Hacker & Moore's Essentials of Obstetrics and Gynecology: With STUDENT CONSULT Online Access,5th ed.

Chapter 39

Ovarian Cancer

Jonathan S. Berek

Ovarian cancer is the fifth most common cancer among females in the United States, accounting for one fourth of all gynecologic cancers. It is the leading cause of death from gynecologic cancer because it is difficult to detect before it disseminates. In 2007, 22,430 new cases and more than 15,280 deaths are expected from this disease. Most women with ovarian cancer are in the fifth or sixth decade of life.

image Etiology and Epidemiology

The cause of ovarian cancer is unknown. The patient characteristics found to be associated with an increased risk for epithelial ovarian cancer include white race, late age at menopause, family history of cancer of the ovary, breast, or bowel, and prolonged intervals of ovulation uninterrupted by pregnancy. There is an increased prevalence of ovarian cancer in nulliparous women and those who have been infertile.

The incidence of ovarian cancer varies in different geographic locations. Western countries, including the United States, have rates that are 3 to 7 times greater than those in Japan. Second-generation Japanese immigrants to the United States have an incidence of ovarian cancer similar to that of American women. White Americans experience ovarian cancer about 1.5 times more frequently than do black Americans.

About 10% of epithelial ovarian cancers occur in women with a hereditary predisposition. In women with hereditary cancers, two or more first-degree relatives on either the paternal or maternal side typically have had breast or ovarian cancer. The pattern of inheritance is autosomal dominant. Breast cancers generally occur in young premenopausal women, whereas ovarian cancers have a median age of about 50 years. The breast-ovarian cancer syndrome is due to germline mutations of BRCA1, which is located on chromosome 17, and BRCA2, which is located on chromosome 13. The Lynch II syndrome, nonpolyposis colorectal cancer syndrome, is associated with mutations in the mismatch repair genes. Adenocarcinomas of the ovary, breast, colon, stomach, pancreas, and endometrium are seen in the families of these individuals.

The use of oral contraceptives has been found to protect against ovarian cancer, possibly because of suppression of ovulation. It has been postulated that incessant ovulation may predispose to malignant transformation in the ovary.

Patients with a known germline mutation (e.g., BRCA1 and BRCA2 mutations) may be offered prophylactic salpingo-oophorectomy once childbearing has been completed, and this operation is highly protective for ovarian and fallopian tube carcinomas. Indeed, the risk for subsequent breast cancer is also significantly reduced in these women. There is still a small risk for peritoneal carcinoma after prophylactic salpingo-oophorectomy.

Some case-control studies have suggested that the use of postmenopausal estrogen replacement therapy may increase the risk for ovarian cancer, but these data are controversial.

It has also been postulated that a causative agent could enter the peritoneal cavity through the lower genital tract. For example, the perineal use of asbestos-contaminated talc has been linked to the development of epithelial ovarian cancer. This possibility remains controversial, although tubal ligation and hysterectomy are both associated with a decreased risk for the disease.

image Screening for Ovarian Cancer

Population screening for ovarian cancer is not feasible because ultrasonography and available tumor markers, for example, CA 125, lack specificity and sensitivity for early-stage disease. CA 125 is more useful in postmenopausal women because false-positive measurements occur commonly in premenopausal women in association with endometriosis, pelvic inflammatory disease, or uterine fibroids. Patients with a strong family history of epithelial ovarian cancer may benefit from surveillance with serial transvaginal ultrasonography and serum CA 125 titers.

image Clinical Features

SYMPTOMS

Unfortunately, many patients in whom ovarian cancer develops have only nonspecific symptoms before dissemination takes place. In early-stage disease, vague abdominal pain or bloating is common, although symptoms of a mass compressing the bladder or rectum, such as urinary frequency or constipation, may bring the patient to a physician. Sometimes the patient complains of dyspareunia. Premenopausal women may experience menstrual irregularity. Only rarely does a patient present with acute symptoms, such as pain secondary to torsion, rupture, or intracystic hemorrhage.

