CLINICAL OBSTETRICS AND GYNECOLOGY

Volume 58, Number 1, 5365

Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.

Adnexal Mass in the

Postmenopausal
Patient
JOSE A. RAUH-HAIN, MD,* ALEXANDER
MELAMED, MD,*w AMA BUSKWOFIE, MD,*w
and JOHN O. SCHORGE, MD*
*Division of Gynecologic Oncology, Vincent Obstetrics and
Gynecology, Massachusetts General Hospital; and w Department of
Obstetrics and Gynecology, Brigham and Womens Hospital,
Harvard Medical School, Boston, Massachusetts
Abstract: The adnexal mass in a postmenopausal
patient poses an important diagnostic and management dilemma for primary care providers and gynecologists. Postmenopausal women are at a
significantly increased risk of gynecologic malignancy; yet even in this population the majority of
adnexal masses are benign. Evaluation and management of these lesions centers on the identification of
malignancy, especially ovarian cancer, while avoiding
unnecessary intervention in patients with benign lesions. Tumor markers and imaging can help in the
evaluation of adnexal mass in postmenopausal women. Transvaginal ultrasound has long been considered
the imaging modality of choice for the evaluation of
adnexal masses. Particularly in the setting of high
frequency utilization of transvaginal probes, which
project high quality images allowing for detailed
descriptions of the macroscopic appearance of the
mass, and remains the least expensive of all imaging
modalities currently available. For adnexal masses
that are highly suspicious for cancer, women should
be referred a gynecologic oncologist and facility for
optimal care.

Key words: adnexal mass, postmenopausal, ovarian

cancer

Introduction
The adnexal mass in a postmenopausal
patient poses an important diagnostic and
management dilemma for primary care
providers and gynecologists.1 Usually
noted incidentally, the finding may represent a benign, borderline, or malignant
neoplasm of the reproductive tract, metastasis from a distant site, or a non-neoplastic process. Postmenopausal women
are at a significantly increased risk of
gynecologic malignancy; yet even in this
population the majority of adnexal
masses are benign.2 Evaluation and management of these lesions centers on the
identification of malignancy, specifically
ovarian cancer, while avoiding unnecessary intervention in patients with benign
lesions. This article reviews the epidemiology, clinical presentation, differential diagnosis, and strategies for the evaluation
and management of the adnexal mass in a
postmenopausal patient.

Correspondence: John O. Schorge, MD, Division of

Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Yawkey 9 E,
Boston, MA. E-mail: jschorge@partners.org
The authors declare that they have nothing to disclose.
CLINICAL OBSTETRICS AND GYNECOLOGY

VOLUME 58

NUMBER 1

MARCH 2015

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Rauh-Hain et al

Epidemiology
Ovarian cancer is the fifth most common
cause of cancer-related mortality in women, and the leading cause of death among
the gynecologic malignancies in the
United States. In 2014 it is estimated that,
21,980 American women will be diagnosed with ovarian cancer, and 14,270
will die as a result of their disease.3 A
womans lifetime risk of developing ovarian cancer is approximately 1 in 70.
Although >90% of patients with cancer
confined to the ovary will be alive 5 years
after diagnosis, the majority of patients
are diagnosed with disseminated disease,
and have only a 27% likelihood of survival at 5 years.4
Age is the most significant risk factor
for ovarian cancer, with steeply increasing
incidence after menopause. Women older
than 65 years are nearly 6 times more
likely to be diagnosed with ovarian cancer
than those under 65.4 Other risk factors
for ovarian cancer include genetic predisposition including BRCA-1 and BRCA-2
mutations and hereditary nonpolyposis
colorectal cancer, as well as nulliparity,
infertility, and endometriosis.5,6
Adnexal masses are more common than
ovarian malignancies. Among 33,260
asymptomatic postmenopausal women enrolled in the Kentucky Ovarian Cancer
Screening Program, 17% were found to
have ovarian enlargement, ovarian cysts,
or solid adnexal masses on first screening
transvaginal ultrasound (US).7 In the Prostate, Lung, Colon and Ovarian Cancer
Screening Trial, the prevalence of simple
adnexal cysts detected by US among nearly
16,000 women older than 55 years was
14%.8 The annual incidence of developing
an adnexal lesion among postmenopausal
women with normal baseline US was approximately 8% in both large screening
studies, and lesions, even with significant
complexity, often resolved spontaneously.79 A similar prevalence rate of adnexal masses was confirmed in an autopsy study
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of 224 women who died from nongynecologic causes.10

