DOI: 10.1148/rg.231025048
(Radiographics. 2003;23:137-150.)
© RSNA, 2003
Transvaginal US and Hysterosonography in Postmenopausal Women with Breast Cancer Receiving Tamoxifen: Correlation with Hysteroscopy and Pathologic Study1
Katherine Fong, MB, BS, FRCPC,
Petrina Causer, MD, FRCPC,
Mostafa Atri, MD, FRCPC,
Alice Lytwyn, MD, MSc, FRCPC and
Rose Kung, MD, MSc, FRCSC
1 From the Departments of Medical Imaging (K.F., P.C., M.A.), Pathology (A.L.), and Obstetrics and Gynecology (R.K.), Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Ontario, Canada. Recipient of a Certificate of Merit award for an education exhibit at the 2001 RSNA scientific assembly. K.F. supported in part by an RSNA Research and Education Foundation Seed Grant. Received March 5, 2002; revision requested April 29 and received June 6; accepted June 10. Address correspondence to K.F., Department of Medical Imaging, Toronto General Hospital, 200 Elizabeth St, Eaton South 1-401C, Toronto, Ontario, Canada M5G 2C4 (e-mail: katherine.fong@uhn.on.ca).
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Abstract
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Tamoxifen citrate therapy increases the prevalence of benign and malignant uterine lesions. At transvaginal ultrasonography (US), the finding of a thickened central endometrial complex, with or without cystic changes, is often nonspecific and may be caused by an endometrial polyp, submucosal leiomyoma (fibroid), endometrial hyperplasia, carcinoma, or cystic atrophy. In addition, because of an increased prevalence of adenomyosis or adenomyosis-like changes in women receiving tamoxifen, proper transvaginal US assessment of endometrial thickness and abnormalities is difficult in some women. Hysterosonography, as an adjunct to transvaginal US, allows identification of intracavitary lesions and focal and diffuse endometrial abnormalities and helps determine whether an abnormality is endometrial or subendometrial. Endometrial polyps may be seen at transvaginal US as nonspecific thickening of the endometrial complex, with or without cystic changes. At hysterosonography, they appear as an echogenic mass with smooth margins. Submucosal leiomyomas may protrude into the endometrial cavity, causing false endometrial thickening at transvaginal US. Hysterosonography shows a round structure arising from the myometrium with a thin, overlying endometrium. At transvaginal US, when the endometrium cannot be accurately measured or when there is a nonspecific thickened central endometrial complex, hysterosonography can provide additional information and can help in the triage for hysteroscopic versus nondirected endometrial biopsy. Correlation of transvaginal US and hysterosonographic findings with hysteroscopic and pathologic findings enhances understanding of these changes, as well as the limitations and potential pitfalls of both imaging techniques.
© RSNA, 2003
Index Terms: Leiomyoma, 854.315 • Tamoxifen, 854.64 • Uterine neoplasms, US, 854.12989 • Uterus, endometrium, 854.64
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LEARNING OBJECTIVES FOR TEST 4
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After reading this article and taking the test, the reader will be able to:
- Identify the pathologic appearances of the endometrium at transvaginal US.
- Describe the pathologic appearances of the endometrium at hysterosonography.
- Discuss the limitations and potential pitfalls of transvaginal US and hysterosonography in the evaluation of the central endometrial complex in postmenopausal women undergoing tamoxifen therapy.
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Introduction
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Tamoxifen citrate is a selective estrogen receptor modulator that is widely used for the treatment of breast cancer (1). Recently, it has been found to prevent breast cancer in high-risk women (2). Although it acts as an antiestrogen in breast tissue, it has an estrogenic effect in the postmenopausal endometrium and myometrium. Long-term tamoxifen therapy is reported to be associated with an increased number of uterine lesions, including endometrial polyps, leiomyomas, endometrial hyperplasia, endometrial carcinoma, and adenomyosis (2–5). However, the beneficial effects of tamoxifen in women with breast cancer outweigh the potential endometrial adverse effects of the drug.
Transvaginal ultrasonography (US) is frequently used for endometrial assessment. A thin, atrophic endometrium requires no further work-up. However, a thickened central endometrial complex, with or without cystic changes, is often nonspecific. Hysterosonography is a useful adjunct to transvaginal US. The procedure involves the instillation of sterile saline solution into the endometrial cavity through a small catheter, under continuous US guidance. It allows identification of intracavitary lesions and focal and diffuse endometrial abnormalities and can be used to determine whether an abnormality is endometrial or subendometrial.
In this article, we review the spectrum of uterine and endometrial findings at transvaginal US and hysterosonography in postmenopausal women with breast cancer who were undergoing tamoxifen therapy. Various pathologic conditions produced within the uterus by this therapy are described and illustrated. The limitations and potential pitfalls of both imaging techniques are also discussed.
