Prevalence and clinico-pathological correlates of adenomyosis in benign hysterectomy specimens: A retrospective cohort study

Authors

Abstract

Aim To investigate the demographic, clinical, and histopathological correlates of adenomyosis in women undergoing hysterectomy for benign gynecologic conditions.
Materials and Methods This retrospective study included 202 total abdominal hysterectomy specimens collected between 2013 and 2015. Adenomyosis was histologically defined as endometrial glands and stroma located ≥2 mm below the endomyometrial junction. Clinical, demographic, and pathological data were compared between patients with and without adenomyosis using appropriate statistical tests.
Results Adenomyosis was identified in 101 cases (50.0%). Women with adenomyosis had significantly lower BMI (p = 0.001), higher parity (p = 0.015), and lower frequency of regular menstrual cycles (p < 0.001). Chronic cervicitis and endometrial polyps were significantly less common among these patients (p = 0.039 and p = 0.013, respectively). Multivariate logistic regression confirmed independent associations between adenomyosis and reduced prevalence of cervicitis and polyps.
Discussion Adenomyosis was highly prevalent and associated with specific reproductive and pathological features. These findings highlight the need for systematic histopathological evaluation and clinical suspicion, particularly in premenopausal women with nonspecific symptoms.

Keywords

Introduction

Adenomyosis is a benign uterine disorder characterized by the presence of endometrial glands and stroma within the myometrium, resulting in an enlarged and frequently tender uterus [1]. Its prevalence ranges from 20% to 30% in the general female population to as high as 65%–70% in hysterectomy specimens, according to modern histopathological studies [2]. Clinically, adenomyosis is known to present with a broad spectrum of nonspecific symptoms, including heavy menstrual bleeding, dysmenorrhea, chronic pelvic pain, and dyspareunia; however, symptom profiles were not assessed in the present study [1, 2].
The pathogenesis of adenomyosis remains incompletely understood. The most widely accepted theory—”tissue injury and repair”—suggests that disruption of the endometrial– myometrial junction, due to pregnancy, cesarean section, curettage, or other uterine procedures, facilitates the invagination of the basalis layer of the endometrium into the myometrium. This process is likely mediated by local inflammation, angiogenesis, and increased estrogen activity [3, 4]. Alternative hypotheses include the persistence of Müllerian remnants and metaplastic transformation of pluripotent Müllerian stem cells, though these lack the mechanistic and histopathological support that backs the invagination model [5]. From a diagnostic perspective, advances in imaging modalities have improved the noninvasive detection of adenomyosis. Transvaginal ultrasonography may show heterogeneous myometrial echotexture, subendometrial echogenic linear striations, or myometrial cysts, with reported sensitivity and specificity ranging from 72%–86% and 74%–93%, respectively [2]. Magnetic resonance imaging (MRI), particularly T2-weighted sequences, can reveal low-signal foci consistent with ectopic endometrial tissue, with diagnostic accuracy exceeding 85% [7]. Despite these improvements, histopathological confirmation— via hysterectomy or targeted myometrial biopsy—remains the definitive diagnostic standard, often limiting early diagnosis and conservative management [8].
Adenomyosis rarely occurs in isolation. It frequently coexists with other gynecological conditions such as leiomyomas, endometriosis, endometrial hyperplasia, and chronic cervicitis [9, 10]. The shared pathophysiological mechanisms likely include estrogen-driven proliferation and chronic inflammation. Risk factors such as multiparity, lower body mass index (BMI), and prior uterine surgery further contribute to this overlap [4, 8].
Despite increased recognition of adenomyosis in recent years, its demographic and clinico-pathological associations remain insufficiently characterized, particularly in hysterectomy- based series. Given its frequent coexistence with other benign uterine conditions and its potential impact on women’s health, a clearer understanding of these relationships is essential. We hypothesized that adenomyosis demonstrates distinct associations with reproductive characteristics and coexisting gynecologic pathologies. To address this, the present study was designed with three main objectives: to determine the prevalence of adenomyosis in benign hysterectomy specimens, to identify demographic and reproductive factors independently associated with its presence, and to characterize the distribution of coexisting uterine pathologies in comparison to cases without adenomyosis. We anticipate that these findings will contribute to improved clinical recognition and support more tailored diagnostic and management strategies for affected patients.

