Dr. Balachandran
is an Assistant Professor and
Dr. Iyer
is an Associate Professor, Department of Diagnostic Imaging, UT
MD Anderson Cancer Center, Houston, TX.
Ovarian cancer is the second most common gynecologic malignancy
and is the fifth leading cause of cancer death in women.
1
Nearly 75% of women with ovarian cancer present with advanced stage
disease, which is associated with a poor prognosis.
2
There has been a relative standstill in the progress of treating
ovarian cancer that has been attributed to the late stage of
disease presentation.
3
Ovarian neoplasms can be classified based on cells of their origin
into epithelial, germ cell, sex cord stromal, or metastatic types.
Epithelial tumors account for nearly 85% to 90% of all ovarian
malignancies.
4
Histologic subtypes in epithelial ovarian cancer include serous,
mucinous, endometrioid, clear cell, and undifferentiated tumors. In
advanced stage disease, they are all associated with a similarly
poor prognosis.
Ovarian cancer can metastasize through intraperitoneal spread
(most common), or lymphatic or hematogenous invasion. Staging of
ovarian cancer is based on the findings at an exploratory
laparotomy. A complete staging exploratory laparotomy includes a
hysterectomy with bilateral salpingo-oophorectomy, omentectomy,
random peritoneal biopsies and washings, and pelvic/para-aortic
lymph node biopsies.
5
The International Federation of Gynecology and Obstetrics (FIGO)
system, which is surgically based, is the most commonly used
staging system (Table 1).
3
The staging of ovarian cancer is critical, as it affects both the
prognosis and the treatment of the patient. The 5-year survival
rate of ovarian cancer varies from 80% for stage I disease to 8%
for stage IV disease.
6
The role of imaging in ovarian cancer involves detection,
characterization, and staging. Imaging plays an important role in
characterization of ovarian masses, as the number of benign ovarian
masses greatly exceeds the number of malignant masses.
Ultrasound
The easy accessibility and relative low cost of ultrasound have
made it the study of choice in the initial evaluation of a patient
with a suspected adnexal mass.
7
Compared with transabdominal ultrasound (3 to 5 MHz), transvaginal
ultrasound uses 8-MHz probes, which provide significantly improved
resolution of the adnexa.
Unilocular simple anechoic cysts <5 cm in diameter are
considered to be seldom malignant even in postmenopausal women.
Multilocular cysts with wall thickness >3 mm, mural nodularity,
papillary projections, septations >3 mm in thickness, and solid
ovarian masses or masses with solid components are considered to be
suggestive of ovarian cancer.
8-11
The single most predictive sonographic feature of malignancy in
cystic masses is papillary projections. The ultrasound appearance
of benign and malignant ovarian lesions is shown in Figures 1
through 3.
Some authors have also proposed morphologic scoring systems.
8-11
Numerical scores are assigned to morphologic features, such as wall
structure, cyst wall thickness, septations, and echogenicity. These
scoring systems have helped to standardize the interpretation of
ultrasound images. The sensitivity of morphologic analysis with
ultrasound in predicting malignancy in ovarian tumors has been
shown to be 85% to 97%, whereas its specificity ranges from 56% to
95%.
7
Color and pulsed Doppler ultrasound have also been used in the
evaluation of ovarian masses. The presence of central blood flow
within an ovarian mass is considered to be suggestive of
malignancy.
12
The resistive index (RI) and pulsatility index (PI) have been used
in the evaluation of ovarian masses because of the expected low
impedance and high diastolic blood flow seen in blood vessels
supplying the malignant tumor. Typically, an RI less than 0.4 to
0.8 and a PI <1 are considered to be suggestive of malignancy.
12-17
However, due to operator dependence and overlap of these indices
between malignant and benign lesions (such as in pelvic
inflammatory disease and endometriosis), the usefulness of color
and pulsed Doppler is limited.
13-17
Currently, there is no consensus opinion on the use of Doppler
ultrasound for the differentiation between benign and malignant
ovarian masses. The combined use of morphologic scoring and Doppler
ultrasound in evaluating ovarian masses has proven to be more
effective than the use of either morphologic assessment or Doppler
assessment alone.
10,17-19
A large multicenter trial comparing ultrasound, computed tomography
(CT), and magnetic resonance imaging (MRI) in the diagnosis and
staging of ovarian cancer showed little difference between these
modalities. The lowest sensitivity and highest specificity for
diagnosis was found with ultrasound. These authors found that if
stage III disease is not detected at the initial abdominal
ultrasound, then CT or MRI should be performed because these
modalities were found to have higher sensitivity in the detection
of peritoneal implants beyond the pelvis.
20
Evaluation of all peritoneal implants by ultrasound has significant
limitations, including operator dependence, that require a
meticulous search of all peritoneal surfaces and the presence of
overlying bowel gas that may obscure lesions.
21,22
At our institution, we perform transabdominal and transvaginal
examinations along with color Doppler for characterization and
diagnosis of ovarian masses. The transabdominal portion of the
study is performed to evaluate the ovaries in patients with
superficially placed ovaries and to evaluate large ovarian masses,
which would be depicted in their entirety on the transabdominal
images.
CT
A surgical procedure leaving the patient with <1 cm maximal
diameter residual disease is considered to be an optimal debulking
procedure.
23
Clinical trials have shown that optimal surgical debulking is
associated with a more favorable response to postoperative
chemotherapy and, therefore, prolonged survival.
24
The role of preoperative CT in identifying patients who are
potential candidates for optimal debulking surgery is extremely
important. Studies have been performed using radiographic data as
tools for selecting candidates for optimal surgery.
