Measurement of Other Tumor Markers
CA19-9 and carcinoembryonic antigen (CEA) are commonly used to follow mucinous tumors. However, the sensitivity and specificity of these markers are lower than those found with CA125 measurement.
Fine-needle aspiration
Fine-needle aspiration (FNA) is not routinely used in the evaluation of pelvic masses. Although it can easily be performed with ultrasound or CT guidance, FNA has limited diagnostic accuracy, especially in the evaluation of cystic structures. In a study of the use of FNA in 235 patients with cystic ovarian masses, 56% of the aspirates were devoid of diagnostic cells. The sensitivity for specific lesions ranged from 35% to 83%, and the specificity approached 100%.11 Thus, FNA is not accurate, and should rupture of the cyst contents occur, dissemination of malignant cells may result.
Biopsy
Rarely, a directed biopsy may be indicated in an individual whose imaging studies are consistent with advanced ovarian in-tra-abdominal disease and in whom surgery is contraindicated because of significant medical problems. A directed biopsy of a peritoneal tumor implant may be used to identify the histology of the tumor and thus assist in selecting appropriate nonsurgical management (e.g., initial or neoadjuvant chemotherapy) for ovarian cancer. Immunohistochemical staining profiles may provide additional information consistent with ovarian or peritoneal cancer.
Age-Specific Considerations in Patient Evaluation
Pelvic mass in prepubertal girls
Ovarian cysts occur in 2% to 5% of prepubertal girls.12 During the first months of life, ovarian cysts are generally functional cysts caused by maternal gonadotropin stimulation of the newborn ovary. Persistence of cysts or the finding of a solid or complex component (i.e., a component in which both cystic and solid elements are present) of the adnexal mass suggests other disorders, including Wilms tumors, neuroblastomas, or gastrointestinal tract abnormalities.
The older literature suggests a very high rate of malignancy for ovarian neoplasms in children, with germ cell tumors being the most frequent malignancy and dysgerminomas being the most common germ cell tumor.13 More recently, it was reported that in girls younger than 10 years who undergo surgery for an adnexal mass, 60% of the masses were not neoplasms, and two thirds of the neoplasms were benign.14 If there are signs of early sexual development, the child should be evaluated for precocious puberty or a hormonally functioning ovarian neoplasm.
If torsion of the adnexal mass is suspected, pelvic ultrasound may confirm this diagnosis. If a solid component of the adnexal mass is detected, the risk of a germ cell tumor must be considered and serum levels of appropriate tumor markers (i.e., AFP, LDH, and | -hCG) must be obtained.
Pelvic mass in adolescents
The differential diagnosis of a pelvic mass in an adolescent girl is broader than that for younger patients because adolescence is accompanied by functioning ovaries and the beginning of sexual activity. A pelvic mass may be caused by a benign neoplasm, a malignant neoplasm, an anatomic abnormality, or an ectopic pregnancy. Sexually transmitted disease (STD) and pelvic inflammatory disease (PID) must be included in the differential diagnosis.
The patient history should include questions about sexual activity, previous history of STD and PID, and use of contraception. Depending on the adolescent’s sexual activity, a vaginal examination may also be appropriate. Adolescents deny sexual activity for multiple reasons, but studies show that 50% of adolescent girls have had sexual intercourse by 17 years of age.15 In adolescents, a pelvic mass that is not associated with pregnancy may require further evaluation by abdominal CT or MRI. When anatomic abnormalities are suspected, the evaluation should include MRI. Genetic studies may also be indicated if a separate adnexal mass is found, because in 25% of the patients with a Y chromosome, dysgenetic gonads are malignant.16
Cystic Adnexal Masses
The majority of cystic adnexal masses are related to the normal physiologic ovary; such masses include follicular cysts, corpus luteum cysts, and theca-lutein cysts. Usually unilocular and less than 8 to 10 cm in diameter, cystic adnexal masses commonly resolve within 6 to 8 weeks. Combination monophasic oral contraceptive pills with progestin, as well as estrogen at a dose higher than 50 ^.g, are reported to reduce the risk of further ovarian cysts. The use of lower-dose oral contraceptives may be less effective.17,18
Theca-lutein cysts that occur in pregnancy are usually bilateral, large, and multicystic. They are associated with high | -hCG levels.3 Spontaneous resolution usually occurs post partum.
