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Management of Adnexal Masses

Obstetrics and Gynecology
Oncology
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Introduction:

Adnexal masses (masses of the ovary, fallopian tube, surrounding connective tissues, or other pelvic organ systems that occur near the adnexa) are common and may be discovered in females of any age.
The etiology of these masses encompasses a wide range of both benign and malignant pathology. A list of common masses by originating organ may be found in Table 1 below. Masses originating from the ovary can be further categorized by the cell of origin: germ cell, sex cord-stromal, or epithelial.
Please see the Controversies, Limitations, and Additional Considerations section for further discussion of the true tissue of origin for epithelial ovarian cancers.
It is important to recognize that adnexal masses are common. Ovarian cysts, for example, have a prevalence of 35% and incidence of 15% in premenopausal women (17% and 8%, respectively, in postmenopausal women) [1]. In premenopausal women, up to 80% of cysts spontaneously resolve within 3 months [2].
Table 1. Common types of adnexal masses
The etiology of the adnexal mass varies throughout the lifespan of a patient and, generally, the chance of malignancy increases with age. In newborns, physiologic ovarian cysts may occur due to maternal hormonal stimulation. After the neonatal period, these cysts are rare due to the lack of hormones. However, despite this, physiologic cysts are still the most common cause of ovarian masses. Ovarian carcinoma, predominantly germ cell tumors, accounts for 1% of childhood cancer overall and 10% of ovarian masses [3]. Other etiologies of adnexal masses, especially GI or GU, should be high on the differential and fully investigated in pre-pubertal patients.
During reproductive years, ovarian masses are often driven by reproductive hormones. Cyst formation driven by the menstrual cycle (functional or corpus luteal cyst, polycystic ovaries, or endometrioma) or pregnancy (corpus luteal cyst, luteoma, or theca lutein cyst) are common in this patient population. Fibroids are also extremely common and can appear as a solid adnexal mass if serosal or pedunculated. Various pelvic abscesses, including tubo-ovarian abscess in the setting of pelvic inflammatory disease, should be considered in the setting of fever and leukocytosis. The most common benign ovarian/tubal neoplasms are mature teratomas, and serous and mucinous cystadenomas [4,5]. Ovarian neoplasms in this age group are malignant 6-11% of the time and are usually of epithelial origin, followed by germ cell [6]. The incidence of germ cell tumors peaks in the 10-30 year old age range [7].
Though most adnexal masses in postmenopausal patients are benign, the incidence of malignancy increases to 30% in women older than 50 years [6]. Epithelial-derived ovarian cancer, specifically high grade serous, is the most common ovarian malignancy [8,9]. The occurrence of masses driven by reproductive hormones decreases in this age group.
Additionally, certain hereditary syndromes, most commonly BRCA mutations and Lynch syndrome, can predispose individuals to higher rates of ovarian cancer at earlier ages. Though screening the general population for ovarian/adnexal masses is not currently recommended, patients at higher risk for ovarian cancer may be eligible. Prophylactic surgery may also be recommended to these patients. Additional risk factors for ovarian cancer, particularly epithelial subtypes, include early menarche/late menopause and nulliparity. Protective factors include late menarche/early menopause, multiparity, breastfeeding, and use of oral contraceptive pills.
Adnexal masses may be detected after evaluation of patient symptoms, via physical exam or imaging. The mainstay of imaging is transvaginal ultrasound, and several systems exist to identify high-risk features and guide management based on imaging results. Tumor markers may be useful for further evaluating the malignant potential of ovarian masses, but often have greater utility in monitoring for response to treatment or disease recurrence.
Next steps after diagnosis may include expectant management or surveillance if the chance of malignancy is low, though cancer often cannot be completely excluded. For patients requiring definitive treatment and/or symptomatic relief, surgery is usually recommended. For patients with a high likelihood of and/or confirmed malignancy, it is important to involve a gynecologic oncologists early to improve outcomes.

