Unexpected ovarian malignancy found after laparoscopic surgery in patients with adnexal masses--a single institutional experience

From January 2000 to December 2012, 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital. All patients had been diagnosed with a benign adnexal tumor before the surgery by pelvic examination and transvaginal or transabdominal ultrasonography. Approximately 70% of the patients had received a preoperative MRI-based diagnosis. Among them, we picked up 471 patients according to the following criteria: 1) Patients aged younger than 50 years 2) Patients who underwent either laparoscope-assisted cystectomy (LAC) or laparoscope-assisted adnectomy (LAA) 3) Patients who completed routine check-up after the surgery All patients underwent laparoscopic surgery, which consisted of laparoscope-assisted adnectomy (LAA) and laparoscope-assisted cystectomy (LAC) under general anesthesia. Each surgical procedure was selected at surgeon’s discretion considering the size of the tumors, age of the patients, and the technical operative feasibility. In all cases, tumors were punctured during the operation for the purpose of reducing their sizes by aspirating intratumoral fluid. We classified the 471 patients by the age, surgical procedures, pathological diagnosis of the tumors, and parity after treatment. We also examined 10 patients with subsequently proven borderline or a higher level of malignancy, regarding their preoperative diagnoses, procedure of second surgery, postoperative chemotherapies, and oncologic outcome.

Patients’ characteristics are shown in Table 1 . The median age of all 471 patients was 31 years, ranging from 13 to 50, but nearly half of them were younger than 30 years. Nulliparous patients numbered 321(68.1%), and the average parity before surgery was 0.57 ± 0.94. More than 90% (N =430) of the patients underwent LAC, of which 79.0% (N =340) was unilateral and 21% (N =41) was bilateral. The remaining women (N =41) received LAA. Ten patients were diagnosed with borderline or higher-level malignancy, 4 of whom underwent second surgery which included 1 laparoscopy and 3 laparotomies. They corresponded to 2.1% (10/471) of all patients. There was endometrioma in 182, benign ovarian neoplasm in 232, and functional cyst in 14 patients. Benign neoplasms included teratoma (N =185), serous cystadenoma (N =16), mucinous cystadenoma (N =29), and struma ovarii (N =2). Figure 1 is a flowchart showing patients’ classification according to the age, surgical procedures, parts of the adnexa where the tumors arose and whether the tumors were benign or malignant. Patients’ characteristics Benign ovarian neoplasm contains teratoma, serous cystadenoma, mucinous cystadenoma and struma LAA : laparoscpe assisted adnectomy LAC : laparoscope assisted cystecomy The classification of all patients according to the age, surgical procedures, parts of the adnexa in which the tumors arose and whether or not the tumors are benign. BOT: borderline ovarian tumor, LAA: laparoscope-assisted adnectomy, LAC: laparoscope-assisted cystectomy Table 2 shows these 10 patients in terms of their preoperative examinations, surgical procedure, histological type, postoperative chemotherapy, and follow-up peroid. There were 6 patients with BOT, 2 with epithelial ovarian carcinoma, 1 with immature teratoma, and 1 with granulosa cell tumor. All patients with BOT were diagnosed with mucinous cystadenoma showing borderline malignancy. Preoperative MRI suggested malignancy (adenoma or carcinoma, mature or immature teratoma) only in 2 cases (case 1 and case 8). The remaining 8 cases showed no findings suspecting as malignancy. Figure 2 shows two typical images leading to diagnoses of mucinous cystadenoma and teratoma, respectively. Elevations of serum tumor markers were observed in cases 6 and 8. Cancer antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) were elevated in cases 6 and 8, respectively. Two patients with BOT (case 6 and 7), one case with epithelial ovarian carcinoma (case 4), and the patient with immature teratoma (case 8) underwent a second surgery. Of them, 2 nulliparous patients who were younger than 30 years (cases 7 and 8) chose fertility-sparing surgery. The other 2 multiparous patients (cases 4 and 6) underwent non-conservative surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy). Case 4 involved a carcinoma suspected to have arisen from a benign tumor that had been treated 6 years previously. She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic lymphnodectomy. The other patients with BOT underwent hysterectomy and left salpingo-oophorectomy. Both received chemotherapies that consisted of carboplatin and taxane for 4 months. Although the period of postoperative follow-up varied from 12 to 120 months, none of them showed evidence of recurrence. Cases of ovarian tumor with borderline malignancy or more BT: benign tumor, CA: carcinoma, N.A.: not available, LAA: laparoscope assisted adnectomy, LAC: laparoscope assisted cystectomy, BOT: borderline ovarian tumor,ATH: abdominal total histerectomy, BSO: bilateral sappingo-oophorectomy, RSO:right sappingo-oophorectomy, LSO:left sappingo-oophorectomy, PLN: retroperitoneal lymphadenectomy, OM: omentectomy Preoperative MRI involving cases 7 and 9 in Table 2 . Image A: case 7, diagnosed with mucinous adenoma. Image B: case 9, diagnosed with teratoma Parity after surgery was observed in 49 patients, all of whom were younger than 40 years ( Table 3 ). Eight of 10 women were given treatments preserving their fertility, which meant conservative surgery and avoiding chemotherapies. However, none of them became pregnant after the treatment. Number of the patients with parity after surgery LAC: laparoscope assisted cystectom, LAA: laparoscope assisted adnectomy

All authors declare that there are no financial disclosures or conflicts of interest.

