To the best of our knowledge, the current study is the first to report the effect of myometrial lesions such as adenomyosis and leiomyoma on the discordance of pathologic findings in patients who were diagnosed as having EH before undergoing hysterectomy. We retrospectively evaluated patients who underwent hysterectomy and their pre-post operative endometrial pathology results. We calculated the discordance rate of these results as 58.52%; 22.11% of patients were underdiagnosed and 36.40% were overdiagnosed. Patients who were classified as underdiagnosed were found to be older and had higher BMI than the others. It was also concluded that discordance rates were higher in patients with adenomyosis.
Adenomyosis is described as the presence of the endometrial glands and stroma within the myometrium. Microscopically, adenomyosis consists of non-neoplastic ectopic endometrial stroma and glands surrounded by hypertophic and hyperplastic myometrium . Although traditionally the diagnosis is made through histopathologic examination, preoperative diagnosis can be made using transvaginal ultrasonography (TVUSG) or magnetic resonance imaging (MRI) due to the developments in imaging techniques . Adenomyosis is found incidentally in 20–25% of benign hysterectomy specimens . The relation between the diagnosis of EH and adenomyosis cannot be demonstrated with the available data. Existing literature focused on EC developing in the presence of adenomyosis. Although the results of studies related to adenomyosis co-existence with EC are contradictory, a 22.6% pooled prevalence of adenomyosis in EC has been reported in recent studies and it has been shown that this rate is not different from co-existence in benign conditions . In our data, the co-existence rate of adenomyosis and EC was 12.5% (6 of 48). Although the underlying disorder is hyperestrogenism, the known etiologic factors of EC and adenomyosis are polar opposites. Multiparity and oral contraceptive use are associated with increased risk of adenomyosis, and these are also associated with a reduced risk of EC . This could suggest that the coexistence of these two pathologies may be related to a high incidence of adenomyosis in peri and postmenopausal patients, rather than a common etiologic cause or direct cause-effect relationship.
In the current study, none of the concurrent ECs originated from adenomyotic foci. Thirty-nine of the ECs were stage 1 and nine were stage 2. None of the stage 2 ECs had co-existing adenomyosis. Although the adenomyosis co-existence rate did not differ between EH subtypes, it was observed that adenomyosis accompanied fewer cases in those who were underdiagnosed in the final pathologic evaluation.
When the presence of myometrial lesions is not taken into account, there are several studies identifying patients with EH who are likely to be underdiagnosed, to avoid possible suboptimal surgery, especially in AEH cases in which concurrent EC rates are reported up to 40% . Vetter et al. evaluated 169 patients with complex AEH and reported that the concurrent EC rate was 48.5% and that the risk of concurrent EC was increased in patients with a preoperative endometrial thickness of more than 2 cm and those aged over 65 years . Erdem et al. reported that age over 50 years, diabetes mellitus, hypertension, and nulliparity were independent risk factors for concurrent EC in AEH . In our study, we found that underdiagnosed patients were significantly older and postmenopausal. In the underdiagnosis group, patients had higher BMI and lower parity. Consistent with our results, Hui et al. examined occult AEH and EC risk factors in NAEH cases and stated that patients with higher grades in the final pathology had significantly lower median parity and higher BMI . A recent study that evaluated risk factors for occult AEH and EC in women diagnosed as having NAEH in endometrial biopsy found that patients aged ≥ 51 years with complex NAEH subtype had a high risk for underdiagnosis . According to the results of the mentioned studies [20, 21] and our study, it could be concluded that although NAEH was considered as benign by the WHO and the first-line treatment option was conservative, hysterectomy may be an option in the presence of risk factors for underdiagnosis in patients with NAEH.
In addition to the aforementioned risk factors about concurrent EC risk, the preferred endometrial sampling method is also relevant. D&C has been widely used; however, in practice, endometrial aspiration biopsy using a pipelle or Endosampler is the most preferred endometrial sampling method because it can be performed easily in an outpatient setting, does not require general anesthesia, and is as accurate as D&C in the diagnosis of endometrial pathologies [8, 22]. In the current study, the Endosampler was preferred for preoperative diagnosis.
Studies about overdiagnosis in EH are limited. In one study, no characteristic features could be identified that distinguished the overestimated group from the other groups among the clinical parameters and imaging findings . In our study, although the preoperative characteristics of patients with overdiagnosis did not differ from those of concordant patients, we found that the presence of leiomyoma did not affect the results, but the presence of adenomyosis increased the rates of overdiagnosis. The patients in the overdiagnosis group could be candidates for close surveillance, hormonal therapy or even surgery, and they face the risk of overtreatment and increased anxiety.
This novel study investigating the relationship between endometrial pathology discordance and myometrial lesions has a large sample size. Besides that, the use of the same endometrial sampling method in all patients, the evaluation of both pre and postoperative pathology results by the same gynecologic pathologists in the same center are strengths of the study. On the other hand, the retrospective design and the conductance of the study in a referral center that might increase the incidence of occult EC could be considered as limitations of the study.
In conclusion, adenomyosis, which is an incidental and common benign pathology, can cause both overdiagnosis and underdiagnosis in patients with EH. For appropriate diagnostic and therapeutic management of EH, it can be underlined that the possibility of discordant results in the presence of adenomyosis should be considered, and those patients should be carefully evaluated together with their clinical features for treatment options.