Coexistence of endometriosis in women with mature cystic ovarian teratoma may not be rare.

We investigated the incidence of endometriosis in women with mature cystic ovarian teratoma and analyzed the clinicopathologic features of this occurrence. Methods From January 2017 through December 2018, we retrospectively studied 71 women who had undergone cystectomy for mature cystic ovarian teratoma (n = 55, teratoma group) and coexistence of endometriosis and mature cystic ovarian teratoma (n = 16, complex group). Serum anti-Müllerian hormone (AMH) levels were measured preoperatively and one month after surgery.


Abstract Background
We investigated the incidence of endometriosis in women with mature cystic ovarian teratoma and analyzed the clinicopathologic features of this occurrence.

Methods
From January 2017 through December 2018, we retrospectively studied 71 women who had undergone cystectomy for mature cystic ovarian teratoma (n = 55, teratoma group) and coexistence of endometriosis and mature cystic ovarian teratoma (n = 16, complex group). Serum anti-Müllerian hormone (AMH) levels were measured preoperatively and one month after surgery.

Results
Sixteen (22.54%) patients had coexistence of endometriosis and mature cystic ovarian teratoma (complex group); 55 patients had mature cystic teratoma alone (teratoma group). Early-stage endometriosis (stage I) was present in eight patients and advancedstage endometriosis (stage III or IV) was present in eight. In five cases (31.25%), the coexistence of endometrioma and mature cystic teratoma in the same ovary was observed. The mean operation time was significantly shorter in the teratoma group than in the complex group (61.02 ± 22.74 vs. 86.31 ± 35.35 min, p = 0.007). The complex group had more dysmenorrhea (43.8% vs. 7.3%, p = 0.002) and a significantly higher rate of decrease in serum anti-Müllerian hormone (AMH) levels (33.06 ± 24.92 vs. 16.31 ± 28.17%, p = 0.048).

Conclusion(s)
The prevalence of coexisting endometriosis and mature cystic ovarian teratoma may be underestimated. Patients with this rare concurrence may present with worsening dysmenorrhea and damage to ovarian reserve after surgery may be greater in patients 3 with coexisting endometriosis than in patients with mature cystic teratoma alone.

Background
Mature cystic ovarian teratomas (MCTs) or dermoid cysts are the most common ovarian tumor in women of reproductive age and account for about 20% of ovarian tumors [1,2].
MCTs account for approximately 70% of benign ovarian tumors in women under 30 year of age and 50% of pediatric tumors [3,4]. They occur bilaterally in 10-15% of cases [1].
These tumors are usually asymptomatic and are often discovered incidentally during routine physical or during radiologic examinations [5, 6] The proportion of asymptomatic tumors has been reported to range from 6-64.5% [7,8,9,10]. In addition, MCTs have a tendency to grow slowly with an estimated growth rate of 1.67 mm/year [1]. Therefore, recently, expectant management of MCTs as an alternative to surgical management has been proposed [1,3].
Endometriosis is a chronic inflammatory condition defined by the presence of endometrial tissue with glands and stroma outside the uterus [11]. Endometriosis is estimated to affect 10% of women in the reproductive age group [12]. The incidence of endometriosis in women with dysmenorrhea is approximately 40-60%, whereas it is up to 20-30% in women with subfertility [11,13].
Although MCTs and endometriosis are common gynecologic disorders occurring in women of reproductive age, concomitant MCTs and endometriosis are notably rare and have been reported in few case reports. However, the author has observed some patients with unusual concomitant MCTs and endometriosis.
The aim of this study was to determine the incidence of endometriosis in patients with a diagnosis of MCT who underwent laparoscopy and to clarify further the clinical manifestations of this condition.

Patients
All patients operated on for MCTs at the Departments of Obstetrics and Gynecology of the Chonbuk National University Hospital from January 2017 through December 2018 were included in this retrospective study. This study was approved by the Institutional Review Board of Chonbuk National University Hospital (File number: 2018-05-018-006). The requirement for obtaining informed consent from the patients was not applicable owing to the retrospective nature of the study.
The inclusion criteria were as follows: (1)  The serum AMH concentrations were measured preoperatively and one month after the surgery. The serum AMH level was determined using an enzyme-linked immunoassay kit, AMH Gen II (Beckman Coulter, USA).
The rate of decrease of serum AMH levels was calculated using the following formula: [(preoperative serum AMH level -postoperative month 1 AMH level)/(preoperative serum AMH level)] ⅹ100(%).
Cyst size was determined by preoperative imaging studies including ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). In the case of bilateral ovarian cysts, the sum of their largest diameters was defined as the cyst size.
The stage of endometriosis was defined according to the revised American Fertility Society classification [14].