Materials and Methods

Study Design and Setting
This retrospective cohort study was conducted at Süleymaniye Training and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey, between December 2013 and July 2015. Institutional permission for the study was obtained from the hospital’s education and planning committee. A total of 202 patient records were reviewed, all of whom had undergone total abdominal hysterectomy (with or without bilateral salpingo- oophorectomy) for benign gynecologic indications. None of the cases had a preoperative diagnosis of adenomyosis; all diagnoses were made based on postoperative histopathological findings.
Inclusion and Exclusion Criteria
Inclusion Criteria:
- Women who underwent total abdominal hysterectomy with or without bilateral salpingo-oophorectomy between December 2013 and July 2015.
- Histopathological confirmation of adenomyosis for the case group.
- Complete availability of preoperative hemogram, demographic data, and surgical indication records.
- Surgery performed for benign gynecological indications. Exclusion criteria:
- Any preoperative suspicion or confirmation of gynecologic malignancy.
- Incomplete or missing surgical, pathology, or laboratory data.
- Patients with previous uterine malignancy or hysterectomy due to cancer.
Case Selection and Grouping
Patients were divided into two groups based on postoperative histopathological diagnosis: the adenomyosis group (n=101) and the control group without adenomyosis (n=101). Patients were matched consecutively based on the time of surgery.
Data Collection
Preoperative data were extracted from hospital archives and included demographic characteristics (age, body mass index), obstetric history (gravidity, parity, number of spontaneous abortions), and hematological parameters (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, platelets, and red cell distribution width (RDW), which reflects variation in red blood cell size and may indicate underlying inflammation or anemia).
Postoperative histopathological analysis confirmed the presence or absence of adenomyosis (defined as the presence of endometrial glands and stroma within the myometrium) and identified coexisting gynecologic conditions such as leiomyoma (benign smooth muscle tumor of the uterus), endometrial polyp, endometrial hyperplasia (thickening of the endometrial lining due to unopposed estrogen stimulation), endometriosis, chronic cervicitis (persistent inflammation of the cervix), ovarian cysts, and endometrial cancer. Ovarian cysts were included without differentiation between benign and malignant forms.
Statistical Analysis
Statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Data normality was assessed using the Shapiro–Wilk test. Continuous variables were presented as mean ± standard deviation or median (interquartile range), and categorical variables were expressed as percentages. Student’s t-test or Mann–Whitney U test was used for between-group comparisons of continuous variables depending on data distribution. Chi-square or Fisher’s exact test was used for categorical variables. A p-value < 0.05 was considered statistically significant. Missing data (<5%) were handled with listwise deletion.
Post Hoc Power Analysis
A post hoc power analysis was conducted using G*Power version 3.1.9.7. Based on the observed BMI difference between groups, using a medium effect size (Cohen’s d = 0.5), a sample size of 101 patients per group, and an alpha level of 0.05, the calculated statistical power was 0.942 (94.2%). This indicates that the study had sufficient power to detect clinically meaningful differences between the groups.
Ethical Approval
This study was approved by the Ethics Committee of Başakşehir Çam and Sakura City Hospital (Date: 2025-05-21, No: E-96317027-514.10-277198945).

Results

The comparison of demographic and reproductive characteristics showed no significant difference in age between groups (p=0.103). However, body mass index was significantly higher and parity significantly lower in the adenomyosis group compared to controls (p=0.001 and p=0.015, respectively). Hematological analysis revealed that hemoglobin levels were similar between groups (p=0.086), while hematocrit was significantly lower in the adenomyosis group (p=0.015). Leukocyte and neutrophil counts were significantly higher, and lymphocyte counts significantly lower in patients with adenomyosis (p=0.001 for all). Platelet count and red cell distribution width showed no significant differences (Table 1). Regarding uterine pathologies, endometrial polyps and chronic cervicitis were significantly less common in the adenomyosis group (p=0.013 and p=0.039, respectively). No statistically significant differences were observed in the frequency of myoma, endometrial hyperplasia, endometriosis, ovarian cysts, or endometrial cancer (p>0.05 for all) (Table 2). In the multivariate logistic regression analysis adjusted for BMI, adenomyosis was independently associated with a lower likelihood of chronic cervicitis (OR: 0.44; 95% CI: 0.20–0.96; p=0.039) and endometrial polyp (OR: 0.39; 95% CI: 0.18–0.87; p=0.021). A non-significant trend toward increased odds of endometriosis was noted (OR: 1.85; 95% CI: 0.92–3.71; p=0.083). BMI was independently associated with an increased risk of endometriosis (p=0.042) and endometrial hyperplasia (p=0.048) (Table 3).