Symptoms:

Patient symptomatology varies based on etiology of the mass and its acuity. Presentation may be subtle and sometimes overlooked (i.e. vague lower abdominal pain or bloating) due to the location of the adnexae deep within the pelvis and the common nature of these symptoms during reproductive years. Symptoms related to mass effect may be seen that include: nausea, vomiting, early satiety, abdominal fullness, constipation or obstruction, or urinary frequency and urgency.
More acute presentations may occur, such as hemoperitoneum in a ruptured ectopic pregnancy and sepsis related to a tubo-ovarian abscess in pelvic inflammatory disorder. Additionally, masses of any size can cause severe unilateral pain if torsion of the ovary occurs, though torsion is more likely for masses greater than 5 centimeters in diameter [10]. These presentations require prompt intervention by a gynecologist, which may include urgent/emergent surgery.
Hormonally active ovarian tumors (e.g. sex cord-stromal tumors) may present with abnormal uterine bleeding due to estrogenic effect. High levels of estrogen can lead to secondary endometrial cancer. In children, precocious puberty may occur. Androgens are often modestly elevated in polycystic ovarian syndrome and may cause hirsutism, acne, alopecia, and oligo- or amenorrhea. High levels of androgens are more likely in the setting of a true ovarian neoplasm like Sertoli-Leydig cell tumor. This results in rapid virilization, including clitoromegaly and temporary balding and deepening of the voice.
In pregnancy, the incidence of adnexal masses is up to 2.4% with up to 6% of masses being malignant [11]. These masses are usually corpora lutea. About 70% of masses discovered in the first trimester spontaneously resolve by the second [12]. Those larger (>5 cm) masses that do not resolve are usually mature teratomas [13]. The most common malignancy is epithelial ovarian carcinoma (51%), followed by germ cell (39%) [14]. More information on management considerations for masses discovered in pregnancy can be found in Limitations, Controversies, and Additional Considerations.
Patients may also be asymptomatic on presentation. In these situations, masses are usually incidentally found on imaging.
Rarer presentations of adnexal masses are below:
  • Ascites/Pleural Effusion: Ovarian cancer at later stages may present with ascites in the abdomen or pleural effusions. Rarely, benign ovarian fibromas may cause ascites and/or pleural effusions, termed Meigs syndrome (pseudo-Meigs syndrome is the constellation of ascites or pleural effusion and non-fibroma, benign ovarian mass).
  • Acute RUQ pain: Perihepatitis, or inflammation of the liver capsule, may occur in up to 10% of patients with acute pelvic inflammatory disease, termed Fitz-Hugh Curtis syndrome [15]. RUQ pain is usually severe and often referred to the right shoulder. Transaminitis is mild if it occurs.
  • Hyperthyroidism: Patients with a monodermal, highly specialized teratoma composed of thyroid tissue may present with symptoms of hyperthyroidism from exogenous production of thyroid hormone by the tumor, termed struma ovarii.
  • Flushing/Diarrhea: Similar to struma ovarii, a monodermal, highly specialized teratoma may form a carcinoid neoplasm similar to those that form in GI or respiratory systems.
  • Rigid/“frozen” abdomen: After the rupture of a mature teratoma, the spillage of sebaceous material can cause an extremely painful and severe granulomatous reaction in the abdomen, termed chemical peritonitis. Physical exam is significant for rigid abdominal wall muscle guarding and rebound tenderness. This reaction causes dense adhesions throughout the peritoneal cavity that can lead to chronic pain and “frozen” abdomen if not promptly cleared out.
  • New neurological or psychiatric issues: Anti-NMDA receptor encephalitis is an autoimmune paraneoplastic syndrome that is rarely associated with ovarian masses, especially teratoma. Symptoms may encompass any of the following: psychiatric manifestations including frank psychosis, sleep disturbance, memory loss, seizure, altered mental status, dyskinesias, autonomic instability, and language dysfunction. Other neurologic syndromes can rarely occur with ovarian masses.
  • Cutaneous manifestations: Rheumatologic autoimmune paraneoplastic syndromes, particularly scleroderma, may rarely occur with epithelial ovarian cancers. Scleroderma is characterized by thickened, fibrotic skin, but may be multisystem and include progressive fibrosis of the internal organs and vascular system.

