Several clinical risk factors have been identified that increase the risk that any ovarian mass will be a malignant neoplasm. One of the most important is age. Before age 15, many ovarian tumors are malignant.⁵ In woman between ages 20 and 45, only the minority of ovarian tumors will be malignant. The risk increases with age thereafter, such that an ovarian tumor discovered in a woman between ages 60 and 69 is 12 times more likely to be malignant than a tumor in a woman between ages 20 and 29.⁶ Other important risk factors for malignant tumors include a positive family history and nulliparity.

SPECIFIC OVARIAN NEOPLASMS

The ovary is a complex and dynamic structure that is associated with an extensive list of benign and malignant neoplasms, and the obstetrician/gynecologist must ultimately be familiar with all of these. The following is a brief description of some of the most commonly encountered ovarian neoplasms.

Epithelial Cell Tumors

Serous and mucinous tumors are the most common ovarian epithelial cell tumors, and the majority are benign (Table 50-3). The fact that they are mostly benign allows a laparoscopic approach.

Table 50-3 Frequency of Malignancy of Ovarian Neoplasms

Type	Percent of Tumor Type
Serous
Benign	60%
Borderline	15%
Malignant	25%
Mucinous
Benign	80%
Borderline	10%
Malignant	10%
Teratoma
Benign	96%
Malignant	4%

From Cotran RS, Kumar V, Collins T, Robbins SL: Robbins Pathologic Basis of Disease. Philadelphia, WB Saunders, 1999.

Serous

Serous cystadenomas and cystadenocarcinomas are common, accounting for roughly 30% of all ovarian neoplasms and 40% of ovarian malignancies. On histologic examination, serous tumors will be found to be lined with ciliated columnar cells. Approximately 60% of serous ovarian neoplasms are benign, 15% are borderline, and 25% are frankly malignant. Benign serous cystadenomas comprise 25% of all benign ovarian tumors, and 25% will be bilateral.

Malignant serous cystadenocarcinomas are the most common ovarian malignancies, accounting for almost 50% of all malignant ovarian tumors. They are the fifth most common cancer in women in the United States. These tumors usually occur in women between ages 40 and 65 and are bilateral in 65% of cases.

Borderline ovarian tumors are less common than either benign or frankly malignant tumors and are bilateral in 30% of cases.

On transvaginal ultrasonography, serous cystadenomas are often seen as large, thin-walled cystic ovarian masses with an echodensity similar to water. Internal septa and solid areas suggest malignancy. During laparoscopy, tumor wall irregularity (papillae, nodularity), fixation to surrounding tissues, and solid components all suggest malignancy. The 10-year survival rate for women with serous cystadenocarcinomas is approximately 15%.

Mucinous

Mucinous cystadenomas and cystadenocarcinomas are also very common, accounting for 20% of ovarian tumors and 10% of malignancies. They can attain a huge size, often filling the entire pelvic and abdominal cavities. Compared to serous ovarian tumors, they are more often unilateral, large, and multiloculated. These loculations contain thick gelatinous fluid. On histologic examination, mucinous tumors are lined with nonciliated columnar cells. Approximately 80% of mucinous ovarian neoplasms are benign, 10% are borderline, and 10% are frankly malignant.

Mucinous cystadenomas account for 25% of all benign ovarian neoplasms. Their peak incidence of occurrence is between ages 30 and 50, and they are bilateral in 5% of cases.

Borderline and malignant mucinous tumors tend to occur in slightly older women, with a peak incidence of occurrence between ages 40 and 70. Malignant mucinous cystadenocarcinomas make up 10% of primary malignant ovarian neoplasms and are bilateral in up to 20% of cases. The 10-year survival rate is approximately 34%.

Mucinous tumors can be associated with an uncommon malignancy called pseudomyxoma peritonei. This condition is characterized by metastatic spread of well-differentiated mucin-secreting columnar cells along the peritoneal surfaces, usually from a primary mucinous tumor of the appendix. It is believed that this condition can result from intraperitoneal spillage of the contents of a borderline or malignant mucinous ovarian tumor. However, most cystic ovarian mucinous tumors associated with pseudomyxoma peritonei will be found to be metastases from a primary appendiceal tumor.

