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Use of Color Doppler in the Evaluation of Suspicious Endometrial Findings
Table 29.2 Patients grouped by menopausal status and benign/ malignant histology
Visualization and Morphology of the Vessels
Menopausal status
Total 23 24.2 % 72 75.8% Premenopausal 2 8.7% 17 23.6 % Perimenopausal 1 4.3 % 13 18.1% Postmenopausal 20 87.0% 42 58.3 %
Table 29.3 Histological diagnoses
Histological diagnosis Number
Endometrium in desquamation phase 1 Endometrium in secretory phase 4 Autolytic endometrium 1 No endometrium detected 3 Residual proliferation or transitional menopausal
endometrium Quiescent, atrophic, or fibrotic endometrium
29
(appropriate for age) Polypous or cystic-glandular hyperplasia 34 Adenomatous hyperplasia (diffuse/polypous) 2 Atypical adenomatous hyperplasia 1 Hydatidiform mole 1
Malignant lesions Benign lesions Number Percent Number Percent
14
11
Visualization of endometrial vessels. We were able to visualize endometrial vessels in 7 % of all the patients in our study. Ves-
sels could be defined in 100% of the patients with malignant
disease (Fig. 29.
1) but in only 66.6% of the patients with a
benign endometrial condition. This difference is statistically
significant (p = 0.0034). It is interesting to note the relatively
higher percentage of patients with benign findings after menopause in whom endometrial vessels could not be visual­ized: 43 % versus 24% of the premenopausal patients (not
statistically significant at p = 0.27431 (Fig. 29.
2). Other authors
also describe d differences in the visualization of endometrial vessels between benign and malignant tumors. Different authors have reported visualization rates of 33.3%
3, 17, 25
100 %
. The differences are even greater in benign en-
12
,56%35, and
dometrial conditions, however, ranging from no endometrial vessels amined
12,17,21,27
1
.
to finding vessels in 100% of the women ex-
Readable waveforms. Readable waveformindices could be rec-
orded in approximately 83% of the cancer patients (Fig. 29.
3)
but in only 38 women with benign endometria (= 52.8%). This difference is also statistically significant. When we consider only women with def inable vessels, we were able to record readable waveforms in approximately 80 % of cases, regardless of whether the lesions were malignant or benign (malignant 83%, benign 79%), enabling us to calculate waveform parame­ters.
Comparison with other studies. Aleem et al.
2
also found signifi­cant differences in the ability to visualize and sample benign and malignant endometrial lesions, but in a substantially
smaller percentage of cases. They could demonstrate en-
dometrial vessels in 43 % of carcinoma cases (and myometrial vessels in 93%) but in only 12% of cases with b enign hyper­plasia and in no cases with leiomyomas (although myometrial vessels were visualized in 63% and 55 % of these cases, respec­tively). Thus, the nonvisualization of blood vessels cannot be
a
282
b
Fig. 29.1 Endometrial carcinoma (pT1c pN0 G2 adenocarcinoma) in
a 72-year-old woman.
a B-mode image. b Color flow image of the endometrial vessels, showing heavy vascu-
larization.
Fig. 29.2 Scant vascularity is observed in postmenopausal bleeding
with a benign etiology (glandular-cystic polyp of the uterine mucosa).
Experience at the Department of Obstetrics and Gynecology, Homburg University Hospital, Saar
a
b
Fig. 29.3 Endometrial carcinoma (pT1 b pN0 G1–2 adenocarcinoma) in a 64-year-old woman.
a Color flow image. b Resistance index = 0.40.
used as a criterion for excluding malignancy—especially since
we found that as we gained experience with the method we were able to define endometrial vessels more frequently even
in cases with a benign histology (Table 29.
4).
Number of vessels sampled. The number of vessels that could be sampled by Doppler sonography in our examinations was six or fewer.This number was similar for benign and malignant lesions: 2.6 1.2 vessels for malignant endometrium versus
2.5 1.3 for benign lesions. The only marked difference was seen in the premenopausal women: 3.5 vessels in patients
with a malignant disease versus 2.1 vessels in patients with a benign condition. A larger population of premenopausal cancer patients would have to be studied in order to draw further conclusions.