Estimating the true frequency of benign
and malignant causes of adnexal masses is
difficult because histology is available only
for patients who undergo surgery. As
asymptomatic patients who are found to
have adnexal lesions with benign sonographic morphology are often managed
with observation, surgical case series overestimate the incidence of both malignant
lesions and benign lesions which have worrisome features. Among postmenopausal
women who undergo surgery for a suspicious adnexal mass, the reported frequency
of malignancy ranges from 36% to
59%.11,12 Epithelial ovarian cancers are
the most common malignancies identified,
whereas serous cystadenomas and benign
cystic teratomas are the most common benign neoplasms.2

Clinical Presentation
PRESENTATION

Although most adnexal masses are asymptomatic, they may also cause insidious pain
or pressure symptoms. Benign and malignant masses may lead to adnexal torsion,
which presents with acute pelvic pain often
accompanied by nausea and vomiting. The
vast majority of patients diagnosed with
ovarian cancer, even at an early stage, experience nonspecific symptoms before diagnosis including increasing abdominal size,
bloating, fatigue, abdominal or pelvic pain,
urinary symptoms, or changes in dietary or
bowel habits. Abdominal pain and distension with or without accompanied dyspnea
may rarely represent Meigs syndromea
benign condition defined by the presence of
an ovarian fibroma, ascites, and pleural
effusion.13 Tuboovarian abscesses are a rare
cause of adnexal mass in the postmenopausal population, but typically present with
pain and fever. In the setting of an ovarian
mass, postmenopausal bleeding may be the
result of estrogen production by a granulosa

Adnexal Mass in the Postmenopausal Patient

cell tumor or thecoma, and virilization suggests an androgen-producing tumor.
PHYSICAL EXAMINATION

Pelvic examination is of low utility in the

identification and differentiation of adnexal
masses.14 A pooled analysis of 5 studies
investigating the sensitivity and specificity
of pelvic examination for the detection of an
adnexal mass, demonstrated a sensitivity of
45% and specificity of 90% for detection of
a mass. Patient obesity and examiner inexperience increases the likelihood of failure to
detect a mass.15 Because of the low prevalence of ovarian cancer, even among postmenopausal women, both the positive
predictive value (PPV) and negative predictive value (NPV) of pelvic examination are
unacceptably low, and cannot justify physical examination as the basis for clinical
decisions. Nonetheless, irregular, fixed, nodular masses, and the presence of ascites are
associated with malignancy.1

Differential Diagnosis
The differential for adnexal masses found
in postmenopausal women is extensive
and can include both gynecologic and
nongynecologic etiologies (Table 1). The
differential diagnosis for simple cystic
TABLE 1.

55

adnexal masses includes gynecologic etiologies such as follicular and corpus luteal
cysts (rare in the postmenopausal woman), hydrosalpinx, and cystadenomas.
Nongynecologic etiologies can include
bladder diverticulum, peritoneal inclusion cysts, paratubal cysts, and cysts of
gastrointestinal (GI) origin. Although
malignancy cannot be completely ruled
out based on a simple cystic nature of the
mass, multiple studies have shown that
risk of malignancy in these lesions is exceptionally low (<1%).8,16
The prevalence of complex ovarian
masses in postmenopausal women has
been reported to be 3.2%, and the majority of these will spontaneously resolve
(55%) within 60 days.16 The differential
diagnosis for complex adnexal masses includes benign causes such as endometrioma, hemorrhagic cysts, cystic teratomas,
tuboovarian abscesses, cystadenomas,
and hematomas, abscesses, and lymphoceles. Malignant primary ovarian cancer
(epithelial, germ cell, stromal) and metastatic cancers (breast, GI, uterus/cervix,
and fallopian tube) can also present as
complex cystic adnexal masses.
Finally, adnexal masses can be characterized as solid or containing solid components. Adnexal masses described as

Differential Diagnosis of Postmenopausal Women With an Adnexal Mass

Gynecologic Ovarian

Gynecologic Extraovarian

Nongynecologic

Benign
Mature teratoma
Ovarian torsion
Polycystic ovaries
Cystadenoma
Endometrioma
Simple cyst

