Chapter 41. Benign Disorders of the Ovaries & Oviducts

• Benign adnexal mass refers not only to ovarian abnormalities but also to masses originating in the fallopian tube (ectopic pregnancy, pyosalpinx), ovaries (ovarian cyst, tuboovarian abscesses, adnexal torsion), uterine ligaments, lateral uterine masses (myomas), and gastrointestinal tract (diverticulitis, appendicitis) and even the urinary system (pelvic kidney).
• Benign adnexal masses originating from the genital system are common in women in the reproductive age group and are caused by physiologic cysts or benign neoplasms.
• Most adnexal masses are discovered incidentally, and the management of these benign masses is dictated by their presentation.
• The evaluation of these masses should be assessed according to the algorithm shown in Figure 41–1, including a thorough patient history, physical examination, laboratory tests, and imaging modalities.

Clinical Findings

Patient history should include review of patient age and family history in particular for the occurrence of ovarian familial cancers. A full physical examination should be performed, including a node survey and breast, abdominal, and pelvic examination. In many cases the radiologic studies, including ultrasonography of the pelvis and sometimes computed tomography (CT), would be of most importance in the assessment of the patient with an adnexal mass (Fig. 41–1). One way to approach the adnexal mass is to think of it in regard to the patient's age. For the young woman, the majority of ovarian cysts are benign: hemorrhagic corpus luteum follicular cysts and dermoid cysts are common in this age group; however, tubal abnormalities, including ectopic pregnancies, and sequela from tubal infection should be strongly considered (Table 41–1). On the other hand, the majority of ovarian or tubal cancers occur postmenopausally.

Differential Diagnosis

The clinical challenge in assessing an adnexal mass is to distinguish between a benign and malignant mass (Table 41–1) or findings that indicate a need for intervention or treatment versus masses that can be followed up conservatively (Fig. 41–1). Generally, when malignancy is not suspected, and if clinically the patient is stable, then expectant management is indicated, as many of these cysts are physiologic in nature and thus are expected to regress over time.

Patients should be re-evaluated 6 weeks after initial presentation, and persistent masses should be considered potentially benign or malignant neoplasms that warrant operative evaluation.

Treatment

Operative intervention is indicated when a patient is symptomatic because of hemorrhage of a ruptured cyst, ovarian torsion, or failure of previous treatments, for example, failure to treat an adnexal abscess. The risk of malignancy must always be assessed and excluded (see Chapter 50 to be checked for proper evaluation). The exclusion of a neoplastic process should be performed mainly through use of imaging modalities. For instance, sonographic indices as suggested in Table 41–2 should indicate whether the adnexal mass is at high risk for involving a neoplastic process.

Pathologic diagnosis by frozen section during surgery can aid in determining what type of treatment is indicated; however, in a young patient, final diagnosis and treatment of an adnexal malignancy should be based on analysis of permanent, rather than frozen sections because pathologic examination of frozen specimens can sometimes lead to incorrect surgical decisions. For most benign ovarian cysts, laparoscopy is the preferred method because of its shorter recovery time, as well as less pain, blood loss, and overall cost compared with laparotomy. Even extremely large ovarian cysts (reaching the umbilicus and higher) currently are being managed laparoscopically. A laparoscopic approach is recommended if the cyst appears benign by preoperative evaluation (Table 41–2). For most young patients, ovarian cystectomy is favored over oophorectomy in order to retain fertility.

Follicular Cysts

Essentials of Diagnosis

• The most common functional cyst is the follicular cyst.
• Follicular cysts (Fig. 41–2) vary in diameter from 3 to 8 cm.
• Histologically, they are seen to be lined by an inner layer of granulosa cells and an outer layer of theca interna cells that may or may not be luteinized.

Pathogenesis

These cysts result from a failure in ovulation, most likely secondary to disturbances in the release of the pituitary gonadotropins. The fluid of the incompletely developed follicle is not reabsorbed, producing an enlarged follicular cyst.