Vascular morphology. With regard to vascular morphology,
2
Aleem
noted a dense vascular distribution in 80% of malig­nant lesions, contrasting with the more isolated vessels sup­plying benign lesions, although he looked only at myometrial
vessels. Carter et al.
7
described the endometrial blood supply of benign lesions as fine vascular branches with no “hot spots,” differing from the increased intratumoral flow seen in carci­nomas. We noted a different vascular distribution in our study as well, finding that long segments of endometrial vessels could be visualized only in association with endometrial cancers (Figs. 29.
1, 29.2). This has been cited as a possible crite-
rion for benign–malignant differentiation, but it must be
viewed very cautiously because of its subjectivity. In patients examined with an advanced ultrasound scanner, there were cases in which long vascular segments could be defined in the endometrium with no histological evidence of malignancy. It appears, then, that technological advances in ultrasound in­struments are basically providing improved sensitivity in visu­alizing blood vessels and defining their morphology.
Gynecological Ultrasound
Table 29.4 Visualization and sampling rates of endometrial vessels reported by various authors under various conditions; large differences in visu-
alization rates are reported in different studies
Author Visualization rates
with malignant lesions
Visualization rates with benign lesions
Influences/special conditions
Achiron 1995 100% (45/45) on tamoxifen Aleem 1995
2
43% 12% Hyperplasia
no hormones, postmenopause
9% Control
Alge 1996 not specified (n = 8) 46 % without hormones
79% with hormones
Bonilla-Musoles
3
100% (n = 2) 45.5 % Hyperplasia
With/without hormone replacement; rates
not reported for cancer cases
With hormone replacement
3.6% Proliferative endometrium Flam 1995 Hata 1991
12
17
33.3% (9/27) 0
100%(n=10) 0(n=31)
Hata 1992 77.7% (7/9)
Juhasz 1990
21
89% (8/9) 21% Leiomyomas
Myometrial vessels in benign cases
0% Adenomyosis
Kupesic-Urek 1993
Sheth 1995
25
35
Our Study 1997 100%
100% (n = 26) 67% (167/250) 56% (5/9) 64% (23/36) No hormone replacement therapy
66.6%
Sampled: 82.6%
Sampled: 52.8%; 79.2 % in patients with definable vessels
283
Use of Color Doppler in the Evaluation of Suspicious Endometrial Findings
Other authors also reported nonsignificant results. Sheth and
Resistance Indices of Endometrial Vessels
RI. In the study by Kupesic-Urek et al.25, the resistance indices
in the endometrial vessels were considerably lower than in the uterine arteries, with an RI of 0.37 for carcinoma and RI = 0.54 for benign endometrium. Juhasz et al.
21
reported similar values, whereas other studies with considerably higher values found significant differences, although the indices for carci­noma in those studies were already as high as those for benign endometrium in the previous studies
2, 37
. In our study popula­tion, the resistance indices tended to show lower values in malignant endometrium, especially when minimum values were compared: 0.54 versus 0.57. This difference is not signifi­cant, however (p = 0.2849). The mean and median values showed very slight differences: RI sus RI
= 0.61 for benign endometrium (Table 29.5). The
mean
= 0.62 for carcinoma ver-
mean
range of RI values was higher in malignant endometrium than in benign endometrium, but there was an almost complete overlap of values between the two groups. This large overlap does not permit a benign-malignant differentiation in any given case.
29
PI and S/D ratio. We obtained similar results for the other waveform parameters—the pulsatility index and S/D ratio.
Sladkevius are the only authors who published values for en­dometrial vessels. Sheth examined only endometrium thicker than 8 mm. Sladkevius did not find significant differences in the endometrial vessels but did in the uterine artery. The min­imum resistance indices reported by Sheth both groups than in our study. Sladkevius, working with the pulsatility index, also found lower values (Tables 29.
29.
RI in pre- and postmenopausal cancers. We did not find a corre-
lation between waveform indices and menopausal status. The only notable finding was a slightly decreased minimum and mean resistance index in carcinomas after menopause com­pared with premenopausal cases (0.53 versus 0.58 for RI
0.61 versus 0.67 for RI minate, however, given the small case numbers of pre­menopausal endometrial cancer. Sohn et al. likewise found no differences in blood flow between cancerous and healthy en­dometria before menopause, but they did observe significant differences in Doppler parameters after menopause (RI benign findings).