Benign
Endometrioma
Hydrosalpinx
Tuboovarian abscess
Paraovarian cyst
Peritoneal inclusion cyst
Pedunculated fibroid

Malignant
Borderline tumors
Epithelial carcinoma
Ovarian germ cell tumor
Ovarian sarcoma
Sex-cord or stromal tumor

Malignant
Endometrial carcinoma
Fallopian tube carcinoma

Benign
Appendiceal abscess
Appendicitis
Bladder diverticulum
Diverticular abscess
Nerve sheath tumor
Pelvic kidney
Peritoneal cyst
Ureteral diverticulum
Malignant
Metastasis (breast, lymphoma, etc.)
Krukenberg tumor
Retroperitoneal sarcomas

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Rauh-Hain et al

predominantly solid or containing solid

components, must be approached with a
great degree of suspicion, given their high
risk for malignancy. The majority of predominantly solid adnexal lesions encountered will represent benign tumors such as
fibroids, fibromas, thecomas, fibrothecomas, benign Brenner tumors, and mature
teratomas. However, primary ovarian
malignancies such as dysgerminomas,
granulosa cell tumors, or malignant Brenner tumors can appear predominantly
solid in appearance. Cystic lesions with
solid components, such as septae, papillary projections, and mural nodules, are
concerning for primary ovarian epithelial
neoplasms.17 As with simple and complex
cystic masses, solid masses may also represent nongynecologic etiologies such as
lymphadenopathy, genitourinary or GI
masses, and metastatic malignancies.

Evaluation and Work-up

LABORATORY STUDIES

Cancer Antigen 125 (CA-125)

CA-125 is the most extensively investigated
ovarian cancer associated tumor marker.
CA-125 is a glycoprotein that is not expressed
by normal ovarian epithelium, but can be
synthesized by both benign and malignant
ovarian tumors. Elevated CA-125 levels have
been reported in 80% to 85% of patients with
ovarian cancer at the time of diagnosis.14
Given this finding, its use has been proposed
for the discrimination between benign and
malignant adnexal masses. However, its utility as a marker for detecting ovarian cancer is
limited by the fact that CA-125 is not only
produced by abnormal ovarian tumors; elevated levels have also been seen in any condition which causes peritoneal or mesothelial
changes.14 Consequently, CA-125 levels may
be elevated in a number of benign conditions
such as endometriosis, adenomyosis, pelvic
inflammatory disease, pregnancy, menstruation, pancreatitis, cirrhosis, and peritonitis.18
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A meta-analysis by Myers and colleagues

investigated the use of CA-125 as a serum
marker for discrimination of adnexal masses
with malignant potential. Using the data
from 66 studies, they calculated a pooled
sensitivity of 0.78 (95% CI, 0.75-0.81) and a
pooled specificity 0.78 (95% CI, 0.71-0.82).
Individual study sensitivities ranged from
0.45 to 1.0 and specificities from 0.46 to
0.99. Of the 66 studies included in their
meta-analysis, only 9 contained data that
allowed for stratification of the results by
menopausal status. All of the test parameters
with the exception of NPV were higher and
the ranges were narrower in postmenopausal
women. Sensitivities within these studies
ranged from 0.69 to 0.97 and specificities
from 0.81 to 1.14 Although CA-125 by itself
has not proven to be a sufficiently sensitive or
specific test to use as a screening tool for the
detection of malignancy in adnexal masses,
multiple studies have shown consistently that
it is more helpful in detecting malignant
lesions in postmenopausal women when
compared with premenopausal women.
A single threshold CA-125 level seems
to be of marginal utility for both screening
for ovarian cancer and for predicting
malignant potential in the setting of an
adnexal mass. However, Skates et al19
have proposed that serial measurements
of the biomarker may be more beneficial.
Using data from 9233 asymptomatic
postmenopausal women with >2 serial
CA-125 values, they were able to show
that the risk calculation obtained from
serial CA-125 values significantly increased the preclinical detection of ovarian cancer when compared with a fixed
threshold value of CA-125 measurement.
However, this strategy of serial CA-125
testing has yet to be applied in the setting
of a known adnexal mass, and remains an
area for further research.