Diagnostic Workup:

Clinical history-taking for these patients, in addition to the standard history of present illness, past medical and surgical history, social and family history, should include thorough investigation of gynecologic and obstetric history.
Menstrual history includes age of first menstruation (menarche), age of menopause (if applicable), date of last period, regularity of cycle and length of cycle, length and severity of menstruation, and other symptoms associated with periods. Characterization of uterine bleeding includes amount and relation to cycle. Pain should be well characterized. Document sexual history and obstetric history. The latter encompasses all pregnancies and their outcomes, regardless of whether they resulted in a living child.
Personal and family history of cancer, especially breast, ovarian, prostate, and colon cancers, can provide insight into hereditary syndromes related to ovarian cancer, which most commonly include BRCA1 or BRCA2 mutation and Lynch syndrome. BRCA1 and BRCA2 mutations are associated with up to a 44% and 17% lifetime probability of developing epithelial ovarian cancer, respectively [16].
Ovarian cancer tends to present at earlier ages in these patients (median age of diagnosis at age 53 for BRCA1 mutation and age 59 for BRCA2 mutation versus age 63 for the general population) [17,18]. Lynch syndrome has up to a 38% lifetime risk of developing ovarian cancer, as well as increased risk of endometrial cancer [19,20]. See Controversies, Limitations, and Additional Considerations, section on Hereditary Syndromes for more information on management of these patients.
Other risk and protective factors for ovarian cancer are as listed in Table 2. These factors can often be conceptualized in the framework of the incessant ovulation theory, whereby factors that increase the number of lifetime menstrual cycles tend to increase the chance of ovarian cancer, while factors that decrease the number of lifetime menstrual cycles tend to lower the chance of ovarian cancer.
Table 2. Risk and Protective Factors for Ovarian Cancer.
Risk FactorsProtective Factors
– Hereditary ovarian cancer syndrome (high grade serous)
– Early menarche/late menopause (high grade serous)
– Infertility/nulliparity (high grade serous)
– Endometriosis (clear cell, endometrioid, low grade serous)
– Cigarette smoking (mucinous)		– Late menarche/early menopause (high grade serous)
– Multiparity (high grade serous)
– Breastfeeding >12 months (high grade serous)
– Use of oral contraceptive pill or intrauterine device (high grade serous)
– Tubal ligation/bilateral salpingectomy (high grade serous)
Physical examination should include abdominal and pelvic components, including bimanual examination with documentation of cervical motion tenderness, uterine size and shape, and adnexal tenderness and fullness. Speculum examination can be useful for evaluating abnormal uterine bleeding and presence of vaginal discharge that may be indicative of infectious etiology.
Laboratory analysis will be guided by symptomatology, but should include quantitative hCG in women of reproductive age. Tumor markers are often obtained but should be selected purposefully and interpreted with caution as some are a better tool for cancer recurrence monitoring than initial diagnosis. CA 125 in particular has relatively low sensitivity and specificity (both less than 80%) for a number of reasons as discussed in the Controversies, Limitations, and Additional Considerations section on Biomarkers [21]. However, capturing a baseline biomarker level is still important upon patient presentation. Tumor markers pertinent to ovarian masses are summarized in Table 3.
Table 3. Biomarkers for Ovarian Tumors.
BiomarkerCancer Subtype
CA 125Epithelial ovarian cancer
HE4Epithelial ovarian cancer
CEAGI cancers > epithelial ovarian cancer
CA 19-9Pancreatic/biliary cancers > epithelial ovarian cancer
AFPYolk sac tumors
hCGEmbryonal tumors, choriocarcinoma
LDHDysgerminoma, yolk sac tumor
E2Sex cord-stromal tumors
InhibinGranulosa cell tumor
TSertoli-Leydig cell tumor
A4Sertoli-Leydig cell tumor
DHEASertoli-Leydig cell tumor, immature teratoma
AMHGranulosa cell tumor
CA: cancer antigen; CEA: carcinoembryonic antigen; HE4: human epididymis protein 4; AFP: alpha-fetoprotein; hCG: human chorionic gonadotropin; LDH: lactate dehydrogenase; E2: estradiol; T: testosterone; A4: androstenedione; DHEA: dehydroepiandrostenedione; AMH: anti-müllerian hormone.
Transabominal and transvaginal ultrasound is a mainstay of characterizing adnexal masses and important in establishing a presumptive diagnosis with which to guide clinical decision-making. Though definitive diagnosis of an adnexal mass is only possible via surgical removal and subsequent histologic analysis, additional imaging and/or surveillance is indicated in certain situations as outlined in below subsections on Management of Adnexal Masses.
Referral to a sonologist who specializes in the assessment of adnexal lesions can sometimes yield additional information. In premenopausal patients, repeat ultrasound timed to a specific phase of the menstrual cycle (usually the end of the follicular phase or days 7 to 12) can minimize new or additional cysts confounding assessment. The role of CT or MRI is limited because these modalities are static studies. Whereas, transvaginal ultrasound has a huge advantage over both because it is dynamic, meaning the sonologist can manipulate the pelvic organs and assess for mobility, or lack thereof. CT scanning has very limited utility in further characterizing an ovarian mass and is largely used to non-invasively stage suspected cancer patients and/or to check for extrapelvic disease. MRI can be helpful in certain situations where the characterization of soft tissue planes or characteristics is important, for example, to better characterize a teratoma, an endometrioma, or to identify extension of nearby tissues into the adnexa. If an expert sonologist is not available, MRI is the next best choice in imaging.
Several classification systems exist to help guide management of adnexal masses, and are largely based on ultrasound findings, as well as suspicion for malignancy. The International Ovarian Tumor Analysis (IOTA) study group has outlined a series of “simple rules” for categorizing ultrasound features of an adnexal mass [22]. These rules help to identify masses that have benign features versus those that have malignant features, and can do so with a sensitivity and specificity of 98% and 64%, respectively. However, many masses have mixed features, in which case an additional analysis by an expert sonographer can increase the sensitivity and specificity to 95% and 98%, respectively [23,24].
Building on the IOTA study group’s data, the Ovarian-Adnexal Reporting and Data System (O-RADS) committee further categorized sonographic findings to malignancy risk and provides a framework for management (see table below) [25]. Masses that are incompletely evaluated on initial imaging (O-RADS 0) should be further evaluated by a specialist in GYN sonography and/or MRI. Normal ovaries (O-RADS 1) need no further work-up, intervention, or follow-up.
Early referral to a gynecologic oncologist for masses suspicious for ovarian cancer (O-RADS 4-5) or for any concerning symptomology, history, or laboratory finding (such as highly elevated CA 125) is extremely important. Surgeons that specialize in this field are more likely to perform optimal surgical staging at the time of first surgery and are additionally able to offer neoadjuvant therapy in certain cases prior to surgery. Patients with late-stage ovarian cancer have a 6 to 9 month median survival benefit when managed by gynecologic oncologists [26].
Table 4. O-RADS Classification System
O-RADS ScoreIOTA Risk CategoryRisk of MalignancyManagement
0Incompletely evaluatedn/aRepeat or alternate study
1Normaln/aNo further intervention
2Almost certainly benign<1%Dependent on sonographic features and menstrual status (may include serial imaging or further characterization by US specialist and/or MRI)
3Low risk1-10%Further characterization by US specialist and/or MRI and management by gynecologist
4Intermediate risk10-50%Further characterization by US specialist and/or MRI and management by or in consultation with a gynecologic oncologist
5High risk>50%Further management by gynecologic oncologist
Figure 1. The Relative Importance of Single Tumor Markers in Patients with Adnexal Masses by Age and Ultrasound Morphology*