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Patient Population
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Our patient population consisted of postmenopausal women with breast cancer who were undergoing tamoxifen therapy. There were two subgroups:
1. Asymptomatic women who were recruited between June 1996 and March 2000 for a prospective study to evaluate transvaginal US and hysterosonography in the diagnosis of endometrial abnormality. They underwent transvaginal US and hysterosonography, followed within 2 weeks by office hysteroscopy (with or without directed biopsy) and Pipelle endometrial biopsy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. The results of this study were previously reported (6). From this series of 117 patients, some cases were chosen as examples for this pictorial essay. There were no cases of endometrial hyperplasia or carcinoma in this group of asymptomatic women.
2. Asymptomatic and symptomatic women who were referred to our institution for transvaginal US with or without hysterosonography between August 2000 and September 2001. These clinical cases were not collected as part of a prospective study and were not consecutive. However, these women underwent Pipelle endometrial biopsy, operative hysteroscopy, or hysterectomy within 4 months of the US examinations, the findings of which were correlated with the final histopathologic diagnosis.
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Normal Appearance
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The normal postmenopausal endometrium is atrophic. It should appear thin, homogeneous, and echogenic at transvaginal US (Fig 1a). At hysterosonography, a smooth, thin endometrium surrounds the anechoic, saline solution–distended endometrial cavity (Fig 1b).
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Figure 1a. Atrophic endometrium in a 58-year-old asymptomatic woman who had undergone tamoxifen therapy for 10 months. (a) Sagittal transvaginal US image shows a thin endometrium (calipers). (b) Sagittal hysterosonogram shows fluid (*) in the endometrial cavity, with thin anterior (solid arrows) and posterior walls. A catheter (open arrow) is in the lower portion of the uterus. Hysteroscopic and histopathologic findings confirmed atrophic endometrium.
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Figure 1b. Atrophic endometrium in a 58-year-old asymptomatic woman who had undergone tamoxifen therapy for 10 months. (a) Sagittal transvaginal US image shows a thin endometrium (calipers). (b) Sagittal hysterosonogram shows fluid (*) in the endometrial cavity, with thin anterior (solid arrows) and posterior walls. A catheter (open arrow) is in the lower portion of the uterus. Hysteroscopic and histopathologic findings confirmed atrophic endometrium.
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Sometimes fluid can be seen in the endometrial cavity at transvaginal US (Fig 2). As an isolated finding, fluid in the endometrial cavity is usually due to cervical stenosis (7). In our prospective study of asymptomatic postmenopausal women with breast cancer who were receiving tamoxifen, 6% had intracavitary fluid at transvaginal US without a mass in the cervix or endometrial cavity at hysteroscopy.
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Figure 2. Fluid in the endometrial cavity due to cervical stenosis in a 59-year-old asymptomatic woman who had undergone tamoxifen therapy for 7 months. Sagittal transvaginal US image shows fluid (*) in the endometrial cavity, with thin anterior (arrows) and posterior walls. Hysteroscopic and histopathologic findings confirmed atrophic endometrium.
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Endometrial thickening at transvaginal US is an important finding, often indicative of endometrial pathologic conditions. In women with postmenopausal bleeding, a recent meta-analysis by Smith-Bindman et al recommended that a double-layer endometrial thickness of >5 mm be considered abnormal, and reported a sensitivity of 92% and a specificity of 81% in the detection of any endometrial disease (cancer, hyperplasia, polyp) (8). However, there is no clear definition of what constitutes an abnormal endometrial thickness for postmenopausal women receiving tamoxifen. If such women present with bleeding and their endometrial thickness is >5 mm, further investigation is necessary.
In asymptomatic women receiving tamoxifen, the upper limit for normal endometrial thickness and the usefulness of US screening remain controversial. Various authors have reported transvaginal sonographic endometrial thicknesses of 5, 9, and 10 mm as abnormal cutoff values for the identification of endometrial disease in asymptomatic postmenopausal women receiving tamoxifen (9–11). However, the results of these studies are limited by verification bias (9,10) and by small sample size (11). A recent study referred all tamoxifen-treated asymptomatic women (n = 117) for outpatient hysteroscopy with or without directed biopsy, as well as Pipelle endometrial biopsy, irrespective of the endometrial thickness measurement at transvaginal US (6). Uterine abnormalities (polyps and submucosal fibroids) were present in 40% of the study population, but there were no cases of endometrial hyperplasia or carcinoma. The optimal endometrial thickness cutoff for identification of abnormalities (polyps and submucosal fibroids) was >6 mm, if maximal test accuracy (sensitivity and specificity) is desired (6). With this cutoff value, the sensitivity was 84.1% and specificity 58.2%.
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Endometrial Polyp
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In postmenopausal women who undergo treatment with tamoxifen, endometrial polyps are common. They are present in 39% of asymptomatic women (6).