35
were lower in
7).
Effect of Menopausal Status and Hormone Use
min
). Statistical significance is indeter-
mean
= 0.54 with malignant findings and RI
min
= 0.65 with
min
6 and
and
284
Table 29.5 Mean (and median) values of RI index) and RI
(mean resist ance index) with standard deviation,
mean
(smallest resistance
min
shown separately for benign and malignant lesions
Lesion category RI
min
Benign 0.57 0.11
(0.56)
0.30 – 0.83
Malignant 0.54 ⫾ 0.18
(0.50)
0.29 – 0.83
RI
mean
0.61 0.10 (0.61)
0.43 – 0.83
0.62 0.14 (0.60)
0.39 – 0.86
Table 29.6 Reference list for endometrial vessels with significant results
Author Number Vessels Indices for
malignant lesions
Juhasz 1990 Hata 1991
21
17
168 Endometrial vessels RI
68 Subendometrial vessels
= 0.38 RI
min
RI
= 0.54 RI
min
(arcuate arteries)
Kupesic-Urek 1993
Kurjak 1993 Kurjak 1994
27
28
276 Endometrial uterine
artery
750 Endometrial vessels RI
5013 Endometrial/myometrial
RI = 0.53 RI = 0.37
= 0.42 RI
mean
25
vessels
Aleem 1995
Sohn 1993 35 Endometrial vessels? RI
a
Includes different groups with benign pathology
2
42 Endometrial/myometrial
Gefäße
RI
= 0.53
mean
= 0.88
PI
mean
= 0.54 Premenopausal
min
Tamoxifen therapy. It is interesting to consider the effects of hormones that influence endometrial metabolism. Patients on tamoxifen therapy are of particular interest, because B-mode ultrasound in these patients often reveals a thickened, irregu­lar endometrium that does not correlate with histological ab­normalities. An average of 2.5 vessels could be sampled in cancer patients receiving tamoxifen therapy (two vessels in one case, three in another). This is consistent with the average number of 2.13 generally reported for this group. The average number of sampled vessels in women with benign en­dometrium on tamoxifen was 0.43, which is well below the general average of 1.33 vessels (Fig. 29.
Indices for
Analysis
4). The waveform pa-
benign lesions
0.50 Cutoff value: RI = 0.50
min
0.68 (
min
RI = 0.76
a)
Statistically significant
Statistically significant
RI = 0.54
= 0.65 Statistically significant
mean
Screening:
min
0.42
RI
0.64
mean
PI 1.11 (*)
6 cancers detected at RI Statistically significant for
myometrial vessels Statistically significant in post-
RI = 0.55
menopausal patients
Experience at the Department of Obstetrics and Gynecology, Homburg University Hospital, Saar
Table 29.7 Studies reporting nonsignificant waveform differences in benign-malignant differentiation
Author Number Vessels Indices for
malignant lesions
Sheth 1995
Sladkevius 1994
35
36
45 (9 cancers)
138
(24 cancers)
Endometrial RI
PI = 0.71
Uterine artery, sub­endometrial and en-
Endometrial: PI = 0.7
dometrial
= 0.48
min
Subendometrial:
PI = 0.8
Uterine artery:
PI = 1.4
Chan 1994
8
67
Uterine artery PI
=2.17 PI
mean
(17 cancers)
Flam 1995
12
39 (27 cancers)
Uterine artery PI
= 1.70
mean
after radiotherapy:
PI = 1.22
Our Data 95
(23 cancers)
Endometrial RI
= 0.54
min
= 0.62
RI
mean
PI
=1.12
mean
Indices for
Remarks
benign lesions
RI
= 0.48
min
PI = 0.72 Endometrial:
Endometrium 8 mm, flow
in 5/9 cancer patients
Significant in uterine arter y PI = 0.7 Subendometrial: PI = 0.8 Uterine artery: PI = 1.8
= 2.28 No significant differences
mean
between cancer and benign lesions
= 1.94 Only significant differences in
PI
mean
cancer cases before and after
radiotherapy
= 0.57
RI RI PI
min
mean
mean
= 0.61 =1.10
No significant differences
Fig. 29.4 F ibrocystic endometrial polyp
with atrophic mucosa in a patient on tamoxifen therapy.
a B-mode image. b Long vascular segments are not visual-
ized.