Cystic Teratoma
Overall, mature cystic teratomas (dermoid cysts) account for more than half of the ovarian neoplasms in children and adolescents younger than 20 years.19 These neoplasms usually range from 5 to 10 cm in diameter; 15% are bilateral. Because they arise from pluripotential germ cell lines, they may contain hair, teeth, sebaceous material, neural elements, and other tissues not usually found in the ovary. Some of these elements show unique imaging patterns (e.g., calcified materials on plain radiograph and fat density on pelvic ultrasound).
Malignant Neoplasms
The risk of ovarian malignant neoplasms is lower in adolescents than in younger children.14 In reports from referral centers, the rate of malignancy in ovarian neoplasms was 35% in prepu-bertal girls and adolescents; however, in community-hospital centers, the rate of malignancy was 10% in these patients.20
Germ cell tumors account for approximately 70% of the malignant ovarian tumors in girls younger than 15 years.14 Dysger-minomas are the most common such tumors, followed by immature or malignant teratomas, endodermal sinus tumors, embryonal carcinomas, and choriocarcinomas. Stromal tumors and epithelial carcinomas each make up 15% of the ovarian tumors.14
Miscellaneous Masses
Pregnancy luteomas, sclerotic ovaries, and endometriotic cysts occur in adolescent girls. These may be incidental findings on physical examination, or they may be associated with symptoms of pain or irregular menses. Torsion, rupture, or leakage of the content of these cysts and subsequent peritoneal irritation may cause the pain. Laparoscopy may be required for full evaluation of the condition that causes the pain.
Anatomic Abnormalities
Around the time of expected menarche, anatomic abnormalities in the development of the mullerian system can cause obstruction of the uterovaginal outflow tract, resulting in a pelvic mass. The anomalies include imperforated hymen, transverse vaginal septa, vaginal agenesis with normal functional endo-metrium, vaginal duplications with obstructing longitudinal septa, and obstructed uterine horns. If these anomalies cause a blockage of the vagina or the uterus, a mass may develop; such masses may result in cyclic pain, prompting these women to seek treatment.
Ectopic Pregnancy
In women younger than 17 years, approximately 82% of pregnancies are unintended; 75% of pregnancies are unintended in women 18 and 19 years of age.21 Ectopic pregnancy is associated with pelvic pain, an adnexal mass, and missed or irregular menses. The risk of ectopic pregnancy is increased in women who have a history of STD or PID, as well as in women who fail to use contraception; oral contraceptives lower the risk.
Inflammatory Processes
The differential diagnosis of a pelvic mass in adolescents includes several infectious processes. When a patient presents with fever, an elevated white cell count, and a lower abdominal, pelvic, or adnexal tender mass that is associated with cervical motion tenderness and mucopurulent cervical discharge, a tubo-ovarian abscess or pyosalpinx must be considered.Laparoscopy may be useful in confirming the diagnosis of PID; the clinical diagnosis of PID has been reported to be incorrect in up to one third of patients.22
Pelvic mass in women of reproductive age
The detection of an asymptomatic pelvic mass is frequent during the reproductive years because women undergo annual examinations for family planning and gynecologic cancer screening. The differential diagnosis includes all the conditions that may cause a pelvic mass in adolescents (i.e., cystic adnexal masses, cystic teratomas, malignant neoplasms, and ectopic pregnancy), as well as leiomyomas, endometriomas, and metastatic neoplasms involving the ovary.