In advanced-stage disease, patients most often present with abdominal pain or swelling. The latter may be from the tumor itself or from associated ascites. On careful questioning, there has usually been a history of vague abdominal symptoms, such as bloating, constipation, nausea, dyspepsia, anorexia, or early satiety. Premenopausal patients may complain of irregular menses or heavy vaginal bleeding. Postmenopausal bleeding is occasionally a symptom of ovarian neoplasms, particularly functional stromal tumors.

SIGNS

The disease is frequently misdiagnosed for several months because patients with nonspecific abdominal symptoms do not receive a vaginal and rectal examination. A solid, irregular, fixed pelvic mass is suggestive of ovarian cancer, and if combined with an upper abdominal mass, ascites, or both, the diagnosis is almost certain.

image Preoperative Evaluation

The diagnosis of ovarian cancer requires a laparotomy or laparoscopy. Routine preoperative hematologic and biochemical studies should be obtained, as should a chest radiograph. A pelvic and abdominal computed tomography scan will exclude liver metastases, but it is not mandatory.

A Papanicolaou smear should be obtained to evaluate the cervix, but this test is of limited value in detecting ovarian cancer. Endometrial biopsy and endocervical curettage are necessary in patients with abnormal vaginal bleeding because concurrent primary tumors occasionally occur in the ovary and endometrium. In the presence of a pelvic mass, it is preferable not to perform abdominal paracentesis for cytologic evaluation of ascitic fluid, unless neoadjuvant chemotherapy is planned, because seeding of the abdominal wall may occur.

An abdominal radiograph may be useful in a younger patient to locate calcifications associated with a benign cystic teratoma (dermoid cyst), which is the most common neoplasm in patients younger than 25 years of age. In patients with occult blood in the stool or significant intestinal symptoms, a barium enema or lower gastrointestinal endoscopy should be obtained to rule out a primary colonic cancer with ovarian metastasis.

Similarly, an upper gastrointestinal endoscopy is important if there are significant gastric symptoms. Breast cancer may also metastasize to the ovaries, so bilateral mammograms should be obtained if there are any suspicious breast masses.

Pelvic ultrasonography, particularly transvaginal ultrasonography with or without color Doppler studies, may be useful for smaller (<8 cm) masses in premenopausal women. Masses that are predominantly solid or multilocular have a high probability of being neoplastic, whereas unilocular cystic masses are generally functional cysts. In postmenopausal women, ultrasonography may also be useful because small, unilocular cysts (<5 cm) that are stable are generally benign.

Several tumor markers have been investigated, but none has been consistently reliable. The tumor-associated antigen CA 125 is elevated in only about 50% of women with stage I ovarian cancer. When this assay is elevated, it is useful for monitoring the clinical course of the disease.

image Differential Diagnosis

Ovarian malignancies must be differentiated from benign neoplasms and functional cysts of the ovaries. In addition, a variety of gynecologic conditions can simulate a neoplastic process, including tubo-ovarian abscess, endometriosis, and a pedunculated uterine leiomyoma. Nongynecologic causes of pelvic tumor must also be excluded, such as an inflammatory or neoplastic disease of the colon, or a pelvic kidney.

image Mode of Spread

Ovarian cancer typically spreads by exfoliating cells that disseminate and implant throughout the peritoneal cavity. The distribution of intraperitoneal metastases tends to follow the circulatory path of peritoneal fluid, so metastases are commonly seen on the posterior cul-de-sac, paracolic gutters, right hemidiaphragm, liver capsule, and omentum. Implants are also common on the bowel serosa and its mesenteries. In general, they grow around the intestines, encasing them with tumor, without invading the bowel lumen. Widespread bowel metastases can lead to a functional obstruction known as carcinomatous ileus.

Lymphatic dissemination to the pelvic and para-aortic nodes is common, particularly with advanced disease. Extensive blockage of the diaphragmatic lymphatics is at least partially responsible for the development of ascites. Hematogenous metastases are not common, and parenchymal metastases to the liver and lungs are seen in only about 2% of patients at initial presentation.

Death from ovarian cancer usually results from progressive encasement of abdominal organs, leading to anorexia, vomiting, and inanition. The bowel obstruction caused by tumor growth is often incomplete and intermittent and may last for several months before the patient’s demise.

image Staging

The standard staging system for ovarian cancer is presented in Table 39-1Ovarian cancer is surgically staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system.

