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Abstract  

Common diagnostic challenges in gynecology and the role of imaging in their


evaluation are reviewed. Etiologies of abnormal uterine bleeding identified on pelvic
sonography and sonohysterography are presented. An algorithmic approach for
characterizing an incidentally detected adnexal mass and use of magnetic resonance
imaging for definitive diagnosis are discussed. Finally, the role of F18-
fluorodeoxyglucose positron emission tomography in the management of gynecological
malignancies, and pitfalls associated with their use are examined.

Keywords: Endometrial polyp, endometrioma, ovarian cyst, ovarian dermoid, pelvic


ultrasound

How to cite this article:


Iyer VR, Lee SI. Gynecologic imaging: Current and emerging applications. J Postgrad
Med 2010;56:117-24

How to cite this URL:


Iyer VR, Lee SI. Gynecologic imaging: Current and emerging applications. J Postgrad
Med [serial online] 2010 [cited 2010 Aug 8];56:117-24. Available
from: http://www.jpgmonline.com/text.asp?2010/56/2/117/65285

Imaging plays a pivotal role in resolving common complaints that present to a


gynecologist's practice. It has a central role in the workup of abnormal uterine bleeding.
Imaging also has wide applications in diagnosing incidentally detected adnexal masses.
Positron emission tomography/computed tomography (PET/CT) has several emerging
applications in the management of gynecological malignancies. These key issues that
radiologists must keep abreast of to reach conclusive diagnoses are discussed in this
review.

 :: Evaluation of Abnormal Uterine Bleeding with Ultrasound and


 
Sonohysterography

Although abnormal uterine bleeding (AUB) is most commonly caused by hormonal


imbalance, it can be a presenting feature of endometrial polyps, hyperplasia or cancer of
the cervix or endometrium. [1] About 20% of postmenopausal bleeding is a manifestation
of gynecologic malignancy, most commonly arising from the cervix or endometrium. [2]
Endometrial cancer accounts for approximately 10% of AUB in postmenopausal women
(and is likely to be lower in premenopausal women). However, as AUB is the most
common presenting sign of endometrial cancer, which is curable in early stages,
imaging is directed towards its diagnosis.

 :: Transvaginal Ultrasonography  
Imaging for diagnosis of AUB begins with transvaginal ultrasonography (TVUS),
which is widely available, well-tolerated and noninvasive. The appearance of normal
and abnormal endometrium in pre- and postmenopausal women is described below.

In a premenopausal woman, the endometrium consists of a superficial functional layer


and a deep basal layer. Thickness and echogenicity of normal endometrium change
during the menstrual cycle. [3],[4] In the early proliferative phase (Days 5 to 9), the
endometrium is relatively thin and displays an echogenicity similar to that of the
myometrium. In the late proliferative phase (Days 10 to 14), the superficial portion of
the endometrium is hypoechoic, whereas the deep portion of the endometrium appears
as a uniformly echogenic band. [5] This gives the characteristic multilayered appearance
of the periovulatory endometrium. Endometrial thickness and echogenicity steadily
increase in the secretory phase (Days 14 to 27). By the end of the secretory phase, the
entire endometrium is hyperechoic. Endometrial thickness should be measured on a
sagittal image of the uterus. [6] The thickness of the endometrium in different menstrual
phases is presented in [Table 1]. [5] However, this normal variation in endometrial
thickness compromises the utility of TVUS in the evaluation of AUB in this population.
In general, a thickness of >16 mm in a symptomatic patient is considered abnormal but
with sensitivity of 67% and specificity of 75%. [7]

The normal postmenopausal endometrium should appear thin, homogeneous and


echogenic. Double-layer endometrial thickness less than 5 mm without focal thickening
is consistent with atrophy. [8] Endometrial thickness greater than 5 mm (measured on
TVUS) is highly sensitive for detecting endometrial cancer in postmenopausal women
with AUB. It is more sensitive than other invasive diagnostic methods such as
endometrial biopsy or sonohysterography for diagnosing endometrial cancer in this
population [Table 2]. [7],[9],[10],[11],[12],[13]

The endometrium in a woman undergoing hormone replacement therapy (HRT) may


vary up to 3 mm if cyclic estrogen and progesterone therapy is being used. In
asymptomatic patients, a thickness of up to 8 mm is considered normal. If a patient
receiving HRT presents with AUB, endometrial thickness ≥5 mm warrants further
workup. [14] However, more recent findings suggest that a thickness of 8 mm, and not 5
mm, on TVUS may be a more appropriate cutoff point for endometrial biopsy in
symptomatic patients. [15]

