S1470-2045(11)70404-1

  • 3

    KimHSKimTHChungHHSongYS. Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis. Br J Cancer (2014) 110:1878–90. doi: 10.1038/bjc.2014.29

  • 4

    WangCLiangZLiuXZhangQLiS. The association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer: meta-analyses. Int J Environ Res Public Health (2016) 13:1138. doi: 10.3390/ijerph13111138

  • 5

    LiJLiuRTangSFengFLiuCWangLet al. Impact of endometriosis on risk of ovarian, endometrial and cervical cancers: a meta-analysis. Arch Gynecol Obstet (2018) 299:35–46. doi: 10.1007/s00404-018-4968-1

  • 6

    KvaskoffMMahamat-SalehYFarlandLVShigesiNTerryKLHarrisHRet al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update (2021) 27:393–420. doi: 10.1093/humupd/dmaa045

  • 7

    MortlockSCoronaRIKhoPFPharoahPSeoJHFreedmanMLet al. A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes. Cell Rep Med (2022) 3:100542. doi: 10.1016/j.xcrm.2022.100542

  • 8

    GuidozziF. Endometriosis-associated cancer. Climacteric (2021) 24:587–92. doi: 10.1080/13697137.2021.1948994

  • 9

    StampJPGilksCBWesselingMEshraghSCeballosKAnglesioMSet al. BAF250a expression in atypical endometriosis and endometriosis-associated ovarian cancer. Int J Gynecol Cancer (2016) 26:825–32. doi: 10.1097/IGC.0000000000000698

  • 10

    WentzensenNPooleEMTrabertBWhiteEArslanAAPatelAVet al. Ovarian cancer risk factors by histologic subtype: an analysis from the ovarian cancer cohort consortium. J Clin Oncol (2016) 34:2888–98. doi: 10.1200/JCO.2016.66.8178

  • 11

    TanhaKMottaghiANojomiMMoradiMRajabzadehRLotfiSet al. Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses. J Ovarian Res (2021) 14:153. doi: 10.1186/s13048-021-00911-z

  • 12

    YounisJS. Endometriosis-associated ovarian cancer: what are the implications for women with intact endometrioma planning for a future pregnancy? a reproductive clinical outlook. Biomolecules (2022) 12:1721. doi: 10.3390/biom12111721

  • 13

    BeckerCMBokorAHeikinheimoOHorneAJansenFKieselLet al. ESHRE guideline: endometriosis. Hum Reprod Open (2022) 2022:hoac009. doi: 10.1093/hropen/hoac009

  • 14

    KimSYLeeJR. Fertility preservation option in young women with ovarian cancer. Future Oncol (2016) 12:1695–8. doi: 10.2217/fon-2016-0181

  • 15

    CheungAShahSParkerJSoorPLimbuASheriffMet al. Non-epithelial ovarian cancers: how much do we really know? Int J Environ Res Public Health (2022) 19:1106. doi: 10.3390/ijerph19031106

  • 16

    Della CorteLMercorioASerafinoPViciglioneFPalumboMDe AngelisMCet al. The challenging management of borderline ovarian tumors (BOTs) in women of childbearing age. Front Surg (2022) 9:973034. doi: 10.3389/fsurg.2022.973034

  • 17

    TagashiraYShimadaMKigawaJIbaTTerakawaN. Ovarian endometrioid adenocarcinoma arising from endometriosis in a young woman. Gynecol Oncol (2003) 91:643–7. doi: 10.1016/j.ygyno.2003.08.005

  • 18

    MatalliotakisIMahutteNGKoukouraOAriciA. Endometriosis associated with stage IA clear cell ovarian carcinoma in a woman with IVF-ET treatments in the Yale series. Arch Gynecol Obstet (2006) 274:184–6. doi: 10.1007/s00404-006-0143-1

  • 19

    SaylamKDevrekerFSimonPFaytINoëlJ-C. Ovarian clear cell carcinoma occurring in a young patient with endometriosis and long-term ovulation stimulations. Acta Obstet Gynecol Scand (2006) 85:1506–7. doi: 10.1080/00016340600603577

