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Practical CME Newsletter for Clinicians

Adnexal masses, defined as masses of the ovary, fallo-pian tube, or surrounding connective tissue, are a common problem encountered in routine gynecologic practice. In the United States, up to 300,000 women are hospitalized, and 60,000 surgeries are performed annually, for evaluation of an adnexal mass.1 Most women are diagnosed with benign conditions; however, epithelial ovarian cancer (EOC) is identified in up to 20% of these patients.2 The risk of devel-oping ovarian cancer in a woman’s lifetime is approximately 1 in 70. Although the 5-year survival rate in women diag-nosed with stage I ovarian cancer exceeds 90%, only 20% of cancers are detected at this early stage. The majority of EOC is diagnosed at advanced stage, when the 5-year sur-vival rate ranges from 30% to 55%.3

There is clear evidence that women with EOC have decreased morbidity and improved survival when surgeons experienced in gynecologic oncology cases perform the initial surgery.4 However, there is a gap in the ideal manage-ment of such patients when referral or consultation with a gynecologic oncologist is not sought preoperatively. This goal of this article is to address this gap by reviewing the patient risk factors, physical examination findings, imaging modalities, and serum markers that should guide the initial

workup and evaluation of new adnexal masses and lead to more effective referral to a gynecologic oncologist. Finding the proper balance of appropriate referral without overtest-ing and performovertest-ing unnecessary surgery is a key component of workup and evaluation of patients with adnexal masses.

First Steps of Evaluation: Developing a

Useful Differential Diagnosis

Workup and evaluation of an adnexal mass may be prompted by patient symptoms, incidental findings on workup for another issue, or physical examination findings on routine examination. Thinking through the first steps of an evaluation requires attention to differential diagnosis, which can be a broad list of conditions.

Adnexal masses, although much less common in children and adolescents than in reproductive-age women, may be consistent with malignancy. The most common type of ovar-ian malignancy in this population is germ cell tumors. In neonates, a physiologic cyst from maternal hormone stimu-lation will typically resolve by 6 months of age. After the neonatal period and before adolescence, physiologic cysts are generally not seen, but when present are often the result of enlargement of a cystic follicle. In adolescents, the devel-opment of simple and complex cysts is much more common, with the differential diagnosis expanding to include imperfo-rate hymen or noncommunicating uterine horn, cystadenomas, paratubal cysts, hydro or pyosalpinx, ectopic pregnancies, and appendicitis. As in adults, ultrasonography is the primary tool for initial evaluation. The use of biomarkers, and improvements in radiographic imaging as part of the initial

Learning Objectives: After participating in this CME activity, the obstetrician/gynecologist should be better able to:

1. Demonstrate understanding of the differential diagnosis and initial workup of adnexal masses.

2. Implement appropriate imaging follow-up and understand the role and limitations of biomarker screening. 3. Identify patients who warrant referral to a gynecologic oncologist.

Key Words: Adnexal mass, Biomarkers, Ultrasonography

Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should

only claim credit commensurate with the extent of their participation in the activity.

To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly. This activity expires on January 30, 2017.

Dr. MacGregor is Clinical Instructor of Obstetrics and Gynecology, and Dr. Cronin is Assistant Professor (Clinical) of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, 101 Dudley St, Providence, RI 02906; E-mail: bcronin@wihri.org.

The authors and all staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations per-taining to this educational activity.

Evaluation and Management of Adnexal Masses

Caitlin MacGregor, MD, and Beth Cronin, MD

TOPICS IN

OBSTETRICS & GYNECOLOGY

TOPICS IN

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evaluation of complex adnexal masses, has facilitated a more conservative approach to the management of neoplasms in children and adolescents. Ovarian preservation is the standard of care except in the setting of a cancer diagnosis.

In premenopausal women, gynecologic causes of an adnexal mass include acute pathologic processes such as ovarian torsion, tubo-ovarian abscess (TOA), and ectopic preg-nancy. Chronic or nonacute causes include a functional or corpus luteal cyst (most com-monly); endometrioma; uterine leiomyoma; or a benign ovarian neoplasm such as a der-moid cyst. Gastrointestinal manifestations such as diverticulitis, appendicitis, peritoneal or omental cysts, or malignancy also should be considered. Metastases from other pri-mary cancers must be included in the dif-ferential diagnosis.1 Differential diagnosis in postmenopausal women is similar, aside from exclusion of pregnancy-related causes.

Acute Presentation of Adnexal

Masses

Case 1. A 22-year-old G0 presents with

acute onset of right lower quadrant pain. She notes severe pain that started 2 hours ago. She notes nausea. She does not have vomiting or fever.

