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Ovarian tumors

Last updated: December 17, 2020

Summary

Ovarian cancer is the most deadly gynecological neoplasm in the United States. Risk factors for developing ovarian cancer include genetic predisposition (e.g., BRCA1/BRCA2 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.

Epidemiology

  • Ovarian tumors are the most common ovarian mass in women > 55 years of age.
  • Lifetime prevalence of malignant ovarian cancer: 1–2% [1]
  • Ovarian cancer is the second most common gynecological cancer (after endometrial cancer) but causes the most deaths (with endometrial cancer causing the second most). [2]
  • Median age at diagnosis of ovarian cancer: 63 years [1][3]
  • Incidence rates highest in non-Hispanic white women [4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Risk factors [5]

Protective factors

Overview of ovarian tumors

Classification of ovarian tumors

  • Epithelial ovarian tumors
  • Germ cell ovarian tumors
    • Arise from the primordial germ cells (e.g., oocytes)
    • Can be benign or malignant
    • Subtypes are determined by structural differentiation
  • 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 [18][19]

  • Histological classification
    • Benign: lack hyperproliferative and invasive behavior
    • Borderline ovarian tumors: a histopathological term that describes an ovarian tumor of low malignant potential that expresses cytologic features of malignancy without frank invasion
    • Malignant: evidence of invasion
  • Clinicopathological classification [20]
    • 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
      • Histologic subtypes include high-grade serous, carcinosarcoma, and undifferentiated carcinoma
      • Account for ∼ 90% of ovarian cancer deaths
      • Associated with high levels of chromosomal instability
      • p53 mutations are common
  • Frequency [4]
    • Most common benign and malignant ovarian tumor subtype
    • Epithelial tumors account for ∼ 90% of all ovarian malignancies
Types of epithelial ovarian tumors
Type Classification Epidemiology Characteristic features Tumor marker
Serous Cystadenoma
  • Benign
  • Most common benign ovarian tumor
Cystadenocarcinoma
  • Malignant
  • Most common malignant ovarian tumor
Mucinous Cystadenoma
  • Benign
  • Second most common benign ovarian tumor
Brenner tumor
  • Benign
  • Rare
  • Most common in women 40–60 years of age
  • Encapsulated, pale yellow solid tumor
  • Similar to transitional cells of the bladder (urothelium)
  • Circular patches of cells with coffee bean nuclei
Cystadenocarcinoma
  • Malignant
Endometrioid carcinoma
  • Malignant
Clear cell tumors
  • Malignant

CA-125 is used as a tumor marker for epithelial ovarian cancer but can also be elevated in endometriosis, uterine leiomyoma, cirrhosis, and other malignancies.

Most ovarian tumors are benign, not malignant.

Ovarian germ cell tumors [18]

  • Frequency: ∼ 5% of all ovarian tumors [4]
Types of ovarian germ cell tumors
Type Classification Epidemiology Characteristic features Tumor markers
Teratoma

Dermoid cysts

(mature teratoma)

  • Benign
  • None
Struma ovarii (mature teratoma)
  • Benign
  • None
Immature
  • Malignant and aggressive
  • Rare
  • Most commonly occurs in women < 20 years of age [25]
Dysgerminoma
  • Malignant
  • Rapid growth; acute onset of symptoms (pelvic mass and pain)
  • A less common female histological equivalent to the male seminoma
  • Histopathologic evaluation shows fried egg cells
Yolk sac tumor of the ovary (endodermal sinus tumor)
  • Malignant and aggressive
  • Rapid growth; acute onset of symptoms (pelvic mass and pain)
  • Mass appears yellow and friable (due to hemorrhage) on gross examination.
  • Characteristic Shiller-Duval bodies, which resemble glomeruli on microscopy [28]

Nongestational choriocarcinoma

  • Malignant
  • Extremely aggressive

Sex cord-stromal tumors of the ovary [18]

  • Frequency: < 5% of all ovarian tumors [31]
Types of sex cord-stromal tumors of the ovary
Type Classification Epidemiology Characteristic features Diagnostic markers
Granulosa cell tumor
  • Malignant
  • Most common type of sex cord-stromal malignancy (∼ 90%) [32]
  • Peak incidence in women between 50–55 years of age
Theca cell tumor (thecoma)
  • Benign
  • Can produce estrogen, which leads to abnormal postmenstrual bleeding
  • Solid yellow-orange tumor on gross examination
  • Ovarian stromal cells filled with lipids on microscopy
  • None
Sertoli-Leydig cell tumor
  • Usually benign
  • Rare tumor
  • Primarily affects women 30–40 years of age [33]
  • None
Ovarian fibroma
  • Benign
  • No hormonal activity
  • Clusters of spindle-shaped cells (fibroblasts)
  • May be associated with Meigs syndrome: ascites and pleural effusion in association with a benign ovarian tumor [37]
    • The cause is unknown.
    • Surgical removal of the tumor leads to complete resolution of symptoms.
  • Often manifests with lower abdominal discomfort and/or a “pulling” sensation in the inguinal area
  • None

Call-Exner bodies are characteristic of Granulosa cell tumors: “Call your Ex and Grandparents!”

