Congenital Anomalies and Benign Conditions of the Ovaries and Fallopian Tubes

Functional Ovarian Cysts and Tumors

Dozens of ovarian follicles form the “cohort of follicles” of each menstrual cycle. To be classified a functional cyst, the follicle must reach a diameter of at least 3 cm. Functional cysts may cause pelvic pain, a dull sensation, or heaviness in the pelvis.

A follicular cyst, lined by one or more layers of granulosa cells, develops when an ovarian follicle fails to rupture. Similarly, a lutein cyst may develop if the corpus luteum becomes cystic, grows to larger than 3 cm, and fails to regress normally after 14 days. Hemorrhagic cysts, especially hemorrhagic corpus luteum cysts, are more likely to cause symptoms and are more vulnerable to rupture toward the end of the menstrual cycle. The hemorrhage within the cyst results from invasion of the ovarian vessels into the corpus luteum cyst 2 to 3 days after ovulation.

Other specific types of lutein cysts may occur with abnormally high serum levels of human chorionic gonadotropin (hCG) or increased ovarian sensitivity to gonadotropins. Theca-lutein cysts may develop in association with the high levels of hCG present in patients with a hydatidiform mole or choriocarcinoma. Patients undergoing ovulation induction with gonadotropins or clomiphene may also develop theca-lutein cysts. Theca-lutein cysts are usually bilateral, may become quite large (>30 cm), and characteristically regress slowly after the gonadotropin level falls. Rarely, when follicles are stimulated with gonadotropins, theca-lutein cysts can become so extensive as to cause massive ascites and dangerous problems with systemic fluid imbalance.

A luteoma of pregnancy is a related condition in which there is a hyperplasic reaction of ovarian theca cells, presumably from prolonged hCG stimulation during pregnancy. The luteomas characteristically appear as brown to reddish-brown nodules that may be cystic or solid. A luteoma of pregnancy (Figure 20-1) may be associated with multifetal pregnancies or hydramnios. They can cause maternal virilization in 30% of women and, less often, ambiguous genitalia in a female fetus. Although ovarian enlargement may be impressive, surgical resection is not indicated because luteomas regress spontaneously postpartum.

FIGURE 20-1 Gross appearance of a luteoma of pregnancy. Note the multiple brown nodules.

(From Voet RL: Color Atlas of Obstetric and Gynecologic Pathology. St. Louis, Mosby, 1997.)

Polycystic ovary syndrome, a functional disorder generally associated with chronic anovulation and hyperandrogenism, can also produce enlarged ovaries with multiple simple follicles (Figure 20-2). The hormonal aspects of this syndrome are discussed further in Chapter 32.

FIGURE 20-2 Ovary with multiple cysts lining the capsule consistent with polycystic ovary syndrome.

(Courtesy of Dr. Sathima Natarajan, Ronald Reagan–UCLA Medical Center.)

∗ Risk of Malignancy Index = A × B × C. A cut-off value of 200 discriminates a benign from a malignant mass with a sensitivity of 87% and a specificity of 97%.

Data from Jacobs I, Oram D, Fairbanks J, et al: A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol 97:922, 1990.

When a patient has delayed menses, abnormal uterine bleeding, or severe pelvic pain, the differential diagnosis must include ectopic pregnancy, pelvic abscess, or adnexal torsion of a neoplastic cyst. A pregnancy test (hCG), diagnostic laparoscopy, or rarely, laparotomy may be needed. Table 20-3 lists the current modalities that are available to evaluate adnexal masses along with the sensitivity and specificity as calculated by the U.S. Agency for Healthcare Research and Quality. None of these modalities is accurate enough to be used alone for diagnosis.

TABLE 20-3 MODALITIES FOR THE EVALUATION OF ADNEXAL MASSES

Data from Agency for Healthcare Research and Quality (AHRQ): Management of adnexal mass. AHRQ Publication No. 06-E004. Rockville, MD, AHRQ, 2006.