Human Epididymis 4 (HE4)

HE4 is a serum protein that was initially
identified in epithelial cells of the human

Adnexal Mass in the Postmenopausal Patient

epididymis. Although the complete function
of this protein remains unknown, recent
studies have shown that ovarian cancer cells
commonly express it.18 HE4 has varying
expression levels in ovarian carcinomas
based on histologic cell type. HE4 was
positive in 93% of serous tumors, 100% of
endometrioid tumors, and 50% of clear-cell
tumors. HE4 was not found to be positive in
any mucinous tumors. Microarray profiling
of genes in ovarian carcinoma found that
not only is HE4 overexpressed in malignant
tissue; it importantly was not amplified in
any of the 19 normal tissue samples from
women with benign ovarian masses.18 Given this unique predilection for ovarian carcinoma, many studies have evaluated HE4
as a potential biomarker for differentiating
between benign and malignant masses. Hellerstrom et al18 evaluated serum from postmenopausal women with known ovarian
cancer and compared it with matched controls of both healthy asymptomatic postmenopausal women and postmenopausal
women with benign ovarian disease. They
found that although HE4 had a sensitivity
and specificity for detecting ovarian cancer
similar to that of CA-125, its main advantage over CA-125 was that it was less frequently positive in postmenopausal women
with benign disease.18 Similarly other investigators have found that HE4 has similar
and possibly increased sensitivity (ranging
from 70% to 84%) and specificity (83% to
84%) for discriminating benign from malignant adnexal masses when compared with
CA-125.20 A recent systematic review and
meta-analysis using a total of 18 studies and
3865 patients found a pooled sensitivity for
HE4 of 74.5% and a pooled specificity of
85.8%.21
Although studies have shown that HE4
alone is comparable with CA-125 in regards
to its sensitivity and specificity for detecting
malignant potential in adnexal masses, several studies have shown that a synergistic
effect between the 2 tumor markers may
exist. Abdel-Azeez et al22 showed that CA125 when combined with HE4 was a more

57

sensitive predictor of early-stage ovarian

malignancy at 84.6% than either CA-125
(61%) or HE4 (76.9%) alone.

Multivariate Index Assay

OVA1 is a multivariate index assay comprised of 5 serum proteins: CA-125, transthyretin (prealbumin), apolipoproteina1,
b2 microglobulin, and transferrin.
Ueland et al,23 in a prospective multiinstitutional trial, evaluated 516 women
preoperatively using the OVA1 assay.
They found that when compared with
physician assessment or CA-125 alone,
the multivariate index assay demonstrated higher sensitivity but lower specificity in detecting ovarian malignancies.23
When stratified by stage of disease and
menopausal status, the multivariate assay
was more sensitive in detecting early-stage
disease in postmenopausal women than
CA-125 alone. These findings were recently confirmed by Longoria et al24
who showed that the multivariate index
assay was superior in sensitivity when
combined with physician assessment
(95.3%), than either physician assessment
or CA-125 alone. Importantly, these findings were significant in postmenopausal
women. It should be noted that there was
a very high incidence of cancer in the
index trial for OVA1 (30%) and thus these
results must be cautiously applied to the
general population in which the incidence
of cancer is much less. Consequently, the
role of the OVA1 test in generalized practice is still evolving.
IMAGING

Pelvic US
The relationship between a tumors macroscopic appearance and the risk of malignancy was first defined in 1989 by Granberg
et al,25 by evaluating 1017 ovarian tumors
and correlating their gross appearance and
classification to their histologic diagnosis;
they noted that unilocular cysts were
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Rauh-Hain et al

associated with a risk of malignancy of

0.3%, whereas complex multiloculated cysts
and predominantly solid cysts were associated with a risk of malignancy of 36% and
39%, respectively. Gray-scale US has long
been considered the imaging modality of
choice for the evaluation of adnexal masses,
particularly in the setting of high-frequency
utilization of transvaginal probes, which
project high-quality images allowing for
detailed descriptions of the macroscopic
appearance of the mass. Discrimination
between benign and malignant masses preoperatively is significantly influenced by the
subjective evaluation of the image using
pattern recognition. However, given that
diagnostic accuracy and thereby interpretation reliability is based on the subjective
assessment and experience of the ultrasonographer, the sensitivity and specificity of
using pattern recognition to discriminate
between benign and malignant pelvic
masses has been shown to vary significantly.
In the literature, the sensitivity of pattern
recognition has been shown to vary between
88% and 100% and the reported specificity
between 62% and 96%.26 As one would
expect, it has been shown that diagnostic
accuracy increases with increasing experience. Timmerman et al27 performed a prospective analysis of 300 consecutive patients
with adnexal masses. The patients were
evaluated using transvaginal US and the
evaluations of the images by 6 different
operators were compared for interobserver
variability and diagnostic accuracy. They
found that the 2 most experienced operators
agreed and were correct in their diagnosis
92% of the time. The least experienced
operators had significantly lower accuracy
(varying between 82% and 87%) with only
moderate intraoperator agreement.27 This
study suggests that the experience of the
operator can significantly affect the diagnostic utility of the study.
Several groups have proposed morphologic scoring systems to increase the accuracy of US discrimination between
benign and malignant adnexal masses.
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The majority of scoring systems included