*The size of the tumor marker correlates to the relative importance in obtaining the tumor marker to aid in diagnosis.

Management of Benign Adnexal Masses:

Adnexal masses that are O-RADS 2, or almost certainly benign, often carry a presumptive diagnosis based on the presence of distinct features on ultrasound (US). The management of specific masses are discussed in the Table 5. Simple cysts and corpus lutea may benefit from additional management including symptomatic relief and suppression of future cysts with combined OCPs. Progression of size or complexity should prompt further imaging by a US specialist and/or MRI and referral to a gynecologist.
Table 5. Specific O-RADS 2 masses and their management in premenopausal and postmenopausal patients.
MassPremenopausalPostmenopausal
Simple cysts≤5 cm: none
>5 to <10 cm: follow-up in 8-12 wks		≤3 cm: none
>3 to <10 cm: follow-up in 1 yr + optional annual follow-up for 5 yrs
Unilocular cyst w/ smooth inner margins≤3 cm: none
>3 to <10 cm: follow-up in 8-12 wks		≤3 cm: follow-up in 1 yr
>3 to <10 cm: US specialist or MRI
Hemorrhagic cyst≤5 cm: none
>5 to <10 cm: follow-up in 8-12 wks		US specialist or MRI, referral to GYN
Dermoid cystGYN surgery (or optional follow-up in 8-12 wks)US specialist or MRI, referral to GYN
EndometriomaGYN surgery or follow-up in 8-12 wks followed by active surveillanceUS specialist or MRI, referral to GYN
Simple para- ovarian cystNoneOptional follow-up in 1 yr
Peritoneal inclusion cystReferral to GYNReferral to GYN
HydrosalpinxReferral to GYNReferral to GYN