Gynecological Ultrasound
ab
rameters of the sampled vessels showed marked differences in these cases, with RI compared with the markedly high values of RI and RI
= 0.72 0.15for benign findings. As far as we can tell
mean
= 0.40 and RI
min
= 0.510.01 for cancer
mean
= 0.72 0.16
min
from the small case numbers, these differences are not statisti­cally significant (p = 0.1025 and 0.1213).
Estrogen/progestin therapy. The differences were smaller and not significant in patients taking other hormones such as estrogens and/or progestins. The resistance indices in patients
with benign histology who were taking estrogens were in the average range for all patients. The RIs were slightly below aver­age in patients taking progestins and slightly above average in patients taking an estrogen–progestin combination. Patients
with cancer who were taking estrogens had slightly higher­than-average resistance indices (RI RI
= 0.64 0.13), and patients without cancer who were
mean
= 0.60 0.18 and
min
taking progestins had slightly lower indices, with RI
= 0.43 0.18 and RI
min
= 0.52 0.10.The differences
mean
were not statistically significant. Zalud could likewise find no significant effect of hormone replacement therapy on re­sistance indices. On the other hand, Achiron et al.
1
found signif-
icantly lower resistance indices when the estrogen level
reached its peak at midcycle. When the progesterone level sub­sequently rises, the resistance indices return to higher values.
Effect of Histopathological Parameters, with Reference to Prognostic Factors
When we looked at the histological diagnoses separately, we
were struck by the particularly low resistance indices in a patient with a müllerian mixed tumor (RI RI
= 0.51) and by the high resistance indices in a patient
mean
with atypical adenomatous hyperplasia (RI
Also, tumors at a higher stage or grade tended to show lower impedance values, although the differences were not signifi­cant: RI
0.610.14 for stage Ib tumors, and RI Ic tumors. As for tumor grades, the resistance indices ranged from RI
grade 2 cancers to RI significant). Hata et al. also noted a tendency toward finding lower resistance indices in tumors of a higher stage (though less pronounced) or grade. Again, the differences were not sig­nificant.
= 0.67 0.20 for stage Ia tumors, RI
mean
= 0.65 in grade 1 tumors and RI
mean
mean
= 0.40,
min
=RI
min
= 0.570.11 for stage
mean
= 0.62 0.16 in
mean
mean
= 0.67).
mean
= 0.570.09 in grade 3 cancers (not
=
285
Use of Color Doppler in the Evaluation of Suspicious Endometrial Findings
Table 29.8 Resistance indices for subendometrial and myometrial
Subendometrial and Myometrial Vessels
vessels
286
In 24 patients, we additionally defined subendometrial and myometrial vessels and sampled their waveforms. We found that the differences between the vessels in patients with cancerous and benign endometria were even smaller: the min­imum and mean resistance indices in cancer patients were slightly (not significantly) higher than in patients with benign histology. In all cases the resistance indices found in the en­dometrial vessels were markedly lower than in waveforms

Summary

On the whole, the color Doppler examination of endometrial vessels and the analysis of waveform indices do not appear to be sufficiently accurate for the differential diagnosis of en­dometrial changes, nor can they provide a reliable screening method for endometrial carcinoma. Despite the fact that the patients in our study whose endometrial vessels could not be visualized with color Doppler consistently had benign histo-
29
logical findings, this is not sufficient to justify the omission of histological evaluation, especially for less experienced ex­aminers. Nevertheless, when resistance indices are combined with the evaluation of vascular structural abnormalities and the visualization of long, branched endometrial vascular seg­ments, which are suggestive of carcinoma, the color Doppler examination provides clues that can advance the differential diagnosis of endometrial disease.
