Borderline ovarian tumors

INTRODUCTION — Borderline tumors of the ovary (also called tumors of low malignant potential) are a heterogeneous group of lesions defined histologically by atypical epithelial proliferation without stromal invasion [1]. The behavior of these tumors is distinct from low-grade ovarian carcinoma, and they are considered a distinct clinical entity.

The epidemiology, diagnosis, and treatment of borderline ovarian tumors are reviewed here. Ovarian cancer is discussed separately. (See "Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer".)

HISTOPATHOLOGY — Borderline ovarian epithelial neoplasms are noninvasive neoplasms that occasionally have intraperitoneal spread [2]. This group of neoplasms exhibits behavior that is intermediate between benign cystadenomas and invasive carcinomas. These have been referred to by different terms, including: borderline, atypical proliferative, and tumors of low malignant potential. Borderline neoplasm is currently the most widely used designation by pathologists, gynecologists, and oncologists, and has been adopted into the World Health Organization (WHO) classification [3].

Borderline tumors account for 14 to 15 percent of all primary ovarian neoplasms [4].

Borderline tumors occur in a variety of histologies, as in epithelial ovarian carcinoma [5,6]. The majority of cases are serous or mucinous. Rarely, endometrioid, clear-cell, or transitional cell (Brenner) borderline tumors are found.

The histopathology of serous and mucinous borderline ovarian tumors is discussed briefly here. The histopathology of borderline ovarian neoplasms is discussed in detail separately. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Histopathology", section on 'Overview of borderline neoplasms'.)

Serous borderline tumors — Among ovarian borderline tumors, approximately 65 to 70 percent are serous histology, and borderline tumors account for an estimated 15 to 20 percent of all ovarian serous neoplasms [6-8].

In the vast majority of patients, serous borderline tumors are confined to the ovary at the time of diagnosis [9,10]. Approximately 70 percent of cases are diagnosed at stage I [11]. However, up to 50 percent of the time, serous borderline tumors are bilateral [9,10].

Micropapillary features are present in 10 to 15 percent of serous borderline tumors, as well as in other types of benign and malignant serous ovarian tumors. The presence of micropapillary features is associated with an increased likelihood of both invasive peritoneal implants and of recurrence [12].

Mucinous borderline tumors — Mucinous tumors are the other common histologic type of borderline ovarian neoplasm; they account for approximately 11 percent of borderline tumors [13]. At diagnosis, the great majority are stage I (100 percent in one study of 15 patients [13]).

EPIDEMIOLOGY AND RISK FACTORS — Based on registry data from the United States, Denmark, and Sweden, the estimated incidence of these tumors ranged from 1.8 to 5.5 per 100,000 women per year [4,14,15]. Some data suggest that the incidence is increasing [16]. As an example, a Danish study reported that the incidence of borderline ovarian tumors increased from 2.6 to 5.5 per 100,000 person-years between 1978 and 2006 [15].

Approximately one-third of patients diagnosed with a borderline ovarian tumor are younger than 40 years of age [4,6]. This makes issues related to ovarian function and fertility preservation of increased importance. (See 'Future pregnancy' below and 'Hormone therapy' below.)

The majority of cases are diagnosed at stage I. As an example, in one literature review including 948 cases, 70 percent presented as stage I, 10 percent presented as stage II, 19 percent presented as stage III, and less than 1 percent presented as stage IV [11].

Some data suggest that infertility or infertility treatments are associated with an increased risk of borderline tumors, but these data are limited by methodologic issues and a small number of cases. Regarding infertility, a meta-analysis of eight case-control studies reported a significant increase in the risk of borderline tumors in patients with an unknown cause of infertility (odds ratio [OR] 1.86, 95% CI 1.26-2.74) [17].

Data are mixed regarding the association between ovulation induction and borderline ovarian tumors. A systematic review including four observational studies found that use of any infertility drug was associated with a two- to threefold increase in the risk of a borderline ovarian tumor [18]. In contrast, a subsequent Danish population-based study (n = 142 cases of borderline tumors) found no increase in risk associated with fertility drug use; however, the study lacked sufficient statistical power [19].

The relationship between BRCA gene mutations and borderline ovarian tumors is uncertain. It appears that the prevalence of BRCA mutations is lower among patients with borderline tumors than in patients with invasive ovarian carcinoma [20-22]. As an example, in one study of Jewish subjects with ovarian neoplasms, the rate of BRCA mutations was higher in those with stage I ovarian carcinoma (24 percent of 256 patients) than in those with borderline tumors (4 percent of 233 patients) [23].