Management of Adnexal Masses Concerning for Malignancy:

While O-RADS is an example of an evolving framework for the treatment of adnexal masses, there is no current universally accepted classification system to guide clinicians. Therefore, while masses that are O-RADS 4 or 5 should be managed either in consultation with or primarily by a gynecologic oncologist, any reason for suspicion of malignancy is appropriate to prompt such referral. This may include concerning family history, uncertainty regarding diagnosis, indeterminate or suboptimal imaging, or abnormal laboratory findings (especially elevated CA 125). Options for management of concerning adnexal masses include surveillance with serial transvaginal ultrasound (with/without serum CA 125 levels) or surgical management.
For patients with low-risk imaging (O-RADS 3) where surgery is not indicated, serial imaging with transvaginal ultrasound, usually in 3 and 6 months, is a reasonable approach for both pre- and post-menopausal women. These patients should be managed by a generalist gynecologist. Patients with intermediate-risk imaging (O-RADS 4) without below indications for surgery, may require more frequent surveillance, as well as consultation with gynecologic oncology.
Premenopausal women may have follow-up imaging in 6 weeks, so the mass may be evaluated at a different time point in the menstrual cycle, then in 6 months and 1 year. If initial CA 125 was elevated, consider trending with imaging. Suggested follow-up for postmenopausal women includes repeat imaging and CA 125 at 6 weeks, 12 weeks, and then every 3-6 months for 1 year.
Surveillance should be stopped with plan to proceed to surgery if concerning features appear on imaging, including an increase in size of the mass past 10 cm, or if tumor markers elevate concerningly (usually >200 in premenopausal women or >35 in postmenopausal women and/or a consistent upward trend). Patients who are O-RADS 5 should be managed by a gynecologic oncologist.

Surgical Intervention:

Patients who are candidates for surgery include patients with acute presentation (hemoperitoneum from ruptured cyst/ectopic pregnancy, likely ovarian torsion, etc.), high-risk imaging (O-RADS 5), markedly elevated CA 125, large mass size ≥10 cm (especially in postmenopausal patients), intermediate-risk imaging (O-RADS 4) with risk factors, patients who require mass resection for definitive diagnosis, and patients who request surgical management out of preference with informed consent or for symptomatic relief.
The type of surgery performed depends on menstrual status, desire for future fertility, and suspicion of malignancy. For low suspicion of malignancy in premenopausal women, the surgery may be limited to resection of the mass itself (i.e. ovarian cystectomy) to preserve fertility and the physiologic benefits of ovarian reproductive hormones.
For patients who have completed their childbearing, opportunistic salpingectomy may be considered to reduce future risk of ovarian cancer. Regardless of level of suspicion for malignancy, peritoneal washings should be obtained at the beginning of the case (as this sample cannot be obtained once tissue is removed or mass is ruptured) and a survey of the entire upper and lower abdomen should be performed. Importantly, care should be taken to avoid rupture of cysts to prevent spillage of material into the abdomen that may contain malignant cells or cause inflammatory reaction. Using appropriately sized extraction bags or converting to open surgery are methods that decrease the risk of rupture. Laparotomy via midline vertical or Pfannenstiel incision must be performed if the mass is too large for the containment bags available, usually for masses around 15 cm. In cases where intraoperative findings are equivocal or concerning, obtaining a preliminary pathologic diagnosis by sending a frozen section or consulting a gynecologic oncologist intraoperatively if available is prudent. Purposeful scheduling of surgery at an institution that has a gynecologic oncology service, even if the surgery is to be performed by the general gynecology service, is advised.
Staging surgery for ovarian cancers should be performed by gynecologic oncologists and includes: collection of free fluid or peritoneal washings, exploration of peritoneal surfaces (bowel, liver, gallbladder, diaphragm, mesentery, omentum, etc.) with biopsy of suspicious lesions/adhesions (if no suspicious areas, several biopsies at random are obtained), omentectomy, exploration and biopsy of pelvic and paraaortic lymph nodes, total extrafascial hysterectomy, and bilateral salpingo-oophorectomy.
When metastatic disease is found, cytoreduction (or surgical debulking) is performed with the goal of completely removing observable disease. This is an important step as the volume of postoperative residual disease is inversely correlated with survival [27].

