Ovarian cancer is the most deadly gynecological neoplasm in the United States. Risk factors for developing ovarian cancer include genetic predisposition (e.g., / mutation) and hormonal factors (e.g., increased number of lifetime ovulations). The ovaries consist of different types of tissue (epithelial, germ cells, and sex cord tissue), which may give rise to benign or malignant tumors. Symptoms depend on the type of tissue affected and range from local abdominal discomfort to endocrinological phenomena caused by hormone-producing tumors. Metastases of other tumors and lymphomas may also affect the ovaries. The most common malignant tumor of the ovaries is serous ovarian cancer, which primarily affects older women (median age of diagnosis is 63 years). The lack of early symptoms of ovarian cancer often delays diagnosis, resulting in an unfavorable prognosis. Ovarian cancers primarily metastasize intraperitoneally and later become noticeable mostly due to increasing abdominal girth caused by malignancy-related ascites. Treatment generally involves radical surgical removal of the tumor and chemotherapy.
- Ovarian tumors are the most common ovarian mass in women > 55 years of age.
- Lifetime prevalence of malignant ovarian cancer: 1–2% 
- Ovarian cancer is the second most common gynecological cancer (after endometrial cancer) but causes the most deaths (with endometrial cancer causing the second most). 
- Median age at diagnosis of ovarian cancer: 63 years 
- Incidence rates highest in non-Hispanic white women 
Epidemiological data refers to the US, unless otherwise specified.
Risk factors 
- / mutation 
- syndrome: The lifetime risk of developing ovarian cancer is ∼ 10%. 
- Family history
- Peutz-Jeghers syndrome 
- Hormonal factors
Classification of ovarian tumors
Epithelial ovarian tumors
- Arise from ovarian surface epithelium
- Most commonly benign
- Germ cell ovarian tumors
Sex cord and stromal ovarian tumors
- Arise from sex cord cells (e.g., Sertoli or granulosa cells) or stromal cells (e.g., fibroblasts or primitive gonadal stroma)
- May be benign or malignant
Epithelial ovarian tumors 
- Histological classification
Clinicopathological classification 
- Type I ovarian tumors: low-grade, indolent tumors that typically manifest as large, unilateral, cystic neoplasms
- Type II ovarian tumors: high-grade, aggressive tumors that typically involve both ovaries and are diagnosed at an advanced stage
- Frequency 
|Types of epithelial ovarian tumors|
|Type||Classification||Epidemiology||Characteristic features||Tumor marker|
|Serous||Cystadenoma|| || |
|Cystadenocarcinoma|| || |
|Mucinous||Cystadenoma|| || |
|Brenner tumor|| || |
|Endometrioid carcinoma|| || |
|Clear cell tumors|| || |
Most ovarian tumors are benign, not malignant.
- Frequency: ∼ 5% of all ovarian tumors 
|Types of ovarian germ cell tumors|
|Type||Classification||Epidemiology||Characteristic features||Tumor markers|
| || |
|Struma ovarii (mature teratoma)|| || || |
|Immature|| || || |
|Yolk sac tumor of the ovary (endodermal sinus tumor)|| || |
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- Frequency: < 5% of all ovarian tumors 
|Types of sex cord-stromal tumors of the ovary|
|Type||Classification||Epidemiology||Characteristic features||Diagnostic markers|
|Granulosa cell tumor|| || |
|Theca cell tumor (thecoma)|| || || |
|Sertoli-Leydig cell tumor|| || || || |
|Ovarian fibroma|| || || || |
Call-Exner bodies are characteristic of Granulosa cell tumors: “Call your Ex and Grandparents!”
Subtypes and variants
- Krukenberg tumor: secondary ovarian tumor that most commonly arises from metastatic spread of gastric carcinoma 
- Traditionally, ovarian cancer was considered an asymptomatic “silent killer.”
- However, up to ∼ 90% of patients do present with symptoms before diagnosis. 
Subacute symptoms 
Ovarian cancer most commonly manifests with subacute symptoms, which occur in women with early-stage disease. These symptoms are nonspecific and often difficult to attribute to ovarian cancer.
- Can be asymptomatic
- Often found on routine pelvic examination or imaging
- Pelvic and abdominal symptoms
Abnormal bleeding 
- Postmenopausal bleeding
- Rectal bleeding
Paraneoplastic syndromes 
- Cerebellar degeneration
Acute presentations and symptoms of metastatic disease 
Acute symptoms typically occur in patients with advanced disease and are an indication for immediate evaluation and treatment.