Data are mixed regarding whether postmenopausal hormone therapy is associated with an increased risk of borderline tumors. A Danish national database study including 703 patients with borderline ovarian tumors reported that four years of use of estrogen or estrogen and progestin therapy was associated with a 1.3- to 1.5-fold increased risk of a borderline tumor [24]. In contrast, two other retrospective studies found limited or no association for most patients. One study found a significant increase in borderline tumors with two to three years of use, but not for other durations [25]. Another study found a significant increase in risk only with unopposed estrogen in patients who developed serous tumors, but not with combined estrogen and progestin therapy in either serous or mucinous tumors [26].

CLINICAL PRESENTATION — The clinical presentation of borderline ovarian tumors is the same as for other adnexal masses. Some patients are asymptomatic at presentation (14 percent in one study) [27]. Symptoms may include:

●Pelvic or abdominal pain or pressure

●Dyspareunia

In contrast with patients with ovarian carcinoma, those with borderline tumors are unlikely to present with ascites, bowel obstruction, pleural effusion, or venous thromboembolism.

In asymptomatic patients, borderline tumors may be detected incidentally as a mass noted on pelvic examination or imaging performed for another indication. In our experience, we suspect a borderline tumor in a younger patient with a relatively asymptomatic ovarian cyst that has evidence of internal papillary growth on ultrasound.

The clinical presentation of patients with an adnexal mass or ovarian cancer is discussed in detail separately. (See "Approach to the patient with an adnexal mass", section on 'Clinical presentation' and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Clinical presentation'.)

DIAGNOSTIC EVALUATION — The diagnostic evaluation of a borderline ovarian tumor is the same as for ovarian carcinoma, with the distinction that serum CA 125 does not appear to be a useful test.

This section will review aspects of the evaluation that are particular to borderline tumors. The evaluation and diagnosis of ovarian cancer and the approach to an adnexal mass are discussed in detail separately. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Diagnostic evaluation' and "Approach to the patient with an adnexal mass".)

In general, the diagnostic evaluation includes:

●Medical history – Symptoms and risk factors (table 1) associated with an ovarian neoplasm and a medical and surgical history.

●Physical examination – The examination may demonstrate fullness in the pelvis or a palpable ovarian mass. However, neither of these are specific to the diagnosis of a borderline ovarian tumor.

●Pelvic and abdominal imaging – A transvaginal ultrasound is typically the first-line imaging study to evaluate an adnexal mass. If an ovarian borderline tumor or carcinoma is suspected, abdominal imaging is performed if metastatic disease is suspected.

●Surgical evaluation – Surgical exploration is typically required to obtain a specimen for histologic diagnosis. Frozen section is often used intraoperatively.

Pelvic ultrasound — There are no sonographic features that differentiate an ovarian borderline tumor from a benign or invasive ovarian neoplasm. The sonographic appearance of borderline ovarian tumors ranges from unilocular cysts to masses with both solid and fluid components; papilla are common [28-31]. (See "Adnexal mass: Ultrasound categorization".)

Tumor markers — The CA 125 tumor marker does not appear to be useful in the detection of a borderline ovarian tumor. This was the finding in a retrospective series of over 1000 patients with borderline tumors [32]. Almost one-half of all patients had a normal CA 125 level, and less than 25 percent had levels above 100 units/mL. If the CA 125 level is high, ovarian cancer should be suspected. (See "Approach to the patient with an adnexal mass", section on 'Role of tumor markers and multimodal tests'.)

Surgical exploration — Borderline tumors present as an adnexal mass suspicious for ovarian cancer. The decision to proceed with surgery is based upon this indication.

Intraoperatively, in our experience, the gross appearance of a borderline tumor includes papillary excrescences (an appearance similar to cauliflower or coral).

As with other suspicious adnexal masses, the goal is to confirm the histology and proceed with the procedure that preserves fertility and ovarian function, if possible. If an ovarian mass is suspected to be malignant, the standard procedure is to remove the ovary intact and send it for frozen section. However, if a mass is suspected to be benign or borderline, a cystectomy may be performed. If both ovaries are involved, the lesion that appears more suspicious should be removed and sent for frozen pathology.

If the histology shows a borderline neoplasm or invasive disease, staging is performed, which may include ovarian conservation. In any surgery for an adnexal mass that has the potential to be borderline or malignant, preoperative counseling should include discussion of patient preferences and options regarding ovarian conservation versus complete staging. (See 'Complete staging versus conservative surgery' below.)

