Borderline ovarian tumors: French guidelines from the CNGOF. Part 1. Epidemiology, biopathology, imaging and biomarkers.

The incidence (rate per 100 000) of borderline ovarian tumors (BOTs) increases progressively with age, starting at 15-19 years and peaking at around 4.5 cases per 100 000 at an age of 55-59 years (LE3) with a median age of 46 years. The five year survival for FIGO stages I, II, III and IV is 99.7 % (95 % CI: 96.2-100 %), 99.6 % (95 % CI: 92.6-100 %), 95.3 % (95 % CI: 91.8-97.4 %) and 77.1 % (95 % CI: 58.0-88.3 %), respectively (LE3). An epidemiological association exists between the individual risk of BOT and family history of BOT and certain other cancers (pancreatic, lung, bone, leukemia) (LE3), a personal history of benign ovarian cyst (LE2), a personal history of tubo-ovarian infection (LE3), the use of a levonorgestrel intrauterine device (LE3), oral contraceptive use (LE3), multiparity (LE3), Hormonal replacement therapy (LE3), high consumption of Coumestrol (LE4), medical treatment for infertility with progesterone (LE3) and non-steroidal anti-inflammatory drug use (LE3). Screening for BOTs is not recommended for patients (Grade C). The overall risk of recurrence of BOTs varies between 2% and 24 %, with an overall survival greater than 94 % at 10 years, and the risk of an invasive recurrence of a BOT ranges from 0.5 % to 3.8 %. The use of scores and nomograms can be useful in assessing the risk of recurrence, and providing patients with information (Grade C). The WHO classification is recommended for classifying BOTs. It is recommended that the presence of a microinvasive focus (<5 mm) and microinvasive carcinoma (<5 mm with an atypical nuclei and a desmoplastic stroma reaction) within a BOT be reported. In cases of serous BOT, it is recommended to specify the classic histological subtype or micropapillary / cribriform type (Grade C). When confronted with a BOT, it is recommended that the invasive or non-invasive nature of peritoneal implants can be investigated based solely on the invasion and destruction of underlying adipose or peritoneal tissue which has a desmoplastic stromal reaction where in contact with the invasive clusters (Grade B). For bilateral mucinous BOTs and / or in cases with peritoneal implants or peritoneal pseudomyxoma, it is recommended to also look for a primitive digestive or pancreato-biliary cancer (Grade C). It is recommended to sample ovarian tumors suspected of being BOTs by focusing samples on vegetations and solid components, with at least 1 sample per cm in tumors with a size less than 10 cm and 2 samples per cm in tumors with a size greater than 10 cm (Grade C). In cases of BOTs and in the absence of macroscopic omental involvement after careful macroscopic examination, it is recommended to perform at least 4-6 systematic sampling blocks and to include all peritoneal implants (Grade C). It is recommended to consult an expert pathologist in gynecology when a BOT suspicion requires intraoperative extemporaneous histology (grade C). Endo-vaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended that a pelvic MRI be performed (Grade A). To analyze an adnexal mass with MRI, it is recommended to use an MRI protocol with T2, T1, T1 Fat Sat, dynamic and diffusion sequences as well as gadolinium injection (Grade B). To characterize an adnexal mass with MRI, it is recommended to include a score system for malignancy (ADNEX MR/O-RADS) (Grade C) in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being a BOT (Grade C). Macroscopic MRI features should be analyzed to differentiate BOT subtypes (Grade C). Pelvic ultrasound is the first-line examination for the detection and characterization of adnexal masses during pregnancy (Grade C). Pelvic MRI is recommended from 12 weeks of gestation in case of an indeterminate adnexal mass and should provide a diagnostic score (Grade C). Gadolinium injection must be minimized as fetal impairment has been proven (Grade C). It is recommended that serum levels of HE4 and CA125 be evaluated and that the ROMA score for the diagnosis of an indeterminate ovarian mass on imaging be used (grade A). In case of suspicion of a mucinous BOT on imaging, dosage of serum levels of CA 19-9 can be considered (Grade C). If the determination of tumor markers is normal preoperatively, routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of preoperative elevation in tumor markers, the determination of serum CA 125 levels is recommended in the follow-up of BOT (Grade B). When conservative treatment of a BOT has been adopted, the use of endovaginal and transabdominal ultrasonography is recommended during follow-up (Grade B).

Borderline ovarian tumors: French guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation.