Endometrioid carcinomas and clear-cell carcinomas make up 20% and 6% of all malignant ovarian neoplasms, respectively, and are bilateral in 40% of cases.

Germ Cell Tumors

Teratomas

Teratomas are the most common ovarian germ cell tumors and can be either benign (mature) or malignant (immature). Mature cystic teratomas are benign tumors commonly referred to as dermoids and account for about 25% of ovarian neoplasms. They are most common during reproductive life and are often incidental findings. Although 20% of dermoids are bilateral, it is not recommended to bivalve the ovary in search of a dermoid that is not seen on preoperative ultrasound.

Mature cystic teratomas are derived from at least two of the three germ layers: ectoderm, endoderm, and mesoderm. Most frequently, their cyst walls contain skin with sebaceous glands and hair follicles and thus contain greasy, yellow sebaceous material and hair. Less commonly, these tumors include cartilage, bone, thyroid tissue, or other structures. Struma ovarii is a particular type of mature teratoma comprised of more than 80% thyroid tissue and can be associated with hyperthyroidism.

Immature teratomas are rare, making up only 4% of ovarian teratomas. Unlike the pattern seen in most ovarian tumors, immature teratomas are more frequent at a younger age, and most present before age 18. Histologically, immature teratomas are composed of partially differentiated structures that resemble fetal or embryonal cell types. Neural elements, cartilage, and epithelial tissues are common. Immature teratomas are often solid; most are unilateral, in contrast to mature cystic teratomas.

Treatment for immature teratomas consists of surgical resection of the affected ovary and postoperative chemotherapy. In younger patients, an attempt is made to preserve fertility by conserving the uterus and unaffected ovary. The 5-year survival rate is between 60% and 90%, depending on the grade and stage of the tumor.

Chemical Peritonitis

A unique management concern regarding benign cystic teratomas is that untreated intraperitoneal spill of their sebaceous contents can result in chemical peritonitis. Clinically, patients present with postoperative fever and ileus, and can develop peritoneal granulomas, adhesions, and even a perihepatic mass.^7,⁸

The risk of chemical peritonitis has two implications for the laparoscopic surgeon. First, if a cyst punctured during laparoscopy is found to contain sebaceous material, a cystectomy or oophorectomy should immediately be performed. Leaving behind a leaking teratoma can lead to serious consequences. Second, when a dermoid cyst is removed laparoscopically, cyst rupture (reported to occur in approximately half the cases) must be appropriately treated with copious irrigation (i.e., 2 to 5L) until no oily material can be seen floating on the fluid surface.⁹^–¹¹ Subsequent peritonitis has not been reported using this approach after spillage from a mature cystic teratoma.

Sex Cord–Stromal Cell Tumors

These are tumors derived from the mesenchymal stroma of the gonad and account for 5% to 10% of all ovarian neoplasms. Probably the most unusual aspect of this group of tumors is that many are able to synthesize and secrete steroid hormones.

Granulosa cell tumors are the most common of this group and account for 5% of all malignant ovarian tumors. They may be nonfunctional, estrogenic or, least commonly, androgenic. Approximately 5% occur before puberty, where they are associated with precious puberty. They are most common in the reproductive years, where they are associated with endometrial cancer. Histologically, they are characterized by Call-Exner bodies. These neoplasms have a good prognosis despite a tendency to recur.

Fibromas are solid benign tumors that consist entirely of fibrous tissue and do not secrete hormones. They make up approximately 4% of ovarian tumors and can be associated with Meig syndrome, a rare combination of an ovarian fibroma, ascites, and pleural effusion.

PREOPERATIVE EVALUATION OF AN OVARIAN MASS

The most important diagnostic questions to be answered before surgery are (1) What is the origin of the mass? and (2) Is it benign or malignant? Although bimanual pelvic examination is the time-honored method of screening for pelvic masses, this technique has marked limitations for evaluating adnexa, especially in the presence of obesity, uterine enlargement, or abdominal scarring.¹² History, physical examination, and ultrasonography can usually determine the origin of an adnexal mass.