Transvaginal US often shows nonspecific thickening of the central endometrial complex, with or without cystic changes (Figs 3a, 4a, 5a, 6a). The presence of a distinct hyperechoic line partially or completely surrounding the abnormal endometrial complex favors a focal intracavitary process such as a polyp, a submucosal fibroid that protrudes into the cavity, or focal endometrial hyperplasia (12). When a hyperechoic line is observed together with cystic spaces in the central endometrial complex, the focal mass is probably a polyp (Figs 3a, 4a, 4b) (12). Color Doppler US may show the feeding artery in the pedicle of the polyp (Fig 4c), a helpful diagnostic feature (13).
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Figure 3a. Benign endometrial cystic polyp in a 70-year-old asymptomatic woman who had undergone tamoxifen therapy for 25 months. (a) Sagittal transvaginal US image shows a thickened central endometrial complex (calipers) with cystic spaces. The presence of a hyperechoic line (arrows) partially surrounding the central endometrial complex favors the diagnosis of a polyp. (b) Sagittal hysterosonogram shows fluid outlining a smooth intracavitary mass (calipers). (c) Photograph obtained at hysteroscopy shows a benign polyp (arrows) that was confirmed at histopathologic study. (Fig 3a and 3b reprinted, with permission, from reference 6.)
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Figure 3b. Benign endometrial cystic polyp in a 70-year-old asymptomatic woman who had undergone tamoxifen therapy for 25 months. (a) Sagittal transvaginal US image shows a thickened central endometrial complex (calipers) with cystic spaces. The presence of a hyperechoic line (arrows) partially surrounding the central endometrial complex favors the diagnosis of a polyp. (b) Sagittal hysterosonogram shows fluid outlining a smooth intracavitary mass (calipers). (c) Photograph obtained at hysteroscopy shows a benign polyp (arrows) that was confirmed at histopathologic study. (Fig 3a and 3b reprinted, with permission, from reference 6.)
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Figure 3c. Benign endometrial cystic polyp in a 70-year-old asymptomatic woman who had undergone tamoxifen therapy for 25 months. (a) Sagittal transvaginal US image shows a thickened central endometrial complex (calipers) with cystic spaces. The presence of a hyperechoic line (arrows) partially surrounding the central endometrial complex favors the diagnosis of a polyp. (b) Sagittal hysterosonogram shows fluid outlining a smooth intracavitary mass (calipers). (c) Photograph obtained at hysteroscopy shows a benign polyp (arrows) that was confirmed at histopathologic study. (Fig 3a and 3b reprinted, with permission, from reference 6.)
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Figure 4a. Benign endometrial polyp with the hyperechoic line sign in a 49-year-old asymptomatic woman who underwent tamoxifen therapy for 12 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show an intraluminal mass (calipers) surrounded by a thin, echogenic endometrium (straight arrows). Several small cysts (curved arrow in b) are seen within the mass. F = fibroid. (c) Transverse transvaginal color Doppler US image shows a single feeding artery in the pedicle of the polyp (arrow). F = fibroid. (d) Sagittal hysterosonogram shows an intracavitary mass (calipers) completely surrounded by fluid. A balloon catheter (arrow) is in the cervix. (e) Light photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows features typical of a benign polyp: fibrotic stroma, irregular endometrial glands, and thick-walled blood vessels.
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Figure 4b. Benign endometrial polyp with the hyperechoic line sign in a 49-year-old asymptomatic woman who underwent tamoxifen therapy for 12 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show an intraluminal mass (calipers) surrounded by a thin, echogenic endometrium (straight arrows). Several small cysts (curved arrow in b) are seen within the mass. F = fibroid. (c) Transverse transvaginal color Doppler US image shows a single feeding artery in the pedicle of the polyp (arrow). F = fibroid. (d) Sagittal hysterosonogram shows an intracavitary mass (calipers) completely surrounded by fluid. A balloon catheter (arrow) is in the cervix. (e) Light photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows features typical of a benign polyp: fibrotic stroma, irregular endometrial glands, and thick-walled blood vessels.
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Figure 4c. Benign endometrial polyp with the hyperechoic line sign in a 49-year-old asymptomatic woman who underwent tamoxifen therapy for 12 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show an intraluminal mass (calipers) surrounded by a thin, echogenic endometrium (straight arrows). Several small cysts (curved arrow in b) are seen within the mass. F = fibroid. (c) Transverse transvaginal color Doppler US image shows a single feeding artery in the pedicle of the polyp (arrow). F = fibroid. (d) Sagittal hysterosonogram shows an intracavitary mass (calipers) completely surrounded by fluid. A balloon catheter (arrow) is in the cervix. (e) Light photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows features typical of a benign polyp: fibrotic stroma, irregular endometrial glands, and thick-walled blood vessels.