TABLE 39-1 INTERNATIONAL FEDERATION OF GYNECOLOGY AND OBSTETRICS (FIGO) STAGING FOR PRIMARY CARCINOMA OF THE OVARY

Stage I

Growth limited to the ovaries

Stage Ia

Growth limited to one ovary; no ascites. No tumor on the external surface; capsule intact

Stage Ib

Growth limited to both ovaries; no ascites. No tumor on the external surfaces; capsules intact

Stage Ic

Tumor either stage Ia or Ib but with tumor on the surface of one or both ovaries or with capsule ruptured or with ascites present containing malignant cells or with positive peritoneal washings

Stage II

Growth involving one or both ovaries with pelvic extension

Stage IIa

Extension or metastases, or both, to the uterus or tubes, or both

Stage IIb

Extension to other pelvic tissues

Stage IIc

Tumor either stage IIa or IIb but with tumor on the surface of one or both ovaries or with capsule or capsules ruptured or with ascites present containing malignant cells or with positive peritoneal washings

Stage III

Tumor involving one or both ovaries with peritoneal implants outside the pelvis or positive retroperitoneal or inguinal nodes, or both. Superficial liver metastasis equals stage III. Tumor is limited to the true pelvis, but with histologically proven malignant extension to small bowel or omentum

Stage IIIa

Tumor grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces

Stage IIIb

Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter. Nodes negative for disease

Stage IIIc

Abdominal implants >2 cm in diameter or positive retroperitoneal or inguinal nodes, or both

Stage IV

Growth involving one or both ovaries with distant metastasis. If pleural effusion is present, there must be positive cytologic test results to allot a case to stage IV. Parenchymal liver metastasis equals stage IV.

Even though all microscopic disease may appear to be confined to the ovaries at the time of laparotomy, microscopic spread may have already occurred; thus, patients must undergo a thorough surgical staging. Procedures necessary to stage ovarian cancer are shown in Box 39-1.

image

BOX 39-1 Requirements for Staging or Second-Look Operations

Multiple Cytologic Assays

Free ascitic fluid, if present

Peritoneal “washings” (50 mL of normal saline)

Pelvic cul-de-sac

Both paracolic gutters

Both hemidiaphragms

Multiple Intraperitoneal Biopsies

Pelvis

Cul-de-sac peritoneum

Bladder peritoneum

Pedicles of infundibulopelvic ligaments

Any adhesions

Abdomen

Both paracolic gutters

Bowel serosa and mesenteries

Omentum

Any adhesions

Extraperitoneal Biopsies

Pelvic and para-aortic lymph nodes

 Procedures performed in patients with no visible evidence of metastatic disease.

image

image Classification

The histologic classification of ovarian neoplasms is listed in Table 39-2. These lesions fall into four categories according to their tissue of origin. Most ovarian neoplasms (80% to 85%) are derived from coelomic epithelium and are called epithelial carcinomas. Less common tumors are derived from primitive germ cells, specialized gonadal stroma, or nonspecific mesenchyme. In addition, the ovary can be the site of metastatic carcinomas, most often from the gastrointestinal tract or the breast.

TABLE 39-2 HISTOGENETIC CLASSIFICATION OF PRIMARY OVARIAN NEOPLASMS

Derivation

Type of Tumor

Coelomic epithelial origin (80%-85%)

“Common” epithelial tumors; benign, borderline, malignant

  Serous tumor

  Mucinous tumor

  Endometrioid tumor

  Clear cell (mesonephroid) tumor

  Brenner tumor

Undifferentiated carcinoma

Carcinosarcoma or malignant mixed mesodermal tumors

Germ cell origin (10%-15%)

Teratoma

  Mature teratoma

  Solid adult teratoma

  Dermoid cyst

  Struma ovarii

  Malignant neoplasms secondarily arising from teratomatous tissues (squamous carcinoma, carcinoid tumor, sarcoma)

  Immature teratoma

Dysgerminoma

Endodermal sinus tumor

Embryonal carcinoma

Choriocarcinoma

Gonadoblastoma

Mixed germ cell tumors

Specialized gonadal-stromal origin (3%-5%)

Granulosa-theca cell tumors

  Granulosa cell tumor

  Thecoma

Sertoli-Leydig tumors

  Arrhenoblastoma

  Sertoli cell tumor

Gynandroblastoma

Lipid cell tumors

Nonspecific mesenchymal origin (fewer than 1%)

Fibroma, hemangioma, leiomyoma, lipoma

Lymphoma

Sarcoma

 Combined germ cell and specialized gonadal-stromal elements.