Frozen section — Frozen section is commonly performed intraoperatively, and the information is used to help determine the extent of the surgical procedure. A meta-analysis of 18 studies on the diagnostic accuracy of frozen section results of ovarian pathology found generally good sensitivity (65 to 100 percent) and excellent specificity (>99 percent) when compared with the final histologic diagnosis [33]. Factors that lower the sensitivity of frozen section diagnosis of malignancy include large neoplasms, mucinous tumors (which have more histologic variation), and borderline tumors, since all require a large number of sections to exclude the presence of a focal area of invasive disease.

DIAGNOSIS — Borderline ovarian neoplasm is a histologic diagnosis. This evaluation is performed following surgical removal of an ovary. Infrequently, peritoneal spread is present, and the diagnosis may be made based upon biopsies of the peritoneum at the time of surgery.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of borderline ovarian neoplasm is the same as for ovarian cancer and other adnexal masses. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Differential diagnosis'.)

The first step in the evaluation of an adnexal mass is to confirm the presence and anatomic location of the mass with pelvic imaging, usually ultrasound. The differential diagnosis of an adnexal mass is shown in the table and discussed in detail separately (table 2).

STAGING AND SURGICAL TREATMENT — The staging system for borderline ovarian tumors is similar to that for other invasive ovarian carcinomas and carcinoma of the fallopian tube or peritoneum (table 3).

The complete staging procedure for patients in whom future pregnancy is not desired includes total hysterectomy and bilateral salpingo-oophorectomy (BSO), peritoneal washing, omentectomy, and resection of grossly visible metastases. More conservative surgery may be performed in patients in whom future pregnancy is desired.

In our practice, we do not perform lymphadenectomy in patients with borderline tumors. The low prognostic utility of lymph node sampling was illustrated in a meta-analysis of 97 studies including over 4000 patients with ovarian tumors of low malignant potential that reported 98 percent survival at 6.5 years in patients with lymph node involvement [34,35].

Complete staging versus conservative surgery — The choice of full staging or ovary-conserving surgery should be individualized. Approximately one-third of borderline ovarian tumors occur in patients younger than 40 years of age, and many young patients desire to conserve at least one ovary to preserve fertility and/or avoid the symptoms and effects of premature menopause [4,6]. Ovarian borderline tumors are not a common condition and most data derive from retrospective cases series of less than 100 patients.

The disease has a good prognosis (stage I five-year survival is 99 percent) and unilateral salpingo-oophorectomy (USO) appears to be an option for patients with unilateral disease [36-39]. Some data suggest that ovarian cystectomy is also acceptable. (See "Management of primary ovarian insufficiency (premature ovarian failure)" and 'Survival' below.)

The overall risk of recurrence after conservative surgery ranges from 7 to 30 percent [36], and recurrences typically show borderline histology, not invasive carcinoma [37]. The efficacy of conservative surgery in early-stage disease was best illustrated in a systematic review and meta-analysis of 120 mostly retrospective studies [40]. For patients with stage I ovarian borderline tumors treated with either USO or ovarian cystectomy, with an average follow-up of three to six years, the borderline recurrence rate was 13 percent, recurrence with malignant disease was 1.6 percent, and the death rate was 0.5 percent. This study was limited because it combined data for USO and cystectomy.

Some data suggest that USO is more effective than ovarian cystectomy, especially if the margins are positive or the resection is incomplete [36,41,42]. The two procedures were compared in a retrospective series of 193 patients with borderline ovarian tumors that was included in the systematic review described above [38,40]. In this study, the five-year disease-free survival rate for all patients was approximately 95 percent. The recurrence rate was higher and recurrence occurred sooner after cystectomy. For USO, 10 of 146 (7 percent) patients had recurrences and the median time to recurrence was 4.8 years (range 1.7 to 7.2 years); two of the recurrences were malignant disease. For cystectomy, 11 of 47 (23 percent) patients recurred and the median time to recurrence was 2.6 years (range 0.3 to 14 years); there were no malignant recurrences.

Recurrence of borderline disease requires surgical resection, typically full staging. If no malignant disease is present, borderline recurrences are not associated with mortality. In some cases, even after a recurrence, the uterus and one ovary or part of an ovary may be conserved to retain fertility.