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Figure 4d. Benign endometrial polyp with the hyperechoic line sign in a 49-year-old asymptomatic woman who underwent tamoxifen therapy for 12 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show an intraluminal mass (calipers) surrounded by a thin, echogenic endometrium (straight arrows). Several small cysts (curved arrow in b) are seen within the mass. F = fibroid. (c) Transverse transvaginal color Doppler US image shows a single feeding artery in the pedicle of the polyp (arrow). F = fibroid. (d) Sagittal hysterosonogram shows an intracavitary mass (calipers) completely surrounded by fluid. A balloon catheter (arrow) is in the cervix. (e) Light photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows features typical of a benign polyp: fibrotic stroma, irregular endometrial glands, and thick-walled blood vessels.
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Figure 4e. Benign endometrial polyp with the hyperechoic line sign in a 49-year-old asymptomatic woman who underwent tamoxifen therapy for 12 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show an intraluminal mass (calipers) surrounded by a thin, echogenic endometrium (straight arrows). Several small cysts (curved arrow in b) are seen within the mass. F = fibroid. (c) Transverse transvaginal color Doppler US image shows a single feeding artery in the pedicle of the polyp (arrow). F = fibroid. (d) Sagittal hysterosonogram shows an intracavitary mass (calipers) completely surrounded by fluid. A balloon catheter (arrow) is in the cervix. (e) Light photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows features typical of a benign polyp: fibrotic stroma, irregular endometrial glands, and thick-walled blood vessels.
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Figure 5a. Benign endometrial broad-based polyp in a 59-year-old woman who had undergone tamoxifen therapy for 3 years and presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows a 9-mm-thick endometrium (calipers) with small cysts. Cystic changes in the myometrium (arrows) are suggestive of adenomyosis. (b) Sagittal hysterosonogram shows fluid outlining a broad-based intracavitary mass (calipers), which extends from the fundus to the lower portion of the uterus. Hysteroscopic and histopathologic findings confirmed a benign polyp.
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Figure 5b. Benign endometrial broad-based polyp in a 59-year-old woman who had undergone tamoxifen therapy for 3 years and presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows a 9-mm-thick endometrium (calipers) with small cysts. Cystic changes in the myometrium (arrows) are suggestive of adenomyosis. (b) Sagittal hysterosonogram shows fluid outlining a broad-based intracavitary mass (calipers), which extends from the fundus to the lower portion of the uterus. Hysteroscopic and histopathologic findings confirmed a benign polyp.
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Figure 6a. Benign endometrial polyp that appears homogeneous and echogenic in a 63-year-old asymptomatic woman who had undergone tamoxifen therapy for 9 months. (a) Sagittal transvaginal US image shows an endometrial thickness of 8 mm (calipers). F = fibroid. (b) Sagittal hysterosonogram shows fluid outlining an echogenic intracavitary mass (calipers). A balloon catheter (arrow) is in the cervix. Hysteroscopic and histopathologic findings revealed a benign polyp.
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Figure 6b. Benign endometrial polyp that appears homogeneous and echogenic in a 63-year-old asymptomatic woman who had undergone tamoxifen therapy for 9 months. (a) Sagittal transvaginal US image shows an endometrial thickness of 8 mm (calipers). F = fibroid. (b) Sagittal hysterosonogram shows fluid outlining an echogenic intracavitary mass (calipers). A balloon catheter (arrow) is in the cervix. Hysteroscopic and histopathologic findings revealed a benign polyp.
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At hysterosonography, a polyp appears as an echogenic mass with smooth margins (Figs 3b, 4d). Often it has a narrow attachment to the adjacent endometrium and is completely surrounded by fluid (Fig 4d) (14), although it could be broad-based (Fig 5b). It often contains cystic areas (Figs 3b, 4d, 5b) but may have a homogeneous echotexture (Fig 6b).
At hysteroscopy, most polyps are pink-gray to white with smooth, glistening surfaces, beneath which small cysts may be visible (Fig 3c). The polyps may be attached on a relatively broad stalk or a narrow pedicle. Typically, they do not bleed easily when touched, unlike endometrial carcinoma. Occasionally, the entire polyp or only its tip is hemorrhagic or infarcted.
At histopathologic examination, a polyp contains a variable amount of glands, stroma, and blood vessels (Fig 4e).
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Submucosal Leiomyoma
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Leiomyomas, or fibroids, are common in postmenopausal women who undergo tamoxifen treatment. As they enlarge, submucosal fibroids may protrude into the endometrial cavity.
At transvaginal US, a submucosal fibroid may appear hypoechoic or show heterogeneous echogenicity and often demonstrate acoustic attenuation (Fig 7a). The fibroid may displace or distort the endometrium or cause false endometrial thickening.