  • 20

    WoodardTLAwonugaAOPuscheckE. Malignant transformation of endometrioma in a woman with a history of ovulation induction and in vitro fertilization. Case Rep Med (2012) 2012:497362. doi: 10.1155/2012/497362

  • 21

    WangSQiuLLangJHShenKYangJXHuangHFet al. Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis. Am J Obstet Gynecol (2013) 208:413.e1–5. doi: 10.1016/j.ajog.2012.12.004

  • 22

    UdomsinkulPTriratanachartSOranratanaphanS. Risk factors for endometriotic-cyst associated ovarian cancer: a case controlled study. Taiwan J Obstet Gynecol. (2020) 59:269–74. doi: 10.1016/j.tjog.2020.01.016

  • 23

    HernándezASanzASpagnoloECarbonellMRodríguezELópezAet al. Evaluation of women’s age and ultrasonographic features to choose surgical treatment for endometriosis associated with ovarian cancer. J Clin Med (2022) 11:2414. doi: 10.3390/jcm11092414

  • 24

    HuangKJLiYXWuCJChangWCWeiLHSheuBC. Sonographic features differentiating early-stage ovarian clear cell carcinoma from endometrioma with atypical features. J Ovarian Res (2022) 15:84. doi: 10.1186/s13048-022-01019-8

  • 25

    LiQSunYZhangXWangLWuWWuMet al. Endometriosis-associated ovarian cancer is a single entity with distinct clinicopathological characteristics. Cancer Biol Ther (2019) 20:1029–34. doi: 10.1080/15384047.2019.1595278

  • 26

    CaiYYinJJinYLiYWuMYangJet al. Endometriosis-associated ovarian cancer is not a distinct clinical entity among young patients: a 12-year cohort study. Eur J Surg Oncol (2020) 46:876–82. doi: 10.1016/j.ejso.2019.11.517

  • 27

    MoroFMagogaGPasciutoTMasciliniFMoruzziMCFischerovaDet al. Imaging in gynecological disease (13): clinical and ultrasound characteristics of endometrioid ovarian cancer. Ultrasound Obstet Gynecol (2018) 52:535–43. doi: 10.1002/uog.19026

  • 28

    PozzatiFMoroFPasciutoTGalloCCiccaroneFFranchiDet al. Imaging in gynecological disease (14): clinical and ultrasound characteristics of ovarian clear cell carcinoma. Ultrasound Obstet Gynecol (2018) 52:792–800. doi: 10.1002/uog.19171

  • 29

    BassiounyDEl-BazMAGamilTMShamsNIsmiilNDubéVet al. Endometriosis-associated ovarian cancer is a subset with a more favorable outcome and distinct clinical-pathologic characteristics. Int J Gynecol Pathol (2019) 38:435–42. doi: 10.1097/PGP.0000000000000533

  • 30

    WanXWangWLiuJTongT. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol (2014) 14:135. doi: 10.1186/1471-2288-14-135

  • 31

    N.I.S.T. Weighted Standard Deviation. DATAPLOT reference manual (1996). Available at: https://www.itl.nist.gov/div898/software/dataplot/refman2/ch2/weightsd.pdf.

  • 32

    Kondi-PafitiAPapakonstantinouEIavazzoCGrigoriadisCSalakosNGregoriouO. Clinicopathological characteristics of ovarian carcinomas associated with endometriosis. Arch Gynecol Obstet (2012) 285:479–83. doi: 10.1007/s00404-011-1957-z

  • 33

    ScarfoneGBergaminiANoliSVillaACiprianiSTaccagniGet al. Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study. Gynecol Oncol (2014) 133:480–4. doi: 10.1016/j.ygyno.2014.03.017

  • 34

    Akbarzadeh-JahromiMShekarkharGSari AslaniFAzarpiraNHeidari EsfahaniMMomtahanM. Prevalence of endometriosis in malignant epithelial ovarian tumor. Arch Iran Med (2015) 18:844–8.