For ovarian masses, a combination of pelvic examination, ultrasonography, and serum CA-125 level is the best way to determine the risk of malignancy.¹²^–¹⁴ Certain ultrasonographic characteristics have been found to be strongly associated with malignancy (see Chapter 30). Ovarian tumors are more likely to be malignant if ultrasonography reveals them to be multiloculated, septated, mixed cystic and solid, bilateral, or associated with ascites.¹⁵ However, almost two thirds of multilocular and solid tumors will be benign.^16,¹⁷

Combining serum CA-125 with these ultrasound criteria has been used in women who are postmenopausal as the risk of malignancy index.¹⁵ Other investigators have found color flow Doppler ultrasonography to be helpful, because an ovarian lesion is more likely to be malignant if a solid element of the mass demonstrates central blood flow.¹⁸

Multiple preoperative assessment models have been developed for adnexal masses.¹⁶^–²⁸ A significant limitation of many of these models is that they were developed and validated on the same population. Mol and colleagues tested the external validity of most of these models and found that although they could be of value in preoperative assessment, their diagnostic performance was not as good as reported in their original publications.²⁷

None of the externally validated likelihood ratios are sufficiently great as to be diagnostically conclusive.²⁷ Likelihood ratios are the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder. Although likelihood ratios may not be as familiar a concept as sensitivity and specificity, they are calculated from these values and are a more logical means of understanding diagnostic value. Pretest probability can be multiplied by the likelihood ratio of a given test to render the post-test probability. Likelihood ratio values can be positive (rule in a diagnosis) or negative (rule out a diagnosis).

What is curious about these models is the relative consistency of the likelihood ratio results and that additional information, such as age and menopausal status, does not dramatically alter the likelihood ratio results between the studies. Unfortunately, these models have significant rates of false-negative and false-positive results, regardless of the criteria and cutoff values used. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) have jointly published guidelines that help determine when a women with a newly diagnosed pelvic mass should be referred to a gynecologic oncologist (Table 50-4).²⁹ This conservative model accurately predicts which women with ovarian masses are at low risk of malignancy, with a negative predictive value of 92% for premenopausal and 91% for postmenopausal women.³⁰ However, the women at highest risk according to this model will often be found to have a benign lesion, with a positive predictive value of 34% for premenopausal and 60% for postmenopausal women.

Table 50-4 Society of Gynecologic Oncologists and American College of Obstetricians and Gynecologists Referral Guidelines for a Newly Diagnosed Pelvic Mass ^*

Premenopausal Woman

CA-125 > 200 U/mL

Ascites

Evidence of abdominal or distant metastasis (by examination or imaging study)

Family history of breast or ovarian cancer (in a first-degree relative)

Postmenopausal Woman

CA-125 > 35 U/mL

Ascites

Nodular or fixed pelvic mass

Evidence of abdominal or distant metastasis (by examination or imaging study)

Family history of breast or ovarian cancer (in a first-degree relative)

* Women with pelvic masses who meet these criteria should be referred to a gynecologic oncologist.

From ACOG: The role of the generalist obstetrician-gynecologist in the early delection of ovarian cancer. ACOG Committee Opinion no. 280, December 2002. Obstet Gynecol 100:1413–1416, 2002.

SURGICAL APPROACH

Laparoscopy versus Laparotomy

An important question that must be answered whenever a patient presents with an ovarian mass is whether the mass should be approached laparoscopically or via laparotomy. The answer is not simple and will ultimately depend on the experience and philosophy of the physician and the desires of the patient.