- Hematologic complications: 
- Intrapelvic symptoms:
- Metastatic dissemination 
The first symptom of ovarian cancer is often increasing abdominal girth (clothes no longer fit at the waist).
Pelvic ultrasound 
- Imaging test of choice for evaluation of adnexal masses and suspected ovarian cancer. 
- Both transabdominal and transvaginal modalities should be utilized.
Ultrasound examination should assess the following:
- Size and structural characteristics
- Mass margins
- Pelvic fluid
|Ultrasound workup of ovarian masses|
|Internal structure||Uniform, thin walls||Irregularly thickened septa|
|Margins||Smooth||Indistinct borders; papillary projections|
|Echogenicity||Anechoic||Hypoechoic, anechoic, and hyperechoic components|
|Content||Cystic||Cystic or solid components|
|Vascularization||Unremarkable||Possible central vascularization|
|Pouch of Douglas||Unremarkable||Possible free fluid (ascites)|
Pelvic ultrasonography should be the first step in evaluating women with suspicious ovarian masses.
Magnetic resonance imaging (MRI) 
- Not routinely recommended for evaluation of suspected ovarian cancer
- May be helpful in determining the origin of pelvic masses that are not clearly arising from the ovary
- Useful for assessing the feasibility of surgical resection
Computed tomography (CT)
- Not recommended in the initial evaluation of adnexal masses
- Useful for determining the extent of ovarian metastases (e.g., omental, liver, and lung lesions)
- General: See “Overview of ovarian tumors” above.
Epithelial ovarian tumors: CA-125 is elevated in ∼ 80% of malignant tumors. 
- The and of CA-125 are different in premenopausal and postmenopausal women. 
- Premenopausal women: Elevated CA-125 points to a benign process.
- Postmenopausal women: Elevated CA-125 > 35 units should raise concern for malignancy.
- Should only be used to monitor disease progression or recurrence after treatment
- Germ cell tumors
|Serum markers of germ cell tumors|
Type of tumor
|Yolk sac tumor|
- Noninvasive biopsy: not recommended due to the risk of tumor seeding and, as a result, advancing the stage of disease 
- Surgical evaluation
- Malignant cause: metastatic cancer
- Benign causes
- Malignant causes
The differential diagnoses listed here are not exhaustive.
Staging of epithelial ovarian cancer including fallopian tube cancer and primary peritoneal cancer 
Staging is based on the 2017 International Federation of Gynecology and Obstetrics (FIGO) and the Tumor, Node, Metastasis ( ) classification systems.
|Curative|| || |
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|Palliative|| || |
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- Surgical staging: used to obtain pathologic specimens and evaluate the extension of cancer spread (see “Stages” above) 
Surgical debulking: Whenever possible, maximal cytoreduction (i.e., removal of visible tumor) should be completed to improve long-term outcomes. 
- Residual disease < 1 cm defines optimal debulking. 
- Utilized in disease stages I–III
For the best patient outcomes, surgical staging and debulking should be performed by expert gynecological oncologists.
- Preferred regimens
Routes of administration
- Intraperitoneal 
Targeted molecular therapy
- Targeted agents: poly (ADP-ribose) polymerase inhibitors
Radiation therapy 
- Not the preferred treatment modality for ovarian cancer
- Reserved as symptomatic treatment for recurrent or metastatic disease
Outcomes for epithelial ovarian cancer 
- Very poor overall prognosis as a result of late diagnosis
- 5-year survival rate of all stages: ∼ 50%
Ovarian cancer screening 
- Routine screening with CA-125 or transvaginal ultrasound is not recommended in patients with an average risk of ovarian cancer. 
- Routine screening is also not recommended in patients with a known, high-risk genetic predisposition (e.g., BRCA mutation carrier or strong family history).
- Potential benefits
- Reduction in mortality
- Diagnosis of ovarian cancer at an earlier stage
- Potential harms
Strategies to reduce the risk of ovarian cancer
See “Protective factors” in “Etiology” above.
Special patient groups
Pregnancy luteoma 
- Definition: rare, benign tumors that arise in response to elevated hormone levels (e.g., ) during pregnancy
- Clinical features
- Most regress spontaneously postpartum.
- (see “Overview” in “ ”)
If surgical removal of an ovarian tumor is indicated during pregnancy, surgery should, if possible, be scheduled for after the 10th week of gestation, as the secretion of progesterone by the corpus luteum is essential for the maintenance of the pregnancy. The placenta takes over this function from approximately the 10th week of pregnancy onwards.