In the Early Stages (ES) of Borderline Ovarian Tumor (BOT), if surgery without risk of tumor rupture is possible, then laparoscopy with protected extraction is recommended over laparotomy (Grade C). In case of bilateral serous ES BOT treatment with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended if possible (Grade B). In case of mucinous BOT treatment with a strategy to preserve fertility and/or endocrine function, unilateral adnexectomy is recommended (grade C). In the case of a mucinous BOT in a patient who has had an initial cystectomy, unilateral adnexectomy is recommended (grade C). In the case of treatment of a serous ES BOT in a patient who has had an initial cystectomy, with a strategy to preserve fertility and/or endocrine function, restaging surgery for adnexectomy is not recommended in the absence of suspicious residual lesions at the time of surgery and/or postoperative imaging (reference ultrasonography or pelvic MRI) (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). In cases of ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only if there is a macroscopically pathological aspect to the appendix (Grade C). Restaging surgery is recommended in case of a serous BOT with a micropapillary aspect and an unsatisfactory inspection of the abdominal cavity during initial surgery (Grade C). Restaging surgery is recommended in cases of mucinous BOT if only a cystectomy has been performed or if the appendix has not been evaluated (Grade C). If restaging surgery is decided for an ES BOT, the following procedures should be performed: peritoneal cytology (grade C), omentectomy (there is no data in literature to recommend which type of omentectomy should be performed) (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix +/- appendectomy in case of pathological macroscopic appearance (grade C) and unilateral adnexectomy in case of a mucinous BOT (grade C). In advanced stages of BOT it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). In cases of an advanced stage BOT, in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed after a multidisciplinary meeting (Grade C). Second surgery aimed at removing all lesions, if not performed initially, is recommended in cases of advanced stage BOT (Grade C). It is not recommended to perform completion surgery after conservative treatment (preservation of the ovaries and the uterus) and after the achievement of fertility desire for a serous BOT (Grade B). After treatment for a BOT, follow-up beyond 5 years is recommended due to the median time to recurrence (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). In the particular case of an initial elevation of CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In cases treated conservatively (ovarian and uterine conservation), it is recommended to use endovaginal and transabdominal ultrasonography during the follow up period (Grade B). In the event of a recurrence of a BOT, in a woman of childbearing age, a conservative treatment strategy can again be proposed (Grade C). In the presence of non-invasive BOT implants, conservative treatment may be considered after a first non-invasive recurrence in women who wish to preserve their fertility (Grade C). Pelvic MRI is recommended after 12 weeks of amenorrhea in case of an undetermined adnexal mass and should be concluded with a diagnostic score (Grade C). The injection of gadolinium, in case of pregnancy, should be discussed on a case-by-case basis due to the proven risks for the foetus (Grade C). If feasible, a laparoscopic approach should be preferred during pregnancy (Grade C). A consultation with a specialist reproductive physician should be offered to patients with a BOT and of childbearing age (Grade C). It is recommended that patients be provided with full information on the risk of decreased ovarian reserve following to surgical treatment. It is recommended that the ovarian reserve be evaluated prior to surgical management of a suspected BOT (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). There is no specific data on the management of infertility following to conservative treatment of BOT. In case of durable infertility following to conservative treatment of BOT, a consultation with a specialist reproductive physician is required (Grade C). In the case of optimally treated BOT, there is no evidence in literature to contraindicate the use of Assisted Reproductive Techniques (ART). The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After treatment of a mucinous BOT, for women aged under 45 years, given the benefit of hormonal replacement therapy (HRT) on cardiovascular and bone risks, and the lack of hormone-sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). After treatment of a mucinous BOT, for women over 45 years of age, there is no argument to contraindicate the use of HRT. HRT can be prescribed in case of a climacteric syndrome, as part of an individual benefit to risk assessment (Grade C).

Diagnostic Algorithm to Differentiate Benign Atypical Leiomyomas from Malignant Uterine Sarcomas with Diffusion-weighted MRI.

Background Improving the differentiation of uterine sarcomas from atypical leiomyomas remains a clinical challenge and is needed to avoid inappropriate surgery. Purpose To develop a diagnostic algorithm including diffusion-weighted MRI criteria to differentiate malignant uterine sarcomas from benign atypical leiomyomas. Materials and Methods This case-control retrospective study identified women with an atypical uterine mass at MRI between January 2000 and April 2017, with surgery or MRI follow-up after 1 year or longer. A diagnostic algorithm including T2-weighted MRI and diffusion-weighted imaging (DWI) signal and apparent diffusion coefficient (ADC) values was developed to predict for sarcoma. The training set consisted of 51 sarcomas and 105 leiomyomas. Two external validation sets were used to evaluate interreader reproducibility (16 sarcomas; 26 leiomyomas) and impact of reader experience (29 sarcomas; 30 leiomyomas). Wilson confidence intervals (CIs) were calculated for sensitivity and specificity. Results Evaluated were 156 women (median age, 50 years; interquartile range, 44-63 years). Predictive MRI criteria for malignancy were enlarged lymph nodes or peritoneal implants, high DWI signal greater than that in endometrium, and ADC less than or equal to 0.905 × 10-3 mm2/sec. Conversely, a global or focal area of low T2 signal intensity and a low or an intermediate DWI signal less than that in endometrium or lymph nodes allowed readers to confidently diagnose as benign a uterine mass demonstrating one or more of these signs (P < .001) in 100% cases in all three data sets. The sensitivities and specificities of the algorithm for diagnosis of malignancy were 98% (50 of 51 masses; 95% CI: 90%, 100%) and 94% (99 of 105 masses; 95% CI: 88%, 98%) in the training set; 88% (14 of 16 masses; 95% CI: 64%, 97%) and 100% (26 of 26 masses; 95% CI: 87%, 100%) in the validation set; and 83% (24 of 29 masses; 95% CI: 65%, 92%) and 97% (29 of 30 masses; 95% CI: 83%, 99%) for the less experienced reader, respectively. Conclusion A diagnostic algorithm with predictive features including lymphadenopathy, high diffusion-weighted imaging signal with reference to endometrium, and low apparent diffusion coefficient enabled differentiation of malignant sarcomas from atypical leiomyomas, and it may assist inexperienced readers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Méndez in this issue.