For women presenting emergently with lower abdominal pain, adnexal mass should be high on the list of differential diagnoses. In the acute setting, this list should include ovarian torsion, ectopic pregnancy, ruptured cyst, TOA, and nongy-necologic issues such as appendicitis. The initial workup in these cases should involve a full history and physical examination, pregnancy test, complete blood count, and pelvic ultrasonography. Pain control as may

be required to facilitate the evaluation should be provided.

Ectopic pregnancy generally presents as a missed menstrual period in the setting of pel-vic pain and/or vaginal bleeding. The finding of an adnexal mass in a pregnant patient without a confirmed intrauterine pregnancy should be considered an ectopic pregnancy until proven otherwise. Immediate evaluation and treatment are required for this poten-tially life-threatening condition. Sonographic evidence suggestive of an ectopic preg-nancy includes lack of yolk sac or fetal pole within the uterine cavity, a noncystic adnexal mass, and possibly echogenic peritoneal free fluid.

Ovarian torsion is caused by complete or partial rotation of the ovary on its support ligaments, which often impedes its vascular supply. Common causes of torsion include ovarian cysts, neoplasms, elongated utero-ovarian ligament, and pregnancy. Rotation of the ovary’s vascular pedicle, the infundibu-lopelvic ligament, causes compression of both lymphatic and venous outflow and arte-rial inflow. Artearte-rial flow is impeded less, which ultimately leads to ovarian swelling and enlargement followed by ischemia and necrosis if left untreated. An ovarian mass is the primary risk factor for torsion, with ovar-ian size greater than 5 cm increasing risk.5

Presenting symptoms of ovarian torsion include pelvic pain, adnexal mass, nausea and vomiting, fever, and vaginal bleeding. On ultrasonography, the torsed ovary may be rounded and enlarged compared with the contralateral ovary and may display hetero-geneous stroma secondary to edema and hemorrhage. Decreased or absent Doppler flow within the ovary on 2-dimensional, color, and 3-dimensional Doppler ultrasonography

EDITORS

William Schlaff, MD

Professor and Chair, Department of Obstetrics and Gynecology, Thomas Jefferson Medical College, Philadelphia, Pennsylvania

Lorraine Dugoff, MD

Associate Professor and Chief, Division of Reproductive Genetics, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania FOUNDING EDITORS Edward E. Wallach, MD Roger D. Kempers, MD ASSOCIATE EDITORS Meredith Alston, MD Denver, Colorado Samantha Buery-Joyner, MD

Falls Church, Virginia

Nancy D. Gaba, MD Washington, DC Jennifer Goedken, MD Atlanta, Georgia Veronica Gomez-Lobo, MD Washington, DC Star Hampton, MD

Providence, Rhode Island

Enrique Hernandez, MD

Philadelphia, Pennsylvania

Nancy Hueppchen, MD

Baltimore, Maryland

Bradley S. Hurst, MD

Charlotte, North Carolina

Peter G. McGovern, MD

New York, New York

Owen Montgomery, MD Philadelphia, Pennsylvania Christopher M. Morosky, MD Farmington, Connecticut William D. Petok, PhD Baltimore, Maryland James M. Shwayder, MD, JD Jackson, Mississippi

The continuing education activity in Topics in Obstetrics & Gynecology is intended for obstetricians, gynecologists, and other health care professionals with an interest in the diagnosis and treatment of obstetric and gynecological conditions.

Topics in Obstetrics & Gynecology (ISSN 2380-0216) is published 18 times per year by Lippincott Williams & Wilkins, Inc., 16522

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were to improve patient care, decrease unnecessary imag-ing, and reduce patient anxiety.8 In premenopausal women, simple cysts smaller than 10 cm are almost always benign. Simple cysts larger than 3 cm should be described in the imaging report. Simple cysts 5 cm or smaller are normal and do not require ultrasonographic follow-up, whereas those larger than 5 cm should be followed yearly with ultra-sonography. If a simple cyst is larger than 7 cm, it may be difficult to assess completely with ultrasonography; further imaging with MRI, or surgical excision, is indicated. In postmenopausal women, simple cysts 1 cm or smaller in size are clinically inconsequential and do not require fol-low-up. However, yearly follow-up is warranted if a simple cyst is between 1 cm and 7 cm in size, with the option to decrease frequency of ultrasonography once stability is documented. Simple cysts larger than 7 cm should be man-aged similarly to those in premenopausal women.