For patients with advanced-stage disease, full staging with total hysterectomy and BSO appears to be more effective, and the risk of progression to invasive disease is clinically significant. In a study of patients with stage I to III disease, tumor recurrence rates after total abdominal hysterectomy and BSO (TAH-BSO), adnexectomy, and cystectomy were 6, 15, and 36 percent, respectively [37]. In a systematic review including 14 studies with 137 patients with stage II to IV serous borderline tumors, there were eight (6 percent) reports of invasive recurrences.

The advantages of comprehensive staging are:

●Detection of advanced-stage disease – If comprehensive staging is not performed, it is possible that pelvic or peritoneal spread may be missed. For presumed stage I serous borderline tumors, if a comprehensive staging procedure is performed after an initial nonstaging procedure (eg, simple oophorectomy), upstaging is not uncommon (12 to 47 percent) [43,44]. For mucinous tumor, presumed stage I disease typically is stage I.

●Detection of occult invasion – Some cases that are thought to be borderline based upon frozen section will turn out to be invasive carcinoma. In such cases, the patient will require a second procedure if comprehensive staging was not performed as the initial procedure.

●Better information for prognostic counseling.

For patients in whom complete staging was not performed because the diagnosis of borderline ovarian cancer was made only at the time of final pathology review, imaging (with computed tomography [CT] with contrast) may be useful to assess for residual disease and to identify those patients in whom additional surgery is warranted.

Desire fertility preservation — For patients with an apparent unilateral stage I borderline ovarian tumor (based upon preoperative and intraoperative imaging and examination) who wish to preserve fertility or endocrine function, we suggest salpingo-oophorectomy of the affected ovary, pelvic washings, an omental biopsy, and a biopsy of any peritoneal lesions rather than full staging for ovarian cancer. All macroscopic disease should be resected. Appendectomy is performed for mucinous tumors.

Borderline tumors may be discovered inadvertently in a patient undergoing surgery for a presumed benign ovarian mass. If the patient may desire future reproduction, conservative surgery is performed. If surgical expertise for staging is available, additional biopsies of omentum or other peritoneal lesions may be performed. Peritoneal washings should be sent and appendectomy should be performed in patients with mucinous tumors. If the final pathology demonstrates a more aggressive (invasive) lesion, additional surgical staging may be performed at a later time. If future reproduction is not desired, full staging may also be considered.

It is controversial whether patients who have fertility-conserving surgery should undergo removal of a remaining ovary or uterus upon completion of childbearing. The National Comprehensive Cancer Network (NCCN) advises consideration of completion surgery upon completion of childbearing for patients with a remaining ovary [45]. Based on the low recurrence rate of borderline tumors and the low risk of malignancy, in our practice, we do not routinely perform completion surgery in these patients [10,11].

In addition, if an ovarian borderline tumor or malignancy is suspected preoperatively, patients who desire to retain fertility should be offered a consultation with a fertility specialist to review options, including embryo or oocyte cryopreservation. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)

Bilateral tumors — For patients with bilateral ovarian borderline tumors, oophorectomy on one side and cystectomy on the other is the usual treatment approach.

An ultraconservative approach using bilateral cystectomy was found to be effective and had better fertility outcomes in a randomized trial of patients with bilateral ovarian borderline tumors (n = 32); most patients had stage I disease (three had stage II to IV) [46]. At 81-month follow-up, there was no significant difference in the recurrence rate for patients who underwent bilateral cystectomy compared with standard surgery, unilateral oophorectomy combined with contralateral cystectomy (60 versus 59 percent). Recurrence occurred sooner in the bilateral cystectomy group (16 versus 48 months), and multiple recurrences were more likely (23 versus 0 percent). There were no invasive recurrences. Fertility outcomes were better following bilateral cystectomy (pregnancy rates: 93 versus 53 percent). The recurrence rate in this study was high, likely due to the inclusion of patients with advanced disease.

Advanced disease — Complete staging with total hysterectomy-BSO is typically performed for patients with stage II or higher disease. However, patients with advanced ovarian borderline tumors may retain fertility, particularly if one ovary is unaffected.

Do not desire fertility preservation — For patients with borderline ovarian tumors who are postmenopausal or who do not wish to preserve fertility or endocrine function, a full staging procedure with total hysterectomy-BSO is performed. Informed consent should include counseling premenopausal patients about the symptoms, effects, and management options for premature menopause. (See "Management of primary ovarian insufficiency (premature ovarian failure)" and 'Hormone therapy' below.)

Laparotomy versus laparoscopy — A laparoscopic approach has not been evaluated in randomized trials. In general, retrospective series have reported that cyst rupture was more likely and complete staging was less likely with laparoscopic surgery than laparotomy, but there was no difference in recurrence rate [47-49].