  • 35

    AciénPVelascoIAciénMCapelloCVelaP. Epithelial ovarian cancers and endometriosis. Gynecol Obstet Invest (2015) 79:126–35. doi: 10.1159/000367597

  • 36

    DinkelspielHEMatraiCPaukSPierre-LouisAChiuYLGuptaDet al. Does the presence of endometriosis affect prognosis of ovarian cancer? Cancer Invest (2016) 34:148–54. doi: 10.3109/07357907.2016.1139716

  • 37

    BounousVEFerreroAFusoLRavarinoNCeccaroniMMenatoGet al. Endometriosis-associated ovarian cancer: a distinct clinical entity? Anticancer Res (2016) 36:3445–9.

  • 38

    KuoHHHuangCYUengSHHuangKGLeeCLYenCF. Unexpected epithelial ovarian cancers arising from presumed endometrioma: a 10-year retrospective analysis. Taiwan J Obstet Gynecol (2017) 56:55–61. doi: 10.1016/j.tjog.2015.09.009

  • 39

    TanaseYKawaguchiRTakahamaJKobayashiH. Factors that differentiate between endometriosis-associated ovarian cancer and benign ovarian endometriosis with mural nodules. Magn Reson Med Sci (2018) 17:231–7. doi: 10.2463/mrms.mp.2016-0149

  • 40

    ParkJYKimDYSuhDSKimJHKimYMKimYTet al. Significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma. Int J Gynecol Cancer (2018) 28:11–8. doi: 10.1097/IGC.0000000000001136

  • 41

    PaikESKimTJChoiCHKimBGBaeDSLeeJW. Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis. J Gynecol Oncol (2018) 29:e18. doi: 10.3802/jgo.2018.29.e18

  • 42

    MuangtanSSuknikhomWSananpanichkulPBhamarapravatanaK. Suwannarurk K.Epithelial ovarian cancer with endometriosis is not associated with menopausal status: a Co-association study at prapokklao hospital. Asian Pac J Cancer Prev (2018) 19:1337–41.

  • 43

    YamamotoYWakikawaAUenoANagaiRMatsumotoMKomatsuJet al. Comparison of endometriotic cysts and ovarian cancer in association with endometriotic cysts. Cancer Treat Res Commun (2018) 14:26–9. doi: 10.1016/j.ctarc.2017.11.002

  • 44

    SonJHYoonSKimSKongTWPaekJChangSJet al. Clinicopathologic characteristics of ovarian clear cell carcinoma in the background of endometrioma: a surveillance strategy for an early detection of malignant transformation in patients with asymptomatic endometrioma. Obstet Gynecol Sci (2019) 62:27–34. doi: 10.5468/ogs.2019.62.1.27

  • 45

    ZhuCZhuJQianLLiuHShenZWuDet al. Clinical characteristics and prognosis of ovarian clear cell carcinoma: a 10-year retrospective study. BMC Cancer (2021) 21:322. doi: 10.1186/s12885-021-08061-7

  • 46

    ZhouLYaoLDaiLZhuHYeXWangSet al. Ovarian endometrioid carcinoma and clear cell carcinoma: a 21-year retrospective study. J Ovarian Res (2021) 14:63. doi: 10.1186/s13048-021-00804-1

  • 47

    ZhangXLiMTangZLiXSongT. Differentiation between endometriosis-associated ovarian cancers and non- endometriosis-associated ovarian cancers based on magnetic resonance imaging. Br J Radiol (2021) 94:20201441. doi: 10.1259/bjr.20201441

  • 48

    SoKAHongSRKimNRYangEJShimSHLeeSJet al. Association between atypical endometriosis and ovarian malignancies in the real world. J Ovarian Res (2021) 14:110. doi: 10.1186/s13048-021-00865-2

  • 49

    KumarSMunkarahAArabiHBandyopadhyaySSemaanAHayekKet al. Prognostic analysis of ovarian cancer associated with endometriosis. Am J Obstet Gynecol (2011) 204:63.e1–7. doi: 10.1016/j.ajog.2010.08.017

  • 50

    GarrettLAGrowdonWBGoodmanABorutaDMSchorgeJOdel CarmenMG. Endometriosis-associated ovarian malignancy: a retrospective analysis of presentation, treatment, and outcome. J Reprod Med (2013) 58:469–76.