Complex cysts are generally benign and are most often characterized as hemorrhagic cysts, endometriomas, or der-moid cysts. The classic ultrasonographic feature of hemor-rhagic cysts is a reticular pattern of echoes that has a lacy appearance secondary to fibrin deposition. These should resolve without intervention; however, if larger than 5 cm, they should be re-imaged within a short interval (6–12 weeks) to ensure resolution. Given that hemorrhagic cysts are the result of ovulation, frankly menopausal patients should not have hemorrhagic cysts; if found, surgical evaluation should be considered. Perimenopausal and newly menopau-sal patients will occasionally ovulate, and short-interval fol-low-up is recommended to ensure resolution (regardless of size) rather than surgical evaluation.

Endometriomas generally demonstrate internal, homoge-neous, ground-glass echoes without internal Doppler flow, wall nodules, or other neoplastic features. Initially, short-interval follow-up with ultrasonography is recommended to exclude hemorrhagic cysts, followed by yearly ultra-sonographic follow-up. Approximately 2.5% of endome-triomas are malignant, although this is mostly in women suggests torsion. The sensitivity of ultrasonography ranges

from 46% to 75% for the diagnosis of ovarian torsion and is made more sensitive when combining multiple sonographic findings, such as abnormal ovarian location, free fluid, and abnormal blood flow.6 Diagnosis of ovarian torsion is clinical, made from a combination of history, physical, and possibly sonographic findings. However, a clear story and concerning examination results in the absence of ultrasonographic find-ings to suggest torsion should not halt surgical evaluation if suspicion is high, as that is the only way to make a definitive diagnosis.

Classic presentation of a ruptured cyst is acute onset of pelvic pain in the mid-menstrual cycle, typically after inter-course. Free fluid in the adnexa or posterior cul-de-sac is generally seen on ultrasonography. A cyst may become hem-orrhagic without rupture. If there is concern for brisk bleeding causing anemia or hemodynamic instability, surgical inter-vention is indicated, but in general, a ruptured cyst can be managed conservatively if adequate pain control is attained.

TOA is also a cause of acute onset of abdominal pain. Its course is generally more indolent, and often patients present with fever, chills, vaginal discharge, lower abdominal pain, and an adnexal mass. Ultrasonographic findings consistent with TOA include a complex, multilocular mass that can obliterate the normal adnexal anatomy, with fluid-contain-ing internal echoes representfluid-contain-ing internal debris.7 Timely initiation of treatment with broad-spectrum antibiotics and possible drainage is necessary to prevent sepsis or further damage to the adnexa. In the case of an unstable patient with findings concerning for ruptured TOA, surgical evalu-ation is the first-line treatment.

Case 1 disposition. First steps in management include

physical examination, pregnancy test, ultrasonography, and pain control as indicated.

Nonacute Presentation of Adnexal Masses

Case 2. A 32-year-old G1P1001 presents for her annual

examination. She is noted to have some fullness on pelvic examination. This is a nonacute presentation of an adnexal mass.

Imaging

Transvaginal ultrasonography is currently the most com-mon and preferred initial imaging modality to evaluate adnexal masses. Premenopausal ovaries vary in appearance throughout the menstrual cycle. Follicles appear as multi-ple, thin, smooth-walled, round or oval, anechoic spaces with no flow on Doppler studies. Multiple developing fol-licles then become one or more dominant follicle. The dominant follicle, generally 2 to 2.4 cm at ovulation, becomes a corpus luteum after ovulation. In contrast, follicu-logenesis has ceased in the postmenopausal ovary. Overall volume is decreased, and the postmenopausal ovary appears homogeneous in echotexture.

In October 2009, the Society of Radiologists in Ultrasound met to develop an evidence-based consensus statement regarding definitive recommendations for monitoring adnexal ultrasonographic findings (Table 1). The goals

Table 1. Summary of Recommendations for Simple Cysts Premenopausal Postmenopausal

≤3 cm: normal finding, does not need follow-up, no need to describe in report

<1 cm: clinically inconsequential, does not need follow-up >3 cm and ≤5 cm: describe in

report as almost certainly benign, does not need follow-up

>1 cm and ≤7 cm: describe in report as almost certainly benign, yearly follow-up initially, may continue yearly or decrease when stable or decreased in size

>5 cm and ≤7 cm: describe in report as almost certainly benign, yearly follow-up with ultrasonography

>7 cm: difficult to assess completely with ultrasonography, further imaging with MRI or surgical evaluation

>7 cm: MRI or surgical evaluation

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older than 45 years with endometriomas larger than 9 cm.9 Development of solid components or a rapid increase in size should be a red flag for clinicians.