Results
A total of 71 patients were included, of whom 55 had teratoma (teratoma group) and 16 had a coexistence of endometriosis and MCTs (complex group). Table 1 presents their demographic and clinical characteristics, including serum AMH levels and surgery data. 6 (8.5) 5 (9.1) 1 (6.2) 2 5 (7) Further, a comparison of the initial clinical presentation in each group during the visit to doctor is shown in Fig. 1. The majority of patients in the teratoma group were asymptomatic (24 cases, 43.6%) and the lesions were discovered incidentally during routine ultrasound examination, whereas the most common symptom in the complex group was dysmenorrhea (7 cases, 43.8%). Dysmenorrhea was more common in the complex group than in the teratoma group (43.8% vs. 7.3%, respectively; p = 0.002).
The complex group was divided into two subgroups according to lesion type of   [1] p value [2] p value [3] Age (years) 26

Discussion
The present study, to the author's knowledge, is the first attempt to investigate the incidence of the coexistence of MCTs and endometriosis and to evaluate the differential clinical characteristics of patients with this complex condition.
Although MCTs and endometriosis are benign diseases that commonly affect women of reproductive age, the coexistence of MCTs and endometriosis, especially in a single ovary, is rare [6,15,16]. However, in this study, this coexistence was not rare. Although this study included a relatively small number of patients, the incidence of coexisting MCTs and endometriosis was 22.54% and its incidence in a single ovary was 7.04%. Recently, Matalliotaki et al. proposed that endometriosis is linked with an increased risk of benign gynecological tumor, such as ovarian cyst, adenomyosis and uterine leiomyomas [17]. In that study, dermoid cysts (1.5%) were observed in women with endometriosis. This data and the present study's findings suggest that coexisting MCTs and endometriosis may be more common than previously reported.
MCTs are often discovered incidentally in asymptomatic women [1,10]. Patients with MCTs develop symptoms such as discomfort or pain when MCTs are complicated by torsion, rupture, and infection [6]. However, various types of pain are associated with endometriosis: dysmenorrhea, deep dyspareunia, and pelvic pain unrelated to intercourse or menstruation, such as pain during defecation or urinating [18]. Sonographic examination is the initial method for identifying adnexal cystic structures, but MCTs can be occasionally difficult to distinguish from endometriomas, hemorrhagic cyst, and mucinous cystic neoplasm based on ultrasonography alone [19], and additional modalities including CT or MRI may be needed. However, the complexity and rarity of coexisting The recommended management of MCTs is generally surgical removal because of a large cyst size, risk of torsion, and concern for occult malignancy. Traditionally, MCTs have been removed by elective surgery and this procedure accounts for 20-35% of the surgical removal of ovarian tumors [1,20]. MCTs are the most common germ cell tumors of the ovary in women of reproductive age, and account for approximately 70% of benign ovarian neoplasms in women under 30 years of age [21,22]. The major concern among these younger women is future fertility.  [23.24]. Several studies reported a reduced number of retrieved oocytes for in vitro fertilization and premature ovarian failure after surgery for endometriosis [25.26].
The present study's results showed that the rate of decline of serum AMH levels was significantly higher in patients with coexisting MCTs and endometriosis than in patients with MCTs alone. The study's small sample size makes generalizing the conclusion difficult, but this result suggests that surgical cystectomy for this condition in a single ovary could cause more damage to the ovarian reserve.
The malignant transformation of MCTs is an uncommon complication, with an incidence of 0.17-2% [3,4]. However, endometriosis is present in about 10-15% of ovarian cancers and is usually associated with endometrioid carcinoma or clear cell adenocarcinoma [27]. Further, a collision tumor is defined as the coexistence of two adjacent, but histologically distinct tumor components [31]. Collision tumors have been reported in various organs including the esophagus, stomach, liver, bone, kidney, central nervous system and lung, and so on, but such tumors are relatively rare in the ovary [32]. In addition, the most common histologic combination of a collision tumor in the ovary is the coexistence of teratoma and mucinous tumors; therefore a combination of teratoma with serous cystadenoma is rare [33].
This study had several limitations. First, not all patients had pathology-confirmed endometriosis. Second, the reverse case-the presence of MCTs in patients with endometriosis-was not considered. In addition, the number of patients analyzed was small.

Conclusions
The findings of this study suggest that the coexistence of MCTs and endometriosis is not as rare as previously thought. This study also showed that among women with MCT, those with coexisting endometriosis had marked dysmenorrhea compared to women with MCT alone and that damage to ovarian reserve after cystectomy in women with coexisting endometriosis may be greater than in women with MCT alone. These results can not only help categorizing this complex disease, but can also be used to standardize its treatment.
Nevertheless, further prospective studies are required to verify whether the coexistence of MCTs and endometriosis is indeed not rare.

Ethics approval and consent to participate
This study was approved by the Institutional Review Board of Chonbuk National University Hospital (IRB File No. 2018-05-018-006 ). Due to the retrospective design of the study an informed consent is not applicable.

Consent for publication
Not applicable

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Figure 1
Bar plot representing sample distribution of clinical presentation between the teratoma group and the complex group. Y axis presented as sample number.
Sample percentage (%) of each clinical presentation presented inside each bar.