Clinical Findings

Typically follicular cysts are asymptomatic, although bleeding and torsion can occur. Large cysts may cause aching pelvic pain, dyspareunia, and occasionally abnormal uterine bleeding associated with a disturbance of the ovulatory pattern.

Treatment

Most follicular cysts disappear spontaneously within 60 days without treatment. Use of oral contraceptive pills (OCPs) has often been recommended to help establish a normal rhythm; however, recent data show that this practice may not produce more rapid resolution than expectant management.

Aspiration of follicular cysts was performed in the past; however, recent data suggest that the diagnostic value of this procedure is relatively low and cysts greater than 8 cm in maximal diameter have a 95% tendency to recur after an aspiration procedure.

Corpus Luteum (Granulosa Lutein) Cysts

Clinical Findings

These are thin-walled unilocular cysts ranging from 3–11 cm in size. After normal ovulation, the granulosa cells lining the follicle become luteinized. In the stage of vascularization, blood accumulates in the central cavity, producing the corpus hemorrhagicum. Resorption of the blood then results in a corpus luteum, which is defined as a cyst when it grows larger than 3 cm. A persistent corpus luteum cyst may cause local pain or tenderness. It can also be associated with either amenorrhea or delayed menstruation, thus simulating the clinical picture of an ectopic pregnancy. A corpus luteum cyst may be associated with torsion of the ovary, causing severe pain, or it may rupture and bleed, in which case the patient presents with peritoneal signs and acute abdomen.

Treatment

Laparoscopy or laparotomy is usually required to control hemorrhage into the peritoneal cavity and /or to perform detorsion of the adnexa. Unless acute complications develop, symptomatic therapy is indicated. As with follicular cysts, corpus luteum cysts usually regress after 1 or 2 months in menstruating patients, and OCPs have been recommended but may be of questionable benefit.

Theca Lutein Cysts

Clinical Findings

Elevated levels of chorionic gonadotropin can produce theca lutein cysts and thus are seen in patients with hydatidiform mole or choriocarcinoma and in patients undergoing chorionic gonadotropin or clomiphene therapy. Rarely, they are seen in normal pregnancy. The cysts are lined by theca cells that may or may not be luteinized, and they may or may not have granulosa cells. They are usually bilateral and are filled with clear, straw-colored fluid. Abdominal symptoms are minimal, although a sense of pelvic heaviness or aching may be described. Rupture of the cyst may result in intraperitoneal bleeding. Continued signs and symptoms of pregnancy, especially hyperemesis and breast paresthesias, are reported.

Treatment

The cysts disappear spontaneously after termination of the molar pregnancy, treatment of the choriocarcinoma, or discontinuation of fertility therapy; however, such resolution may take months to occur. Surgery is reserved for complications such as torsion and hemorrhage.

Endometriomas

Clinical Findings

In women with endometriosis, endometriotic foci on the ovarian surface may develop a fibrous enclosure and manifest cyst formation as a result of accumulation of fluid and blood. These endometrial cysts vary from several millimeters to even 10 cm in size. Endometriomas are also referred to as “chocolate cysts” because they contain thick, brown blood debris inside. Filmy or fibroid adhesions from these cysts to the pelvic sidewall, cul-de-sac and fallopian tubes are common and may obscure visualization of the cyst.

Endometriomas are usually associated with chronic pelvic pains, dyspareunia, dysmenorrhea, and infertility.

Differential Diagnosis

The tumor marker CA-125 is commonly elevated in these forms of cysts, which creates a serious clinical problem in distinguishing these cysts from malignant epithelial tumors.

Hyperthecosis

Clinical Findings

Hyperthecosis, or thecomatosis, commonly produces no gross enlargement of the ovary (Fig. 41–3). Thus the lesions are demonstrable only by histologic examination of the excised gonad. They are characterized by nests of stromal cells demonstrating increased cytoplasm, simulating the changes seen in the normal theca after stimulation by pituitary gonadotropin. In the premenopausal woman, hyperthecosis is associated with virilization and clinical findings similar to those seen in polycystic ovarian disease (see following text). These alterations may also be associated with postmenopausal bleeding and endometrial hyperplasia.