morphology, wall structure/thickness,
ovarian volume, and septations. Some
studies also included echogenicity, vegetations, and shadowing. Myers et al14
performed analysis on the most frequently used scoring systems, and noted
that the pooled sensitivity and specificity
of detecting malignancy using these systems varied from 82% to 91% and 68 to
77%, respectively. These investigators also noted no statistical difference between
the 4 established scoring systems. Overall,
the scoring systems had poor specificity
and PPVs (<0.5 in the majority of studies). Despite different designs, no significant difference between the scoring
systems was noted when comparing them
head to head within the same study population. The authors suggest that one of
the reasons for the poor performance with
regard to PPV could be secondary to the
misclassification of dermoid tumors.
When stratifying the results by menopausal status, there was no significant
difference in test performance for sensitivity, specificity, or NPVs. However, the
PPV was slightly increased for postmenopausal women, which likely reflects the
higher prevalence of ovarian malignancy
in this population.14
It is well known that in comparison with
normal or benign tissue, malignant neoplasms have increased vascularity secondary to continued creation of new blood
vessels to keep up with their increased
metabolic demand. Malignant tissue not
only has increased vascularity, but there
tends to be decreased peripheral flow resistance and increased blood flow velocity
within these vessels, when compared with
benign tissue.14 The use of color Doppler
during US for the assessment of tumor
vascularity has thus been suggested as a
modality for the evaluation of adnexal
masses and the differentiation between benign and malignant tumors. However, given that there are significant similarities in
Doppler flow indices between benign and

Adnexal Mass in the Postmenopausal Patient

malignant ovarian tumors, Doppler flow as
an individual modality for the differentiation of benign and malignant ovarian tumors has not been shown to be sufficiently
sensitive or specific.14
Computed Tomography (CT)
Even though US remains the most common imaging modality in the evaluation
and diagnosis of adnexal masses in postmenopausal women, newer technologies
such as CT scan are available. Because
ovarian cancer often presents with vague,
nonspecific abdominal signs and symptoms such as bloating, abdominal pain/
pressure, abdominal distention, and early
satiety, CT scans are often obtained as
part of the work-up and adnexal masses
are discovered in the process. Given the
small number of prospective studies using
CT to evaluate adnexal masses, the data
regarding the diagnostic value of CT scan
in the evaluation of postmenopausal
women with an adnexal mass is limited.
Studies have demonstrated a sensitivity of
CT imaging with contrast that ranges
from 86% to 96% and specificity from
35% to 89%.14 Tsili et al28 prospectively
analyzed the results of 102 consecutive
women with preoperative CT scans. The
objective of the study was to differentiate
between benign and malignant adnexal
masses; the authors utilized surgical and
pathologic results as the standard reference. They noted that the multidetector
CT detected 129 (90%) of the 143 adnexal
masses, with an overall accuracy for the
diagnosis of malignancy of 89.1%.
To directly compare CT to US morphology, Buist et al29 performed a prospective
study of women with suspected primary or
recurrent ovarian cancer. Sixty-four women
were evaluated using physical examination,
US, CT, and MRI in the detection and
differentiation of adnexal masses. Imaging
diagnosis was compared with the pathology
diagnosis following surgery which took
place within 3 weeks of the initial evaluation.
Using 2 experienced radiologists, they found

59

that although intraobserver variability was

high, CT was comparable with US and may
be more accurate in assessing adnexal
masses.29 However, this study was limited
by the high pretest probability of cancer
among the women included in the study.
Although these studies suggest that CT is
comparable with US, given the paucity of
data, more information is needed to make
this modality a first-line tool in evaluating
adnexal masses. However, despite the unclear role of CT in the initial evaluation of
adnexal masses, CT is the preferred modality for preoperative imaging of patients with
a high suspicious or known ovarian cancer,
to optimize surgical planning.