Classic ultrasonographic features of dermoid cysts (mature cystic teratomas) are focal or diffuse hyperechoic compo-nents, hyperechoic lines, an area of acoustic shadowing, and absent internal Doppler flow. These findings reflect a der-moid’s cystic and mature tissue composition such as skin, hair follicles, sebaceous glands, and muscle. Dermoid cysts are bilateral in 10% to 17% of cases. Ultrasonographic fol-low-up is recommended every 6 to 12 months to ensure size stability. Indeterminate features should be followed more closely. Postmenopausal women with features of dermoids should be referred for surgical evaluation. The rate of malignant components in a dermoid cyst is about 0.2% to 2%, with women older than 50 years and with tumors larger than 10 cm most likely to be affected.10 Features that are concerning for malignancy include isoechoic branching structures, solid areas with flow, and evidence of invasion into adjacent structures. In general, thick septations, solid elements with internal flow, focal areas of wall thickening, ascites, and nodularity are concerning for malignancy and warrant further investigation.

Peritoneal inclusion cysts and hydrosalpinges are also common ultrasonographic findings seen in the evaluation for adnexal masses. In general, peritoneal inclusion cysts are seen in women with a history of abdominal or pelvic surgery, pel-vic inflammatory disease, or endometriosis. On ultrasonogra-phy, a peritoneal inclusion cyst appears as a cystic mass that follows the contour of adjacent pelvic organs, with the ovary at its edge or suspended within the mass. If ultrasonographic findings are classic for an inclusion cyst, no further follow-up is indicated. Hydrosalpinges appear as tubular-shaped cystic masses that may have short, round projections or indentations on opposite sides of the mass. In general, they should be separate from the ipsilateral ovary. Similar to peritoneal inclu-sion cysts, if there are classic features for hydrosalpinx, no follow-up is indicated unless symptoms develop. However, if the patient also presents with infertility, referral to a reproduc-tive endocrinologist is indicated.

CT and MRI are not recommended for the initial workup of adnexal masses. These modalities should be reserved for specific indications, such as use of CT to evaluate the abdo-men for metastases when cancer is suspected on the basis of ultrasonographic findings, physical examination, or serum biomarkers. Peritoneal implants, pelvic and periaortic lym-phadenopathy, omental caking, obstructive uropathy, and a possible different primary cancer site are all examples of important CT findings. MRI may have superior ability compared with transvaginal ultrasonography at classifying malignant masses, although the data are limited, and overall there is a lower detection rate.11 Expense and inconvenience are frequent barriers to the use of these modalities. During pregnancy, MRI is a helpful modality to decrease radiation exposure to the developing fetus.

Ultrasound-guided aspiration of ovarian cysts for diagnosis and treatment may seem to be a practical next step in the workup of cystic adnexal masses. Indeed, it is less expensive,

less invasive, and provides diagnostic results sooner than surgical intervention. However, aspiration is contraindicated in postmenopausal women, especially when there is concern for malignancy. The sensitivity of diagnostic cytology to detect malignancy ranges from 25% to 82%.12

Case 2 disposition. You perform ultrasonography, which

shows a 4-cm simple cyst. Follow-up imaging is not required in this premenopausal woman with a simple cyst smaller than 5 cm.

Biomarkers

Serum biomarkers can be a useful addition to the initial workup and evaluation of new adnexal masses in helping to distinguish benign from malignant disease. CA-125 is a glycoprotein produced by the mesothelial cells lining the peritoneum, pericardium, and pleura, which is elevated in approximately 80% of women with EOC.13 However, only 50% of patients with stage I disease have an elevated CA-125 level at the time of diagnosis, thus precluding its use as a screening test.14 Many conditions can cause an increase in CA-125 level, including menses, pregnancy, cirrhosis, ascites, congestive heart failure, acute or chronic pelvic inflamma-tory disease, fibroids, and endometriosis. The reported sensi-tivity of CA-125 testing to differentiate between benign and malignant adnexal masses ranges from 61% to 90%, with specificity ranging from 35% to 91%.1

With regard to nongynecologic etiology, both carbohy-drate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are helpful biomarkers. CA 19-9 level can be ele-vated in association with gastric, gallbladder, and pancreatic cancers. CEA level can be raised in patients with mucinous cancers associated with the gastrointestinal tract or ovary. Elevated serum CEA can be documented in patients with breast, pancreas, thyroid, and lung malignancies. Other condi-tions associated with elevated CEA level include pancreatitis, inflammatory bowel disease, pancreatitis, diverticulitis, chol-ecystitis, pulmonary infection, liver cirrhosis, cigarette smok-ing, and mucinous cystadenoma of the appendix or ovary.15

