Ovarian Cysts 

An ovarian cyst is a sac filled with liquid or semi-liquid material arising in an ovary. The number of diagnoses of ovarian cysts has increased with the widespread implementation of regular physical examinations and ultrasound technology. The finding of an ovarian cyst causes considerable anxiety for women because of the fear of malignancy, but the vast majority of ovarian cysts are benign.

Each month, normally functioning ovaries develop small cysts called Graafian follicles.^[1] At mid cycle, a single dominant follicle up to about 2.8 cm in diameter releases a mature oocyte.

The ruptured follicle becomes the corpus luteum, which, at maturity, is a 1.5- to 2-cm structure with a cystic center. In the absence of fertilization of the oocyte, it undergoes progressive fibrosis and shrinkage. If fertilization occurs, the corpus luteum initially enlarges and then gradually decreases in size during pregnancy.

Ovarian cysts arising in the normal process of ovulation are called functional cysts and are always benign. They may be follicular and luteal, sometimes called theca-lutein cysts. These cysts can be stimulated by gonadotropins, including follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). A theca-lutein cyst is shown in the sonogram below.

Multiple functional cysts can occur as a result of excessive gonadotropin stimulation or sensitivity. In gestational trophoblastic neoplasia (hydatidiform mole and choriocarcinoma) and rarely in multiple and diabetic pregnancy, hCG causes a condition called hyperreactio luteinalis. In patients being treated for infertility, ovulation induction with gonadotropins (FSH and luteinizing hormone [LH]), and rarely clomiphene citrate, may lead to ovarian hyperstimulation syndrome, especially if accompanied by hCG administration.

Neoplastic cysts arise by inappropriate overgrowth of cells within the ovary and may be malignant or benign. Malignant neoplasms may arise from all ovarian cell types and tissues. By far, the most frequent are those arising from the surface epithelium (mesothelium), and most of these are partially cystic lesions. The benign counterparts of these cancers are serous and mucinous cystadenomas. Other malignant ovarian tumors may contain cystic areas, and these include granulosa cell tumors from sex cord stromal cells and germ cell tumors from primordial germ cells. A clear cell carcinoma is shown in the image below.

Teratomas are a form of germ cell tumor^[2] containing elements from all 3 embryonic germ layers, ie, ectoderm, endoderm, and mesoderm. A mature cystic teratoma is shown in the image below.

Endometriomas are cysts filled with blood arising from the ectopic endometrium. In polycystic ovary syndrome, the ovary often contains multiple cystic follicles 2-5 mm in diameter as viewed on sonograms. The cysts themselves are never the main problem, and discussion of this disease is beyond the scope of this article.

Frequency

United States

Ovarian cysts are found on transvaginal sonograms in nearly all premenopausal women and in up to 18% of postmenopausal women.^[3] Most of these cysts are functional in nature and benign. Mature cystic teratomas or dermoids represent more than 10% of all ovarian neoplasms. The incidence of ovarian carcinoma is approximately 15 cases per 100,000 women per year. Annually in the United States, ovarian carcinomas are diagnosed in more than 21,000 women, causing an estimated 14,600 deaths.^[4] Most malignant ovarian tumors are epithelial ovarian cystadenocarcinomas. Tumors of low malignant potential comprise approximately 20% of malignant ovarian tumors, whereas fewer than 5% are malignant germ cell tumors, and approximately 2% granulosa cell tumors.

Mortality/Morbidity

• Benign cysts can cause pain and discomfort related to pressure on adjacent structures, torsion, rupture, hemorrhage (both within and outside of the cyst), and abnormal uterine bleeding. They rarely cause death. Mucinous cystadenomas may cause a relentless collection of mucinous fluid within the abdomen, known as pseudomyxoma peritonei, which may be fatal without extensive treatment.
• Mortality associated with malignant ovarian carcinoma is related to the stage at the time of diagnosis, and patients with ovarian carcinoma generally present late in the course of disease. The 5-year survival rate overall is 41.6%, varying between 86.9% for International Federation of Gynecology and Obstetrics (FIGO) stage Ia and 11.1% for stage IV.^[5] Granulosa cell tumors are associated with an 82% survival rate, whereas squamous cell carcinomas arising in a dermoid cyst have a very poor outcome. Most germ cell tumors are diagnosed at an early stage and have an excellent outcome. Advanced-stage dysgerminomas are associated with a better outcome compared to nondysgerminomatous germ cell tumors. A distinct group of less aggressive tumors of low malignant potential has a more benign course but is still associated with mortality.^[6] The overall survival rate is 86.2% at 5 years.
• Malignant ovarian cystic tumors can cause severe morbidity, including pain, abdominal distension, bowel obstruction, nausea, vomiting, early satiety, wasting, cachexia, indigestion, heartburn, abnormal uterine bleeding, deep venous thrombosis, and dyspnea. Cystic granulosa cell tumors may secrete estrogen, which leads to postmenopausal bleeding and precocious puberty in elderly patients and young patients, respectively.

Race

Malignant epithelial ovarian cystadenocarcinomas are the only ovarian cysts associated with racial differences.

• Women from northern and western Europe and North America are affected most frequently, whereas women from Asia, Africa, and Latin America are affected least frequently.
• Within the United States, age-adjusted incidence rates in surveillance areas are highest among American Indian women, followed by white, Vietnamese, Hispanic, and Hawaiian women. Incidence is lowest among Korean and Chinese women.^[7]
• Among women for whom sufficient numbers of cases are available to calculate rates based on age, incidence in those aged 30-54 years is highest in white women, followed by Japanese, Hispanic, and Filipino women. For those aged 55-69 years, the highest rates occur in white women, followed by Hispanic and Japanese women. Among women aged 70 years or older, the highest rate occurs among white women, followed by those of African descent and Hispanic women.

Age

• Functional ovarian cysts occur at any age (including in utero), but are much more common in reproductive-aged women. They are rare after menopause. Luteal cysts occur after ovulation in reproductive-aged women. Most benign neoplastic cysts occur during the reproductive years, but the age range is wide and they may occur in persons of any age.
• The incidence of epithelial ovarian cystadenocarcinomas, sex cord stromal tumors, and mesenchymal tumors rises exponentially with age until the sixth decade of life, at which point the incidence plateaus. Tumors of low malignant potential occur at a mean age of 44 years, with a span from adolescence to senescence. The average age is more than a decade less than that for invasive cystadenocarcinoma. Germ cell tumors are most common in adolescence and rarely occur in those older than 30 years.