References
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RI
min
RI
mean
Number
Malignant 0.66 0.10 0.71 0.09 4 Benign 0.65 0.15 0.69 0.15 20
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28 Kurjak A, Shalan H, Kupesic S et al.: An attempt to screen asympto-
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Gynecological Ultrasound
287

Malignant Uterine Tumors

30
Because ultrasonography can detect even subtle changes in the endometrium and myometrium, it is the modality of choice in the evaluation of many uterine tumors. This chapter explores
A. Kurjak and S. Kupesic

Endometrial Carcinoma

Incidence
The interest of oncologists in endometrial carcinoma has grown considerably in recent years, due primarily to the in-
30
creased prevalence of this disease dometrial cancer is due in part to better socioeconomic condi­tions, enabling more women to reach the advanced age at which the disease is most common. Other factors are the grow­ing popularity of estrogen replacement therapies and also nutritional factors, especially higher cholesterol levels.
Endometrial carcinoma has become the leading cancer of the female genital tract in many developed countries. Except for Japan, the incidence is highest in industrialized nations. More than 39,000 new cases are reported annually in the United States alone
More than 70% of endometrial carcinomas are stage I tumors at diagnosis, which currently have a five-year survival rate of 80 %. Five-year survival rates fall dramatically as the tumor stage increases invasion, the more swiftly the disease progresses
14
.
34
. The greater the extent of myometrial
6
. The rising incidence of en-
23
.
the diagnostic capabilities of transvaginal color and pulsed Doppler ultrasound as a noninvasive method of investigating malignant uterine tumors.
histological grade and clinical stage compared with the general population. If myometrial invasion is present, the foci tend to be superficial and generally have a good prognosis.
Although it is possible for a complex or atypical hyperplasia to progress to endometrial cancer, endometrial hyperplasia is considered more of an indicator of carcinoma than an actual precursor.
Obesity and diabetes. The link between endometrial cancer and other risk factors has been analyzed in various epidemio­logical studies. Obesity increases the risk of endometrial cancer as a result of increased endogenous estrogen produc­tion and greater bioavailability of the estrogen that is pro-
5, 37
duced dometrial carcinoma and thus ranks behind age, weight, and socioeconomic status. Hypertension is common in women with endometrial cancer but does not appear to be an indepen­dent risk factor
. Diabetes is associated with a 2.8 relative risk for en-
5
.
Target Group for Screening
288
Risk Factors
Age and genetic factors. Age is the greatest risk factor for the
development of endometrial carcinoma. Less than 25 % of all cases occur before menopause. The incidence of endometrial cancer is highest between 55 and 65 yearsof age tors also appear to play an important role, as the disease is more prevalent among white women than black women.
Estrogen. Nearly 40–50 % of all endometrial cancers develop from atrophic endometrium, independent of hormonal in­fluences. Nevertheless, a link is believed to exist between hor­monal therapy and endometrial carcinoma. Unopposed high­dose estrogen therapy administered for a prolonged period of time increases the relative risk compared with short-term, low-dose therapy. The incidence in women who are treated with estrogen and progestin during menopause is even lower than in the general female population develop during unopposed estrogen use tend to show a lower
14, 37
31
. Genetic fac-
. Even cancers that
The American Cancer Society has recommended selective screening for all women who are considered to be at high risk for endometrial cancer. Unfortunately, even the screening of women with risk factors such as obesity, nulliparity, late menopause, diabetes, unopposed estrogen use, or a history of colon cancer, breast cancer, or pelvis radiation will detect only around 50% of all endometrial cancers. Moreover, the cancers in women who do not have these risk factors tend to be more aggressive and poorly differentiated.
Because the principal risk factor is age, screening should be extended to all postmenopausal women. One extra screening examination per year is also advisable for women who are at increased risk.
Screening: Dream or Reality?
Endometrial carcinoma has traditionally been viewed as a very treatable form of cancer. Generally it takes a less fulminating course than other gynecological malignancies, with the result
Endometrial Carcinoma
that, in many cases, a lower priority is placed upon en­dometrial cancer in terms of screening and early detection.
Increased incidence. Three decades ago, cervical carcinoma had a four times higher incidence than endometrial carcinoma.
Today, however, the incidence of endometrial carcinoma is
twice that of cervical carcinoma
5
. On the one hand, these changes document the success of early screening programs for cervical cancer; but they also reflect an absolute increase in en­dometrial carcinoma and underscore the need for a reliable screening method.