Tamoxifen is a selective estrogen receptor modulator used in the treatment of breast


cancer and has a weak estrogen-agonist effect in the uterus. In asymptomatic
postmenopausal women treated with tamoxifen, endometrial thickness greater than 6
mm on TVUS suggests an abnormality. [16] In symptomatic patients, however, a cutoff of
5 mm warrants further investigation. The thickness of the endometrium increases with
duration of tamoxifen therapy. [17]

If the endometrium appears abnormal in thickness or morphology, the next step in the
diagnosis of AUB is nonfocal endometrial biopsy. In premenopausal women with AUB
unresponsive to hormonal therapy and risk factors for endometrial cancer (age >35
years, morbid obesity, chronic diabetes or hypertension, or chronic tamoxifen usage),
endometrial biopsy is recommended irrespective of TVUS findings.

 :: Sonohysterography  

If TVUS shows normal endometrial thickness, or if biopsy findings are benign, a search
must be initiated for focal pathology to explain the AUB. Sonohysterography and
hysteroscopy are both highly accurate in detecting focal endometrial pathology, such as
subendometrial fibroid and endometrial polyps [Table 2]. Sonohysterography involves
placement of a 5F catheter through the cervix and distension of the uterine cavity with
sterile normal saline (<20 ml) under ultrasound visualization. It is a minimally invasive
procedure, well-tolerated with no sedation and not associated with major complications.

Endometrial polyps [Figure 1] typically appear as well-defined, homogeneous,


polypoidal lesions that are isoechoic to the endometrium with preservation of the
endometrial-myometrial interface. They are usually attached to the endometrium with a
stalk containing a well-defined vascular supply. Polyps with atypical features, such as
cystic components, multiplicity, broad base, and hypoechogenicity or heterogeneity, are
sometimes seen. [18]

Submucosal fibroids appear as broad-based, hypoechoic, well-defined solid masses with


shadowing. An overlying layer of echogenic endometrium confirms their
subendometrial location, thus distinguishing them from endometrial polyps. In contrast
to endometrial polyps, submucosal fibroids distort the endometrial-myometrial interface
and show acoustic attenuation. [19] Pedunculated submucosal fibroids, fibroids that have
prolapsed into the endocervical canal and fibroids with a multilobulated surface are
unusual presentations. [20]

Sonohysterography is less useful for characterizing diffuse lesions like hyperplasia and
endometrial carcinoma. Endometrial hyperplasia appears as a diffuse thickening of the
echogenic endometrial stripe without focal abnormality. Distinguishing focal
endometrial hyperplasia from polyps is difficult because of similar characteristics of
focal endometrial thickening. [18]

Endometrial cancer should be suspected when the single layer of endometrium is thicker
than 8 mm, irregular, broad-based, or the endometrial-myometrial junction is lost.
Single layer thickness <2.5 mm is rarely associated with malignancy. [21] Chronic
tamoxifen therapy is associated with higher rates of endometrial pathologies, including
cancer. In addition, cystic subendometrial atrophy is also seen which results in an
apparently increased thickness on TVUS evaluation. In such patients sonohysterography
is useful in localizing the pathology to either the endometrium or the inner
myometrium. However, cystic hypertrophy is, at times, extensive enough to be mistaken
for diffuse or focal endometrial thickening, even at sonohysterography. [22]

 :: Evaluation of the Incidental Adnexal Mass with US, CT and MRI  

Incidental adnexal masses encountered on sonography pose a challenging problem


because features of benign and malignant adnexal masses overlap. Majority of
malignant ovarian neoplasms have a rapid rate of growth, and complete surgical
resection has been shown to improve prognosis. Thus, surgery is usually indicated if
imaging features cannot adequately characterize the lesion as benign. In order to prevent
unnecessary oophorectomies, while not missing early malignancy, the goal of imaging
must be to confidently assess a lesion as benign and refer all indeterminate lesions
expeditiously for surgical evaluation [Figure 2].