Magnetic Resonance Imaging

(MRI)
The value of MRI for characterization of
adnexal masses was recognized within the
first few years of its introduction as a
clinical tool. Descriptions of the MRI
appearances of common adnexal lesions
such as endometrioma and mature cystic
teratoma followed. Early users of this
technology recognized the ability to identify tissue characteristics of fat, blood,
fibrous tissue, and vascularized tumor,
as well as the value of direct multiplanar
imaging to define the site of origin of the
mass.30 In addition, investigators found
that dynamic multiphase contrast-enhanced MRI after administration of intravenous gadolinium is very useful for
the characterization of adnexal masses.
Solid components will demonstrate enhancement, enabling the distinction between fibrinous debris or retracting clot in
the cyst wall from papillary projections.
Gadolinium also improves the detection
of peritoneal and omental implants in the
case of ovarian carcinoma.31
Most studies have shown MRI to be
superior to US in the differentiation
of benign from malignant adnexal
lesions.17,32,33 Studies have shown that
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Rauh-Hain et al

MRI demonstrates sensitivity of 67% to

100% and specificity of 77% to 100% in
the diagnosis of cancer.17,34,35 All these
studies suggest that although MRI can be
helpful in cancer detection, the preponderant contribution of MRI in adnexal mass
evaluation is the additional anatomic information and tissue characterization,
which improves the characterization of
these lesions. These analyses also imply
that MRI is in some circumstances recommended as a second-line investigation for
the characterization of complex adnexal
masses that are indeterminate on US,
although it is a more expensive investigation and is less readily available than US.
A meta-analysis evaluating the incremental value of a second test for an indeterminate adnexal mass detected on gray-scale
US determined that MRI with IV contrast
administration provided the highest posttest
probability of ovarian cancer when compared with CT, Doppler US, or MRI without contrast administration.36 When used
for further evaluation of an indeterminate
mass seen on US in a prospective series,
contrast-enhanced MRI showed sensitivity
and specificity of 100% and 94%, respectively, in diagnosis of malignancy.37 Furthermore, in a prospective study of women
with suspected adnexal masses, both Doppler US and MRI were highly sensitive for
identifying malignant lesions (US = 100%,
MRI = 96.6%), but the specificity of MRI
was significantly greater (US = 39.5%,
MRI = 83.7%). Therefore, women who
clinically have a low risk of malignancy
but have indeterminate lesions on US are
the ones most likely to benefit from MRI.38
Fenchel et al39 compared transvaginal
Doppler US, MRI, and positron emission
tomography (PET) with respect to assessing malignancy in 99 women with an
asymptomatic adnexal mass. Each mass
was assessed using each modality separately and then in combination with all 3
techniques and results compared with
final histopathologic diagnosis. On the
basis of these results, PET and MRI have
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a PPV of 25% and 42%, respectively.

Transvaginal US carried a 92% sensitivity
and 60% specificity and a PPV of 24%.
Furthermore, the sensitivity of US examination was not significantly improved by
the addition of PET or MRI. Therefore, the
authors concluded that the use of US is the
most important diagnostic tool in the detection and assessment of asymptomatic
adnexal masses.39 This analysis suggests
that PET and MRI in conjunction with
US may provide marginal improvements in
specificity; however, the additional cost of
these expensive supplementary studies in
most situations is not justified.

PET
Until relatively recently, [18F]fluorodeoxyglucose (FDG)-PET and PET/CT have had
only a limited role in the diagnosis and
staging of disease in patients presenting with
ovarian cancer. The strength of PET lies in
its ability to identify abnormal biological
processes associated with cancer, such as
increased glucose metabolism using FDG.
Ovarian cancer is typically characterized by
increased glucose metabolism and present
with increased FDG uptake, whereas benign
tumors are usually negative on PET.40
Although the number of false-positive
FDG-PET findings in the abdomen and
pelvis is low, in patients with suspicious
ovarian masses, a number of benign conditions can cause a significant false-positive
rate. For example, normal ovaries during
ovulation, physiological activity in bowel,
endometrium, ureters, benign cystadenomas, teratomas, schwannomas, endometriomas, and inflammatory processes exhibit
increased glucose metabolism.40,41 Increased
FDG uptake in the pelvis has also been
found in healthy premenopausal women,
and most premenopausal women show
FDG uptake in the ovaries and uterine
endometrium in the late follicular and early
luteal phases of the menstrual cycle.42 The
coregistration of CT images with the PET

Adnexal Mass in the Postmenopausal Patient

TABLE 2.