We analyzed 471 patients who underwent laparoscopic surgery for adnexal masses in a single institution, and picked up 10 patients with malignancy to assess the appropriateness of the treatments that they received. All 10 subjects with malignant tumors have shown no evidence of recurrence to date. However, we became aware of several issues to consider regarding surgical methods on reviewing the previous literature. In the present study, the rate of patients with unsuspected ovarian cancers was 0.4% (2 patients), which was similar to the report by Leng et al. 8 ) . Of these, one patient was multiparous, who accepted radical treatment including chemotherapy. She had been treated for a mucinous cystadenoma 6 years before the mucinous cystadenocarcinoma had arisen. According to the classification of BOT 7 ) , the first tumor (mucinous cystadenoma) is considered to be a precursor of the second tumor (mucinous cystadenocarcinoma). The other was a nulliparous 33-year-old woman who strongly desired only conservative treatment despite our recommendation of second surgery with full comprehensive staging. Consequently, she finished the treatment with LAC alone. The pathological diagnosis was a well-differentiated mucinous adenocarcinoma. Morice et al. reported that conservative surgery in patients with ovarian cancer could only be considered when tumors are serous, mucinous, or endometrioid with grade 1 or 2, and stage IA to IC, and when close follow-up is possible 10 ) . However, Fruscio et al. reported that the recurrence rate of early-stage ovarian cancer with or without a second surgery reached 11% 4 ) . At present, we think that laparoscopic surgery alone as a fertility-sparing treatment should not be recommended and it is better to perform second staging surgery. Owing to the lack of adequate staging, the patient requires very close follow-up, although 12 months have passed so far without any signs of recurrence. We identified six patients (1.2%) with BOT, which was three times as many as in the report by Leng et al. (0.3%) 8 ) , but far fewer than reported by Demir et al. (5.0%) 3 ) . There were 2 patients with histologically rare tumors. The patient with an immature teratoma underwent ipsilateral adnectomy and pelvic lymphadenectomy as second surgery and completed the treatment without adjuvant chemotherapy. Malignant ovarian germ cell tumor patients have been reported to show an excellent prognosis, mainly because of the tumor’s marked sensitivity to chemotherapy 1 ) . Although the risk of upstaging only involved the intraoperative puncture of the tumor in this case, she should be followed carefully, considering the absence of chemotherapy. The patient with a granulosa cell tumor received neither second surgery nor chemotherapy. The pathological diagnosis did not revealed a high mitotic rate of the tumor, which is a risk factor of recurrence 13 ) , but the procedure (LAC) was insufficient to avoid recurrence because the chemotherapy is not effective and complete resection of the tumor is essential. As relapses more than five years after surgery are characteristic of granulosa cell tumors, she needs to undergo long-term follow-up. As laparoscopic procedures always involve the intra-abdominal puncture of a tumor, which worsens the disease stage, our 10 patients would be staged as intraoperative-rupture-IC. However, none of the 4 patients who underwent second surgery were upstaged based on pathological findings. A number of researchers have discussed the issue of whether the intraoperative rupture of tumors negatively affects the oncologic outcome. While Bakkum-Gamez JN et al. reported the increased risk of recurrence due to intraoperative rupture of a tumor 2 ) , several recent studies have reported that cyst puncture may not affect the prognosis 5 , 6 , 8 ) . Needless to say, our cases should receive careful follow-up even though they have not exhibited any signs of recurrence to date. However, these results from previous studies at least support laparoscopic surgery as a feasible treatment for BOT. Most of the patients with malignancy in our study were young and preferred to avoid multiple surgeries, which resulted in the lack of accurate staging. The study by Muzii et al. described laparoscopic fertility-sparing staging in early-stage ovarian malignancies as a feasible and safe procedure 11 ) . The staging consisted of peritoneal washing for cytology, multiple peritoneal biopsies, infracolic omentectomy, biopsy of the contralateral ovary, etc. As they did not impair the fertility of patients, they would be acceptable for patients undergoing laparoscopic surgery for adnexal masses. In conclusion, laparoscopic surgery for at least early-stage BOT or higher-level malignancy may be feasible when accurate staging is carried out. Intraoperative pathological evaluation is necessary to consider whether procedures for accurate staging, such as peritoneal washing cytology and biopsies of the peritoneum or contralateral ovary, should be performed. We need to accumulate a larger number of cases. The possibility of laparoscopic surgery for ovarian neoplasm may be expanded by the continuous and careful inspection of outcomes in the future.

Patients who undergo treatment for adnexal masses are seen at a relatively high incidence. Laparoscopy has become the standard surgery due to the treatment of benign adnexal masses for its minimal invasiveness. Laparoscopic surgery is superior to laparotomy because of its various benefits, such as shorter hospitalization, less intraoperative complications, and quicker recovery 9 ) . It is cosmetically preferable for younger patients because it requires only small incisions in the skin. It also causes less adhesion in the abdomen 12 ) , which means that it is appropriate for patients who desire to have children. As the prevalence of adnexal masses with malignancy is relatively low, we seldom encounter malignant ovarian tumors in patients undergoing laparoscopy. However, when ovarian malignant tumors are treated by laparoscopy, there are concerns that spillage and misdiagnosis of the stage may lead to a poor prognosis. Despite the fact that preoperative assessments including transvaginal ultrasonography, MRI and serum tumor marker tests are performed routinely, it sometimes remains difficult to discriminate malignant from benign ovarian tumors. In the present study, focusing on the oncologic outcome, we reviewed 471 patients who underwent laparoscopy in Social Insurance Chukyo Hospital to examine the characteristics, frequency, and the recurrence rate of patients with unexpected ovarian malignancy diagnosed after surgery.