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Ovarian tumors

Last updated: March 22, 2022

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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.

Epidemiological data refers to the US, unless otherwise specified.

Risk factors [5]

Protective factors

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]
  • 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 Cystadenoma Brenner tumor [21] Cystadenocarcinoma Endometrioid carcinoma [4][22] Clear cell tumors [4][23]
Ovarian serous cystadenoma Ovarian mucinous cystadenoma Serous Mucinous [24]
Classification
  • Benign
  • Malignant
Epidemiology
  • Most (serous) and second most common (mucinous) benign ovarian tumor
  • Rare
  • Peak age: 40–60 years
  • Most common malignant ovarian tumor
Clinical features
  • Typically asymptomatic
  • Symptoms of abdominal displacement may be present (e.g., pain, ↑ urinary frequency)
Ultrasound appearance
  • Unilocular cystic mass
  • Absent flow on Doppler
  • Large, multilocular cystic tumor
  • Mostly small tumors with a solid component and calcifications
  • Absent or only minimal flow on Doppler
  • Mostly large, unilateral, solid or multilocular-solid tumor with papillary projections
  • Large (up to 30 cm in diameter), cystic/solid unilateral masses
  • Tumor with mixed cystic/solid components and heterogeneous texture
  • May contain papillary projections and/or thick septations
  • Similar to mucinous cystadenoma
  • Additional solid components and signs of malignancy (e.g., invasion of adjacent structures) may be present
  • Mural thickening

Pathology

 Gross examination
  • Cysts with watery fluid
  • Smooth or bosselated appearance
  • Cyst is loculated; loculi contain gelatinous material
  • Encapsulated, pale yellow solid tumor
  • Cysts filled with mucoid material, cellular debris, and/or blood
  • Possible appearances are:
    • Smooth surface with cystic spaces filled with blood-stained fluid
    • Completely solid with necrosis/hemorrhage
  • Endometriosis-associated tumors are filled with chocolate-colored fluid
Histology
  • Cystic or colloid type, depending on intracellular or extracellular mucin deposition
    • Cystic type: > 50% of intracellular mucin in ≥ 90% of tumor cells
    • Colloid type: large quantities of extracellular mucin (≥ 50% of tumor volume)
  • Characteristic confluent glandular/expansile pattern
    • Tightly packed, back-to-back glands lined with tumor cells
    • Absent intervening stroma
  • Variable appearance: tubulocystic, papillary, and solid
Tumor marker

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

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 Teratoma Yolk sac tumor of the ovary (endodermal sinus tumor) [26] Dysgerminoma [27] Nongestational choriocarcinoma [28]
Dermoid cysts (mature cystic teratoma) Struma ovarii (mature teratoma) [29] Immature teratoma [30]
Classification
  • Benign
  • Malignant, aggressive
Epidemiology
  • Most common of all germ cell tumors (90% of all cases)
  • Most common ovarian tumor in women < 30 years [31]
  • Rare
  • Peak age: women < 20 years of age [33]
Clinical features
  • Mostly asymptomatic
  • Unspecific symptoms, including:
  • Rapid growth; acute onset of symptoms (pelvic mass and pain)
  • Larger tumors may cause:
    • ↑ Abdominal girth
    • Pressure symptoms (e.g., ↑ urinary frequency)
    • Lower abdominal pain
Ultrasound appearance
  • Heterogeneous mass
  • Hyperechoic nodule
  • Echogenic shadowing
  • Absent internal vascularity and/or fluid-fluid levels
  • Multilocular solid appearance
  • Struma pearl may be present.
  • Large tumor with a solid component
  • Solid component arises from the wall of the cyst and makes up ≥ 15% of total cyst size; contains smaller, fluid-filled cysts (e.g., blood, mucus).
  • Small areas of calcification
  • Large, solid, well- vascularized, multilobulated tumor that is well-defined relative to its surroundings
  • Heterogeneous internal echogenicity
  • Well-vascularized mass with inhomogeneous texture
  • Irregular contour
  • Ovarian crescent sign may be present
Histopathology
Tumor markers
  • None
  • LDH (rare) [35]
Risk of malignant transformation
  • N/A

Sex cord-stromal tumors of the ovary [18]

  • Frequency: < 5% of all ovarian tumors [40]
Types of sex cord-stromal tumors of the ovary
Type

Ovarian fibroma [41]

 Theca cell tumor (thecoma) [42] Sertoli-Leydig cell tumor [43][44][45][46] Granulosa cell tumor [43][47][48]
Classification
  • Benign
  • Usually benign
  • Malignant
Epidemiology
  • Rare
  • Peak age: 30–40 years
  • Most common type of sex cord-stromal malignancy (∼ 90%)
  • Peak age: 50–55 years
Clinical features
  • No hormonal activity
  • Lower abdominal discomfort and/or a pulling-sensation in the inguinal area
  • May be associated with Meigs syndrome: ascites and pleural effusion in association with a benign ovarian tumor; surgical removal of the tumor leads to complete resolution of symptoms. [50]
  • Abnormal postmenstrual bleeding due to estrogen production
Ultrasound appearance
  • Round or oval solid tumor with minimal to moderate vascularization
  • Regular to slightly irregular internal echogenicity
  • Cystic spaces may be present.
  • Most commonly between 5 and 15 cm in diameter
  • Large papillary projections may be visible.
  • Typically, large tumor with multilocular solid appearance with > 10 small locules
  • Typically mixed or low level echogenicity
Pathology Gross examination
  • Smooth, lobulated
  • Cut surface: chalky, firm, yellow-to-white color
  • Solid yellow-orange tumor
  • Small, yellow-brown tumor
  • Tan/yellow color
  • Encapsulated; smooth lobulated surface, possibly with areas of necrosis/hemorrhage
Histology
  • Ovarian stromal cells filled with lipids on microscopy
  • Call-Exner bodies: granulosa cells arranged in clusters surrounding a central cavity with eosinophilic secretions, resembling primordial follicles
Tumor markers
  • None

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

Subtypes and variants

Overview [52][53]

  • Traditionally, ovarian cancer was considered an asymptomatic “silent killer.”
  • However, up to ∼ 90% of patients do present with symptoms before diagnosis. [52][54]

Subacute symptoms [53][54]

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 [53]

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).

Imaging

Pelvic ultrasound [59]

  • Imaging test of choice for evaluation of adnexal masses and suspected ovarian cancer. [60]
  • 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) [59]

  • 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

Serum markers of germ cell tumors

Type of tumor

 Tumor marker
Dysgerminoma
Yolk sac tumor
Immature teratoma
Choriocarcinoma
Embryonal carcinoma

Tissue diagnosis

  • Noninvasive biopsy: not recommended due to the risk of tumor seeding and, as a result, advancing the stage of disease [62]
  • Surgical evaluation

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

Gynecologic [59]

Nongynecologic [59]

The differential diagnoses listed here are not exhaustive.

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

Surgery [64][65]

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

Chemotherapy [65]

Targeted molecular therapy

Radiation therapy [78]

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

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%

Ovarian cancer screening [79][80]

Strategies to reduce the risk of ovarian cancer

See “Protective factors” in “Etiology” above.

Pregnant women

  • Pregnancy luteoma [85]
    • 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
    • Treatment
      • Observation
      • Most regress spontaneously post partum.
  • Theca lutein cysts
  • Corpus luteum cyst

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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