Polycystic Ovarian Syndrome (Stein-Leventhal Syndrome)

Clinical Findings

Polycystic ovarian syndrome (PCOS) is characterized by persistent anovulation that can lead to clinical manifestations, including enlarged polycystic ovaries, secondary amenorrhea or oligomenorrhea, obesity, hirsutism, and infertility. The syndrome has a prevalence of 5–10%, with variance among races and ethnicities. Approximately 50% of patients are hirsute, and 30–75% are obese. A presumptive diagnosis of PCOS often can be made based on the history and initial examination. According to an international consensus group, the syndrome can be diagnosed if at least 2 of the following conditions are present: oligomenorrhea or amenorrhea, hyperandrogenism, and polycystic ovaries on ultrasound. Polycystic ovaries have been called “oyster ovaries” because they are enlarged and “sclerocystic” with smooth, pearl-white surfaces without indentations. Many small, fluid-filled follicle cysts lie beneath the thickened fibrous surface cortex (Fig. 41–4). Luteinization of the theca interna is usually observed, and occasionally focal stromal luteinization is seen. Laboratory testing often reveals mildly elevated serum androgen levels, an increased ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH), lipid abnormalities, and insulin resistance. Anovulation is identified in women with persistently high concentrations of LH and low concentrations of FSH, a low day-21 progesterone level, or on sonographic follicular monitoring. PCOS is presumably related to hypothalamic pituitary dysfunction and insulin resistance. A primary ovarian contribution to the problem has not been clearly defined.

Treatment

Most patients with PCOS seek treatment for either hirsutism or infertility. The hirsutism can be treated with any agent that lowers androgen levels, and OCPs are typically the first choice in patients not desiring pregnancy. Infertility in PCOS patients is often responsive to clomiphene citrate. In the recalcitrant case, the experienced clinician can add human menopausal gonadotropin to produce the desired ovulation. Recent studies indicate that therapy with metformin improves fertility rates both when given alone and, even more so, when given in conjunction with clomiphene. Studies show that a small reduction in body weight, as little as 2–7%, is associated with improved ovulatory function in women with PCOS. As patients with PCOS are chronically anovulatory, the endometrium is stimulated by estrogen alone. Thus endometrial hyperplasia, both typical and atypical, and endometrial carcinoma are more frequent in patients with PCOS and long-term anovulation. Many of these markedly atypical endometrial features can be reversed by large doses of progestational agents, such as megestrol acetate 40–60 mg/d for 3–4 months. Follow-up endometrial biopsy is mandatory to determine endometrial response and subsequent recurrence.

Luteoma of Pregnancy

Clinical Findings

Tumorlike nodules of lutein cells may form in the ovaries during pregnancy and are often both multifocal and bilateral. The nodules range up to 20 cm in diameter, but most often they range from 5–10 cm. On section they reveal well-delineated, soft, brown masses with focal hemorrhage. Microscopically, they are formed of sheets of large luteinized cells with abundant cytoplasm and relatively uniform nuclei with occasional mitoses. Clinically, they appear ominous to the obstetrician, who becomes aware of them only when the abdomen is open at the time of caesarean delivery. Unilateral salpingo-oophorectomy can be performed for frozen section in the belief that the large masses are malignant. A confirmatory biopsy is adequate, and follow-up will reveal total regression a few months later.

Evaluation

Ovarian neoplasms may arise from any histologic element of the ovary and are most often benign, especially in premenopausal women. The characteristics of the mass and the age of the patient are important factors guiding diagnosis and treatment. The overall risk of malignancy of an ovarian cyst is 13% in a premenopausal woman versus 45% in a postmenopausal woman. Therefore, vigilant workup of these masses with the aid of ultrasound and close follow-up is essential. Use of cancer antigen-125 (CA-125) for diagnostic purposes is controversial. New tumor markers are being pursued fervently such that soon we may be able to more accurately distinguish malignant from benign adnexal masses. With the increased use of imaging studies has come discovery of incidental, asymptomatic, small ovarian cysts. These cysts should be evaluated by ultrasound. If they do not contain septa or solid components, they can be closely followed. However, any mass that enlarges or changes in character, especially in postmenopausal women, should be explored surgically.