In a series of 100 women undergoing laparotomy for a pelvic mass, the most common diagnoses by age group were cancer, reported in 56% in women 50 years of age or older; endometrio-sis, reported in 27% of women 31 to 49 years of age; and cystic teratomas, reported in 33% of women younger than 30 years. In women younger than 30 years, only 10% had an ovarian malignancy, and most of these were tumors of low malignant potential. Thus, most pelvic masses that occur during reproductive years will be benign uterine neoplasms or benign ovarian neoplasms.23
A pregnancy test is required in all women of reproductive age who present with a suspected pelvic mass. In pregnant women, the use of abdominal and pelvic CT scans must be avoided. If ultrasound studies are inconclusive, an MRI may help identify the source of the mass.5 If patient age, physical examination, and findings on ultrasound suggest malignancy, it is appropriate to measure epithelial serum tumor markers, such as CA125. However, elevated levels of CA125 may be associated with normal gynecologic conditions, as well as benign uterine and ovarian neoplasms. Risk of malignancy increases with patient age, positive family history, severity of symptoms, and number of imaging findings consistent with malignancy.
Uterine Neoplasms
Epidemiology Leiomyomas (fibroids) are the most common benign uterine neoplasm. They can also rarely arise from the ovary, the cervix, the pelvic ligaments, or other pelvic structures.
Leiomyomas are clinically apparent on examination in approximately 25% of women, but there is a marked difference in racial groups. In the United States, in women 25 to 44 years of age, the incidence rates of leiomyomas that were confirmed by ultrasound or hysterectomy were 8.9 for white women and 30.6 for black women per 1,000 women-years.24 When uteri are surgically removed for treatment of noncancerous presentations, pathologic examination reveals leiomyomas in 89% of black women and 59% of white women.25 Similar results are obtained when screening women with ultrasonography: by 50 years of age, more than 80% of black women and 70% of white women will show fibroids.26
Leiomyomas are hormonally dependent; thus, these benign neoplasms usually shrink after menopause. They also frequently increase in size during pregnancy, as well as with the use of high-dose exogenous estrogens and, occasionally, with tamoxifen.
Sarcomatous degeneration of leiomyomas is rare. The incidence is reported to range from 0.4% to 1.4%. However, rapid increase in the size of a leiomyoma raises concern, although the definition of rapid growth has not been quantified. In fact, in a retrospective review of 371 patients operated on for rapidly growing leiomyomas, the incidence of leiomyosarcoma was 0.23%. When rapidly growing leiomyoma was defined as an increase of 6 weeks’ gestational size over 1 year, none of 198 patients who satisfied this criterion were found to have a sarcoma.27
Clinical manifestations Most women with leiomyomas are asymptomatic, but symptoms may occur during the third and fourth decades. Leiomyomas, which are usually nontender, are most frequently found on clinical pelvic examination; but increasingly, they are identified by pelvic ultrasound during evaluation of nonspecific abdominal or pelvic symptoms.
Symptomatic patients may complain of pelvic discomfort, pressure, pain, menorrhagia, and dysmenorrhea. With degeneration or infarction, severe lower abdominal or pelvic pain develops. This may be associated with fever and an elevated white cell count. If the leiomyoma is pedunculated, torsion may cause severe pain, which may be intermittent. The pain may become part of a chronic pelvic pain pattern. Urinary symptoms include urinary frequency from extrinsic pressure on the bladder or, rarely, urinary retention secondary to urethral obstruction from a cervical or lower uterine leiomyoma. Depending on the location and the size of the leiomyoma, rectosigmoid compression and constipation may develop.
Leiomyomas coming through the cervical os can cause severe cramping; if necrotic, a foul vaginal discharge may develop. Abnormal uterine bleeding may be associated with a leiomyoma that disrupts the endometrial lining; the bleeding associated with a leiomyoma is cyclic, occurring in response to ovarian hormones.
Leiomyomas are usually discrete, firm, rounded, rubbery masses; they can vary in size from several millimeters to masses large enough to fill the abdominal pelvic cavity. They can be hard (if calcified) or soft (if cystic). Usually they cause an asymmetrical enlargement of the uterus, but multiple small leiomyomas cause a symmetrically enlarged uterus. Within the uterus, the leiomyoma may be located within the myometrium, beneath the endometrial lining, or on the surface of the uterus. When pe-dunculated or located posterior in the cul-de-sac, leiomyomas can give the clinical impression of a solid adnexal mass.