MANAGEMENT

When a reproductive-aged patient who is asymptomatic or experiencing only mild symptoms presents with an adnexal cyst, a pelvic ultrasound and serum CA-125 titer should be obtained and the RMI determined. If the RMI is low and the cyst is considered to be functional, it is appropriate to wait and reexamine the patient after her next menses. Low-dose contraceptive agents may be given to suppress gonadotropin levels and prevent development of another cyst.

If the lesion does not fulfill the requirements for observation because it is solid, painful, or fixed or has an elevated RMI, surgical exploration or referral to a gynecologic oncologist is indicated. Laparoscopic cystectomy to allow histologic evaluation may be needed to differentiate between a functional and a neoplastic ovarian cyst. Aspiration of the fluid as a diagnostic tool is inappropriate because the false-negative rate for the cytologic examination is high and slow leakage of the fluid disseminates cancer if the cyst is malignant.

When the patient is in her late 40s, the chances of an ovarian neoplasm are increased, and observational delays should be undertaken with caution.

EPITHELIAL OVARIAN NEOPLASMS

These tumors are believed to be derived from the mesothelial cells lining the peritoneal cavity and also lining the surface of the ovary. The mucinous ovarian neoplasm cytologically resembles the endocervical epithelium, the endometrioid neoplasm resembles the endometrium, and serous tumors resemble the lining of the fallopian tubes. The most common epithelial ovarian tumors are serous cystadenomas. Figure 20-3 shows the gross appearance of a mucinous and serous cystadenoma.

FIGURE 20-3 Gross appearance of a mucinous (A) and serous (B) cystadenoma of the ovary. The mucinous type is generally multiloculated and can be quite large. (A, From Voet RL: Color Atlas of Obstetric and Gynecologic Pathology. St. Louis, Mosby, 1997, Fig. 6.31; B, from Voet RL: Color Atlas of Obstetric and Gynecologic Pathology. St. Louis, Mosby, 1997, Fig. 6.20.)

Each of the epithelial ovarian neoplasms has characteristic clinical and histologic features. The serous tumors are bilateral in about 10% of cases. Of all serous tumors, about 70% are benign, 5% to 10% have borderline malignant potential, and 20% to 25% are malignant, depending largely on the patient’s age. Larger serous cystadenomas tend to be multilocular, although small unilocular serous cystomas also occur. Histologically, serous tumors characteristically form psammoma bodies (from the Greek psammos, meaning sand), which are calcific, concentric concretions. Psammoma bodies occur occasionally in benign serous neoplasms and frequently in serous cystadenocarcinomas. Papillary patterns are also common.

The mucinous neoplasms of the ovary can attain a huge size, often filling the entire pelvis and abdomen. They are often multilocular, and benign mucinous tumors are bilateral in less than 10% of cases. About 85% of mucinous tumors are benign. Mucinous tumors are often associated with a mucocele of the appendix. Rarely, a benign mucinous tumor may be complicated by pseudomyxoma peritonei, a condition in which a great many benign implants are seeded onto the surface of the bowel and other peritoneal surfaces and produce large quantities of mucus.

The Brenner tumor is a small, smooth solid ovarian neoplasm, usually benign, with a large fibrotic component that encases epithelioid cells that resemble transitional cells of the bladder (Figure 20-4). In about 33% of cases, Brenner tumors are associated with mucinous epithelial elements.

FIGURE 20-4 Gross appearance of a cut-open Brenner tumor.

(Courtesy of Dr. Sathima Natarajan, Ronald Reagan–UCLA Medical Center.)

SEX CORD–STROMAL OVARIAN NEOPLASMS

These tumors include fibromas, granulosa-theca cell tumors, and Sertoli-Leydig cell tumors. Combinations of the latter two types are termed gynandroblastomas.