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Figure 7a. Submucosal leiomyoma in a 71-year-old asymptomatic woman who had undergone tamoxifen therapy for 5 years. (a) Sagittal transvaginal US image shows an enlarged uterus with fibroids (F). A 2-cm echogenic fibroid (calipers) displaces the endometrial echo posteriorly (arrowheads). (b) Sagittal hysterosonogram shows thin endometrium (arrowheads) overlying the fibroid (F), which arises from the myometrium with a wide attachment (arrows).
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Figure 7b. Submucosal leiomyoma in a 71-year-old asymptomatic woman who had undergone tamoxifen therapy for 5 years. (a) Sagittal transvaginal US image shows an enlarged uterus with fibroids (F). A 2-cm echogenic fibroid (calipers) displaces the endometrial echo posteriorly (arrowheads). (b) Sagittal hysterosonogram shows thin endometrium (arrowheads) overlying the fibroid (F), which arises from the myometrium with a wide attachment (arrows).
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At hysterosonography, a submucosal fibroid is seen as a round structure arising from the myometrium. The thin, overlying echogenic endometrium usually can be identified (Fig 7b) (15). It usually appears with a wide attachment to the myometrium but may be pedunculated.
At hysteroscopy, submucosal fibroids appear as rounded masses that bulge to varying extents into the endometrial cavity. They may also form pedunculated tumors that appear as soft or firm polypoid masses protruding through the external cervical os or, rarely, through the vaginal introitus. The mucosal surface tends to be smooth and relatively flat, although it may also be congested, ulcerated, or hemorrhagic. The fibroid may be vascular but tends to be of a firmer consistency than an endometrial polyp. To help differentiate fibroids from polyps, hysteroscopists often probe the lesion with the grasper to determine its consistency. Upon resection of the fibroid, it has a typical swirl appearance similar to that of myometrium.
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Endometrial Hyperplasia
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Endometrial hyperplasia can be divided into two broad categories at histopathologic examination: hyperplasia without cytologic atypia and hyperplasia with cytologic atypia. In up to 23% of patients with atypical hyperplasia, versus 2% of patients with hyperplasia without atypia, the hyperplasia progresses to carcinoma (16).
Transvaginal US shows well-defined endometrial thickening, with or without cysts (Fig 8a). At hysterosonography, diffuse, smooth thickening of the endometrium suggests endometrial hyperplasia. However, focal or asymmetric endometrial thickening with surface irregularity has also been described for hyperplasia (Fig 8b) (14). Because endometrial carcinoma can have a similar appearance, biopsy is required.
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Figure 8a. Endometrial hyperplasia in a 55-year-old asymptomatic woman who underwent tamoxifen therapy for 5 years. (a) Sagittal transvaginal US image shows a thick endometrium (calipers) with cystic areas. (b) Sagittal hysterosonogram shows circumferentially thickened endometrium (solid arrows) that contains cystic areas. A catheter (open arrow) is in the cervix. (c) Light photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows endometrial hyperplasia with atypia. Architecturally complex, closely packed endometrial glands are lined by cells that exhibit cytologic atypia. (Fig 8a and 8b reprinted, with permission, from reference 25.)
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Figure 8b. Endometrial hyperplasia in a 55-year-old asymptomatic woman who underwent tamoxifen therapy for 5 years. (a) Sagittal transvaginal US image shows a thick endometrium (calipers) with cystic areas. (b) Sagittal hysterosonogram shows circumferentially thickened endometrium (solid arrows) that contains cystic areas. A catheter (open arrow) is in the cervix. (c) Light photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows endometrial hyperplasia with atypia. Architecturally complex, closely packed endometrial glands are lined by cells that exhibit cytologic atypia. (Fig 8a and 8b reprinted, with permission, from reference 25.)
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Figure 8c. Endometrial hyperplasia in a 55-year-old asymptomatic woman who underwent tamoxifen therapy for 5 years. (a) Sagittal transvaginal US image shows a thick endometrium (calipers) with cystic areas. (b) Sagittal hysterosonogram shows circumferentially thickened endometrium (solid arrows) that contains cystic areas. A catheter (open arrow) is in the cervix. (c) Light photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows endometrial hyperplasia with atypia. Architecturally complex, closely packed endometrial glands are lined by cells that exhibit cytologic atypia. (Fig 8a and 8b reprinted, with permission, from reference 25.)
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At hysteroscopy, endometrial hyperplasia is usually thicker than the typical glistening, mucoid, pink-gray appearance of normal proliferative endometrium. It may also be polypoid. Small cysts may be visible, and dilated congested sinusoids may be seen just beneath the surface.
Histopathologic examination shows architecturally complex, closely packed endometrial glands, which if lined by cells exhibiting cytologic atypia, would be diagnosed as endometrial hyperplasia with atypia (Fig 8c).