Ovarian Neoplasms
About two thirds of all ovarian neoplasms are discovered during the reproductive years; however, in women younger than 45 years, the chance that such neoplasms are malignant is 5% to 18%.23,28,29 The most common ovarian neoplasms are endometri-omas, cystic teratomas, and epithelial ovarian neoplasms. Most ovarian neoplasms produce few specific symptoms, the most common being vague abdominal pelvic pain or discomfort, abdominal distention, pelvic pressure, and urinary or gastrointestinal symptoms. Occasionally, in hormonally active neoplasms, irregular vaginal bleeding may occur.
Endometriomas Endometriomas are benign ovarian masses arising from ectopic endometrial tissue. Their incidence has not been determined. Frequently, endometriomas partially or almost completely replace normal ovarian tissue. Bilateral involvement of the ovaries has been reported in one third to one half of cases.30 Endometriomas, which are usually less than 15 cm in diameter, may spontaneously rupture or resolve.
Patients who have an endometrioma usually complain of pelvic pain, dysmenorrhea, and dyspareunia; often, patients have an established history of endometriosis and infertility. On imaging evaluation, a mass 6 to 8 cm in diameter may be found. Endometriomas may by characterized by septations, debris, or solid components. These masses may not resolve over time. Endometriomas may be accompanied by an elevation in the CA125 serum level, which may cause concern regarding a malignancy; generally, however, CA125 serum levels associated with endometriomas are less than 200 U/ml.
Cystic teratomas Cystic teratomas, or dermoid cysts, are benign ovarian germ cell tumors. More than 80% of cystic ter-atomas are diagnosed during the reproductive years.31 In a 10-year retrospective review, cystic teratomas constituted 62% of all ovarian neoplasms in women younger than 40 years.29 The malignant transformation of these tumors is less than 2% and mostly occurs in women older than 40 years. There is a 15% risk of torsion and a 10% chance of bilateral presentation.
The risk of epithelial ovarian neoplasms increases with age. Bilateral ovarian neoplasms carry a 2.6-fold increased risk of malignancy, as compared with unilateral neoplasms.29 Other causes of ovarian enlargement in this age group include metastatic cancer, especially from the breast or the gastrointestinal tract.
Pelvic mass in postmenopausal women
A pelvic mass in postmenopausal women may arise from the gynecologic organs, but increasingly in this age group, a mass may arise from nongynecologic organs. With decreasing ovarian hormone production, leiomyomas should undergo regression, and functional ovarian cysts are less likely. Endometriotic tumors are also not usually found in this age group. Thus, a newly found pelvic mass raises the suspicion of a malignancy.
Epidemiology The incidence of ovarian cancer increases with age, and 30% to 60% of ovarian masses in women older than 50 years are malignant.23 The average age of a woman when diagnosed with ovarian cancer is 56 to 60 years. The majority of these tumors are epithelial malignancies. Fallopian tube cancer is rare. The differential diagnosis for a pelvic mass in postmenopausal women includes colon cancer, which is the third most common cancer in women.
Ovarian cysts have been reported in 3% to 17% of asymptomatic postmenopausal women undergoing pelvic ultrasound. In a study of 83 patients with thin-walled ovarian cysts less than 5 cm in diameter, 43 underwent surgery; no ovarian cancers were found in this group. In the remaining patients, 32 underwent serial ultrasound studies. In this group, 12 cysts resolved, seven decreased in size, four remained unchanged, and one increased slightly in size. The remaining eight patients underwent cyst aspirations; all the aspirated cysts were benign.32
Clinical manifestations The presentation of ovarian cancer is not specific. Patients may complain of vague gastrointestinal symptoms, including dyspepsia, early satiety, anorexia, bloating, and, occasionally, constipation. In a retrospective survey of 1,725 patients with ovarian cancer, 95% reported symptoms that were categorized as abdominal (77%), gastrointestinal (70%), pain (58%), constitutional (50%), urinary (34%), and pelvic (26%).33 Fallopian tube cancer may present as uterine bleeding, pelvic pain, and an adnexal mass. Classically, profuse watery vaginal discharge is seen, although this finding is rare.