Treatment

The preferred treatment of all ovarian tumors is surgical excision with careful exploration of the abdominal contents. If the risk of malignant neoplasia is confidently low, laparoscopy is preferred. In patients requesting future fertility, cystectomy is performed if possible; otherwise a unilateral oophorectomy is performed. Frozen section is helpful in identifying the type and neoplastic potential of the tumor. However, because adequate sampling of a large ovarian neoplasm often is impossible, final opinion and prognosis must be based on analysis of permanent, rather than frozen, sections. Therefore, in a patient desirous of retaining fertility, the surgeon must act on the side of retention of the uterus and contralateral ovary if the pathologist has the slightest doubt as to tumor malignancy.

Epithelial Tumors

Clinical Findings

Epithelial tumors account for approximately 60–80% of all true ovarian neoplasms and include the common serous, mucinous, endometrioid, clear cell, and transitional cell (Brenner) tumors, as well as the stromal tumors with an epithelial element. The epithelium of these tumors arises from a common anlage (ie, the mesothelium lining the coelomic cavity and ovarian surfaces) (Fig. 41–5). This basic thesis explains the similarity of the epithelia of the upper genital canal—endocervix, endometrium, and endosalpinx—to those found in the ovarian tumors. Most tumors presumably arise from invaginated surface epithelium and proliferation or malignant degeneration in the epithelial lining of the resulting surface inclusion cyst (Fig. 41–6). The epithelial tumors are classified on the basis of their histologic appearance.

Serous Tumors

Clinical Findings

Serous tumors have been reported in all age groups and are responsible for approximately 50% of all epithelial ovarian neoplasms. Low-grade neoplasms generally are found in patients in their 20s and 30s, whereas their anaplastic counterparts occur more commonly in perimenopausal and postmenopausal women. Serous cystadenomas are benign lesions, commonly unilocular, with a smooth surface, and containing thin, clear yellow fluid. The cells lining the cyst are a mixed population of ciliated and secretory cells similar to those of the endosalpinx. They may grow large enough to fill the abdominal cavity, but usually they are smaller than their mucinous counterparts. Benign serous tumors are bilateral in approximately 15–20% of cases. Focal proliferation of the underlying stroma may produce firm papillary projections into the cyst, forming a serous cystadenofibroma (Fig. 41–7). These tumors appear to be simple on ultrasonographic evaluation, and although there may be some small internal aches, these are purely cystic in appearance (Table 41–1). It is important to study these papillary projections thoroughly to rule out atypical proliferation. Some serous tumors consist of benign stromal proliferation interspersed with tiny serous cysts; these are known as serous adenofibromas.

Mucinous Tumors

Clinical Findings

Mucinous tumors account for approximately 10–20% of all epithelial ovarian neoplasms, of which approximately 75%–85% are benign. The benign tumors are typically found in women in their 30s through 50s. Bilateral tumor development occurs in 8–10% of all cases, whether the tumors are benign or malignant. They are the largest tumors found in the human body; 15 reported tumors have weighed more than 70 kg (154 lb). Consequently, the more massive the tumor, the greater the possibility that it is mucinous. They generally are asymptomatic, and patients present with either an abdominal mass or nonspecific abdominal discomfort. In postmenopausal patients, luteinization of the stroma rarely may result in hormone production (usually estrogen) leading to associated endometrial hyperplasia with vaginal bleeding. During pregnancy, hormonal stimulation may result in virilization.

Histologically, they are usually smooth-walled; true papillae are rare (compared with the serous variety). The tumors generally are multilocular, and the mucus-containing locules appear blue through the tense capsule (Fig. 41–8). The internal surface is lined by tall columnar cells with dark, basally situated nuclei and mucinous cytoplasm (Fig. 41–9).

The epithelium of mucinous cysts resembles that of the endocervix in approximately 50% of cases; in the other 50%, mucin-containing goblet cells resembling intestinal epithelial cells are present. Careful study of mucinous neoplasms has shown that the histologic appearance may vary greatly from area to area; some areas appear benign, whereas others are of low malignant potential or are frankly malignant. Hence sampling must be more extensive than in the typical serous tumor. Metastases from appendiceal and other primary tumors may simulate closely a mucinous cystadenoma.