Various tools are available that combine serum biomark-ers with ultrasonographic findings to calculate preopera-tive risk of malignancy; however, none have been widely adopted at this point. The Risk of Ovarian Cancer Algorithm (ROCA) categorizes women as at low, intermediate, and high risk, and recommendations for care are stratified into annual follow-up, repeat serum CA-125 testing, or trans-vaginal ultrasonography, depending on score.16 The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial was a large randomized controlled trial that evaluated the effect on mortality of screening with CA-125 testing and trans-vaginal ultrasonography. There were an increased number of ovarian cancer diagnoses in the intervention group com-pared with the usual care group, but the screening interven-tion had no effect on mortality rate. An increased rate of adverse effects was associated with diagnostic evaluation of women with false-positive screening results.17 At this time, the Society of Gynecologic Oncology (SGO) does not rec-ommend routine CA-125 testing with or without trans-vaginal ultrasonography to screen low-risk women. SGO

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Although nonspecific, these symptoms are typically present for less than a year and occur more than 12 days per month. Pregnancy

Before the widespread use of ultrasonography, many adnexal masses went unrecognized during pregnancy unless they became symptomatic. Now, many asympto-matic adnexal masses are seen on dating or growth ultra-sonography in the first half of pregnancy. In addition to ectopic pregnancy, there are several adnexal masses that are uniquely associated with pregnancy.

Corpus luteal cysts are commonly seen with an early intrauterine pregnancy and help support the growth of the developing pregnancy. Typically, these cysts are less than 2.5 cm; however, they may become painful or enlarged secondary to hemorrhage within corpus luteum. A luteoma is a nonneoplastic ovarian change associated with the increases of sex hormones, particularly of progesterone and testosterone, during pregnancy that simulates a neoplasm on microscopic, gross, or clinical examination.26 Luteomas spontaneously involute postpartum and should be sus-pected in pregnant women with an adnexal mass and signs of virilization. Theca lutein cysts are luteinized follicle cysts associated with pregnancy. They result from over-stimulation associated with high beta-HCG levels or increased sensitivity of beta-HCG. Suspicion for a theca lutein cyst should be raised in a pregnant woman with bilat-eral multiseptated adnexal masses, multiple gestations, ovarian hyperstimulation, or gestational trophoblastic dis-ease. These cysts resolve spontaneously in the weeks to months after removal of the beta-hCG source.

Other causes of adnexal masses are similar to those for reproductive-age women. Asymptomatic adnexal masses in pregnancy should be resected if they are larger than 10 cm in diameter, solid, or contain solid or cystic areas with or with-out septae, as these findings increase the likelihood of malig-nancy.27,28 Furthermore, resection of large adnexal masses, regardless of whether the underlying cause is benign or malignant, reduces the risk of torsion or rupture during preg-nancy. The optimal timing of surgery for adnexal masses is after the first trimester, when most functional cysts will resolve, organogenesis is complete, and placental takeover of hormonal production from the corpus luteum has occurred.

Referral to Gynecologic Oncology

Research has shown that there is improved morbidity and mortality when patients diagnosed with EOC have their ini-tial surgery performed by a gynecologic oncologist. Guidelines for referring a woman with a new pelvic mass to gynecologic oncology have been created by both the American College of Obstetricians and Gynecologists and SGO (Table 2).

Im et al29 validated these referral guidelines in a study of 1035 women who underwent surgery for a pelvic mass at 6 referral centers. Primary ovarian cancers were found in 30.7% of the cases, and an additional 4.8% of patients had metastases to the ovary. The referral guidelines captured 70% of malignancies in premenopausal women and 94% in postmenopausal women.

recommends that cost-effectiveness analysis be performed before a universal screening program is adopted.18

Ova1 is another tool developed to identify high-risk ovar-ian tumors preoperatively. It measures CA-125, beta 2-microglobulin, transferrin, apolipoprotein A1, and tran-sthyretin levels. OvaCalc software assigns a score on the basis of menopausal status. In a trial of 516 women referred for surgery for adnexal masses, sensitivity and specificity were 92.5% and 42.8%, respectively.19 A more recent study of 590 women with various malignancies (including none-pithelial ovarian cancer, enone-pithelial ovarian cancer, malig-nancies metastatic to the ovary, pelvic cancer, and border-line tumors), Ova1 had a higher sensitivity to detect ovarian cancer than CA-125 level and physician assessment.20

