Ultrasonographic diagnosis and surgical outcomes of adnexal masses in children and adolescents

This study aimed to evaluate the incidence, clinical diagnosis, surgical treatment, and histopathological findings of adnexal masses in children and adolescents. This retrospective study included patients aged < 20 years who were diagnosed with adnexal masses between January 2005 and December 2018 at the Konkuk University Medical Center. Adnexal masses were diagnosed in 406 patients. The mean age of patients was 17.3 years at the time of diagnosis. The primary presenting symptoms and signs were abdominal pain (81.4%), mass per abdomen (13.7%), dysmenorrhea (3.4%), incidental finding (2%), and abdominal distention (0.5%). In total, 204 patients underwent surgery for adnexal masses, and 202 patients were observed without surgery. Histopathological examination revealed 110 benign neoplasms, 72 non-neoplastic lesions, 3 ectopic pregnancies, 3 tubo-ovarian abscesses, 7 borderline malignant tumors, and 9 non-epithelial ovarian malignant tumors. Abdominal pain was the most common reason for hospital visits and surgery in adolescents and young women with adnexal masses. The ultrasonographic diagnosis was consistent with the histopathological diagnosis. In recent years, the use of minimally invasive surgery such as laparoscopy and robotic, has increased in young patients with adnexal masses.

In total, 204 patients underwent surgery for adnexal masses, and 202 patients were observed without surgery. Significant differences between the observation and surgery groups were found in the size of the mass (3.7 ± 1.4 cm vs. 8.1 ± 4.6 cm, P < 0.0001) and clinical diagnosis based on ultrasonography (non-neoplastic tumor vs. neoplastic tumor, P < 0.0001) ( Table 2). No differences were found in age (P = 0.589) or symptoms (P = 0.542) between the groups. The mean follow-up period was 16.5 months in the observation group. Most patients in the observation group demonstrated spontaneous regression of ovarian cysts, including hemorrhagic cysts, corpus luteum cysts, functional cysts, benign cysts, and tubo-ovarian abscesses. Seven patients with endometriosis and one patient with tubo-ovarian abscess had lesions persistent for > 30 days.