Endometrioid Lesions

Clinical Findings

Endometrioid tumors are characterized by proliferation of benign nonspecific stroma in which bland endometrial-type glands may be found. The only clearly recognizable benign endometrioid tumors are the uncommon endometrioid adenofibroma and the proliferative endometrioid adenofibroma. If the epithelial growth is exuberant but cytologically benign, it is termed a proliferative rather than a low malignant potential tumor, as the prognosis appears to be invariably excellent (Fig. 41–10).

Endometriosis of the ovary (see Chapter 56) represents a benign “tumorlike” condition rather than a true neoplasm. Because pelvic endometriosis may be found in association with endometrioid lesions, one hypothesis is that these lesions arise from preexisting endometriosis.

Clear Cell (Mesonephroid) Tumors

Clinical Findings

Like the endometrioid tumors, clear cell tumors in their benign form are rare and are virtually limited to clear cell adenofibromas in which a solid proliferation of nonspecific stroma contains small cytologically bland glands formed by columnar cells with clear cytoplasm. The clear cell component usually coexists with another epithelial type. The clear cell histology also is associated with endogenous endometriosis in the pelvic in up to 25% of cases. Clinically, they appear like any other benign ovarian mass and are diagnosed only on histologic examination. The prognosis is excellent.

Transitional Cell (Brenner) Tumors

Clinical Findings

Transitional cell tumors are adenofibromas in which the proliferating epithelial element has a transitional cell appearance, which represents metaplasia. Brenner tumors account for 1–2% of primary ovarian tumors; more than 98% are benign, and nearly 95% of cases are unilateral. They frequently are so small that they are incidental operative findings. However, the tumor may reach 5–8 cm in diameter and present as an adnexal mass on pelvic examination. On section they are firm and pale yellow or white (Fig. 41–11). The epithelium is composed of nests of cells with ovoid nuclei having a prominent longitudinal groove (“coffee-bean nuclei”; Fig. 41–12). Occasionally there is a mucinous metaplasia of the cells in the center of one or more of these nests, which may account for the 10% incidence of mucinous cystadenomas found associated with Brenner tumors.

Brenner tumors are considered benign, although a malignant variant has been identified.

Sex Cord-Stromal Tumors

Thecoma

Clinical Findings

This type of tumor can occur at any age, although they are most commonly found in postmenopausal women. They account for only 2% of all ovarian tumors and may not be a true neoplasm but instead a condition of hyperplasia of the cortical stroma. Histologically, the mass is filled with lipid-containing cells that are similar to theca cells, and the tumor is known to produce estrogen. As such, these tumors often present with dysfunctional uterine bleeding or postmenopausal bleeding. Occasionally they have presented with adenocarcinoma of the endometrium given the unopposed estrogen production by the tumor. The tumors range from nonpalpable to more than 20 cm in size. They are rarely bilateral and rarely malignant.

Treatment

Treatment of thecoma is tailored to patient age and ranges from a total hysterectomy and bilateral salpingo-oophorectomy for menopausal or postmenopausal women to a salpingo-oophorectomy or ovarian cystectomy if possible in patients who desire to retain fertility.

Fibroma

Clinical Findings

Unlike thecomas, fibromas produce no hormones. They can occur at any age but most often occur in the years before menopause. They range in size from incidental findings to greater than 20 cm. They are multinodular and whorled, and they are formed from bundles of collagen-producing spindle cells. They can be found as part of Meigs' syndrome, in which a patient is found to have a pelvic mass (fibroma or thecoma or granulose cell tumor) in concert with ascites and hydrothorax. Fibromas are also part of a hereditary basal cell nevus syndrome in which basal cell carcinoma is found with mesenteric cysts, calcification of the dura, and keratocysts of the jaw.

