- Clinical science
The ovaries consist of different kinds 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 (with the exception of those who are genetically predisposed) mostly affects older women. The lack of early symptoms of ovarian cancers 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.
- Lifetime prevalence of malignant ovarian cancer: 1–2%
- Peak incidence: 60–70 years
- Genetic predisposition may play a role in familial incidence and in younger patients (< 30 years) developing tumors.
- Epithelial ovarian carcinomas account for 70% of all ovarian malignancies.
Epidemiological data refers to the US, unless otherwise specified.
- 65–75% of all ovarian tumors; ∼ 70% of all malignant ovarian tumors
- Second most common ovarian tumor
- Up to 75% of cases are benign.
- Endometrioid carcinoma
- Borderline ovarian tumors
- Clear cell carcinoma
- Undifferentiated carcinoma
- Brenner tumor (mostly benign, derived from embryonic coelomic epithelium)
Epithelial ovarian tumors may be benign, malignant, or borderline!
- 15–25% of all ovarian tumors
- Dermoid cysts: most common of all germ cell tumors (90% of cases)
- Struma ovarii: teratoma with endodermal differentiation into thyroid tissue
- Rare, undifferentiated
- May contain tissue of embryonic/fetal period
- High risk of malignancy
- Dysgerminoma; : most common malignant ovarian tumor in young women (20–30 years); female histological equivalent to the male seminoma
- Yolk sac tumor of the ovary: often malignant; occurs mainly in childhood and adolescence
- Non-gestational choriocarcinoma; : rare and extremely malignant; normally accompanied by beta hCG production
- 5–10% of all ovarian tumors
Estrogen producing: granulosa cell tumor and theca cell tumor
- ∼ 75% of cases affect postmenopausal women.
Androgen producing: Sertoli-Leydig cell tumor
- Occurs very rarely; ∼ 20% malignant transformation
- Production of androgens → virilization
- Primarily affects women aged 30–40 years
- Benign, although may cause Meigs' syndrome
- ∼ 4% of all ovarian tumors
- Malignant fibrosarcoma
- Very rare but extremely malignant tumor
- 10–15% of all ovarian tumors
- Primary tumors are most often found in the gastrointestinal tract, breast, or endometrial cancer
- Krukenberg tumor: bilateral ovarian metastases; from an undifferentiated gastric carcinoma (mucin-secreting, signet ring cell carcinoma)
- In most cases, there are no early symptoms.
- In advanced stages, the size and growth of the tumor can lead to:
- Complication: tumor can cause ovarian torsion→ tissue infarction → surgical emergency
The first symptom is often increasing abdominal girth (clothes no longer fit at the waist)!
- Granulosa cell tumor: Granulosa cells express aromatase (estrogen synthesis occurs in 25% of tumors).
- Sertoli-Leydig cell tumor: can produce either estrogen or testosterone
- Yolk sac tumor, dysgerminoma: rapid growth, acute onset of symptoms (pelvic mass and pain)
- Struma ovarii: symptoms of hyperthyroidism
Extra-ovarian primary peritoneal carcinoma
- Frequency: up to 10% of all ovarian cancers!
- Mostly mucinous, serous, or seropapillary ovarian carcinoma, with predominantly extraovarian involvement
- Both ovaries are either of normal size or only enlarged by a benign process
- Invasion of max. 5 x 5 mm of the ovary surface/periphery
- Pseudomyxoma peritonei
- Meigs syndrome
- Lymphatic spread: especially along the pelvic and para-aortic lymph nodes; less often along the inguinal lymph nodes
- Hematogenous spread: rare; metastases can occur in the lungs, liver, bones, and CNS
- Spread by continuity: peritoneal carcinomatosis with intraperitoneal spread and superficial metastases.; commonly spreads to to the omentum (omental caking)
TNM Classification of malignant tumors and FIGO Cancer Staging
|T1||I||Tumor limited to one (T1a) or both ovaries (T1b) (with intact or ruptured (T1c) capsule)|
|T2||II||Tumor involving one or both ovaries with extension to the pelvis or peritoneal cancer|
|T3||III||Tumor involving one or both ovaries with extension outside the pelvis|
|N1||Metastasis to regional lymph nodes|
|M1||IV||Distant metastasis (excluding peritoneal metastasis)|
- Hypercalcemia due to paraneoplastic synthesis of PTHrP
- Tumor markers
Imaging: Transvaginal ultrasound is the gold standard, but abdominal or rectal ultrasound may also be conducted.