Discussion

The reported prevalence of adenomyosis in hysterectomy specimens varies widely, ranging from approximately 5% to 70%. This broad range is largely attributed to differences in histological definitions, sampling protocols, and the thoroughness of myometrial examination by pathologists [11, 12, 13]. Earlier studies often diagnosed adenomyosis based on the presence of ectopic endometrial tissue within a single low-power field. However, the lack of standardization in field size and sectioning methods has prompted the development of more quantitative diagnostic thresholds [14].
To enhance diagnostic accuracy in adenomyosis, various authors have proposed more stringent histological and surgical criteria. Rasmussen et al. emphasized the importance of defining a specific depth of myometrial invasion beyond the endomyometrial junction to ensure accurate diagnosis of intrinsic adenomyosis [14]. In addition, Yoon et al. proposed a combined resection and reconstruction technique to better delineate lesion margins, particularly in cases of diffuse adenomyosis, while preserving fertility [15]. Kuo et al. highlighted the advantages of laparoscopic excision using the four-petal method in facilitating precise histopathological assessment of focal adenomyomas [16]. Furthermore, Habiba and Benagiano discussed the ongoing challenges in developing a standardized classification system and emphasized the need for consensus on histological and imaging-based diagnostic criteria to improve reproducibility and interstudy comparisons [17]. Collectively, these findings underscore the need for a comprehensive and standardized approach in both imaging and histological evaluation to optimize diagnostic yield.
Recognizing the diagnostic complexity, Benagiano and Brosens called for a unified approach combining histopathology with clinical context [3]. Abbott drew attention to the role of chronic inflammation and hyperestrogenism in adenomyosis pathogenesis, suggesting that clinical suspicion should guide pathological examination [1]. Halvorson et al. emphasized the importance of consensus definitions to facilitate reproducibility in research and enable robust meta-analyses [4].
In our study, adenomyosis was identified in 50% of 202 consecutive hysterectomy cases. This rate is comparable to that reported in a recent multicenter analysis of postpartum hysterectomies, where the prevalence reached 39.4% [18]. The similarity in prevalence across distinct surgical populations reinforces the notion that adenomyosis remains underdiagnosed, particularly in the absence of standardized histological protocols.
Importantly, adenomyosis frequently coexists with other gynecologic pathologies, affecting up to 80% of cases. In our cohort, leiomyomas were present in 47.5%, chronic cervicitis in 77.2%, and endometriosis in 29.7% of women with adenomyosis. These findings are in line with previous studies reporting high rates of fibroid coexistence, as well as clinico-pathological data from West African and European populations [19]. Bulun et al. recently proposed that overlapping molecular mechanisms involving estrogen biosynthesis and inflammatory signaling may explain these associations [20].
The pathophysiological link between adenomyosis and coexisting lesions is thought to involve local hyperestrogenism, abnormal cytokine expression, and repeated mechanical trauma at the endomyometrial interface [8]. These same factors contribute to the growth of fibroids and the ectopic implantation seen in endometriosis [6, 7]. Van den Bosch and Schoubroeck have emphasized the influence of a hyperestrogenic and pro-inflammatory uterine microenvironment in driving both adenomyotic and leiomyomatous changes [2].
Clinically, this shared environment leads to overlapping symptoms such as menorrhagia, dysmenorrhea, and chronic pelvic pain, which complicate preoperative diagnosis and management [1]. Although high-resolution imaging modalities like transvaginal ultrasound and MRI have improved non- invasive detection of myometrial abnormalities, definitive diagnosis still requires meticulous pathological assessment [11, 14].
Given the high rate of coexisting findings and their impact on quality of life, a multidisciplinary diagnostic approach is crucial. Integrating clinical symptoms, imaging results, and systematic histopathology allows for more accurate diagnosis and the development of individualized treatment strategies [18].
Clinical symptom profiles such as menometrorrhagia or pelvic pain were not available for analysis in our dataset. This supports the idea that adenomyosis presents with non-specific symptoms, contributing to its reputation as a “missed disease” [21]. Despite advances in imaging-based diagnosis using revised MUSA criteria, histopathological evaluation remains the gold standard due to persistent variability and limited interobserver agreement in ultrasound interpretation [22].
Although menopausal status was not directly analyzed, previous studies have associated adenomyosis with estrogen- dependent pathogenesis. Nonetheless, emerging evidence of fibrotic and epithelial-mesenchymal transition (EMT) activity in postmenopausal uteri suggests that non-hormonal mechanisms, such as fibrosis, may sustain the disease beyond the reproductive years [23].

Limitations

This study has several limitations. First, its retrospective design carries an inherent risk of selection and information bias. Second, the histopathological evaluation was limited to hysterectomy specimens, which restricts the generalizability of findings to women who undergo surgery. Third, imaging findings and symptom severity scores were not uniformly available in the data, limiting the ability to correlate clinical presentation with pathological extent. Despite these limitations, the large sample size and multivariate analysis strengthen the reliability of the results.

Conclusion

Our findings indicate that adenomyosis is a highly prevalent histopathological condition among women undergoing hysterectomy for benign gynecologic indications. It is independently associated with certain demographic, reproductive, and coexisting pathological features, including lower body mass index, higher parity, and reduced frequencies of chronic cervicitis and endometrial polyps. These results highlight the importance of routine histopathological evaluation and increased clinical suspicion, especially in premenopausal women presenting with nonspecific gynecologic symptoms. An integrated approach combining clinical, laboratory, and pathological data may enhance the early recognition and management of adenomyosis.

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