Subtypes and variants

Clinical features

Overview [39][40]

  • Traditionally, ovarian cancer was considered an asymptomatic “silent killer.”
  • However, up to ∼ 90% of patients do present with symptoms before diagnosis. [39][41]

Subacute symptoms [40][41]

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.

Acute presentations and symptoms of metastatic disease [40]

Acute symptoms typically occur in patients with advanced disease and are an indication for immediate evaluation and treatment.

The first symptom of ovarian cancer is often increasing abdominal girth (clothes no longer fit at the waist).

Diagnostics

Imaging

Pelvic ultrasound [46]

  • Imaging test of choice for evaluation of adnexal masses and suspected ovarian cancer. [47]
  • Both transabdominal and transvaginal modalities should be utilized.
  • Ultrasound examination should assess the following:
    • Size and structural characteristics
    • Laterality
    • Mass margins
    • Vascularity
    • Pelvic fluid
Ultrasound workup of ovarian masses
Benign Malignant
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) [46]

  • 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)

Tumor markers

Tissue diagnosis

  • Noninvasive biopsy: not recommended due to the risk of tumor seeding and, as a result, advancing the stage of disease [49]
  • Surgical evaluation
    • Recommended method for diagnosing ovarian cancer [50]
    • Should only be utilized in patients with a high probability of a malignant ovarian mass
    • If a malignancy is found, it can be staged and cytoreduction can be performed (see “Surgery” in “Treatment” below).

Fine needle aspiration is absolutely contraindicated in ovarian tumors because it may directly spread tumor cells to the peritoneum!

Differential diagnoses

Gynecologic [46]

Nongynecologic [46]

The differential diagnoses listed here are not exhaustive.

Stages

Staging of epithelial ovarian cancer including fallopian tube cancer and primary peritoneal cancer [18]

Staging is based on the 2017 International Federation of Gynecology and Obstetrics (FIGO) and the Tumor, Node, Metastasis (TNM) classification systems.

Management approach

FIGO Stage

TNM

Description
Curative
  • Stage IA
  • T1a, N0, M0
  • Stage IB
  • T1b, N0, M0
  • Stage IC
  • T1c, N0, M0
  • Stage IIA
  • T2a, N0, M0
  • Stage IIB
  • T2b, N0, M0
  • Tumor extension to or implants on other pelvic tissues
  • Stage IIIA1
  • T1–T2, N1, M0
  • Stage IIIA2
  • T3a, N0–N1, M0
  • Stage IIIB
  • T3b, N0–N1, M0
  • Stage IIIC
  • T3c, N0–N1, M0
Palliative
  • Stage IVA
  • T1–T3, N0-N1, M1a
  • Stage IVB
  • T1–T3, N0-N1, M1b

Treatment

Surgery [51][52]

For the best patient outcomes, surgical staging and debulking should be performed by expert gynecological oncologists.

Chemotherapy [52]

Targeted molecular therapy

Radiation therapy [65]

  • Not the preferred treatment modality for ovarian cancer
  • Reserved as symptomatic treatment for recurrent or metastatic disease

Prognosis

Outcomes for epithelial ovarian cancer [1]

  • Very poor overall prognosis as a result of late diagnosis
  • 5-year survival rate of all stages: ∼ 50%
FIGO Anatomic extension 5-year survival rate
I Limited to one or both ovaries 80–90%
II Infiltration of the lesser pelvis 50–70%
III Extension outside pelvis 30–40%
IV Distant metastases 10–20%

Prevention

Ovarian cancer screening [18]

  • Indications
    • Routine screening with CA-125 or transvaginal ultrasound is not recommended in patients with an average risk of ovarian cancer. [66][67]
    • Routine screening is also not recommended in patients with a known, high-risk genetic predisposition (e.g., BRCA mutation carrier or strong family history).
      • Alternatively, high-risk patients may undergo risk-reducing salpingo-oophorectomy (rrBSO) if no future pregnancies are desired. [13]
      • Intensive and regular screening with pelvic ultrasound (e.g., every 6 months after age 35) is an alternative to rrBSO. [68]
  • 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

Pregnant women

  • Pregnancy luteoma [69]
    • Definition: rare, benign tumors that arise in response to elevated hormone levels (e.g., β-hCG) during pregnancy
    • Clinical features
      • The majority of patients are asymptomatic.
      • Occasionally, they are functionally active (i.e., cause androgen hypersecretion) and manifest with symptoms of virilization of the mother or the fetus.
    • Diagnostics
      • Pelvic ultrasound
        • Solid adnexal mass
        • Can be unilateral or bilateral
        • Significant venous or arterial flow
        • 4–10 cm in diameter
      • Luteomas are often diagnosed incidentally during cesarean delivery.
    • Treatment
      • Observation
      • Most regress spontaneously postpartum.
  • Theca lutein cysts (see “Overview” in “Ovarian cysts”)

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.

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