The tumors in this category derive from the sex cords and specialized stroma of the developing gonad. The embryologic origins of granulosa and theca cells, as well as their counterparts in the testes, the Sertoli and Leydig cells, arise from cells that make up this specialized gonadal stroma. If the ultimate differentiation of cell types occurring in the tumor is feminine, the neoplasm becomes a granulosa cell tumor, a theca cell tumor, or in many instances, a mixed granulosa-theca cell tumor. Neoplasms containing cells that take on a masculine differentiation become Sertoli-Leydig cell tumors. This is far less common. The fibroma represents a stromal cell neoplasm developing from mature fibroblasts in the ovarian stroma.

The granulosa-theca cell neoplasms, as well as their androgenic counterparts, are generally referred to as functioning (not functional) ovarian tumors. They occur in any age group, from birth on, but more commonly in the postmenopausal years. Their functioning characteristics are responsible for a variety of associated presenting signs and symptoms. The granulosa-theca cell tumors promote feminizing signs and symptoms, such as precocious menarche, precocious thelarche, or premenarchal uterine bleeding during infancy and childhood. In the reproductive years, menorrhagia (with alternating amenorrhea), endometrial hyperplasia, and not infrequently, endometrial cancer, breast tenderness, and fluid retention occur. Postmenopausal bleeding may occur in older women with granulosa-theca cell tumors. In contrast, the less frequent Sertoli-Leydig cell tumors are responsible for virilizing effects, such as hirsutism, temporal baldness, deepening of the voice, clitoromegaly, and a defeminizing change in body habitus to a muscular build. Fifteen percent of these tumors produce no obvious endocrinologic effects. Except for the pure thecoma, all these tumors have low malignant potential and are discussed further in Chapter 39.

The ovarian fibroma, another ovarian stromal tumor, forms a solid, encapsulated, smooth-surfaced tumor made up of interlacing bundles of fibrocytes. It is not hormonally active. It is glistening white on its cut surface (Figure 20-5), as opposed to the soft yellow appearance of the granulosa-theca cell or the smaller hilus cell tumor. On occasion, this tumor is associated with ascites caused by the transudation of fluid from the ovarian fibroid. The flow of this ascitic fluid through the transdiaphragmatic lymphatics into the right pleural cavity may result in Meigs’ syndrome (ascites and hydrothorax in association with an ovarian fibroma). The ovarian fibroma may be associated with theca cell elements called a fibrothecoma.

FIGURE 20-5 Gross appearance of an ovarian fibroma.

(Courtesy of Dr. Sathima Natarajan, Ronald Reagan–UCLA Medical Center.)

GERM CELL TUMORS

Germ cell neoplasms can occur at any age. They make up about 60% of ovarian neoplasms occurring in infants and children.

The most common ovarian neoplasm is the benign cystic teratoma, a germ cell tumor that can take on a great variety of forms, with virtually all adult tissues being represented within the mass. Ten percent to 15% of teratomas are bilateral. The benign cystic teratoma, commonly referred to as a dermoid cyst, is composed primarily of ectodermal tissue (such as sweat and sebaceous glands, hair follicles, and teeth), with some mesodermal and rarely endodermal elements. These are slow-growing tumors. Half are diagnosed in women between 25 and 50 years of age. Most are less than 10 cm in diameter. Because of the oily secretion of the sebaceous glands, the desquamated squamous cells, the presence of hair, and the presence of a dermoid tubercle (of Rokitansky), which often contains a hard, well-formed tooth, the dermoid cyst has a characteristic gross and histologic appearance (Figure 20-6). Other tissue components commonly found in benign cystic teratomas include mature brain, bronchus, thyroid, cartilage, intestine, bone, and carcinoid cells. As opposed to similar tissues found in a malignant immature teratoma, the tissues making up the benign (mature) teratoma are all of an adult, well-differentiated form.

FIGURE 20-6 Gross appearance of a cut-open dermoid cyst. Note the presence of hair-bearing skin.