Hilus Cell Tumor

Clinical Findings

These tumors are a subset of Leydig cell tumors, which originate from the ovarian hilum or less frequently from the ovarian stroma. The typical presentation includes hirsutism, virilization, and menstrual irregularities. Hilus cell tumors rarely attain a palpable size. Histologically, groups of steroid cells containing eosinophilic cytoplasm and lipochrome pigment are found. For the tumor to be defined as a Leydig cell neoplasm, elongated eosinophilic crystalloids of Reinke must be found.

Germ Cell Tumors

Mature Teratomas

Clinical Findings

Mature cystic teratomas, commonly referred to as dermoid cysts, compose some 40–50% of all benign ovarian neoplasms. They contain well-differentiated tissue derived from any of the 3 germ cell layers, including hair and teeth as ectodermal derivatives. They account for the majority of benign ovarian neoplasms in reproductive-age women and usually are asymptomatic unless complications such as torsion or rupture occur. Transvaginal ultrasound is known to be very accurate in the diagnosis of dermoid cysts, with the hair and sebum, rather than calcium, creating highly reflective irregular solid components within fluid-containing masses. Up to 15% of cases are bilateral, and these tumors can grow to a large size, weighing several kilograms.

Differential Diagnosis

Although most mature teratomas contain cells from all germ cell layers, a subset of monodermal teratomas exists. Those tumors composed mostly or entirely of thyroid tissue are called struma ovarii. These tumors account for only 3% of all teratomas, and only 5% of these will produce symptoms of thyrotoxicosis.

Cases in which immature neuroepithelial tissue is present should always be suspected as immature cystic teratoma, which have some malignant potential.

Treatment

Studies have detailed several advantages to the laparoscopic approach to removal of dermoids, including less postoperative pain and blood loss, shorter hospital stay, and lower overall cost. Recent studies have shown that dermoid cysts can usually be removed laparoscopically without intraperitoneal spillage. If intraoperative spillage does occur, the potential for chemical peritonitis or excess adhesion formation has led to the recommendation of copious saline irrigation until the lavage is clear. The risk of peritonitis, however, is quite low (<0.2%) with laparoscopic removal of dermoid cysts.

Benign lesions of the uterine tube are routinely asymptomatic and rarely large enough to be palpable—with the exception of the paratubal or parovarian cyst—so the diagnosis is made incidentally during a routine ultrasonographic examination or at the operating table or in the pathology laboratory.

Cystic Tumors

Clinical Findings

Hydatid cysts of Morgagni are cystic tumors of the uterine tube located at or near the fimbriated end. They are lined by tubal-type epithelium, filled with clear fluid, and are usually approximately 1 cm in diameter. They are most often found inadvertently during a pelvic operative procedure. On rare occasions, torsion produces an acute surgical emergency.

Occasionally, larger paratubal or parovarian cysts develop, especially in the broad ligament (Fig. 41–13). These cysts are almost always serous tumors of low malignant potential with a benign clinical outcome.

A third type of cyst associated with the fallopian tubes is the Walthard cell rest. This type is found as a 1-mm cyst beneath the serosa of the fallopian tube. It appears to represent an inclusion cyst in which the mesothelium has undergone metaplasia similar to transitional cell (Brenner) tumors.

Epithelial Tumors

Benign epithelial tumors of the uterine tube are extremely rare. The polyps that occur in the cornual portion appear to be of endometrial rather than tubal origin.

Adenomatoid Tumors

The adenomatoid tumor probably is the most common benign tumor found in the uterine tube. It actually represents a benign mesothelioma, but the compact nature of the adenomatous pattern may be mistaken for malignancy Fig. 41–14. Adenomatoid lesions rarely measure more than 1–1.5 cm. They are always incidental findings when the adnexa are removed for other purposes. Similar lesions, usually cystic, may involve the myometrium or ovary.

Other Benign Tubal and Paratubal Tumors

Other benign tubal tumors, such as leiomyomas and teratomas, are rare, as are benign adnexal tumors of probable wolffian origin. Adrenal cortical nests, however, are common incidental embryologic rests found in the broad ligament, seen as yellowish ovoid nodules 3–4 mm in diameter.