61

The Society of Gynecologic Oncologists and the American College of Obstetrics and
Gynecology Guidelines for Patients With Newly Diagnosed Pelvic Masses

Premenopausal women (younger than 50 y)

CA-125 antigen level >200 U/mL
Ascites
Evidence of abdominal or distant metastasis (by results of examination or imaging study)
Family history of breast or ovarian cancer (in a first-degree relative)
Postmenopausal women (50 y or older)
CA-125 antigen level >35 U/mL
Ascites
Nodular or fixed pelvic mass
Evidence of abdominal or distant metastasis (by results of examination or imaging study)
Family history of breast or ovarian cancer (in a first-degree relative)

images has overcome many of these

difficulties.
Early studies that assessed women with
asymptomatic adnexal masses found PET
to have a sensitivity of 58% and specificity
of 76% to 80%.40 More recent investigators assessed PET for characterization of
a suspicious pelvic mass on US and found
sensitivities and specificities to range from
58% to 78% and from 78% to 87%,
respectively.4345 Despite the relatively
low sensitivity of PET in the detection of
ovarian cancer, all of the false-negative
results were either invasive stage I tumors
or tumors of low malignant potential
(borderline ovarian tumors). More advanced stages of ovarian cancer demonstrated intensely increased FDG uptake
and were well visualized. Abdominal or
pelvic masses containing large cystic components as well as mucinous tumors will
often not be metabolically active.40
In a study of 50 patients with a suspicious
pelvic lesion, the authors found the sensitivity and specificity of PET-CT in the diagnosis of ovarian cancer to be 87% and
100%, respectively.45 Regarding the extent
of disease, they reported 69% concordance
between PET-CT staging and surgical staging. The authors concluded that the use of
this imaging tool could improve the specificity and accuracy of the pretreatment diagnosis and staging of ovarian cancer in
comparison with contrast-enhanced CT
alone. Although the results of PET-CT
reported in these studies are impressive,

currently this technology is not recommended in the management of postmenopausal women with adnexal mass, except in
particular circumstances.

Management Strategy
For adnexal masses that are highly suspicious for cancer, women should be referred
to a gynecologic oncologist, as outcomes of
staging and cytoreduction have been shown
to be better than when the procedure is
performed by a subspecialist.1,46 The findings of a systematic review of observational
studies support this approach. This analysis
showed that in women with advanced disease, there was a 6- to 9-month median
survival benefit for patients operated on by
gynecologic oncologists and that, in patients
with early-stage disease, gynecologic oncologists were significantly more likely to perform optimal staging.46 In addition, women
with ovarian cancer who are referred to a
high-volume expert cancer center have improved overall survival. Bristow et al47 investigated the quality of care in patients with
ovarian cancer by evaluating adherence to
National Comprehensive Cancer Network
(NCCN) guidelines. High-volume physicians were more likely to perform proper
surgery, administer correct chemotherapy,
and deliver appropriate treatment to ovarian cancer patients than low-volume physicians. There was a statistically significant
difference seen in the 5-year disease-specific
survival rates between patients receiving
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Rauh-Hain et al

adherent versus nonadherent NCCN care.