A wide range of sensitivity and specificity have been reported with US ranging from
84-97%, and 56-95%, respectively for the detection of ovarian malignancies. [23],[24],[25],[26],
[27],[28]
While readily available and a powerful first step, US performance is limited by
operator variability and patient body habitus. Thus, when an adnexal mass is
indeterminate on US, MRI has been shown to be more useful than CA-125 or CT as the
follow-up test [29] as it can definitively characterize as benign certain lesions that are
indeterminate on ultrasound.

Extra-ovarian adnexal lesions, whether solid or cystic, are likely to be benign and
should be followed up with MRI, a useful adjunctive in reaching a definitive diagnosis.
Solid-appearing ovarian lesions in both premenopausal and postmenopausal women and
cystic ovarian lesions in postmenopausal women should be followed up with MRI,
which can accurately characterize them as benign.

Most intra-ovarian cysts in premenopausal women are functional. A premenopausal


woman with a cystic ovarian lesion with some features of benign lesions should be
followed up with MRI, which can aid in reaching a conclusive diagnosis. Lesions with
features suggestive of malignancy, e.g. irregular and thick walls and septa, papillary
projections or large amount of ascites, should be referred for surgical evaluation. [30]
However, if the lesion is a complex cyst with no definite features of either malignancy
or benignity, it should be followed up with sonography in six weeks, then referred for
surgical evaluation if it persists.

Common extra-ovarian lesions include pedunculated and broad-ligament fibroids,


hydro- or pyosalpinx, parovarian cyst and peritoneal inclusion cysts, all of which can be
well-characterized by MRI. Certain intra-ovarian lesions like dermoids, endometriomas
and fibromas also have some classic MRI features.

 :: Pedunculated and Broad-Ligament Fibroid  

Although most fibroids can be identified on US, small subserosal pedunculated fibroids
and fibroids arising from the broad ligament can be difficult to characterize on TVUS as
arising outside the ovary. The US appearance is variable, ranging from hypoechoic or
echogenic with or without acoustic shadowing. On MRI, fibroids are well-rounded,
discretely-marginated structures with a whirling internal architecture. Signal intensity
on T1 and T2 weighted images and enhancement pattern varies widely. Continuity with
the uterine myometrium establishes the diagnosis of subserosal myoma. [31],[32],[33] MRI
can demonstrate the presence of normal ovaries, separate from the adnexal mass.

 :: Fibromas, Thecomas and Fibrothecomas  


These are the most common types of ovarian sex-cord stromal tumors, and together
represent 8% of ovarian neoplasms. [34] On US a hypoechoic and attenuating mass within
the ovary is characteristic. In cases where there is no attenuation and when the ovarian
origin is doubtful, MRI features are helpful. On MRI, fibromas and fibrothecomas are
well-marginated ovarian lesions with homogeneous internal architecture, isointense on
T1 images, and hypointense on T2 images with low-level gadolinium enhancement. [35]

 :: Endometrioma  

The most common US appearance of endometrioma [Figure 3] is that of a


hypoechoechoic lesion within the ovary which has diffuse low-level internal echoes. [36]
The presence of hyperechoic foci in the wall, different from the wall nodularity seen in
malignant lesions, increases the confidence in diagnosis; 4.9% of endometriomas appear
solid on sonography. [37] MRI helps in the characterization of endometriomas when US
imaging features are inconclusive or if malignant degeneration is suspected. On MRI,
endometriomas appear as "light-bulb" bright lesions on T1 weighted images, due to the
high concentration of blood products. A T2 "shading" effect has been described due to
the varying effect of the blood products [Figure 3]. Punctate or plaque-like T1 bright
lesions in the pelvis, irrespective of the T2 signal also indicate endometriosis.
Enhancement of the solid portions should raise concern for malignancy. [38]

Dermoids

Mature cystic teratomas are composed of tissue of ectodermal, mesodermal and


endodermal origin, with a predominance of ectodermal tissue. They are bilateral in 10%
of cases and more common in women in the reproductive age group. Dermoids are
usually unilocular cysts filled with sebaceous material and with a solid mural nodule
consisting of teeth, hair or sebaceous material. The sonographic appearance of a
dermoid is a cystic lesion with a densely echogenic tubercle [Figure 4]. It can also
appear as a diffusely or partially echogenic mass with sound attenuation or as a cystic
mass with thin echogenic bands. [39] MRI identifies macroscopic fat in dermoids as T1
bright lesions [40] that lose signal on fat saturation sequences. A few dermoids do not
contain macroscopic fat, but lipid is present in the cyst wall and in the Rokitansky
nodule. In these cases, gradient-recalled opposed-phase imaging can demonstrate loss of
signal within the wall or nodule. [35] The solid portion of dermoids demonstrate restricted
diffusion on diffusion-weighted imaging (DWI). [41]