CHEMOTHERAPY — Chemotherapy is rarely indicated for patients with borderline ovarian tumors. While most clinicians would agree that there is no advantage for chemotherapy in patients with early-stage, completely resected disease [50], its use for those with more advanced-stage disease is controversial.

Some retrospective studies suggest benefit for adjuvant chemotherapy following optimal debulking of stage III or IV borderline tumors [51,52], while others do not [53,54]. The largest of these reports consisted of 80 patients with stage II to IV serous borderline tumors [54]. No patient with stage II disease received adjuvant chemotherapy, while of the 65 patients with stage III or IV disease, 17 received adjuvant chemotherapy (with a variety of both intravenous and intraperitoneal regimens) and the remainder did not. None of the patients with residual disease after initial surgery received chemotherapy. Major findings were that:

●Treatment with chemotherapy was associated with a lower progression-free survival rate at three years compared with no treatment (71 versus 90 percent, respectively).

●At a median follow-up of 4.8 years, 17 (21 percent) developed recurrent disease, all of whom had metastasis to the omentum or to multiple sites at original presentation. The sites of recurrent disease included pelvis in 15, omentum in 29, isolated lymph nodes in two, axilla in one, and multiple sites in 32.

Thus, the use of chemotherapy did not appear to impact the risk of recurrence. Given the apparently favorable outcome of advanced-stage serous borderline tumors, and the fact that a survival benefit from administration of adjuvant chemotherapy has not been clearly demonstrated, most clinicians recommend chemotherapy after aggressive surgical debulking only if invasive implants are identified [55].

Borderline ovarian tumors, which are on the same genetic spectrum as low-grade serous carcinomas of the ovary, may be responsive to other hormonal or other targeted therapies, beyond traditional chemotherapy; however, these therapies are investigational.

FOLLOW-UP

Posttreatment surveillance — There is no high quality evidence to support one posttreatment surveillance strategy over another. The Society of Gynecologic Oncology (SGO) and National Comprehensive Cancer Network (NCCN) have each published guidelines for posttreatment surveillance for patients with ovarian cancer [56,57], and it is reasonable to extrapolate them for patients with borderline tumors. These surveillance guidelines are discussed separately. (See "Approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma", section on 'Post-treatment surveillance'.)

Future pregnancy — There is no evidence that patients who undergo fertility-sparing surgery and become pregnant are at increased risk of mortality from disease progression [37,58-65]. Fertility treatments, such as ovulation induction, also appear to be safe, if indicated [63,66,67].

A systematic review of 120 studies reported a 54 percent pregnancy rate at three to six years in patients treated conservatively for borderline tumors [40].

Hormone therapy — There are no data regarding the risk of recurrence of borderline tumor with use of postmenopausal hormone therapy, although some data suggest that hormone therapy is a risk factor for developing the disease. In our practice, we offer postmenopausal patients hormone therapy after comprehensive counseling about risks and benefits. (See 'Epidemiology and risk factors' above.)

The rare endometrioid tumor of low malignant potential, just like endometriosis, could theoretically (and anecdotally) be stimulated to grow by estrogens; one could test estrogen receptors and if they are highly positive, one might avoid estrogens in these tumors.

Postmenopausal hormone therapy in ovarian cancer survivors is discussed in detail separately. (See "Approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma", section on 'Menopause'.)

PROGNOSIS — Higher-stage disease is the major risk factor associated with recurrence; it is less clear whether the presence of invasive peritoneal implants, histologic subtype (eg, serous borderline with micropapillary pattern, mucinous peritoneal), DNA aneuploidy, and/or microinvasion affect overall prognosis [68-72].

Survival — The prognosis depends upon the stage and histologic features of the tumor, but is generally good (table 4). A series of 2818 patients with ovarian tumors of low malignant potential from the Surveillance, Epidemiology, and End Results (SEER) database from the National Cancer Institute reported the following 5- and 10-year relative survival rates [73]:

●Stage I – 99 and 97 percent, respectively

●Stage II – 98 and 90 percent, respectively

●Stage III – 96 and 88 percent, respectively

●Stage IV – 77 and 69 percent, respectively

Progression — The risk of malignant transformation is unclear. For example, a serous ovarian tumor of low malignant potential may recur with similar histology or as a low-grade serous carcinoma, or both histologies may be present. In one series of 339 patients with borderline tumors, only 2 percent went on to develop invasive carcinoma [10]. Progression to invasive cancer may represent true transformation, de novo development of an ovarian cancer, or a peritoneal cancer.