A useful approach for the woman presenting with a pelvic mass has been proposed, which places each patient into one of three risk categories for having a malignancy: low, intermediate, and high (Fig. 50-1).²² A woman at low risk can be observed for 3 months or evaluated with diagnostic laparoscopy according to the patient’s preference. A woman at intermediate risk can be evaluated with diagnostic laparoscopy. Laparoscopic treatment of the mass is appropriate in the absence of surgical evidence of malignancy. Women at high (10% or greater) risk of malignancy should be evaluated surgically, most commonly via laparotomy. In select circumstances, laparoscopy can be used for surgical evaluation, assuming that the laparoscopist has both the appropriate experience and gynecologic oncologist backup.

Figure 50-1 Algorithm for preoperative evaluation of an ovarian cyst. A distinction is made here between a diagnostic laparoscopy and surgical evaluation. Depending on surgeon skill, availability of gynecologic oncology backup, and overall clinical suspicion for malignancy, surgical evaluation could include laparoscopy, yet consideration should be given in these circumstances to performing a laparotomy.

Intraoperative Tumor Rupture

Intraoperative rupture of some ovarian cysts that are later found to be malignant is unavoidable, regardless of the preoperative criteria or surgical approached used. One study of 32 patients found an overall rate of tumor rupture of 25% for laparoscopy compared to 9% for laparotomy.³¹ This occurrence appears to worsen the patient’s prognosis, although there are conflicting data. Although some studies have found no impact of intraoperative tumor rupture on subsequent survival,³²^–³⁴ others have shown decreased survival.³⁵^–³⁸

The only prospective assessment of the impact of intraoperative tumor rupture found a significantly lower survival rate for women with stage I ovarian carcinoma after rupture, although not as low as for women whose tumor ruptured spontaneously before surgery.³⁸ The greatest impact of intraoperative rupture was for serous tumors, where the 9-year survival rate declined from 86% to 50%. Furthermore, many oncologists will recommend chemotherapy after an intraoperative spill of a well-differentiated stage I a cancer that usually would not have received such treatment. Certainly, spillage of cyst contents into the peritoneal cavity should be avoided when ovarian malignancy is a possibility.

Surgical Staging

Regardless of the surgical approach used to treat an ovarian malignancy, adequate surgical staging is imperative (Table 50-5). One study of 100 women with ovarian cancer referred to a gynecologic oncologist after surgical diagnosis found that only 25% had adequate staging.³⁹ More than 30% were ultimately found to have more advanced stage disease than reported based on the initial surgery.

Table 50-5 Surgical Staging for Ovarian Cancer

Evaluate

Is the tumor unilateral or bilateral?

Does the tumor appear on the external surface of the ovary?

Is the tumor capsule intact?

Has the tumor ruptured?

One factor that contributes to inadequate staging at the initial surgery is the discordance between intraoperative frozen section and subsequent diagnosis based on permanent section. Making a diagnosis of borderline malignancy is especially difficult on frozen section. Several studies have documented a greater than 5% discordance between these two techniques.^40,⁴¹

The problem is that patients erroneously determined intraoperatively to have benign disease based on frozen section are unlikely to be adequately staged. In light of the inherent inaccuracy associated with frozen section, surgeons should consider staging patients with suspicious ovarian masses even if the interoperative diagnosis is benign. Moreover, surgeons should discuss intraoperative diagnostic limitations with their patients before surgery, irrespective of approach.

LAPAROSCOPY APPROACH FOR OVARIAN MASSES

Laparoscopic management of properly selected ovarian masses has become a standard part of modern obstetrics and gynecology.³ In one study of 396 women who underwent laparoscopy for a low-risk adnexal mass, only 2% of patients were ultimately found to have a malignancy.³ This low rate is related both to a low prevalence of malignancy among women with ovarian cysts in a general population and the efficacy of preoperative diagnostic testing. Because the possibility of a malignancy can never be eliminated preoperatively in patients with an ovarian mass, consideration should be given to obtaining consent for an open staging procedure in patients with a suspicious mass.

Oophorectomy versus Cystectomy

Two approaches are commonly used for evaluation and treatment of ovarian cysts: oophorectomy and cystectomy. Oophorectomy, with or without removal of the fallopian tube, is the preferred approach for women no longer desiring fertility and for any lesion at moderate to high risk of being malignant to minimize the risk of intraperitoneal spillage. Cystectomy is preferred for low-risk ovarian lesions in women who want to preserve their fertility and young women with only one remaining ovary to preserve hormonal function.