 :: Tubo-ovarian Abscess, Hydrosalpinx and Pyosalpinx  

The natural history of pelvic inflammatory disease is progression from a phase of acute
salpingitis to involvement of the ovary in the form of a tubo-ovarian complex. Further
breakdown of the adnexal architecture results in a tubo-ovarian abscess (TOA). In the
acute phase, the wall of the  Fallopian tube More Details becomes edematous and thickened.
The fimbrial occludes, causing the tube to fill with pus and fold on itself. On US, the
folding of the tube gives rise to the appearance of incomplete septa on longitudinal
sections. On cross-section, the "cog-wheel" appearance is noted due to the sonolucent
tube with inflammed endosalpingeal folds. Chronic disease leads to hydrosalpinx which
appears sonolucent with hyperechoic projections on the wall, due to the flattened
endosalpingeal folds. [42] On CT, an adnexal mass with uniformly thick, enhancing walls,
regular, thickened septa and a thickened mesosalpinx are indicative of a TOA. Gas
bubbles, when seen in the mass, are diagnostic. [43]

On MRI, pyosalpinx and hydrosalpinx are tortuous, elongated adnexal lesions. Wall
thickening and contrast enhancement, [44] as well as enhancement of the surrounding
inflammation are seen in pyosalpinx. The signal intensity of the mass depends on the
protein content. However, they are typically hyperintense on T2 weighted images with
areas of shading and hypointensity in the periphery. On DWI, TOAs, similar to most
abscesses, demonstrate restricted diffusion.

 :: Peritoneal Inclusion Cyst  

Inflammation and adhesions of the pelvic peritoneum traps fluid secreted by the normal
ovary, giving rise to peritoneal inclusion cysts. The US appearance is that of a
multilocular cyst, with thin walls and septation, surrounding the ovary. [45] Fine
peritoneal adhesions extend to and distort the ovary, but do not penetrate the
parenchyma. When the ovary is thus entrapped, it appears like a "spider in a web". [46]
The cysts can be mistaken for hemorrhagic cysts, hydrosalpinx, pyosalpinx, serous or
mucinous cystadenoma, malignant ovarian lesions or dermoid cyst. [46] MRI helps in
definitive diagnosis of the entity when a normal ovary cannot be identified on
sonography, ipsilateral to the multiloculated cyst. The T1 hypo- and T2 hyperintense
cysts have a thin pseudo-wall formed by pelvic organs, bowel and the pelvic wall, and
conform to the shape of the surrounding space.

 :: Physiological Cysts and Hemorrhagic Cysts  

Follicular or corpus luteal cysts can be seen on US depending on the menstrual phase.
On US, follicular cysts are smaller than 5 cm in size, thin-walled, sharp-margined and
with posterior acoustic shadowing. They are T1 hypointense, T2 bright and with
postcontrast wall enhancement. Corpus luteal cysts and hemorrhagic cysts may have
walls thicker than 3 mm. The presence of blood products may result in the T1
hyperintense appearance of hemorrhagic cysts. [35]

 :: Parovarian Cyst  

Parovarian cysts are developmental remnants of the mesonephric ducts. The features of
parovarian cysts are similar to follicular cysts, except that they do not regress on US
follow-up. On MRI, the ovary can be identified separate from the lesion.

 :: Normal and Abnormal PET-CT Findings in the Female Pelvis  


The applications of 2-[fluorine 18] fluoro-2-deoxy-D-glucose (FDG) positron emission
tomography (PET) imaging in the management of gynecological malignancy are
manifold. PET, when concurrently performed and fused with CT images (PET/CT),
helps in the detection of lymph node spread of cervical cancer, to assess tumor volume
and to determine local control after radiotherapy. [47] The utility of PET in the detection
of malignancy stems from the ability to differentiate tissues with increased metabolism,
such as cancer cells. Several physiologic processes with increased metabolism show
abnormally high PET activity leading to misdiagnoses. Both the normal endometrium
and the ovary show varying uptake depending upon the menstrual phase. Therefore, for
routine clinical interpretation of PET/CT images, one must know the appearance of
normal physiologic uptake in the endometrium and ovary.