The findings on examination consistent with advanced disease include abdominal distention with ascites, an abdominal/pelvic mass, and nodularity in the cul-de-sac on rectovagi-nal examination. An ultrasound of the abdomen and pelvis may show ascites, bilateral complex adnexal masses, and omental implants. In addition, there may be a pleural effusion. Evaluation of these patients should include abdominal and pelvic CT scans and chest x-ray. Again, if imaging studies raise the suspicion of malignancy, it is important to measure serum levels of CA125. An elevated CA125 level in postmenopausal women with a pelvic mass suggests a malignancy, because the positive predictive value for elevated CA125 (i.e., > 65 U/ml) in this age group has been reported to be 97%.10 Early referral to a gynecologic oncologist is appropriate for patients with a mass that raises suspicion of malignancy.
A pelvic ultrasound may also identify nonmalignant cysts. Studies have suggested that women with simple cysts that are less than 10 cm in diameter and that are without any excrescences, septations, or ascites should undergo serial ultrasound studies.
A pelvic mass in a postmenopausal woman with a history of bowel symptoms may suggest colon cancer; the evaluation of the stool may be positive for occult or frank blood. Diverticular disease must also be considered.
Management
The management of a pelvic mass depends on the patient’s age, history, tumor characteristics, and likelihood of malignancy. For all age groups, surgery is required for masses that are greater than 10 cm in diameter and for those that are solid, fixed, or bilateral. When these findings are accompanied by significantly elevated levels of tumor markers, the presence of ascites, or a finding on imaging or physical examination that suggests malignancy, the patient should be referred to a gynecologic oncologist.
Infants and prepubescent girls
Infants and prepubescent girls with suspected physiologic or functional cysts should undergo serial ultrasound studies approximately every 6 weeks. Aspiration of unilocular cysts in prepubescent girls, either with ultrasound guidance or lap-aroscopy, is associated with a 50% recurrence rate3 and is usually not recommended. If the mass increases in size, persists after 6 months, or becomes complex, surgery via either laparotomy or laparoscopy is necessary. Conservative management is indicated if the malignancy is confined to one ovary. Consultation with a gynecologic oncologist is necessary.
Adolescent girls
The management of adnexal masses in adolescent girls should have as its aim the preservation of ovarian function. An asymptomatic simple cyst that measures less than 10 cm in diameter may be observed and followed with serial ultrasound studies. To prevent new formation of physiologic cysts, ovarian suppression with oral contraception should begin. If the cyst increases in size, becomes complex, or causes symptoms, then surgery should be performed.
For benign neoplasms, cystectomy is recommended. Because most malignant tumors are unilateral, only the ovary or adnexa need be removed. The contralateral ovary should be inspected. If the ovary appears grossly normal, biopsy need not be performed, nor should the ovary be bivalved (i.e., the surface of the ovary divided and the cortex inspected), because these procedures could lead to peritubal or periovarian adhesions. However, if suspicious areas are identified, biopsies must be performed and a frozen section ordered for histiologic analysis during surgery. Histiologic analysis will help determine malignancy and indicate the need for consultation with a gynecologic oncologist to establish surgical staging. If the frozen section does not clearly establish malignancy, a second surgery is preferable to performing unnecessary initial surgery. However, the choice of surgery should be undertaken cautiously, because any adnexal surgery may result in tubal adhesions, which could interfere with future fertility.
PID in adolescents should be managed medically. Surgical management of nonmalignant presentations is rarely indicated in adolescents. Surgery, however, may be required to treat a ruptured tubo-ovarian abscess; it may also be required if the disease fails to respond to broad-spectrum antibiotics. Ectopic pregnancy can be managed medically, providing the pregnancy is small and the patient is hemodynamically stable; surgical management is required if these conditions are not met. If surgery is indicated, the procedure should be conservative and aimed at preserving fertility.