Incomplete removal of a cyst is not the procedure of choice but is sometimes necessary. In the case of a small cyst that appears to be functional in nature, aspiration of the cyst contents for cytology, followed by full-thickness biopsy of the cyst wall, is a reasonable technique to resolve the cyst while verifying that it is not a neoplasm. In the case of an endometrioma with no identifiable cyst wall that can be removed, aspiration of the chocolate cyst contents followed by ablation of the internal surface of the cyst may be necessary, but it is associated with an increased recurrence risk. In every case, a full-thickness biopsy of the cyst wall should be sent for pathologic evaluation.

Laparoscopic Setup

Any standard laparoscopic technique can be used for entry. When dealing with a large lesion it is prudent to use an open laparoscopic technique or a left upper quadrant site. The latter is especially useful for removal of a mass in a pregnant patient. If an open umbilical technique is used, the mass can be removed through this port as well. During removal, the laparoscope is placed through one of the secondary ports to visualize the removal.

Most laparoscopists use two or three secondary 5-mm ports for operative procedures. The most common configuration is a suprapubic port 3 to 4 cm above the pubic symphysis and lateral ports at McBurney’s point on the right and the corresponding Hurd’s point on the left, taking care to avoid the epigastric vessels. Many laparoscopic surgeons do not use the suprapubic site but rather place an accessory port just above the level of the umbilicus lateral to the rectus muscle on the patient’s left side. The latter approach allows the surgeon to operate comfortably with two hands.

Specimen removal will often require placement of a 10-mm or greater port in one of the secondary sites. This larger port can be placed initially, or a 5-mm site can be dilated to 10 mm.

Pelvic Washings and Peritoneal Cavity Inspection

Before beginning the operative procedure, pelvic washings should be collected. In the absence of ascites, 50 to 100 mL of saline solution is introduced into the peritoneal cavity and aspirated from the cul-de-sac, paracolic gutters, and beneath each hemidiaphragm. The abdominal cavity should be carefully inspected for signs of metastases by taking note of the appearance of the uterus, fallopian tubes, ovaries, cecum, paracolic gutters, colon, liver, gallbladder, diaphragm, omentum, and peritoneal surfaces. The ovarian capsule should be carefully inspected to determine if it is intact or has been penetrated by tumor. Any suspicious excrescences should be biopsied and sent for pathologic evaluation. If malignancy is encountered, a gynecologic oncologist should be consulted intraoperatively. If malignancy is encountered and an oncologist is not available, minimal tissue manipulations and irrigation of trocar sites is recommended. Prognosis is best with rapid reoperation.

Laparoscopic Oophorectomy

Laparoscopic oophorectomy is an important technique to be mastered by obstetrician/gynecologists. In addition to minimizing the risk of intraperitoneal spill of ovarian cyst contents, special efforts need to be made to avoid ureteral injury.

Knowing the course of the ureters and their relation to the ovarian blood vessels is essential. The ovarian artery originates from the abdominal aorta and courses with the ovarian vein and lymphatics through the infundibulopelvic ligament (i.e., ovarian suspensory ligament). At the superior end of the infundibulopelvic ligament, the ureter crosses beneath the ovarian vessels. The ureter then courses immediately beneath the ovary in the retroperitoneal space adjacent to the peritoneum. It is at these two locations that the ureter is at risk of injury during oophorectomy.