In a premenopausal woman with normal menstrual cycle and no gynecological


malignancy, physiological endometrial uptake has two peaks. One peak is at mid-cycle
[48]
and the other on the first three days of the menstrual flow. [48],[49],[50] Standardized
uptake values [SUV] of 5 ± 3.2 during menses and 3.7 ± 0.9 in ovulatory phase are
normal. [48] The endometrial uptake appears like an inverted triangle on axial images and
like a curvilinear or ellipsoid over the urinary bladder in sagittal images. [49] Neither
hormonal contraceptives nor intrauterine contraceptive devices increase the endometrial
uptake significantly. [48] In patients with menstrual irregularities, oligomenorrhea has
been shown to have high SUV similar to those seen during the normal ovulatory phase
endometrium, and amenorrhea has been shown to have values similar to
postmenopausal endometrium. FDG uptake should not be seen in the endometrium of
postmenopausal women. The SUVs in postmenopausal women taking HRT was not
seen to be higher in a study by Lerman et al.

In premenopausal women, physiological ovarian uptake of FDG PET is seen in the late
follicular, ovulatory and early luteal phase of the menstrual cycle. [49] Most commonly
increased FDG uptake is seen during the early luteal phase [Figure 5]. In women with a
known malignancy, FDG accumulations in corpus luteal cysts have been misinterpreted
as metastasis to iliac lymph nodes. [51],[52],[53] Physiological ovarian uptake is often
unilateral and appears round to oval with an SUV greater than 3. Lerman et al, found
that an SUV of 7.9 separated benign from malignant ovarian uptake; however, the
sensitivity for the detection of malignancy is only 57%. Disappearance on imaging
performed soon after the subsequent menstrual cycle most reliably confirms the
physiologic nature of the cyst. In order to avoid the confusion arising from functional
ovarian uptake, PET/CT scans in premenopausal women should be scheduled in the first
week after menses. Any FDG accumulation in the ovaries in a postmenopausal woman
should be considered suspicious for malignancy.

Heterogeneous and moderately intense FDG uptake has been seen in uterine fibroids. [54],
[55],[56],[57],[58],[59],[60]
The cause of this increased uptake may be related to the presence of
receptors for certain growth factors and to the high endometrial and cervical tissue
glycogen in myomatous uteri. [55],[56] No correlation was seen between the uptake in the
fibroid and the menstrual phase. [57] Kitajima et al, recently showed that the size of the
fibroid, and presence of degeneration did not significantly correlate with SUV.
However, a negative correlation was seen with age.
The utility of PET/CT in cervical cancers is well studied. Although MRI is more
sensitive in assessing local spread of cervical cancers, PET/CT has a high sensitivity in
detecting nodal metastases. The SUV max of the primary tumor can predict the presence
of lymph node involvement, tumor persistence following treatment and pelvic
recurrence. A higher SUV max also indicates a more aggressive tumor, and hence, the
need for more aggressive treatment. [61],[62] In ovarian cancer patients, PET/CT is useful
to detect macroscopic recurrence of ovarian cancer [63] and has been shown to be more
accurate than CT alone. [64] In advanced disease, it can be used to predict response of to
neoadjuvant therapy and survival. [65] PET/CT has been shown to modify treatment in
post-therapy surveillance of endometrial cancer in 33-73% patients in various studies.
[66],[67],[68]
Preliminary studies investigating the utility of PET/CT in uterine sarcoma, [69]
vulvar [70] and vaginal cancer [71] and gestational trophoblastic disease [72],[73] have shown
promising results. The role of PET/CT in gynecological malignancy is evolving from a
diagnostic tool into one that predicts survival and modifies treatment.

 :: Teaching Points  

In postmenopausal women with AUB, endometrial thickness >5 mm on TVUS warrants


further investigation.

In pre- and postmenopausal women with AUB, sonohysterography is useful in detecting


endometrial polyps and submucosal fibroids.

For adnexal masses indeterminate on US, MRI has been shown to be the next best test
for definitive characterization, especially if the lesion is thought to be benign.

In premenopausal women imaged with PET/CT hypermetabolic tracer uptake is seen in


the normal endometrium and ovary during certain phases of the menstrual cycle.

In postmenopausal women imaged with PET/CT, hypermetabolic tracer uptake in the


endometrium or the ovary should be considered suspicious for underlying pathology.

 
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