Uterine bleeding. The earliest sign of endometrial cancer is uterine bleeding
7
. The most frequent cause of postmenopausal
bleeding, however, is sclerotic vascular changes leading to
venous or arterial rupture
4
; fewer than 10% of women with postmenopausal bleeding have endometrial cancer. The estab­lished diagnostic protocol is based upon fractional dilation and curettage, which is performed mainly in selected patients at risk (e.g., dysfunctional bleeding during menopause). The costs and risks that are associated with inpatient fractional curet­tage, plus the low diagnostic yield of endometrial cancers with this procedure, have prompted the development of numerous new devices for obtaining endometrial material for cytological analysis or tissue samples for histological evaluation in the am­bulatory setting.
Cytological Methods
Improved screening by cervical cytology has resulted in the early detection of cervical premalignant lesions. This method has little importance in the early diagnosis of endometrial cancer, however, and it is unreliable as a screening test for that disease
38, 40
.
Smears taken directly from the uterine cavity could solve this problem. It is hoped that this cytological method will be easier to perform, cause less discomfort, reduce costs, and pro-
vide interpretable samples of atrophic endometrium. En­dometrial smears are difficult to interpret, however, and there are no standard morphological criteria for diagnosing hyper­plasia. Moreover, a positive cytological sample still requires histological confirmation
8, 17
.
Histological Methods
Intracervical curettage is not a practical screening method for endometrial cancer, as it has been estimated that up to 14% of postmenopausal women have an obliterated cervical canal Endometrial biopsy is generally diagnostic in women who have postmenopausal bleeding and endometrial cancer. The main advantages of endometrial biopsy over cytology are its significantly greater sensitivity and higher specimen quality. It is an invasive procedure, however, and the cost–benefit ratio is an important factor to be considered.
In summary, it would be very beneficial to have a procedure that is less invasive than diagnostic biopsy, provides a com­parably high detection rate, and has an acceptably low false­positive rate. If this method could detect endometrial cancer at an early stage in asymptomatic women, it could substantially reduce the morbidity and mortality of this disease.
28
Ultrasound
In recent years there have been remarkable advances in imag­ing procedures that allow clinicians to detect physiological and pathological changes in the fetal genital tract. The various sonographic procedures in particular have evolved into an im­portant modality for the evaluation of uterine tumors.
Transabdominal Ultrasound
Since ultrasound has become widely utilized in gynecology, many reports have been published describing the sonographic appearance of the normal uterus and of uterine abnormalities.
The typical appearance of the postmenopausal endometrium is a single, echogenic line that is markedly thinner than the premenopausal endometrium. The inner layer of the myo­metrium appears as a thin hypoechoic ring surrounding the endometrium. B-mode ultrasound has also proved to be a very accurate method for determining endometrial thickness,
yielding results that show very good agreement with actual measurements in surgical specimens
Endometrial thickness. Endometrial carcinoma typically pro­duces a thickened endometrium of varying echogenicity.There are other lesions that closely mimic this appearance, however, including endometrial hyperplasia, endometrial polyps, ovar­ian carcinoma that has spread to the endometrium, hema­tometra, mucometra, and pyometra (5 mm) is a significant finding in postmenopausal women
with vaginal bleeding, because a thin endometrium is usually associated with atrophic or benign changes. This finding, then, can obviate the need for endometrial biopsy or curettage. A major disadvantage of transabdominal ultrasound is the fact that endometrial thickness cannot be accurately measured in a retroflexed uterus. The endometrium is also difficult to eval­uate in patients with uterine prolapse
Echogenicity. Investigators have looked for a possible connec­tion between endometrial echogenicity and tissue differentia­tion (tumor grade). High-intensity echoes were a more com­mon finding in well differentiated or moderately differentiated carcinomas, probably because these tumors contain large numbers of glands
10
. Heterogeneous echo patterns were found in poorly differentiated carcinomas dometrial echo patterns may also be seen in other conditions, such as endometrial hyperplasia, hematometra, pyometra, and adenomyosis.
.
Depth of invasion. The most appropriate treatment for en­dometrial carcinoma depends on the depth of myometrial in-
vasion. Deep invasion means a considerably higher risk of metastasis, and preoperative irradiation or a more extensive surgical procedure is indicated
3
correlates closely with the depth of myometrial invasion:
93.7% with no invasion, 88.1% with the invasion of superficial myometrial layers, and 36.2% with deep invasion cases the degree of myometrial invasion can b e determined
very accurately with ultrasound accuracy of the measurement is compromised by intracavitary exophytic tumor growth, leiomyomas, or other lesions that
24
.