The first step in a laparoscopic oophorectomy is to identify the ureter. If the ureter can be clearly identified transperitoneally by its peristalsis and found to be safely beneath the level of the infundibulopelvic ligament, oophorectomy can be performed without opening the pelvic sidewall peritoneum. However, in cases where the ureter cannot be seen because of obesity, adhesions, or thickened peritoneum, the pelvic sidewall peritoneum should be opened. The infundibulopelvic ligament is put on tension and the peritoneum is opened to identify the ureter. The ovarian vessels are skeletonized and occluded using one of a variety of techniques: bipolar cautery, ultrasonic scalpel, a stapling device, or an endoligature (Fig. 50-2). Careful dissection using scissors or one of these power sources is then used to isolate and occlude the utero-ovarian ligament, thereby separating the ovary and tube from their attachments. The dissection bed should be inspected for hemostasis before removal of the ovary from the peritoneal cavity. At the conclusion of laparoscopy, the hemostasis of all vascular pedicles should be reevaluated as the intra-abdominal insufflation pressure is decreased.

Figure 50-2 A, The retroperitoneal space has been opened and the ovarian vessels are retracted laterally. The ureter is located on the medial leaf of the peritoneal incision. B, After isolation of the ovarian vessels from the surrounding structures, a bipolar device can be safely applied.

Laparoscopic Ovarian Cystectomy

For women with ovarian cysts at low risk of being malignant who desire to maintain their fertility, an ovarian cystectomy is often the best option. With the exception of functional cysts and endometriomas, the cyst wall of benign ovarian cysts can often be easily separated from the ovarian cortex and the cyst removed intact from the peritoneal cavity intact. The goal is to preserve as much normal ovarian cortex as possible, because this is the area containing primordial follicles. In cases where little ovarian tissue remains, the contribution of a small remnant to subsequent fertility and hormone secretion may be minimal.

As with oophorectomy, ovarian cystectomy begins with collection of peritoneal washings and careful inspection of the peritoneum for signs of possible implants. Considerable finesse is then required to remove ovarian cysts intact without spillage. Ovarian cysts are ordinarily contained beneath a layer of ovarian epithelium that can be extremely thin. To begin a cystectomy, the ovarian tissue overlying the cyst must be carefully incised without rupturing the cyst. Having carefully inspected the ovary, a site on the ovary should be selected that appears (1) to have the thinnest layer between the cortex and the cyst wall and (2) to have good laparoscopic exposure. Some surgeons use monopolar cautery with the cutting current set at 10 amperes for this purpose. Others prefer gently incising the tissue with sharp scissors.

Once a defect is made, the ovarian tissue is bluntly separated from the cyst wall (Fig. 50-3A). The ovarian cortex is held with a grasper and gently peeled away from the underlying cyst (see Fig. 50-3B). This can be facilitated with aid of water dissection from the laparoscopic suction–irrigator. In areas where connections between the cortex and cyst wall do not separate easily, sharp dissection should be used to avoid cyst rupture and spill.

Figure 50-3 A, An incision is made on the ovarian cortex to identify the underlying cyst. B, The cortex is dissected off the cyst and the intact cyst is free.

Removal of the Ovary or Cyst from the Peritoneal Cavity

Once the ovary or a cyst has been excised, the next challenge is to remove the specimen from the peritoneal cavity without spilling any cyst fluid into the peritoneal cavity. The ideal approach is to place the entire specimen intact into a retrieval bag for extraction.

Laparoscopic Endometrioma Resection

Removal of an endometrioma is referred to as cystectomy, but the procedure is markedly different from that used for other ovarian cysts. Endometrioma cyst walls are usually densely adherent to the overlying ovarian tissue. This makes it difficult or impossible to find a surgical plane in many patients, and removing an endometrioma cyst wall intact is rarely possible.

The first step in removal of an endometrioma is mobilization of the ovary from any adhesions to the pelvic sidewall or adjacent organs. Many endometriomas will rupture at this point and exude thick “chocolate” fluid. If the cyst remains intact, it will often rupture as the ovarian epithelium covering the cyst is incised.

The edge of the cyst wall is separated from the ovarian tissue and is stripped using a combination of blunt and sharp dissection (Fig. 50-5A and B). Bleeding is common from the dissection bed, and bipolar cautery can be used to cauterize bleeding sites (see Fig. 50-5C). Excessive use of cautery can cause ovarian damage. The cyst wall is then placed in an endoscopic retrieval bag and extracted through a port incision.