Women of reproductive age
The management of a pelvic mass in women of reproductive age will depend on the malignant potential of the mass. Most often, the mass will be a benign uterine leiomyoma. The initial approach will depend on whether the patient is symptomatic and has completed childbearing.
Leiomyomas Asymptomatic leiomyomas should be followed with periodic pelvic examinations to ensure that there is not a rapid growth in size. The clinical records should document the location; a pelvic ultrasound can more accurately estimate the size. Rapid growth in the postmenopausal years may indicate transformation into a sarcoma. The risk, however, is reported to be less than 2 to 3 per 1,000.
In patients who will soon enter menopause or who are planning to undergo surgery for mildly symptomatic leiomyo-mas, hormonal therapy using gonadotropin-releasing hormone (GnRH) analogues results in a 40% to 60% decrease in uterine volume. GnRH treatment causes hypoestrogenic states that result in bone loss and hot flashes. Regrowth of the leiomyoma occurs within a few months of treatment cessation in one half of patients. Use of GnRH may be considered (1) as neoadjuvant therapy to shrink the size of the leiomyoma before surgery to permit a vaginal approach, (2) as treatment for anemia secondary to hemorrhage associated with leiomyomas, and (3) as treatment in perimenopausal women in an effort to avoid surgery.
Symptomatic leiomyomas require surgery. The usual indications include abnormal uterine bleeding with anemia that is unresponsive to hormone therapy; chronic pelvic pain with dys-menorrhea and dyspareunia; acute pelvic pain associated with torsion of pedunculated leiomyoma; prolapsing leiomyoma; urinary frequency with hydronephrosis; and symptoms of pelvic or rectal pressure caused by a significantly enlarged leiomyoma. Rarely, infertility caused by a leiomyoma obstructing the fallopian tubes or loss of a pregnancy secondary to a leiomyoma may be an indication for myomectomy. The finding of a mass during pregnancy demands the same management approach as for a nonpregnant patient. If surgery is necessary during pregnancy, the second trimester is the safest period.
Once childbearing is complete, hysterectomy is traditionally the definitive management for symptomatic leiomyomas. However, other treatment options have become available, including laparoscopic myomectomy and hysteroscopic resection of sub-mucosal leiomyoma. In addition, endometrial ablation (e.g., laser, thermal, or chemical ablation, as well as selective arterial em-bolization) can decrease the bleeding caused by intramural leiomyomas.36
Endometriomas Endometriomas that do not spontaneously resolve are managed with surgical excision.
Cystic teratomas In women younger than 45 years, the treatment for a cystic teratoma is ovarian cystectomy, which often can be performed laparoscopically, especially if the mass is less than 10 cm in diameter.
Epithelial ovarian neoplasms Surgical management of epithelial ovarian neoplasms includes removal of the adnexa and surgical staging. Whether the surgery can be conservative (i.e., a unilateral salpingo-oophorectomy) will depend on the extent of the disease and the degree of malignancy (i.e., invasive tumor versus tumor of low malignant potential). These decisions are made in consultation with a gynecologic oncologist.
Postmenopausal women
The risk of a malignancy increases with age, and thus, the threshold for conservative management decreases in post-menopausal women. It has been reported that a suspicious mass seen on ultrasound combined with a CA125 level greater than 65 U/ml has a specificity of 96.1%, a sensitivity of 91.7%, and an accuracy of 94.3% for detecting an ovarian neoplasm in postmenopausal women.37 On the other hand, a postmenopausal woman with an ovarian simple cyst that is less than 5 cm in diameter and a normal CA125 serum concentration has a 0% risk of malignancy. Thus, the former patient should be referred to a gynecologic oncologist for appropriate management, whereas the latter may be followed with serial ultrasound studies every 4 to 6 months for a year and, provided the tumor remains stable and the patient asymptomatic, annually thereafter.