(From Voet RL: Color Atlas of Obstetric and Gynecologic Pathology. St. Louis, Mosby, 1997.)

MIXED OVARIAN NEOPLASMS

The most common ovarian tumor in which the neoplastic elements are composed of more than one cell type is the cystadenofibroma, or the fibrocystadenoma. These tumors generally take their characteristics from the epithelial component, although they tend to be more solid than the epithelial ovarian neoplasms.

The gonadoblastoma is a tumor composed of cells resembling those of a dysgerminoma and others resembling granulosa and Sertoli cells. Characteristically, calcific concretions are a prominent feature of this neoplasm. Almost all patients with a gonadoblastoma have dysgenetic gonads, and a Y chromosome has been detected in more than 90% of cases. Although the gonadoblastoma is initially benign, about half of these tumors may predispose to the development of dysgerminomas or other malignant germ cell tumors.

DIAGNOSIS OF BENIGN OVARIAN TUMORS

The clinical features of benign ovarian tumors are often nonspecific. Except for the functioning ovarian neoplasms, most benign ovarian tumors are asymptomatic unless they undergo torsion or rupture. They usually enlarge very slowly, so that an increase in abdominal girth or pressure on surrounding organs is not perceived until the later stages of growth. Any pelvic pain is generally mild and intermittent, unless the tumor twists on its pedicle (torsion), when infarction may induce severe pain and tenderness. On rare occasions, an ovarian cyst may rupture spontaneously from internal hemorrhage or intracystic pressure, resulting in pain and peritoneal irritation. A cyst may also rupture occasionally during or after a bimanual pelvic examination or with intercourse. Depending on the cystic contents, pain of varying degrees of severity can result. The escape of thin serous fluid without hemorrhage may evoke little pain or tenderness, but the oily contents of a dermoid cyst or the thick mucinous fluid of a mucinous cystadenoma may be irritating to both the parietal and the visceral peritoneum, with the development of chemical peritonitis and possibly the subsequent formation of troublesome intraabdominal adhesions.

Bimanual pelvic examination generally indicates the presence of the tumor in the pelvis, but the tumor may be too small to be palpated. On the other hand, if the tumor is large enough, it may be detected by abdominal palpation. Examination may suggest a cystic mass or a solid tumor. Movement of the mass separate from the uterus supports the suspicion of an adnexal mass instead of a uterine leiomyoma. Percussion of the abdomen in a patient with a large ovarian cyst reveals dullness anteriorly with tympany in the flanks as the bowel is displaced laterally by the tumor.

If the tumor undergoes torsion and infarction or rupture, signs of peritoneal irritation may be present. If complete infarction has occurred, there may be abdominal rigidity. Paralytic ileus may also be present.

Pelvic ultrasonography, particularly transvaginal ultrasonography, with or without color Doppler, may be helpful. A pelvic ultrasound will be highly suggestive of a dermoid cyst, especially if it is found to include a tooth-like calcification.

Tumor markers, such as serum CA 125, as part of the RMI (see Table 20-2) may help to distinguish between benign and malignant masses, particularly in a postmenopausal patient. When clinical evaluation, pelvic ultrasonography, and tumor markers all indicate malignancy, the positive predictive value of the combination is high in postmenopausal women. Such patients should be referred to a gynecologic oncologist for surgical evaluation.

Laparoscopy is helpful in distinguishing between a uterine myoma, a quiescent hydrosalpinx, and an ovarian tumor, but it will not distinguish between a functional cyst, a benign neoplasm, and an encapsulated malignant ovarian neoplasm. On occasion, laparoscopy may identify endometriosis on the surface of the ovary. An ovarian endometrioma cannot be distinguished unequivocally from an ovarian neoplasm by visualization alone. In general, laparotomy is preferable to laparoscopy in the ultimate evaluation of a suspicious adnexal mass unless the entire mass can be removed laparoscopically without rupture for histologic examination.