Chemotherapy and Radiation:

Please review the GMKA Section on Ovarian Cancer (Ovarian Cancer – GMKA – Global Medical Knowledge Alliance) for more information on treatment and management.

Controversies, Limitations, and Additional Considerations:

Tissue Origin: Foundational research into the origins of epithelial ovarian cancers has revealed that the cellular origin of many of these ovarian masses may actually derive from nearby tissues. Abnormal cells from organs such as the Fallopian tube, uterus, or GI tract are hypothesized to implant in the ovary, leading to a primary mass there. It is now widely accepted that the majority of high grade serous ovarian cancer originates in the Fallopian tube epithelium, and the presence of precancerous lesions, called serous tubal intraepithelial carcinomas (STICs), in the Fallopian tube may be identified on pathologic examination. Clear cell and endometrioid subtypes are thought to possibly progress from endometriotic implants in the ovary.
The origins of these subtypes of ovarian cancer are important for several reasons. First, in select patients, treatment or removal of the originating organ may be risk-reducing for ovarian cancer. This is discussed further in Hereditary Syndromes below and most relevant for prophylactic salpingectomy in high-risk populations. Secondly, the finding of ovarian cancer may prompt investigation of the originating organ. For example, the finding of mucinous ovarian cancer may precipitate further investigation for possible GI lesions.
Biomarkers: CA 125 is the most commonly used biomarker for ovarian cancer of epithelial origin. However, it has relatively low sensitivity of 78% and low specificity of 78% driven by a number of physiologic and pathologic variables [21]. CA 125 is a protein produced by tissues of Müllerian origin (fallopian tubal, endometrial, and endocervical epithelia), as well as coelomic structures (pericardium, pleura, and peritoneum). It can be elevated in a large number of normal and disease states, including but not limited to menstruation, pregnancy, endometriosis, PID, leiomyoma, benign ovarian masses, epithelial ovarian cancer, endometrial cancer, UTI, GI pathologies (colitis, pancreatitis, cirrhosis), cardiac pathologies (heart failure, MI, cardiomyopathy), pulmonary pathologies (pneumonia, pulmonary embolism, pleural effusion), and recent surgery. Given that many of the above conditions affect women of reproductive age, sensitivity and specificity of CA 125 in premenopausal women is particularly low (as low as 50% and 69%, respectively) [28].
Therefore, higher thresholds for CA 125 (>200 in premenopausal women versus >35 in postmenopausal women) have been proposed [29]. Additionally, diagnostic performance is highest for the high-grade serous subtype of epithelial ovarian cancer versus mucinous, clear cell, and mixed subtypes and in later stages of disease versus earlier. CA 125 is FDA approved for monitoring response to therapy with initial evaluation of a mass constituting an off-label use.
HE4 is also FDA-approved for monitoring response to therapy, especially in cases where CA 125 is not initially elevated. It may also have prognostic value but is affected by patient age and pregnancy. CEA is often useful in attempting to distinguish ovarian versus colon cancer. The ratio of CA 125 to CEA is consistent with primary ovarian cancer in 82% of patients when greater than 25 [30]. Similarly, CA 19-9 may be useful in distinguishing pancreatic cancer from ovarian cancer as both cancers frequently metastasize throughout the peritoneal cavity in later stages.
Screening Average Risk Patients: Given the low sensitivity and specificity of the above biomarkers in combination with the low prevalence of ovarian cancer in the general population relative to the high incidence of adnexal masses, screening for ovarian cancer is not indicated for a person of average risk at this time. Several studies have attempted to combine biomarkers and transvaginal ultrasound to increase the utility of these potential screening modalities. To date, no study of average-risk women has shown a survival benefit.
Hereditary Syndromes: High risk patients are usually identified by concerning family history of breast, ovarian, pancreatic, prostate, or colon cancers and often have completed genetic counseling that has uncovered pathogenic gene variants, most commonly in BRCA1, BRCA2, or genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM). Recommendations for the management of these patients in regard to ovarian cancer (and endometrial cancer in Lynch syndrome patients) are outlined in Table 6. It is important to note that similar to screening for ovarian cancer in the average-risk patient, ovarian cancer screening among high-risk patients is not associated with improvement in survival. That said, the most effective risk-reducing strategy is risk-reducing surgery.