  • 51

    TaySKCheongMA. Evidence for ethnic and environmental contributions to frequency of ovarian clear cell carcinoma. Aust N Z J Obstet Gynaecol (2014) 54:225–30. doi: 10.1111/ajo.12188

  • 52

    WangKCChangWHLeeWLHuangNHuangHYYenMSet al. An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis. BMC Cancer (2014) 14:831. doi: 10.1186/1471-2407-14-831

  • 53

    WangQWang LLYDingXLiuA. Expression and significance of ARID1A mRNA in endometriosis- associated ovarian cancer. J BUON (2017) 22:1314–21.

  • 54

    HeZXShiHHFanQBZhuLLengJHSunDWet al. Predictive factors of ovarian carcinoma for women with ovarian endometrioma aged 45 years and older in China. J Ovarian Res (2017) 10:45. doi: 10.1186/s13048-017-0343-2

  • 55

    HaraguchiHKogaKTakamuraMMakabeTSueFMiyashitaMet al. Development of ovarian cancer after excision of endometrioma. Fertil Steril (2016) 106:1432–1437.e2. doi: 10.1016/j.fertnstert.2016.07.1077

  • 56

    RenTSunTTWangSSunJXiangYShenKet al. Clinical analysis of chemo-resistance risk factors in endometriosis associated ovarian cancer. J Ovarian Res (2018) 11:40. doi: 10.1186/s13048-018-0418-8

  • 57

    TangHLiuYWangXGuanLChenWJiangHet al. Clear cell carcinoma of the ovary: clinicopathologic features and outcomes in a Chinese cohort. Med (Baltimore) (2018) 97:e10881. doi: 10.1097/MD.0000000000010881

  • 58

    VassardDSchmidtLGlazerCHLyng FormanJKamper-JørgensenMPinborgA. Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study. Hum Reprod (2019) 34:2290–6. doi: 10.1093/humrep/dez165

  • 59

    SampsonJA. Endometrial carcinoma of the ovary arising in endometrial tissue in that organ. Arch Surg (1925) 10:1–72. doi: 10.1001/archsurg.1925.01120100007001

  • 60

    ScottRB. Malignant changes in endometriosis. Obstet Gynecol (1953) 2:283–9.

  • 61

    Van GorpTAmantFNevenPVergoteIMoermanP. Endometriosis and the development of malignant tumours of the pelvis. A Rev literature. Best Pract Res Clin Obstet Gynaecol. (2004) 18:349–71. doi: 10.1016/j.bpobgyn.2003.03.001

  • 62

    MachidaHMatsuoKYamagamiWEbinaYKobayashiYTabataTet al. Trends and characteristics of epithelial ovarian cancer in Japan between 2002 and 2015: a JSGO–JSOG joint study. Gynecol Oncol (2019) 153:589–96. doi: 10.1016/j.ygyno.2019.03.243

  • 63

    SEER Ovarian Cancer. Available at: https://seer.cancer.gov/statfacts/html/ovary.html (Accessed December 20, 2022).

  • 64

    RaffiFMetwallyMAmerS. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab (2012) 97:3146–54. doi: 10.1210/jc.2012-1558

  • 65

    YounisJSShapsoNFlemingRBen-ShlomoIIzhakiI. Impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve: a systematic review and meta-analysis. Hum Reprod Update (2019) 25:375–91. doi: 10.1093/humupd/dmy049

  • 66

    SölétormosGDuffyMJAbu HassanSOVerheijenRHTholanderBBastRCet al. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European group on tumor markers. Int J Gynecol Cancer (2016) 26:43–51. doi: 10.1097/IGC.0000000000000586

  • 67

    SisodiaRCdel CarmenMG. Lesions of the ovary and fallopian tube. N Engl J Med (2022) 387:727–36. doi: 10.1056/NEJMra2108956