Discussion
Adnexal masses are uncommon in children and adolescents, and they can represent a wide range of pathologies, from non-neoplastic to benign neoplasms and malignant tumors. In this study, 89.2% of the adnexal masses were benign and non-neoplastic, and only 7.8% of adnexal masses were malignant. Furthermore, mature teratomas are the most common benign ovarian tumors, consistent with the findings of recent studies 4,5,8 . Adnexal masses related to ectopic pregnancies or pelvic inflammatory disease are common in late adolescence (18-20 years). This finding seems to be associated with an increase in sexual activity with increasing age. Older teens are more likely to visit the emergency department for pelvic inflammatory disease than younger teens 9 .
The rate of malignant tumors in children and adolescents varies from 4 to 22% 10 . Germ cell tumors are the most common malignant ovarian tumors in children and adolescents. In this study, malignant tumors were found in 16 patients (seven patients with borderline tumors and nine patients with non-epithelial malignant tumors), the most common non-epithelial malignant tumor was germ cell tumor (five cases), followed by choriocarcinoma Table 3. Clinical characteristics of patients with surgical treatment (n = 204). www.nature.com/scientificreports/   www.nature.com/scientificreports/ (two cases), sex cord-stromal tumor (one case), and desmoplastic small round cell tumor (one case). Patients aged < 17 years were more likely to develop non-epithelial malignancies than those aged > 18 years (P < 0.006). An accurate preoperative diagnosis is challenging since the symptoms of adnexal masses are diverse and nonspecific 11 . Abdominal pain was the most common cause of surgery in the present study. It is often confused with adnexal torsion or appendicitis. Abdominal palpation and bimanual recto-abdominal or vaginal examinations in sexually active patients are required for an accurate diagnosis.
Surgical treatment of adnexal masses in children and adolescents is controversial. Removal of the suspected mass while preservation of fertility is a critical issue at this age 12,13 . In the present study, 33% of patients underwent surgery, even though they had a preoperative diagnosis of non-neoplastic tumors on ultrasonography. These patients had a mean adnexal mass size of 6.3 cm, and could not be differentiated from adnexal torsion due to severe abdominal pain. However, 10.9% of patients diagnosed with neoplastic tumors did not undergo surgery because of incidental findings and small-sized adnexal masses.
Various modalities can be used to diagnose adnexal masses and determine treatments. Most masses are detected using ultrasonography, which is the first-line imaging test 14 . Because of its high accessibility, relatively low risk, cost-effectiveness, and diagnostic accuracy, ultrasonography is a useful diagnostic tool for differentiating adnexal masses 15 . Ultrasound findings are good indicators of whether the patient should be operated or managed conservatively 16 . Furthermore, ultrasonography allows continuous imaging follow-up for relatively small ovarian masses without surgical treatment 17 . The results of this study demonstrated that the size of nonneoplastic tumors was smaller than that of neoplastic masses. Patients who underwent surgery had large tumors and showed neoplastic features on ultrasonography compared to those who were observed without surgery (P < 0.0001). Reassuringly, the ultrasonographic diagnosis was consistent with the histopathological diagnosis (k = 0.722, P < 0.0001). A previous study has shown that 90% of simple cysts measuring 5-7 cm on ultrasonography decreased in size or resolved on follow-up 18 .
In addition to ultrasonography, CT or MRI can be helpful in the diagnosis of malignant ovarian tumors with high accuracy. Additional information, such as the nature of the adnexal mass and metastatic involvement of the pelvic and para-aortic lymph nodes can be determined with CT or MRI 19,20 . In malignant ovarian tumors, the levels of serum tumor markers (AFP, β-hCG, CA-125, CA-19-9, and CEA) tended to rise 21 . However, in this study, 44% of patients with malignant tumors had normal levels of serum tumor markers. Approximately 50% of malignant tumors present with elevated tumor marker values 22 . Therefore, normal serum tumor marker levels cannot exclude a malignancy.
Generally, if a malignant tumor is not suspected, ovarian-sparing surgery is the standard treatment for benign ovarian tumors 23,24 . Surgery for benign ovarian tumors is conservative, and ovarian cystectomy or simple excision is usually performed 25,26 . Ovarian-sparing surgery has successful clinical outcomes, with low rates of recurrence and repeated surgery 7,26 . Approximately 87% of the patients in this study underwent ovarian-sparing surgery. Most patients underwent MIS (laparoscopy or robotic surgery), and none of the patients required a laparotomy. MIS has been widely used in many surgeries, including those involving the female genital tract 27 . MIS is associated with greater cost-effectiveness, less pain, shorter hospitalization, reduced recovery time, lower incidence of surgical site infection, less bleeding, more satisfaction with scars, and fewer postoperative complications than laparotomy surgery 28,29 . Because of these advantages, MIS usage has increased over time (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) to treat young women with adnexal masses in our institution. However, the choice between laparotomy and MIS, especially if a malignant tumor is suspected, is controversial.
In conclusion, abdominal pain is the most common reason for hospital visits and surgery in adolescents and young women with adnexal masses. The ultrasonographic diagnosis was consistent with histopathological diagnosis. In recent years, ovarian-sparing surgery with laparoscopy or robotic surgery has been increasingly used for the treatment of young patients with adnexal masses. Long-term follow-up is needed to fully assess the effects of ovarian-sparing surgery on future fertility and ovarian function in this population.

Methods
This retrospective study included young women aged < 20 years, diagnosed with adnexal masses between January 2005 and December 2018 at the Konkuk University Medical Center. Patients with secondary ovarian malignancies or a history of malignancy were excluded. After obtaining institutional review board approval (No. KUMC 2020-04-055), we reviewed the medical charts of the patients, including clinical characteristics and surgical and histopathological reports. Data on presenting symptoms, age at diagnosis, tumor size on ultrasonography, surgical procedures, and serum tumor markers were extracted. According to the surgical reports, the type of surgery was defined as (1) cystectomy, (2) salpingectomy, (3) oophorectomy or salpingo-oophorectomy; and (4) cytoreductive surgery, including unilateral salpingo-oophorectomy, pelvic lymphadenectomy, omentectomy, and peritoneal washing.
Statistical analysis. Categorical variables are presented as numbers and percentages, and continuous variables are presented as means with standard deviations. To assess differences between groups, we used the t test and chi-square test for continuous and categorical variables, respectively. Cohen's kappa statistic was used to evaluate the diagnostic agreement between the ultrasonography and histopathological findings. Linear trend estimation was used to make statements about tendencies in surgery from 2005 to 2018. The R 2 statistic shows how significantly the slope of the fitted line differs from zero. Statistical analyses were performed using IBM SPSS (version 21.0; SPSS Inc., Chicago, IL, USA). Statistical significance was set at P < 0.05. Ethical approval. The  www.nature.com/scientificreports/ standards of the institution and with the 1964 Helsinki Declaration and its later amendments. Informed consent was obtained from all participants from a parent and/or legal guardian, as the patients involved in the study were below 18 years of age.

Data availability
The datasets used and analyzed during the current study are provided by the corresponding author upon reasonable request. www.nature.com/scientificreports/ Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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