Table 6. Recommendations for mitigation of gynecologic cancer risk for patients with BRCA1/2 mutation or Lynch syndrome.
ScreeningConcurrent transvaginal ultrasound and CA 125 (between days 6 and 10 of the menstrual cycle) every six months beginning at age 30 or 5 to 10 years before the earliest age of first diagnosis of ovarian cancer in the family is recommended for BRCA1/2 carriers and Lynch syndrome [31]. Annual endometrial sampling is also recommended beginning concurrently with ovarian cancer screening in Lynch syndrome due to the increased risk of endometrial cancer in these patients [31,32].
ChemopreventionCombined oral contraceptive pills (OCPs) are associated with a reduced risk of ovarian cancer (RR 0.50, 95% CI 0.33-0.75) which improves with duration of use (5% decrease in risk for every year of use) [33,34]. OCPs, as well as hormonal implants and injections, may additionally decrease the risk of endometrial cancer in Lynch syndrome by 60% after one year of use [35]. However, given the increased protection of risk-reducing surgery and the theoretical increased risk of breast cancer in these patients with exogenous hormone use, risk-reducing surgery should be strongly recommended over OCP use.
Risk-Reducing SurgeryRisk-reducing bilateral salpingo-oophorectomy (rr-BSO) is recommended for BRCA mutation carriers who have fulfilled their childbearing goals by age 35 to 40 for BRCA1 carriers and by age 40 to 45 for BRCA2 carriers. This surgery is associated with an 80% reduction in risk of ovarian cancer and 68% reduction in all-cause mortality in this patient population [36]. Risk-reducing surgery for Lynch syndrome patients additionally includes total hysterectomy due to the increased risk of endometrial cancer in these patients and should be performed by age 35-45, depending on the society guideline referenced [32,37].
Pregnancy: Most adnexal masses found in pregnancy have no concerning features of malignancy and can be managed expectantly. MRI (without gadolinium-based contrast) may be a useful secondary imaging modality, as it poses no risk of ionizing radiation to the fetus. Obtaining serum tumor marker levels is generally avoided due to difficulty in interpreting these results in pregnancy. If a mass persists past the first trimester and has concerning features (large size >10 cm, specific ultrasound findings, etc.), surgical resection is usually indicated. Once in the second trimester, the pregnancy is no longer maintained by the corpus luteum in the ovary if it must be removed and organogenesis is mostly complete, reducing risk to the fetus of medications administered under anesthesia.
For similar reasons, chemotherapy administration is avoided in the first trimester for desired pregnancies. Informed consent and counseling are important as there is limited data on maternal and fetal outcomes for chemotherapy in pregnancy. For early-stage disease, it may be reasonable to defer chemotherapy until after delivery, whereas women with advanced-stage disease should start chemotherapy as soon as reasonably possible after surgery (usually 2-4 weeks post-op). Briefly, for epithelial ovarian cancers, the preferred platinum/taxane regimen is carboplatin (over cisplatin) and paclitaxel (over docetaxel) as they are generally better tolerated, less toxic agents.
If an adnexal mass is incidentally found during cesarean section that is concerning for malignancy, it should be resected and sent for frozen section evaluation. If malignant, salpingo-oophorectomy should be performed as full staging is not usually possible given the specifics of the anesthesia and incision involved in routine cesarean section, and the patient should be referred to gynecologic oncology for further expedient surgical staging and treatment.

Summary:

The management of adnexal masses may seem daunting given the wide spectrum of etiologies, patient demographics, and presentations. After triage of more acute presentations, the mainstay of diagnosis is based on patient history and transvaginal ultrasound. Tumor markers are to be thoughtfully and purposefully utilized given their low sensitivity and specificity as a diagnostic tool.
The O-RADS classification system provides a framework that can guide treatment and referral to appropriate providers. Treatment is generally a choice between surveillance and surgery, based on likelihood of malignancy. Gynecologic oncologists should be involved in care early if malignancy is in any way suspected, in order to ensure patients have appropriate staging and adjunct treatment/s up front, which has been shown to greatly improve patient outcomes.

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