- CT/MRI for staging
Call your Ex and Grandparents! – Call-Exner bodies are characteristic of Granulosa cell tumors.
|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)|
- Tubo-ovarian abscess
The differential diagnoses listed here are not exhaustive.
- Frozen section and histology positive for carcinoma: radical surgical staging
- Removal of the greater omentum
- Lymphadenectomy (pelvic and para-aortic)
- Hysterectomy with bilateral salpingo-oophorectomy (removal of uterus, ovaries, tubes, and supporting structures)
- The prognosis is directly correlated with the extensiveness of the radical tumor removal.
- Exception: A fertility-sparing surgery is possible in cases of verified stage FIGO IA and of grade G1 (i.e., tissue is well differentiated)
- Appendectomy if involvement is suspected during surgery
- Biopsy from all noticeable locations/adhesions (peritoneal biopsy and washing cytology
- Frozen section negative for carcinoma: tumor resection, but no surgical staging
- Second-look surgery
- Frozen section and histology positive for carcinoma: radical surgical staging
- Indicated for all patients as adjuvant therapy
- First-line therapy: carboplatin; polychemotherapy and antimitotics (e.g., paclitaxel)
Second-line therapy and platinum-refractory recurrent carcinoma
- Recurrent, platinum-resistant ovarian cancer: as alternative, monotherapy with, e.g., topotecan, anthracyclines (pegylated liposomal doxorubicin), gemcitabine, paclitaxel, treosulfan
- Recurrent, platinum-sensitive ovarian cancer: combination therapy (all therapeutic schemes, if necessary, can be combined with anti-VEGF antibody bevacizumab)
- Radiation therapy: rarely used due to the intraperitoneal location and low radiosensitivity of the tumor
Malignant germ cell tumors respond particularly well to polychemotherapy because they are highly aggressive!
- Very poor overall prognosis as a result of late diagnosis
- 5-year survival rate of all ovarian carcinomas: ∼ 30–40%
|FIGO||Anatomic extension||5-year survival rate|
|I||Limited to one or both ovaries||80–90%|
|II||Infiltration of lesser pelvis||60–70%|
|III||Extension outside pelvis||30–50%|
- Genetic predisposition
- Hormonal contraceptives; , GnRH analogs, breast feeding, and tubal ligation appear to reduce the risk of ovarian carcinoma.
- Definition: : rare benign tumors that develop specifically during pregnancy.
- Majority of patients are asymptomatic
- When clinically apparent, it presents typically with symptoms of virilization during pregnancy
Diagnostics: tumor often diagnosed incidentally (during cesarean delivery)
- Apparent as solid adnexal masses (unilateral or bilateral; usually nodular)
- The size of the tumor is usually < 10 cm in diameter.
- Treatment: observation only; regresses spontaneously post-partum
Theca lutein cysts
Definition: a type of benign enlargement of the ovaries. It is a functional ovarian cyst that is thought to originate due to excessive amounts of circulating gonadotropins such as beta-hCG.
- Highly associated with gestational trophoblastic disease and multiple gestations.
- Diagnostics: Ultrasonography shows bilateral enlarged, multilocular, cystic masses of the ovaries.
- No treatment required because they typically regress spontaneously once beta-HCG levels fall
- Treatment of underlying cause, if present (e.g., )
- Definition: a type of benign enlargement of the ovaries. It is a functional ovarian cyst that is thought to originate due to excessive amounts of circulating gonadotropins such as beta-hCG.
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.