Human epididymis protein 4 (HE4) is a newer serum biomarker for EOC, which is overexpressed by EOC tumors, creating elevated serum levels. Its sensitivity is similar to CA-125 level for detection of malignancy; how-ever, it is much less likely to be elevated in benign condi-tions.21 An initial study by Moore et al22 led to the develop-ment of the Risk of Malignancy Algorithm (ROMA), which is a scoring system that incorporates serum levels of CA-125 and HE4 with menopausal status. ROMA score was evalu-ated as a preoperative risk stratification tool and found to have sensitivity of 92.3% and specificity of 76% for detect-ing EOC in postmenopausal women, and it had 100% sen-sitivity and 74.2% specificity in premenopausal women.22

In children and adolescents, there are additional biomark-ers for consideration. Alpha-fetoprotein is an oncofetal antigen found in endodermal sinus tumors, immature terato-mas, and mixed germ cell tumors. Lactate dehydrogenase (LDH) level is often elevated in association with dysgermi-nomas. Human chorionic gonadotropin (hCG) level is ele-vated in patients with embryonal ovarian carcinomas and nongestational choriocarcinoma. CEA can be elevated in association with both epithelial or germ cell tumors. Inhibin- and müllerian-inhibiting substance levels are raised in patients with granulosa-theca cell tumors.

Special Considerations

Patient History

Specific patient risk factors should increase one’s suspi-cion for malignancy. The incidence of malignancy increases after menopause, with the median age of ovarian cancer diagnosed at age 63 years.23 Family history of breast or ovarian cancer is also important, with BRCA1, BRCA2, and hereditary nonpolyposis colon cancer syndrome (Lynch syndrome) being the most prominent, increasing the patient’s risk of ovarian malignancy 60-, 30-, and 13-fold, respectively.24 Other considerations are nulliparity, early menarche, late menopause, white ethnicity, endometriosis, and primary infertility. In contrast, bilateral salpingectomy, hysterectomy, multiparity, and use of oral contraceptives reduce the risk of ovarian cancer.

Goff et al25 established a list of symptoms commonly asso-ciated with ovarian cancer, which includes pelvic or abdom-inal pain, increased abdomabdom-inal size or bloating, early satiety or difficulty eating, and urinary urgency or frequency.

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REFERENCE S

1. ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol.

2007;110(1):201-214 .

2. Curtin JP. Management of the adnexal mass. Gynecol Oncol. 1994;55(3 Pt 2):

S42-46 .

3. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin.

2006;56(2):106-130 .

4. Earle CC, Schrag D, Neville BA, et al. Effect of surgeon specialty on pro-cesses of care and outcomes for ovarian cancer patients. J National Cancer Inst. 2006;98(3):172-180 .

5. Houry D, Abbott JT. Ovarian torsion: a fifteen-year review. Ann Emerge Med. 2001;38(2):156-159 .

6. Mashiach R, Melamed N, Gilad N, et al. Sonographic diagnosis of ovarian tor-sion: accuracy and predictive factors. J Ultrasound Med. 2011;30(9):1205-1210 .

7. Wiesenfeld HC, Sweet RL. Progress in the management of tuboovarian abscesses. Clin Obstet Gynecol. 1993;36(2):433-444 .

8. Levine D, Brown DL, Andreotti RF, et al. Management of asymptomatic ovar-ian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology. 2010;256(3):943-954 .

9. Van Gorp T, Amant F, Neven P, et al. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):349-371 .

10. Comerci JT, Jr, Licciardi F, Bergh PA, et al. Mature cystic teratoma: a clinicopathologic evaluation of 517 cases and review of the literature. Obstet Gynecol. 1994;84(1):22-28 .

11. Sohaib SA, Mills TD, Sahdev A, et al. The role of magnetic resonance imag-ing and ultrasound in patients with adnexal masses. Clin Radiol. 2005;60(3):

340-348 .

12. Moran O, Menczer J, Ben-Baruch G, et al. Cytologic examination of ovar-ian cyst fluid for the distinction between benign and malignant tumors.

Obstet Gynecol. 1993;82(3):444-446 .

13. Bast RC, Jr, Feeney M, Lazarus H, et al. Reactivity of a monoclonal anti-body with human ovarian carcinoma. J Clin Invest. 1981;68(5):1331-1337 .

14. National Institutes of Health Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and follow-up. Gynecol Oncol. 1994;

55(3 Pt 2):S4-14 .

15. Menon U JI. Principles and Practice of Gynecologic Oncology. Philadelphia,

PA: Lippincott Williams & Wilkins; 2000 .

16. Skates SJ. Ovarian cancer screening: development of the risk of ovarian cancer algorithm (ROCA) and ROCA screening trials. Int J Gynecol Cancer.

2012;22(Suppl 1):S24-26 .

17. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-2303 .

18. Use of CA125 in Screening for Ovarian Cancer. Public Policy. 2010; http:// www.sgo.org/newsroom/position-statements-2/use-of-ca125-in-screening-for-ovarian-cancer/. Accessed October 21, 2 015.