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Endometrial Carcinoma
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Tamoxifen therapy is associated with an increased risk of the development of endometrial cancer. According to the National Surgical Adjuvant Breast and Bowel Project B-14 trial, the annual rate of endometrial cancer is 1.6 per 1,000 tamoxifen-treated women, a relative risk of 2.2 in comparison with population-based rates of endometrial cancer (3). The risk of endometrial cancer increases with total duration of tamoxifen use and cumulative dose, prior estrogen replacement therapy, obesity, hypertension, and diabetes, as well as the presence of endometrial pathologic conditions before the use of tamoxifen (4). Most of the reported cases of endometrial cancers in tamoxifen users were in women with vaginal bleeding (17).
At transvaginal US, most endometrial carcinomas are either diffusely or partially echogenic (13). The endometrial thickening may be well defined (Fig 9a). Irregular or poorly defined endometrial thickening generally is suggestive of malignancy. However, in women who undergo treatment with tamoxifen, because of underlying adenomyosis, poor definition of endometrial thickening is not a helpful diagnostic feature for the diagnosis of endometrial carcinoma.
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Figure 9a. Endometrial carcinoma in a 68-year-old woman who had undergone tamoxifen therapy for 5 years and presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows the uterus in a military position and hence suboptimal for measurement of endometrial thickness. There is well-defined thickening of the endometrium (calipers). (b) Sagittal T2-weighted MR image shows the thick, well-defined heterogeneous endometrium (calipers). No evidence of extension of the carcinoma beyond the endometrium is apparent. (c) Light photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows endometrial carcinoma. Confluent, fused endometrial glands exhibit cribriform architecture and nuclear atypia. (Fig 9a and 9b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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Figure 9b. Endometrial carcinoma in a 68-year-old woman who had undergone tamoxifen therapy for 5 years and presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows the uterus in a military position and hence suboptimal for measurement of endometrial thickness. There is well-defined thickening of the endometrium (calipers). (b) Sagittal T2-weighted MR image shows the thick, well-defined heterogeneous endometrium (calipers). No evidence of extension of the carcinoma beyond the endometrium is apparent. (c) Light photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows endometrial carcinoma. Confluent, fused endometrial glands exhibit cribriform architecture and nuclear atypia. (Fig 9a and 9b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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Figure 9c. Endometrial carcinoma in a 68-year-old woman who had undergone tamoxifen therapy for 5 years and presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows the uterus in a military position and hence suboptimal for measurement of endometrial thickness. There is well-defined thickening of the endometrium (calipers). (b) Sagittal T2-weighted MR image shows the thick, well-defined heterogeneous endometrium (calipers). No evidence of extension of the carcinoma beyond the endometrium is apparent. (c) Light photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows endometrial carcinoma. Confluent, fused endometrial glands exhibit cribriform architecture and nuclear atypia. (Fig 9a and 9b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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At hysterosonography, an irregular inhomogeneous mass or irregular, focally thickened endometrium is highly suggestive of endometrial carcinoma. Lack of distensibility of the endometrial cavity has been described as a potential sign of endometrial carcinoma (14). Magnetic resonance (MR) imaging is valuable in the evaluation of endometrial carcinoma, especially in cancer staging (Fig 9b) (18).
At hysteroscopy, endometrial carcinomas typically look polypoid, either sessile or pedunculated. The tumor is composed of irregularly heaped-up tissue that often has a granular surface. It appears opaque, dry, pale yellow or white, and friable. Dark yellow areas are often conspicuous as a result of necrosis or the accumulation of lipid-filled cells of stromal origin between the neoplastic glands. Hemorrhage and ulceration are common, particularly when the tumor is poorly differentiated, and abnormal vascular patterns may be seen on the surface of the tumor.
At histopathologic study, confluent, fused endometrial glands exhibit cribriform architecture and nuclear atypia (Fig 9c).
It is not uncommon for more than one pathologic process (endometrial polyp, hyperplasia, and carcinoma) to be seen in any given patient (Fig 10). Therefore, complete evaluation of the entire endometrium is essential.
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Figure 10a. Coexisting endometrial polyp, endometrial hyperplasia, and endometrial carcinoma in a 74-year-old asymptomatic woman who had undergone tamoxifen therapy since March 1999. (a) Sagittal transvaginal US image obtained in June 1999 shows a small amount of intracavitary fluid (*), thin anterior and posterior walls (arrows), and 4-mm-thick endometrium (calipers) in the lower uterine segment. Pipelle endometrial biopsy showed atrophic endometrium. (b) Sagittal transvaginal US image obtained in April 2001 shows intracavitary fluid (*), 11-mm endometrial thickening in the lower uterine segment (calipers), thin anterior and posterior walls (straight arrows), and a polypoid mass more superiorly (curved arrow). F = fibroid. Pipelle endometrial biopsy showed endometrial hyperplasia with atypia. The patient underwent subsequent hysterectomy. Histopathologic findings showed a benign endometrial polyp, as well as microscopic foci of endometrial carcinoma in the polyp and adjacent endometrium.