Data from Hart WR, Morrow CP: The ovaries. In Romney SL, Gray MJ, Little AO, et al (eds): Gynecology and Obstetrics: The Health Care of Women, 2nd ed. New York, McGraw-Hill, 1981.

image Epithelial Ovarian Carcinomas

PATHOLOGIC FEATURES

The main histologic subtypes of epithelial carcinomas are serous (about 55%), mucinous (about 20%), endometrioid (about 15%), and clear cell (about 5%). Malignant Brenner tumors and undifferentiated carcinomas are uncommon.

Serous tumors resemble fallopian tube epithelium histologically (Figure 39-1). About 30% of patients with stage I and stage IIa disease have bilateral involvement. On gross examination, serous carcinomas have an irregular and multilocular appearance (Figure 39-2).

image

FIGURE 39-1 Papillary serous cystadenocarcinoma. This tumor frequently contains numerous psammoma bodies, which are shown here. Their origin is uncertain, but it has been suggested that they may reflect an immune reaction against the tumor or, more simply, represent alteration to the secretions from the malignant cells. There is no relationship between the presence of psammoma bodies and the malignancy of the tumor.

image

FIGURE 39-2 Bilateral serous cystadenocarcinomas. A uterus with both ovaries grossly enlarged by multilocular tumors with papillary excrescences on their serosal surfaces is shown.

Mucinous tumors histologically resemble endocervical epithelium and are often large, measuring 20 cm or more in diameter. They are bilateral in 10% to 20% of patients.

Endometrioid tumors closely resemble carcinomas of the endometrium and arise in association with primary endometrial cancer in about 20% of patients. In early-stage disease, they are bilateral in about 10% of cases. About 10% of endometrioid ovarian carcinomas are associated with endometriosis, although malignant transformation of endometriosis occurs in fewer than 1% of patients.

Clear cell carcinomas of the ovary are uncommon. In about 25% of cases, they occur in association with endometriosis.

The Brenner tumor represents only 2% to 3% of all ovarian neoplasms, and fewer than 2% of these tumors are malignant. About 10% of Brenner tumors occur in conjunction with a mucinous cystadenoma or dermoid cyst in the same or opposite ovary.

Tumors of low malignant potential or borderline histologic appearance exist for each histologic type. About 5% to 10% of malignant serous tumors are borderline (Figure 39-3), whereas 20% of malignant mucinous tumors fall into this category. The endometrioid, clear cell, and Brenner tumors are only rarely borderline.

image

FIGURE 39-3 A: Serous tumor—borderline (papillary serous cystadenocarcinoma of low malignant potential). The papillary pattern filling the cyst lumen is very complex, and the epithelium is, in places, more than one cell thick. Mitotic figures are present, although not abundant. B: Large borderline tumor mobilized out of the pelvis. Note the smooth surface and large blood vessels coursing over the surface.

MANAGEMENT OF EPITHELIAL OVARIAN CANCER

The initial approach to all patients with ovarian cancer is surgical exploration of the abdomen and pelvis.

Early-Stage Disease

Definitive diagnosis requires an intraoperative frozen section. In patients with no gross evidence of disease beyond the ovary, the standard operation is total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and thorough surgical staging, as shown in Box 39-1. Patients who wish to preserve fertility may have a unilateral salpingo-oophorectomy. In patients with grade 1 or 2 tumors confined to one or both ovaries after surgical staging, no further treatment is necessary. Patients with poorly differentiated (grade 3) tumors are subsequently treated with systemic chemotherapy.