  • 68

    TimmermanDAmeyeLFischerováDEpsteinEMelisGBGuerrieroSet al. Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group. Br Med J (2010) 341:c6839. doi: 10.1136/bmj.c6839

  • 69

    AndreottiRFTimmermanDStrachowskiLMFroymanWBenacerrafBRBennettGLet al. O-RADS US risk stratification and management system: a consensus guideline from the ACR ovarian-adnexal reporting and data system committee. Radiology (2020) 294:168–85. doi: 10.1148/radiol.2019191150

  • 70

    GuerrieroSVan CalsterBSomiglianaEAjossaSFroymanWDe CockBet al. Age-related differences in the sonographic characteristics of endometriomas. Hum Reprod (2016) 31:1723–31. doi: 10.1093/humrep/dew113

  • 71

    SeidmanJDChoKRRonnettBMKurmanRJ. Urface epithelial tumors of the ovary. In: KurmanRJEllensonLHRonnetBM, editors. Blaustein’s pathology of the female genital tract, 6th ed. Boston, MA, USA: Springer (2011). p. 679–784.

  • 72

    RobinsonKAMeniasCOChenLSchiappacasseGShaabanAMCasertaMPet al. Understanding malignant transformation of endometriosis: imaging features with pathologic correlation. Abdom Imaging (2019) 45:1762–75. doi: 10.1007/s00261-019-01914-7

  • 73

    TanakaYOYoshizakoTNishidaMYamaguchiMSugimuraKItaiY. Ovarian carcinoma in patients with endometriosis: MR imaging findings. Am J Roentgenol (2000) 175:1423–30. doi: 10.2214/ajr.175.5.1751423

  • 74

    HajatiAHajatiO. A review of more than 2000 cases of site-specific pelvic endometriosis rates by MRI: a guide to minimizing under/overdiagnosis non-invasively. Insights Imaging (2022) 13:129. doi: 10.1186/s13244-022-01270-z

  • 75

    AlsonSJokubkieneLHenicESladkeviciusP. Prevalence of endometrioma and deep infiltrating endometriosis at transvaginal ultrasound examination of subfertile women undergoing assisted reproductive treatment. Fertil Steril (2022) 118:915–23. doi: 10.1016/j.fertnstert.2022.07.024

  • 76

    AbaidLNCuppJSChangMBeanesSRGoldesteinBH. Clear cell carcinoma of the pelvic side wall arising from endometriosis. Gynecol Oncol Rep (2018) 25:24–6. doi: 10.1016/j.gore.2018.05.006

  • 77

    CucinellaGSozziGDi DonnaMCUntiEMarianiAChianteraV. Retroperitoneal squamous cell carcinoma involving the pelvic side wall arising from endometriosis: a case report. Gynecol Obstet Invest (2022) 87:159–64. doi: 10.1159/000520983

  • 78

    LiBWangYWangYLiSLiuK. Deep infiltrating endometriosis malignant invasion of cervical wall and rectal wall with lynch Syndrome: a rare case report and review of literature. Front Oncol (2022) 12:832228. doi: 10.3389/fonc.2022.832228

Summary

Keywords

endometriosis, endometrioma, endometriosis-associated ovarian cancer, clear-cell ovarian carcinoma, endometrioid ovarian cancer, reproductive age, age at diagnosis.

Citation

Younis JS and Izhaki I (2023) At what age endometriosis-associated ovarian cancer is diagnosed? The implications for women in the reproductive age. Front. Oncol. 13:1193123. doi: 10.3389/fonc.2023.1193123

Received

24 March 2023

Accepted

15 May 2023

Published

23 May 2023

Volume

13 - 2023

Edited by

Annamaria Ferrero, Mauriziano Hospital, Italy

Reviewed by

Emanuele Perrone, Agostino Gemelli University Polyclinic (IRCCS), Italy

Updates

Copyright

© 2023 Younis and Izhaki.

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: Johnny S. Younis,

†ORCID: Johnny S. Younis, orcid.org/0000-0002-3793-6377; Ido Izhaki, orcid.org/0000-0002-4525-4683

Disclaimer

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.

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