25
. A thin endometrium
30
.
10
. However, these en-
. The five-year survivalrate also
24
. There are cases in which the
24
. In most
Gynecological Ultrasound
289
Malignant Uterine Tumors
alter the structure of the myometrium and distort the uterine wall. Obesity and a retroflexed uterus can also make it difficult to accurately determine the depth of myometrial invasion by endometrial carcinoma with transabdominal ultrasound.
Transvaginal Ultrasound
Transvaginal ultrasound has several advantages over trans­abdominal scanning: there is no need for a full urinary bladder, and higher transducer frequencies can be used for the more detailed visualization and assessment of genital tract mor­phology. Transvaginal sonography can define the extent of my­ometrial or cervical invasion by endometrial carcinoma and can thus make an important contribution to preoperative stag­ing.
Endometrial thickness. The thickness of the endometrium, as measured by transvaginal ultrasound, correlates closely with the presence of endometrial carcinoma found that the normal postmenopausal endometrium is thin, showing a total (double layer) thickness of 6–8 mm. Fleischer
11
et al. (single layer) should be considered a normal finding in post-
30
even stated that an endometrial thickness of 2–3 mm
menopausal women. In any case, a double-layer endometrial thickness of more than 10mm in postmenopausal women is suggestive of hyperplasia or carcinoma
Cutoff value. In a prospective study, 539 asymptomatic post­menopausal women were examined by transvaginal sonography. Every fifth woman whose endometrial thickness (single layer) measured more than 4 mm at ultrasound was found to have en­dometrial carcinoma. The authors concluded that a cutoff value of 4 mm (single layer) appeared to be a better indicator of en­dometrial carcinoma than postmenopausal bleeding center study that included eight Scandinavian gynecology depart­ments, Wikland et al. menopausal bleeding who had been admitted for fractional curet-
tage. They did not find endometrial carcinoma when the en­dometrial thickness was 4 mm (single layer). The average en­dometrial thickness in patients with endometrial carcinoma was 18mm (range of 5–55 mm).
Nasri et al. 111 postmenopausal women. Of the 103 women with bleeding, 93 underwent fractional curettage and 10 were managed conserva-
tively with a repeat scan at six months. The authors found that 29
29
39
examined 1000 women with post-
performed transvaginal ultrasound scanning on
25
. Schoenfeld et al.
15
(Fig. 30.1).
33
. In a multi-
patients (31%) had abnormal endometrial histology when en­dometrial thickness was ⬎5 mm. They r ecommended an en- dometrial thickness of 5 mm as an appropriate cutoff level for the conservative management of patients with postmenopausal bleed­ing or in screening programs for endometrial cancer.
Practical recommendations. This concept can be applied clini-
cally in postmenopausal women. Finding an endometrial thickness less than 5 mm at ultrasound could avoid unneces-
sary surgery in these women, which is important in this age
group. An endometrial thickness of 5 mm (single layer) or
10mm (double layer) may also be a useful screening criterion
for endometrial carcinoma.
The studies cited above are sufficient to justify a recom­mendation that all postmenopausal women undergo trans­vaginal sonography. If the maximum endometrial thickness is only 1 mm, the next follow-up should be performed one year later. In women with an endometrial thickness of 2–3 mm, re­peat scans should be obtained every 2–3 months. Women with
35
an endometrial thickness of 4 mm or more should undergo di­lation and curettage, and a repeat scan should be obtained three months later. It should be noted in this regard that thick­ening of the endometrium can occur in women who are receiv­ing estrogen therapy. Transvaginal ultrasound scanning is not beneficial in this subset of patients.
The surrounding hypoechoic ring should not be included in the measurement of endometrial thickness, as it represents the inner layer of the myometrium. This layer is symmetrical and intact in the normal postmenopausal uterus and also in women with endometrial polyps and simple or atypical hyper­plasia. With invasive endometrial carcinoma, however, ultra-
sound demonstrates absence or irregularity of this layer
30
.