Advanced-Stage Disease

In patients with advanced disease, cytoreductive surgery (“debulking”) is required. The objectives are to remove the primary tumor and all of the metastases, if possible. If all macroscopic disease cannot be removed, an attempt should be made to reduce individual tumor nodules to 1 cm or less in diameter. Patients in whom this goal is achieved are said to have had “optimal” cytoreduction, which can be achieved in about 70% of patients. In addition to a total or subtotal abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal metastases, optimal cytoreduction may necessitate bowel resection; therefore, all patients having surgery for suspected ovarian cancer should have a bowel preparation preoperatively.

In retrospective studies, patients whose individual residual tumor nodules are 1 cm in diameter or less before the commencement of chemotherapy have been shown to have longer median survivals and more complete responses to therapy. The longest survival is seen in patients in whom all visible tumor has been removed before treatment.

In patients who are medically unfit or have a poor performance status, usually because of a large pleural effusion and massive ascites, it may be prudent to give two or three cycles of neoadjuvant chemotherapybefore undertaking radical surgery. If the disease does not respond to chemotherapy, as evidenced by the failure to resolve the malignant effusions, the patient should be offered palliative care only. Usually, the effusions resolve completely, and an “interval” cytoreductive operation can be safely undertaken.

Following primary cytoreductive surgery, combination chemotherapy is given, most commonly intravenous carboplatin and paclitaxel, or intraperitoneal cisplatin and paclitaxel. Intraperitoneal treatment is only useful for patients with minimal residual disease. Single-agent therapy with paclitaxel, or carboplatin, is occasionally used for frail or elderly patients. During chemotherapy, the patient’s response is monitored with serial CA 125 levels. If the values rise or plateau within 6 months, it is advisable to change to second-line drugs, such as liposomal-encapsulated doxorubicin, topotecan, etoposide, gemcitabine, or experimental chemotherapeutic agents. If the progression-free interval has been longer than 6 to 12 months, the patient may respond to further paclitaxel or carboplatin chemotherapy. Response to second-line chemotherapy is in the range of 20% to 50%, but patients are not considered to be curable after their initial relapse. Secondary cytoreduction may be appropriate if the disease-free interval is 24 months or longer.

It is unclear whether patients with “metastatic” borderline tumors benefit from chemotherapy.

Second-Look Laparotomy

In patients who are clinically free of disease after completing a prescribed course of chemotherapy (usually about six cycles), a second-look laparotomy may be performed to determine whether the patient has had a complete response to chemotherapy. However, it is unclear whether the performance of a second-look laparotomy and the administration of further treatment ultimately prolong survival, so the surgery should be confined to research settings. If there is no macroscopic or microscopic evidence of disease at second-look laparotomy, essentially the same procedures as are carried out for surgical staging should be performed (see Box 39-1). If gross disease is present, an attempt should be made to resect persistent disease to facilitate a response to subsequent therapy.

PROGNOSIS

Patients with stage I disease have 5-year survival rates of 75% to 95%, depending on the histologic grade.

Almost all patients with carefully staged Ia grade 1 ovarian cancer are cured surgically, whereas the 5-year survival rate for patients with poorly differentiated bilateral lesions is as low as 75%.The 5-year survival rate for patients with stage II disease is about 65%. Despite aggressive primary surgery and combination chemotherapy, the 5-year survival rate for patients with advanced-stage disease is about 20%, although the median survival is between 2 and 3 years. Patients with advanced-stage disease who have negative findings on second-look laparotomy have a 5-year survival rate of about 60%. Patients whose tumors are associated with BRCA1 and BRCA2 mutations may have a somewhat better prognosis, but this issue is unclear.

Patients who have borderline ovarian tumors can be expected to have a prolonged survival. If the disease is confined to the ovary, most tumors never recur. Five- and 10-year survival rates are 95% to 100%, but late recurrences may occur, and 20-year survival rates are about 85% to 90%. Patients who initially present with metastatic disease are more likely to exhibit subsequent clinical evidence of disease, although the rate of progression is slow; most live at least 5 years.

image Germ Cell Tumors

Germ cell tumors of the ovary account for only about 2% to 3% of all ovarian malignancies. They occur predominantly in young patients and frequently produce either human chorionic gonadotropin (hCG) or alpha-fetoprotein (AFP), which serve as tumor markers. The most common germ cell tumors are the dysgerminoma and immature teratoma. Endodermal sinus tumors, embryonal tumors, and nongestational choriocarcinomas are less common. Mixed germ cell tumors are not uncommon.