19. Muller CY. Doctor, should I get this new ovarian cancer test-OVA1? Obstet Gynecol. 2010;116(2 Pt 1):246- 247.

20. Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol. 2011;117(6):1289-1 297.

21. Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endo-metrioid ovarian carcinomas. Cancer Res. 2005;65(6):2162-2 169.

22. Moore RG, Miller MC, Disilvestro P, et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pel-vic mass. Obstet Gynecol. 2011;118(2 Pt 1):280- 288.

23. SEER Stat Facts: Ovarian cancer. http://seer.cancer.gov/statfacts/html/ ovary.html. Accessed October 30, 2015.

24. Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA J Am Med Assoc. 2006;296(2):18 5-192.

25. Goff BA, Mandel LS, Drescher CW, et al. Development of an ovarian can-cer symptom index: possibilities for earlier detection. Cancer.

2007;109(2):22 1-227.

26. Clement PB. Tumor-like lesions of the ovary associated with pregnancy. Int J Gynecol Pathol. 1993;12(2):108-115.

27. Leiserowitz GS. Managing ovarian masses during pregnancy. Obstet Gynecol Surv. 2006;61(7):46 3-470.

28. Schmeler KM, Mayo-Smith WW, Peipert JF, et al. Adnexal masses in preg-nancy: surgery compared with observation. Obstet Gynecol. 2005;105(5 Pt 1):

1098 -1103.

29. Im SS, Gordon AN, Buttin BM, et al. Validation of referral guidelines for women with pelvic masses. Obstet Gynecol. 2005;105(1):35-41.

Conclusion

Management of a patient with an adnexal mass is a common scenario for generalist obstetrician/gynecologists. Whether identified incidentally on imaging for an unrelated issue, asymptomatically palpated on annual pelvic examination, or found in the workup of acute pain, balancing the risks of intervention with ensuring that women at high risk for malig-nancy are appropriately referred to a gynecologic oncologist should form the core of management. Transvaginal ultra-sonography should be the first-line imaging modality for diagnosis of adnexal masses, with CT and MRI saved for unique circumstances.

Table 2. SGO and ACOG Referral Guidelines for Patients With a Newly Diagnosed Pelvic Mass

Premenopausal (<50 yrs) CA-125 >200 U/mL Ascites

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

Family history of breast or ovarian cancer (in a first-degree relative) Postmenopausal (>50 yrs)

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)

ACOG, American College of Obstetricians and Gynecologists; SGO, Society of Gynecologic Oncology.

Adapted from Im et al.29

Clinical Pearls

• Simple cysts as large as 10 cm in premenopausal women are almost always benign, and they require intervention only in the setting of pain or discomfort. • Acute presentation of pelvic pain requires expanding

the differential diagnosis, providing pain management, and performing appropriate workup.

• CA-125 level can be falsely elevated in many circum-stances other than EOC, including menses, pregnancy, cirrhosis, ascites, congestive heart failure, acute or chronic pelvic inflammatory disease, fibroids, and endometriosis.

• Referral guidelines have been developed to identify patients at high risk for malignancy who should be evaluated by a gynecologic oncologist.

• Pelvic masses in pregnancy are generally benign. However, if there is any question or the size is large enough to warrant surgical evaluation, the second tri-mester is the ideal time.

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7

1. A 32-year-old G4P4 presents for annual examination. She

notes occasional pelvic pain and dyspareunia, with no signifi-cant medical, surgical, or family history and no obvious masses or nodularity on examination. Ultrasonography demonstrates a 3.0-cm simple cyst on the right ovary, normal uterus, and left adnexa. Which one of the following describes the appropriate next step?

A. Surgical evaluation

B. Repeat ultrasonography in 6 months C. Repeat ultrasonography in 1 year D. Routine annual care.

2. A 34-year-old G3P2012 presents with increased abdominal

girth and a history notable for tubal ligation 8 years previ-ously. CT demonstrates a 23 × 14 × 26-cm, predominantly cystic mass with thick internal septations, likely arising from the right ovary; and no ascites, lymphadenopathy, or addi-tional masses. Her CA-125 level is 28. Which one of the following describes the appropriate next step?

A. Pelvic ultrasonography B. MRI

C. Aspiration of cyst fluid for cytologic diagnosis D. Exploratory laparotomy and removal of mass

3. A 52-year-old, premenopausal woman presents to the

emer-gency department with pressure and pain. Ultrasonography reveals a complex, 10.7 × 15.9 × 8.5-cm mass on the left ovary. Given the size of the mass, CT is performed, which confirms the mass arising from the pelvis. No ascites, caking, or lym-phadenopathy is observed. The patient’s CA-125 level is 33.2 (laboratory normal <35). Which one of the following aspects in her history would prompt you to refer this patient to a gyneco-logic oncologist?