At present, transvaginal ultrasound appears to be the pre­ferred study for evaluating the endometrium. It is a simple, noninvasive procedure that is well tolerated by most patients and can be used for concomitant screening of the ovaries.
Transvaginal Color and Pulsed Doppler Sonography
The introduction of transvaginal color and pulsed Doppler ul­trasound has made it possible to investigate the vasculariza­tion of benign and malignant pelvic tumors. When color Dopp­ler is applied to the endometrium, it can increase the sensitiv­ity of the transvaginal scan by displaying blood vessels as color-encoded areas superimposed on the B-mode image
20
.
290
Fig. 30.1 Anteflexed uterus with an endometrial thickness of 11 mm
in a postmenopausal woman. Histological examination revealed a well-differentiated stage Ia adenocarcinoma by the FIGO classifica­tion.
Uterine arteries. When the uterine arteries occupy a normal
anatomical location, they can usually be seen lateral to the cer­vix in a longitudinal scan. A characteristic flow velocity waveform can be recorded from the uterine arteries
21
. A study done in postmenopausal women showed a marked difference in uterine artery flow resistance between patients with en­dometrial carcinoma and healthy subjects
1c
. This could be a re-
sult of tumor angiogenesis. It should be noted in this regard
that a marked decrease of uterine artery flow resistance occurs during estrogen replacement therapy and that this effect is only partially reversed with progestin
1c
.
Tumor vessels. When endometrial carcinoma is present, areas of neovascularization can be seen within the tumor itself (Fig. 30.
2). These areas typically appear as thin, irregular ves-
Endometrial Carcinoma
Fig. 30.2 Color Doppler appearance of peripheral and intratumoral neovascularity in a patient with endometrial carcinoma.
sels that are irregularly distributed in the tumor and exhibit abnormal blood flow patterns
12,18,22, 36
. Analysis of the
waveforms sampled from these areas indicates a very low flow
resistance (Fig. 30.
3). This shows that flow assessment can be
used to decrease the false-positive rates in screening examina­tions based on endometrial thickness
2, 22
.
Protocol for Transvaginal Sonography
Transabdominal sonographywas used for many yearsto detect
endometrial carcinoma and assess the depth of myometrial in-
24
vasion high-frequency endovaginal probe, as the transvaginal route permits a better evaluation of the endomyometrial junction,
which is very important in terms of myometrial invasion. With the advent of color and pulsed Doppler ultrasound, we developed a protocol for transvaginal sonography in order to standardize both the examination and its interpretation.
tention to the uterus, which was examined in both longitudinal and transverse scans so that all of the endometrium could be evaluated.
. Better results can be achieved by scanning with a
We evaluated the entire genital tract
22
, giving particular at-
Fig. 30.3 Analysis of intratumoral blood flow in endometrial carci­noma indicates a low resistance index (RI = 0.41).
Gynecological Ultrasound
Fig. 30.4 Analysis of peritumoral blood flow in the same patient indi­cates a slightly higher resistance index (RI = 0.46).
B-mode ultrasound. B-mode imaging was used to evaluate the following:
Endometrial thickness, which is measured in longitudinal section from the anterior subendometrial halo to the op­posite side (double-layer measurement, Fig. 30.
Endometrial echogenicity, which is classified as hypoechoic
4).
or hyperechoic to the myometrium or as nonhomogeneous.
Presence or absence of intracavitary fluid (Fig. 30.5).
Integrity of the subendometrial halo or presumed depth of myometrial invasion (less than half the myometrium= su­perficial; more than half = deep).
Color Doppler sonography. Color Doppler sonography was used to evaluate the following:
Signs indicative of irregular vascular structures (Fig. 30.6).
Localization of tumor vessels (intratumoral = within the en­dometrial echo; peritumoral= around the outside of the en­dometrial echo).
Fig. 30.5 Postmenopausal uterus with thickened endometrium con-
taining small cysts. The patient is receiving t amoxifen therapy. A small
intracavitary fluid collection is visible on the left side.
Measurements of peak systolic flow velocities and im­pedance in these vessels using the resistance index (RI). In women on hormone replacement therapy, the ef fect of the therapy on endometrial thickness and blood flow velocities should be taken into account (Fig. 30.
7).
291