Despite these findings, >50% of women
with ovarian cancer are never seen by gynecologic oncologist.48
The American Congress of Obstetricians
and Gynecologists in conjunction with the
Society of Gynecologic Oncologists have
developed guidelines for referral of patients
with pelvic masses to a gynecologic oncologist (Table 2).1,49 Studies have evaluated the
performance of this guideline for the diagnosis of ovarian cancer. In a study by Im
et al,11 a total of 1035 patients were identified, including 318 (30.7%) with primary
malignancies of the ovary, fallopian tube, or
peritoneum. Seventy-seven patients were
younger than 50 years (premenopausal
group), and 240 were 50 years old or above
(postmenopausal group). The referral
guidelines captured 70% of the ovarian
cancers in the premenopausal group and
94% of the ovarian cancers in the postmenopausal group. The PPV was 33.8% for
the premenopausal group and 59.5% for the
postmenopausal group, whereas the NPVs
were >90% for both groups. Elevated CA125 level was the single best predictor of
malignancy in both groups. In a subsequent
study of 837 patients, 44% (263/597) of
postmenopausal women were diagnosed
with ovarian cancer, whereas 20% (48/
240) of premenopausal women had ovarian
cancer. For postmenopausal women, the
guidelines were 93.2% sensitive and 59.9%
specific, and had a PPV of 64.6%. The
referral guidelines performed better for
late-stage than early-stage cancers in both
sensitivity and PPV, especially in postmenopausal women. Although only 28 patients
would not have been referred by the guidelines, the majority of these had early-stage
disease.50
In asymptomatic postmenopausal woman with an adnexal mass, van Nagell and
DePriest51 have developed the following
management approach on the basis of their
studies. Postmenopausal women diagnosed with an adnexal mass on examination should undergo transvaginal US and
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CA-125 testing. Women with unilocular

cystic tumors <5 cm in diameter and normal serum CA-125 are at negligible risk of
malignancy, and may be monitored without surgical intervention at 3- to 6-month
intervals with repeat transvaginal US, CA125 testing, and tumor morphology indexing (MI). Almost 70% of these lesions will
regress spontaneously within 60 days of
diagnosis. Women with a complex ovarian
tumor <5 cm in diameter and a normal
serum CA-125 should undergo repeat
transvaginal US, CA-125, and tumor MI
in 4 weeks. If the tumor is increasing in
volume or complexity (MI rising), or if the
serum CA-125 is rising, the tumor should be
removed surgically. If the tumor is decreasing in size or complexity (MI falling) and the
serum CA-125 remains normal, the patient
can be followed conservatively at 3- to 6month intervals. Any postmenopausal
woman with a complex ovarian tumor and
an elevated serum or rising CA-125 should
undergo immediate surgery. Patients who
have a complex ovarian tumor Z5 cm in
diameter with a papillary projection from
the tumor wall or evidence of extratumoral
fluid on US are at particularly high risk for
malignancy and should be considered for
referral to a gynecologic oncologist.
In women with an adnexal mass, surgical evaluation allows a definitive histologic
diagnosis. Surgery could be performed laparoscopically or through a laparotomy,
and the approach depends upon the degree
of suspicion of cancer. Laparotomy with
vertical midline incision is recommended
for any patient with an obvious malignancy, and complete staging should be
performed. If there is a low or moderate
suspicion of malignancy, a laparoscopic
approach is typically used. Frozen sections
for the intraoperative diagnosis of a suspicious adnexal mass is recommended in
settings in which availability and patient
preference allow. Covens et al,52 in a review
of 15 studies published since 2004 looking
at the accuracy of primary frozen section,
found in a bivariate random effects analysis

Adnexal Mass in the Postmenopausal Patient

an overall sensitivity of 89.2% (95% CI,
86.3%-91.5%) and specificity of 97.9%
(95% CI, 96.6%-98.7%). Of note, borderline tumors were considered malignant in
this analysis.

Conclusions
The adnexal mass in a postmenopausal
patient poses an important diagnostic and
management dilemma for primary care
providers and gynecologists. Evaluation
and management of these lesions centers
on the identification of malignancy, especially ovarian cancer, while avoiding unnecessary intervention in patients with
benign lesions. Tumor markers and imaging can help in the evaluation of adnexal
mass in postmenopausal women. Transvaginal US has long been considered the
imaging modality of choice for the evaluation of adnexal masses. Particularly in
the setting of high-frequency utilization of
transvaginal probes, which project highquality images allowing for detailed descriptions of the macroscopic appearance
of the mass, and remains the least expensive of all imaging modalities currently
available. CT, MRI, and PET are not
routinely indicated in the evaluation of
an asymptomatic adnexal mass due to
their inherent costs and little additional
information they afford. For adnexal
masses that are highly suspicious for cancer, women should be referred a gynecologic oncologist and facility for optimal
care. Surgery could be performed laparoscopically or through a laparotomy,
and the approach depends upon the degree of suspicion of cancer.

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