A. Mobile mass on examination

B. History of prostate cancer in maternal grandfather C. Maternal history of breast cancer at age 40 years D. Paternal history of pancreatic cancer

4. During examination of a 34-year-old G2P2, a mass is

pal-pated. A CA-125 level is obtained, and ultrasonography is performed. Ultrasonography reveals a simple, 2.8-cm, right ovarian cyst without nodularity or free fluid, but the patient’s CA-125 level is significantly elevated. Which one of the fol-lowing is the least likely cause of this CA-125 elevation?

A. Pancreatic cancer B. Endometriosis C. Renal failure D. Hepatic failure

5. A 22-year-old woman presents to the emergency

depart-ment with left-sided lower abdominal pain and spotting. She has regular cycles, and her last menstrual period was 7 weeks previously. Her beta-hCG level is 2650. Two days later, her beta-hCG level is 2790. No intrauterine preg-nancy is seen on ultrasound, but a 2.5-cm, right adnexal, nonovarian mass is seen. The patient’s vital signs are all normal. Which one of the following describes the appropri-ate next step?

A. Check CA-125 level

B. Treat for ectopic pregnancy with either methotrexate or

surgery

C. Recheck the beta-hCG level in 1 week D. Start the patient on an antibiotic regimen

6. During pelvic examination of a 57-year-old woman,

bilat-eral pelvic masses are palpated. Ultrasonography reveals cystic and solid masses involving both ovaries. CT of the abdomen demonstrates an omental “cake.” Which one of the following tumor marker tests is indicated?

A. Alpha-fetoprotein B. CA-125

C. LDH D. Beta-hCG

7. During pelvic examination of a 43-year-old G3P3, fullness is

noted. Ultrasonography demonstrates bilateral tubular cyst-ic masses with short, round projections. Whcyst-ich one of the following describes the appropriate next step?

A. Immediate surgical excision

B. No further follow-up unless the patient becomes

symp-tomatic

C. Evaluation of tumor marker levels D. Repeat ultrasonography in 1 year

8. A 38-year-old G2P2 with a history of left salpingectomy

pre-sents to the emergency department with right lower abdom-inal pain, fever, spotting, and vomiting. She has no signifi-cant medical history, although a paternal aunt has premeno-pausal breast cancer. On examination, the patient is noted to have cervical motion tenderness, and her white blood cell count is 14.2. Ultrasonography demonstrates a 6 × 6.3 × 4-cm, complex, loculated, right adnexal mass with free fluid. Which one of the following describes the appropriate next step?

A. Diagnostic laparoscopy B. Treatment with antibiotics

C. Repeat ultrasonography in 6 weeks D. CA-125 level and CT scan

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(8)

10. A 36-year-old G0 presents for follow-up ultrasonography.

She moved from out of state and does not remember the result of her prior ultrasonography, but she was told to have a repeat at some point. She is asymptomatic with mild, left-sided fullness on pelvic examination. Ultrasonography dem-onstrates a 6-cm mass with homogeneous, ground-glass echoes. Which of the following is the most likely diagnosis?

A. Corpus luteum cyst B. Simple follicular cyst C. Endometrioma D. Ovarian neoplasm 9. A 64-year-old G4P3013 with a history of hypertension

pre-sents to the office with pelvic pressure and fullness. She is worried that she has cancer, but the discomfort is not sig-nificant enough that she would want surgery. The remain-der of this patient’s history is notable for tubal ligation at age 36 years and a sister with breast cancer diagnosed at age 57 years. Pelvic examination demonstrates a small, mobile uterus with fullness on the right. No discrete nodu-larity is observed. Ultrasonography demonstrates a 5.5-cm simple right ovarian cyst—no free fluid and normal left adnexa. Which one of the following describes the appropri-ate next step?

A. Pelvic CT

B. Repeat ultrasonography in 12 months C. Immediate surgical excision

D. Drainage to decrease size of the cyst

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With this volume 36, we are pleased to introduce the new name of this newsletter: Topics in Obstetrics & Gynecology: Practical CME Newsletter for Clinicians. We have changed the title to highlight the newsletter’s mission of providing

continuing medical education for practitioners who provide obstetric and gynecologic health care to women. You will notice two other changes:

• The annual frequency of Topics in Obstetrics & Gynecology will be 18 issues (reduced from 24 issues).

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References

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