VOLUME 36 • NUMBER 2 www.topicsinobgyn.

com January 31, 2016

TOPICS IN
OBSTETRICS & GYNECOLOGY
Practical CME Newsletter for Clinicians

Evaluation and Management of Adnexal Masses

Caitlin MacGregor, MD, and Beth Cronin, MD

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

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
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.
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 performing 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

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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.
1

PGOv36n2.indd 1 12/18/15 4:06 PM

 Topics in Obstetrics & Gynecology January 31, 2016

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
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. Arterial 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

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.
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PGOv36n2.indd 2 12/18/15 4:06 PM

 January 31, 2016
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 representing 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
PGOv36n2.indd 3
Topics in Obstetrics & Gynecology
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
Table 1. Summary of Recommendations for Simple Cysts
Premenopausal Postmenopausal
≤3 cm: normal finding, does not <1 cm: clinically inconsequential,
need follow-up, no need to does not need follow-up
describe in report
>3 cm and ≤5 cm: describe in >1 cm and ≤7 cm: describe in report
report as almost certainly as almost certainly benign, yearly
benign, does not need follow-up initially, may continue
follow-up 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 >7 cm: MRI or surgical evaluation
completely with
ultrasonography, further
imaging with MRI or surgical
evaluation
Adapted from Levine et al.8
12/18/15 4:06 PM
 Topics in Obstetrics & Gynecology
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,
PGOv36n2.indd 4
January 31, 2016
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
12/18/15 4:06 PM
 January 31, 2016
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, epithelial 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 abdominal size or bloating, early satiety
or difficulty eating, and urinary urgency or frequency.
5
PGOv36n2.indd 5
Topics in Obstetrics & Gynecology
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.
12/18/15 4:06 PM
 Topics in Obstetrics & Gynecology
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
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.
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.
PGOv36n2.indd 6
January 31, 2016
REFERENCES
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, 2015.
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):1289-1297.
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):2162-2169.
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):185-192.
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):221-227.
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):463-470.
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.
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 January 31, 2016 Topics in Obstetrics & Gynecology

CME Quiz: Volume 36, Number 2

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. Select the best answer and use a blue or black pen to completely fill in the corresponding box
on the enclosed answer form. Please indicate any name and address changes directly on the answer form. If your name and address do
not appear on the answer form, please print that information in the blank space at the top left of the page. Make a photocopy of the completed
answer form for your own files and mail the original answer form in the enclosed postage-paid business reply envelope. Your answer form
must be received by Lippincott CME Institute by January 30, 2017. Only two entries will be considered for credit. At the end of each quarter,
all CME participants will receive individual issue certificates for their CME participation in that quarter. Participants will receive CME certificates
quarterly in April, July, October, and the fourth quarter in January of the following year. For more information, call (800) 638-3030.
Online quiz instructions: To take the quiz online, log on to your account at www.topicsinobgyn.com, and click on the “CME” tab at
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com. Enter your username and password. Follow the instructions on the site. You may print your official certificate immediately. Please
note: Lippincott CME Institute, Inc., will not mail certificates to online participants. Online quizzes expire on the due date.

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. Which 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

PGOv36n2.indd 7 12/18/15 4:06 PM

 Topics in Obstetrics & Gynecology January 31, 2016

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
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

Dear Subscribers:

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).
• Each CME article will be designated for a maximum of 2.0 AMA PRA Category 1 Credits™, for the same annual total
of 36 CME credits that had been available previously.

Thank you for your continued support of this newsletter.

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