There is increasing evidence that the pathogenesis of low-grade serous carcinomas and of serous tumors of low malignant potential involves similar genes and pathways, and is distinct from that of high-grade serous carcinomas. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Histopathology", section on 'Overview of borderline neoplasms'.)

MANAGEMENT OF RECURRENCE — The optimal approach to management of recurrent disease has not been determined, but appears to be surgical cytoreduction, which is associated with improved survival in observational series [74-78]. As an example, one retrospective series of 21 patients with recurrent serous borderline tumors (micropapillary pattern) reported median overall survival of 61 months with optimal resection versus 26 months with suboptimal resection [77]. Five patients did not undergo secondary surgery and were treated with chemotherapy alone; their median survival was 30 months.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian, fallopian tube, and peritoneal cancer".)

SUMMARY AND RECOMMENDATIONS

●Ovarian borderline tumors (also called tumors of low malignant potential) are a heterogeneous group of lesions defined histologically by atypical epithelial proliferation without stromal invasion. These tumors account for 14 to 15 percent of ovarian epithelial tumors. (See 'Introduction' above and 'Histopathology' above.)

●The majority of borderline tumors are serous. Approximately 75 percent of patients are diagnosed with stage I disease; 25 to 50 percent of tumors are bilateral. Mucinous tumors are the other common cellular type; 90 percent are stage I and less than 10 percent are bilateral. (See 'Histopathology' above.)

●The estimated incidence of these tumors ranges from 1.8 to 5.5 per 100,000 women per year. Approximately one-third of patients diagnosed with a borderline ovarian tumor are younger than 40 years of age. (See 'Epidemiology and risk factors' above.)

●Most patients present with an asymptomatic adnexal mass noted either on bimanual examination or as an incidental finding on sonography; however, symptoms (eg, abdominal/pelvic pain or dyspareunia) may occur, as with any adnexal mass. (See 'Clinical presentation' above.)

●There are no sonographic features strongly suggestive of borderline histology. Sonographic appearance ranges from unilocular cysts to masses with both solid and fluid components; papilla are common. Measurement of CA 125 does not reliably predict borderline histology. (See 'Diagnostic evaluation' above.)

●The diagnosis of these neoplasms is based upon histopathologic examination. Frozen section is commonly performed intraoperatively, and the information is used to help determine the extent of the surgical procedure. (See 'Diagnosis' above.)

●Borderline tumors are staged using the same criteria as other ovarian neoplasms (table 3). Most patients present with stage I disease (approximately 70 percent); stage II to IV disease is relatively infrequent. (See 'Staging and surgical treatment' above and 'Epidemiology and risk factors' above.)

●Complete staging with total hysterectomy and bilateral salpingo-oophorectomy (BSO) is required for patients with stage II or higher disease. For patients with borderline ovarian tumors who are postmenopausal or who do not wish to preserve fertility or endocrine function, a full staging procedure with total hysterectomy-BSO is performed. Informed consent should include counseling premenopausal patients about the symptoms, effects, and management options for premature menopause. (See 'Advanced disease' above.)

●For patients with an apparent unilateral stage I borderline ovarian tumor, we suggest salpingo-oophorectomy of the affected ovary, pelvic washings, an omental biopsy, and a biopsy of any peritoneal lesions rather than full staging for ovarian cancer (Grade 2C). Appendectomy is performed for mucinous tumors. BSO is required in patients with bilateral borderline ovarian tumors. (See 'Desire fertility preservation' above.)

●The use of adjuvant chemotherapy is controversial; there is no advantage to treatment of patients with early-stage disease. While patients with more advanced disease may be rendered disease-free, survival benefit related to the administration of adjuvant chemotherapy has not been clearly demonstrated. We recommend chemotherapy after aggressive surgical debulking only if invasive implants are identified (Grade 1B). (See 'Chemotherapy' above.)

●There is no evidence that estrogens stimulate the growth of borderline serous or mucinous tumors of the ovary, or that their use in any way adversely affects the likelihood of relapse or survival. (See 'Hormone therapy' above.)

●Borderline tumors have an excellent prognosis (stage I five-year survival is 99 percent). The risk of malignant transformation is unclear. Progression to invasive cancer may represent true transformation, de novo development of an ovarian cancer, or a peritoneal cancer. (See 'Survival' above and 'Progression' above.)