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Figure 10b. Coexisting endometrial polyp, endometrial hyperplasia, and endometrial carcinoma in a 74-year-old asymptomatic woman who had undergone tamoxifen therapy since March 1999. (a) Sagittal transvaginal US image obtained in June 1999 shows a small amount of intracavitary fluid (*), thin anterior and posterior walls (arrows), and 4-mm-thick endometrium (calipers) in the lower uterine segment. Pipelle endometrial biopsy showed atrophic endometrium. (b) Sagittal transvaginal US image obtained in April 2001 shows intracavitary fluid (*), 11-mm endometrial thickening in the lower uterine segment (calipers), thin anterior and posterior walls (straight arrows), and a polypoid mass more superiorly (curved arrow). F = fibroid. Pipelle endometrial biopsy showed endometrial hyperplasia with atypia. The patient underwent subsequent hysterectomy. Histopathologic findings showed a benign endometrial polyp, as well as microscopic foci of endometrial carcinoma in the polyp and adjacent endometrium.
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Limitations and Pitfalls
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Transvaginal US may not depict the true endometrial thickness or may give a false-positive appearance of thick endometrium owing to adenomyosis or endometrial cystic atrophy (19,20). A recent study reported low specificity of transvaginal US (56.6%) in the identification of endometrial abnormalities in asymptomatic women receiving tamoxifen, whereas hysterosonography has a higher specificity (79.2%) (6).
Adenomyosis
Adenomyosis is characterized pathologically by the presence of ectopic endometrial glands and stroma within the myometrium. In women receiving tamoxifen, there is an increased prevalence of adenomyosis or adenomyosis-like changes (5).
The reported features of adenomyosis at transvaginal US, correlated with histopathologic specimens obtained from women who were not receiving tamoxifen, include uterine enlargement, asymmetric thickening of the anterior or posterior uterine wall, increased echotexture of the myometrium, heterogeneous poorly circumscribed areas within the myometrium, myometrial or subendometrial cysts, lack of contour abnormality or mass effect, subendometrial echogenic linear striations, subendometrial echogenic nodules, and poor definition of the endometrial-myometrial junction (21,22). Some of these uterine changes are seen in tamoxifen-treated women, but to our knowledge, no study has correlated US findings with those from histopathologic specimens. The US findings include heterogeneity of the myometrium, subendometrial or myometrial cysts, and poor definition of the endometrium. These features create difficulty in obtaining an accurate measurement of the endometrial thickness (Fig 11). Adenomyosis may give a false-positive appearance of a thickened endometrium at transvaginal US (Figs 12a, 12b, 13a). If the endometrium in patients who present with postmenopausal bleeding cannot be reliably measured at transvaginal US, further investigation is necessary. At hysterosonography, changes of adenomyosis, including small cysts, appear in the inner myometrium and account for the apparent endometrial thickening at transvaginal US (Fig 12c, 12d). MR imaging can also help confirm the subendometrial or myometrial location of cysts and a thin endometrium (Fig 13b). Diffuse thickening of the junctional zone greater than or equal to 12 mm has been found to be an accurate measurement for the diagnosis of adenomyosis at MR imaging in women who are not receiving tamoxifen (23). The thickening is characterized pathologically as hyperplasia of the smooth muscle that surrounds ectopic endometrial glands (Fig 13c).
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Figure 11. Poorly visualized endometrial echo at transvaginal US owing to adenomyosis in a 66-year-old asymptomatic woman who had undergone tamoxifen therapy for 45 months. Sagittal transvaginal US image shows a poorly defined, irregular endometrial echo, such that endometrial thickness cannot be reliably measured. Subendometrial cysts (arrows) are suggestive of adenomyosis. Hysterosonographic assessment was unsuccessful because of cervical stenosis. MR imaging allowed confirmation of adenomyosis. Hysteroscopy and histopathologic study showed atrophic endometrium.
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Figure 12a. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 59-year-old asymptomatic woman who had undergone tamoxifen therapy for 37 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show a thick, poorly defined central endometrial complex (calipers) with cystic areas. (c, d) Sagittal (c) and transverse (d) hysterosonograms show thin endometrium (small solid arrows). Changes due to adenomyosis, including small cysts (large solid arrows) in the inner myometrium, account for the apparent endometrial thickening at transvaginal US. A balloon catheter (open arrow in c) is in the lower portion of the uterus. Endometrial biopsy revealed atrophic endometrium.