DYSGERMINOMAS

Dysgerminomas occur predominantly in children and young women. About 10% are bilateral. These tumors, of varying malignant virulence, are occasionally seen in patients with gonadal dysgenesis or the testicular feminization syndrome. In such patients, the dysgerminoma may arise in a gonadoblastoma. In about two thirds of patients, the disease is confined to the ovaries at the time of diagnosis. About 10% of dysgerminomas are associated with other germ cell malignancies. Pure dysgerminomas do not produce the tumor markers hCG and AFP but commonly produce lactate dehydrogenase.

Treatment

In most patients, the contralateral ovary and the uterus can be preserved. Surgical staging, as outlined earlier in this chapter, is important. Particular attention should be paid to the pelvic and para-aortic lymph nodes because of the propensity of these tumors for lymphatic dissemination. If disease extends beyond one ovary, the treatment of choice is resection and chemotherapy. The regimen employed for these patients is usually bleomycin, etoposide, and cisplatin. Carboplatin and paclitaxel are also being tested in these patients. Dysgerminomas are uniquely radiosensitive, and radiotherapy was previously the treatment of choice. However, it is now best reserved for the management of recurrent, chemoresistant disease.

Prognosis

The 5-year survival rate for patients with stage Ia pure dysgerminoma treated with unilateral oophorectomy is about 95%, whereas it is 80% for stage II and 60% to 70% for stage III disease. Recurrences following conservative surgery have at least an 80% 5-year survival rate.

IMMATURE TERATOMAS

Immature teratomas are the second most common malignant ovarian germ cell tumor. About 75% of malignant teratomas are encountered during the first two decades of life. Bilateral lesions are rare, although the other ovary may contain a benign dermoid cyst in about 5% of cases. Like other germ cell tumors, immature teratomas grow fairly rapidly, cause pain early, and are found confined to the ovary in about two thirds of cases at the time of diagnosis. Pure immature teratomas do not produce hCG or AFP. Histologically, the tumors can be graded from 1 to 3 according to the degree of differentiation, with grade 3 tumors being the least differentiated. Neural elements are most frequently seen, but cartilage and epithelial tissues are also common.

Treatment

The primary tumor should be removed. In young patients, the uterus and contralateral ovary should be preserved to maintain fertility. All patients with other than stage Ia grade 1 immature teratomas should receive postoperative chemotherapy using bleomycin, etoposide, and cisplatin. Three cycles of chemotherapy should be given for stage I disease.

Prognosis

Survival correlates with grade and stage of disease. The 5-year survival rate for patients with grade 1 immature teratomas is about 95%, compared with 80% for grade 2 and 60% to 70% for grade 3 disease.

OTHER GERM CELL TUMORS

The endodermal sinus tumor is a rare malignancy. It is also referred to as a yolk sac tumor. Endodermal sinus tumors produce AFP, which can serve as a useful serum marker for this neoplasm. Embryonal carcinomas produce both hCG and AFP, whereas choriocarcinomas produce hCG only. All occur in children and young women, and all grow rapidly. Bilateral tumors are rare.

Therapy for these lesions includes surgical resection of the primary tumor followed by systemic combination chemotherapy with bleomycin, etoposide, and cisplatin. Before the advent of effective chemotherapy, these tumors were usually fatal. The overall 5-year survival rate is now about 70% to 80%.

image Specialized Gonadal-Stromal Tumors

A group of relatively uncommon tumors is derived from the specialized ovarian stroma. As such, they are often endocrinologically functional, many of them being capable of synthesizing gonadal or adrenal steroid hormones. Because the ovarian stroma has sexual bipotentiality, hormones that are secreted can be either female or male. Estrogen and progesterone are typically associated with granulosa-theca cell tumors, whereas testosterone and other androgens may be secreted by many Sertoli-Leydig cell tumors. Rarely, lipid cell tumors, which are usually virilizing, produce adrenal corticoids and a clinical cushingoid syndrome.