23,25
The pattern of tumor growth, such as diaphragmatic involvement,
infiltration of the pelvic sidewall, and hydronephrosis, has been
implicated in precluding an optimal surgical outcome. In these
patients, neoadjuvant therapy is used to reduce the extent of
metastatic disease prior to surgical debulking.
CT has been used extensively in the staging of ovarian cancer.
Reported rates of accuracy of CT in preoperative staging vary from
60% to
20,26
Preoperative CT can be used to identify sites of disease that are
difficult to assess and debulk at surgery. These sites include the
surface of the diaphragm, the lesser sac, the mesenteric root, the
splenic hilum, and the para-aortic nodes above the renal vessels.
23
CT is also used preoperatively to evaluate the lung parenchyma and
pleural surfaces for metastatic deposits as well as the paracardiac
regions for metastatic lymphadenopathy.
Peritoneal metastases are well depicted on CT due to the
rapidity of the scan in evaluating both the abdomen and the pelvis
and the use of contrast to distend the bowel. With the use of
multidetector CT, there is improved detection of peritoneal
implants due to the thinner sections, quicker acquisition, absence
of section misregistration, and ability to reformat multiplanar
images.
27
The CT appearance of peritoneal implants and malignant ovarian
masses is shown in Figures 4 through 7. CT is still limited in its
ability to detect peritoneal implants <1 cm in size.
At our institution, we use oral, rectal, and intravenous
contrast in our CT studies. Oral contrast is consumed over a period
of 90 minutes. Following this, the helical CT scan is performed at
5-mm collimation in the portal-venous phase of contrast enhancement
at 60 seconds following the contrast injection. The importance of
the use of oral and rectal contrast is to optimally distend both
the small and large bowel. This improves the detection of those
peritoneal implants that, in the absence of good oral contrast
opacification, would not likely be detected because of volume
averaging with adjacent small bowel.
MRI
MRI can be used as a problem-solving tool in sonographically
indeterminate ovarian masses by providing better tissue
characterization. MRI can be extremely accurate in the diagnosis of
benign lesions, such as mature cystic teratomas (containing fat),
endometriomas (containing blood products), and nondegenerative
leiomyomas in the adnexa.
28
In most studies, including a large multicenter trial, MRI was shown
to be superior to both ultrasound and CT in diagnosing malignancy
in indeterminate ovarian masses.
20
The findings most predictive of malignancy on MRI are vegetations
in a cystic mass and necrosis in a solid tumor. Gadolinium-enhanced
imaging is useful in characterizing the internal architecture of
cystic lesions. Papillary projections, necrosis in a solid tumor,
and septations can be readily detected on contrast-enhanced MRI.
Peritoneal implants are best detected on postcontrast, breath-hold,
fat-saturated T1-weighted images. MRI and CT have been shown to be
equally effective for staging of advanced ovarian cancer.
20,26
Limitations of MRI include the cost, long acquisition time, and the
resultant motion artifact. The appearances of benign ovarian masses
and peritoneal implants on MRI are shown in Figures 3, 4, and
8.
At our institution, we use a 1.5T magnet and acquire coronal
T1-weighted, axial T2-weighted, sagittal T2-weighted, and pre- and
post-gadolinium axial fat-saturated T1-weighted images. The
postcontrast fat-saturated axial T1-weighted images are extremely
useful in the detection of peritoneal implants, necrosis in a solid
mass, and enhancing septations or vegetations in a cystic mass.
Benign mature cystic teratomas contain macroscopic fat, which is
suppressed on the fat-saturated sequences and, hence, will be
helpful in making the diagnosis.
Ovarian masses with fibrous components include fibroma,
fibrothecoma, cystadenofibroma, and Brenner tumor. The fibrous
components of these masses tend to have very low signal intensity
on T2-weighted MRI. Hemorrhagic cysts can be diagnosed by the
signal intensity of the hemorrhage within the cyst with lack of
contrast enhancement on the postcontrast images. Typically,
hemorrhagic cysts are of high T1 signal intensity and of variable
T2 signal intensity.
PET
Positron emission tomography (PET) using 18F-labeled
fluorodeoxyglucose (FDG) is a relatively new imaging modality. The
role for PET and PET/CT in the diagnosis and staging of ovarian
cancer is controversial. The reported sensitivity for the diagnosis
varies between 83% and 86%, and specificity varies between 54% and
86%.
29
The PET appearance of peritoneal implants is shown in Figure 4.
Borderline and early-stage ovarian cancers can be falsely
negative on PET imaging due to the small amount of FDG-avid tissue.
False-positive results can also arise from inflammatory processes
and benign ovarian tumors. Due to the limited resolution of PET,
small tumor implants may not be detected despite increased FDG
uptake.
29,30
There appears to be a role for PET/CT in detecting sites of
recurrent ovarian cancer when CT or MRI is negative despite a rise
in cancer antigen (CA) 125 levels.
31
Conclusion
The role of imaging in ovarian cancer is threefold: Detection,
characterization, and staging. The detection of ovarian cancer can
often be difficult by physical examination alone. Imaging has come
to play a key role in the detection of ovarian cancer. Imaging
plays an equally important role in the characterization of ovarian
masses, as the number of benign ovarian masses greatly exceeds the
number of malignant masses. Preoperative staging by imaging is also
crucial to identify patients who are potential candidates for
optimal debulking surgery. This article reviewed the roles of the
different imaging modalities in the evaluation of ovarian
cancer.