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Figure 12b. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 59-year-old asymptomatic woman who had undergone tamoxifen therapy for 37 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show a thick, poorly defined central endometrial complex (calipers) with cystic areas. (c, d) Sagittal (c) and transverse (d) hysterosonograms show thin endometrium (small solid arrows). Changes due to adenomyosis, including small cysts (large solid arrows) in the inner myometrium, account for the apparent endometrial thickening at transvaginal US. A balloon catheter (open arrow in c) is in the lower portion of the uterus. Endometrial biopsy revealed atrophic endometrium.
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Figure 12c. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 59-year-old asymptomatic woman who had undergone tamoxifen therapy for 37 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show a thick, poorly defined central endometrial complex (calipers) with cystic areas. (c, d) Sagittal (c) and transverse (d) hysterosonograms show thin endometrium (small solid arrows). Changes due to adenomyosis, including small cysts (large solid arrows) in the inner myometrium, account for the apparent endometrial thickening at transvaginal US. A balloon catheter (open arrow in c) is in the lower portion of the uterus. Endometrial biopsy revealed atrophic endometrium.
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Figure 12d. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 59-year-old asymptomatic woman who had undergone tamoxifen therapy for 37 months. (a, b) Sagittal (a) and transverse (b) transvaginal US images show a thick, poorly defined central endometrial complex (calipers) with cystic areas. (c, d) Sagittal (c) and transverse (d) hysterosonograms show thin endometrium (small solid arrows). Changes due to adenomyosis, including small cysts (large solid arrows) in the inner myometrium, account for the apparent endometrial thickening at transvaginal US. A balloon catheter (open arrow in c) is in the lower portion of the uterus. Endometrial biopsy revealed atrophic endometrium.
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Figure 13a. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 69-year-old woman undergoing tamoxifen therapy who presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows a thick, poorly defined endometrium (calipers), with cystic changes (arrows) in the myometrium. (b) Sagittal T2-weighted MR image shows a thick junctional zone (between the calipers) and hyperintense cystic changes (arrows) in the ventral myometrium. The thin endometrium (arrowheads) indicates that most of the thickening at transvaginal US is caused by the underlying adenomyosis. Endometrial biopsy showed atrophic endometrium. (c) Light photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows an endometrial gland with surrounding endometrial stroma (arrows) within uterine myometrium. (Fig 13a and 13b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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Figure 13b. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 69-year-old woman undergoing tamoxifen therapy who presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows a thick, poorly defined endometrium (calipers), with cystic changes (arrows) in the myometrium. (b) Sagittal T2-weighted MR image shows a thick junctional zone (between the calipers) and hyperintense cystic changes (arrows) in the ventral myometrium. The thin endometrium (arrowheads) indicates that most of the thickening at transvaginal US is caused by the underlying adenomyosis. Endometrial biopsy showed atrophic endometrium. (c) Light photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows an endometrial gland with surrounding endometrial stroma (arrows) within uterine myometrium. (Fig 13a and 13b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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Figure 13c. False-positive appearance of thickened endometrium at transvaginal US owing to adenomyosis in a 69-year-old woman undergoing tamoxifen therapy who presented with postmenopausal bleeding. (a) Sagittal transvaginal US image shows a thick, poorly defined endometrium (calipers), with cystic changes (arrows) in the myometrium. (b) Sagittal T2-weighted MR image shows a thick junctional zone (between the calipers) and hyperintense cystic changes (arrows) in the ventral myometrium. The thin endometrium (arrowheads) indicates that most of the thickening at transvaginal US is caused by the underlying adenomyosis. Endometrial biopsy showed atrophic endometrium. (c) Light photomicrograph (original magnification, x50; hematoxylin-eosin stain) shows an endometrial gland with surrounding endometrial stroma (arrows) within uterine myometrium. (Fig 13a and 13b courtesy of Carolyn Reinhold, MD, Department of Radiology, McGill University, Montreal, Canada.)
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Endometrial Cystic Atrophy
Endometrial cystic atrophy is a benign process, diagnosed histologically when multiple cystic spaces (dilated glands) lined with atrophic epithelium are present within a dense fibrous stroma. Atrophic endometrium is usually very thin. However, the presence of endometrial cysts may lead to a spuriously widened endometrial measurement (Figs 14a, 15a, 16a). According to one study, in 17% of tamoxifen-treated postmenopausal women with a thickened endometrium (>5 mm) at transvaginal US, endometrial cystic atrophy is the only possible cause (20). At hysterosonography, endometrial cysts can be shown and distinguished from intraluminal pathologic conditions (Fig 14b). At hysteroscopy, the endometrium appears white but hypervascularized, with scattered protuberances (Fig 14c) (24). This "tamoxifen-like" mucosa can be seen as early as 6 months after the start of tamoxifen therapy. At histopathologic examination, these protuberances 
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Abstract
LEARNING OBJECTIVES FOR TEST...