PATHOLOGIC FEATURES

Granulosa cell tumors are the most common stromal carcinomas. They have a distinct histologic pattern: small groups of cells called Call-Exner bodies are the hallmark. They may secrete large amounts of estrogen and can be associated with endometrial cancer in adults or sexual pseudoprecocity in children.

Thecomas, which are only one third as common as granulosa cell tumors, are rarely malignant. Mixtures of the two types of tumor exist.

Sertoli-Leydig cell tumors (arrhenoblastomas) contain both Sertoli-type and Leydig-type stromal cells and are classically associated with masculinization. Only 3% to 5% of these tumors are malignant.

Lipid cell tumors are often referred to as hilar cell tumors because they are located in the ovarian hilus. Only a rare lipid tumor, usually larger than 8 cm in diameter, behaves in a malignant fashion.

TREATMENT

Most stromal tumors occur in postmenopausal women and are best treated by a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Conservation of the uterus and contralateral ovary is appropriate for carefully staged young patients with stage I disease provided that the possibility of an associated adenocarcinoma of the endometrium has been excluded by dilation and curettage. The tumors are not very chemosensitive.

PROGNOSIS

Granulosa cell tumors, which tend to grow slowly, are usually confined to one ovary at the time of diagnosis. The 5-year survival rate is about 90% for stage I disease. Recurrences are usually detected late and may result in death 15 to 20 years after removal of the primary lesion.

image Metastatic Cancers

About 4% to 8% of ovarian malignancies are metastatic, most commonly from either the gastrointestinal tract or the breast. The Krukenberg tumor is a specific type of metastatic tumor in which signet-ring cells are seen in the ovarian stroma histologically. Most Krukenberg tumors are bilateral and metastatic from the stomach. Rarely, it has not been possible to locate a primary focus, and removal of the ovarian disease has produced apparent cures.

image Fallopian Tube Carcinoma

Primary carcinoma of the fallopian tube accounts for only 0.1% to 0.5% of gynecologic cancers and is diagnostically confused with ovarian carcinoma. The incidence of fallopian tube carcinoma may be higher than previously suspected because some are misclassified as primary ovarian carcinomas. Most are adenocarcinomas, but sarcomas and mixed tumors can occur. There is no official staging system for fallopian tube carcinoma, but in general they are staged like ovarian cancer because the mode of dissemination is similar. Bilateral carcinomas are seen in 10% to 20% of patients.

CLINICAL FEATURES

Clinically, patients can present with a vaginal discharge that is typically watery in nature, as well as vaginal bleeding, pelvic pain, or some combination of symptoms. In postmenopausal patients, the vaginal discharge may be yellow, watery, and similar to that seen with a urinary fistula. Physical examination may reveal an adnexal mass but is often unremarkable. A fallopian tube cancer should be suspected in a postmenopausal patient whose bleeding or abnormal cytologic findings are not explained by endometrial or endocervical curettage. In most patients, the diagnosis is not made preoperatively.

TREATMENT

The treatment for fallopian tube carcinoma is total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Surgical staging should be performed in patients whose disease appears to be confined to the pelvis, and cytoreductive surgery is appropriate in patients with metastatic disease. Postoperatively, combination chemotherapy, including carboplatin and paclitaxel, is usually used for patients with stages II or IV disease.

PROGNOSIS

The prognosis for fallopian tube carcinoma is similar to that for ovarian cancer.

SUGGESTED READING

Armstrong D.K., Bundy B., Wenzel L., et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.

Berek J.S. Epithelial ovarian cancer. In: Berek J.S., Hacker N.F., editors. Practical Gynecologic Oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004:443-509.

Bristow R.E., Tomacruz R.S., Armstrong D.K., et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: A meta-analysis. J Clin Oncol. 2002;20:1248-1259.

Haber D. Prophylactic oophorectomy to reduce the risk of ovarian and breast cancer in carriers of BRCA mutations. N Engl J Med. 2002;346:1660-1661.

Ozols R.F., Bundy B.N., Greer B., et al. Phase III trial of carboplatin and paclitaxel versus cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194-3200.