Patients and methods
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- Patients and methods
This was a retrospective observational study including all patients in our institution's oncology database diagnosed with endometrial malignancy from 1994 until 2003, in whom a preoperative ultrasound examination was performed. Patients seen primarily at our institution as well as patients referred from regional hospitals for further oncological therapy were included; the women in the latter group had already undergone endometrial sampling before referral and underwent a preoperative ultrasound examination at our institute for staging.
The total maximum endometrial thickness (double layer) was measured by transvaginal ultrasound (Acuson Sequoia, Mountain View, CA, USA) in the sagittal plane2. All cases in which the endometrium could not be delineated clearly were recorded as ‘not measurable’. The files of those women with an endometrial thickness of < 5 mm were examined in more detail as to patients' characteristics, symptoms, history, menopausal status, previous endometrial sampling within 3 months of the ultrasound examination, sonographic features and histological examination of the endometrial sampling following the transvaginal ultrasound examination.
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- Patients and methods
One hundred and eighty-seven patients diagnosed with endometrial malignancy were retrieved from the database. The histological types of the endometrial malignancies are summarized in Table 1. The mean age of the population was 65.8 (SD, 10.0) years. Twenty (11%) women were nulliparous. One hundred and seventy-two (92.0%) women were postmenopausal. The median endometrial thickness was 15 (range, 2–65) mm. In 84 (45%) patients, the endometrium had been sampled within 3 months before the ultrasound examination. The median endometrial thickness in these patients was 12 (range, 2–43) mm vs. 17 (range, 2–65) mm in the women who did not undergo endometrial sampling beforehand (P = 0.0086; Mann–Whitney test). In those who underwent endometrial sampling before the ultrasound examination, the average interval between the endometrial sampling and the ultrasound examination was 23.5 (SD, 14.9; range, 0–68) days; there was no significant association between this interval and endometrial thickness. Endometrial sampling was performed by dilatation and curettage (D&C) in 64 cases and by Pipelle biopsy in five cases; in 15 patients the sampling method was not specified in the file. The median endometrial thickness in the D&C subgroup was 12 (range, 3–42) mm vs. 12 (range, 2–43) mm in the Pipelle subgroup. One hundred and seventy-one (91.4%) patients had an endometrial thickness measured at ultrasound of at least 5 mm; in three (1.6%) patients the endometrial lining was not visualized distinctly (not measurable) and in 13 (7.0%) women the endometrium was reported to be < 5 (range, 2–4.5) mm (Table 2).
Table 1. Histological features versus endometrial thickness on ultrasound in 187 women with endometrial malignancy
|Histology||n||%||Endometrial thickness (mm, median (range))|
|Endometrioid adenocarcinoma||137||73.3||20 (2–65)|
|Serous papillary adenocarcinoma||16||9.6||23 (5–37)|
|Clear-cell adenocarcinoma||7||3.7||13 (4–33)|
|Mucinous adenocarcinoma||10||5.3||14 (6–39)|
|Papillary adenocarcinoma||7||3.2||17 (9–41)|
|Papillary clear-cell adenocarcinoma||2||1.1||17 (15–19)|
|Adenoacanthoma, adenosquamous carcinoma||4||1.6||26 (17–33)|
|Poorly differentiated adenocarcinoma (metastasis of breast carcinoma)||1||0.5||—|
|Squamous mucinous carcinoma||1||0.5||—|
Table 2. Details of cases of malignancy in women with an endometrial thickness < 5 mm
|Case||Age (years)||Endometrial thickness (mm)||Histology||Grade||Stage||Comments|
|4||68||4||Endometrioid||3||Ib||Measurement of intracavitary lesion not recorded|
|8||53||4||Endometrioid||2||Ib||Lesion in the isthmus not recorded|
|9||54||4||Endometrioid||1||Ia||Previous D&C; myomatous uterus (endometrium difficult to delineate)|
|12||89||4||Clear-cell||3||Ic||Endometrium difficult to delineate|
|13||63||2||Adenocarcinoma||3||IV||Metastasis of breast carcinoma|
All 13 of the women with endometrial thickness < 5 mm were postmenopausal, with a mean age of 64.5 years, and three (23.1%) of them were nulliparous. Histology showed an endometrioid adenocarcinoma in 10 of these women, one poorly differentiated adenocarcinoma (not otherwise specified), one serous papillary adenocarcinoma and one clear-cell adenocarcinoma (Table 2). Nine (69.2%) of these women had undergone endometrial biopsy prior to ultrasound examination: eight by curettage and one by office Pipelle sampling. Of the remaining four cases (2.1% of the total study population), in two the lesion confirmed to be malignant at histology had been visualized on ultrasound and described and measured, but the recorded thickness did not include the focal malignant lesion: in one case (Case 4) there was spontaneous intracavitary fluid and a 10-mm lesion was located high in the uterine cavity (Figure 1), whereas in the other case (Case 8), a 13 × 10 × 7-mm focal thickening was described at the level of the isthmus (Figure 2). In the third patient (Case 12), the uterus was enlarged and although the endometrial lining could not be delineated over its total length, a short segment with a thickness of 4 mm was recorded as ‘endometrial thickness’. The sonologist, however, stated that endometrial pathology could not be excluded. The fourth patient (Case 13) presented with slight uterine bleeding. Although at ultrasound the endometrial thickness was 2 mm, because of a previous history of breast cancer, curettage was performed: the endocervical and endometrial fraction as well as punch biopsies from the cervix demonstrated a poorly differentiated carcinoma compatible with metastases of a breast cancer.
Figure 1. Diagram and ultrasound image showing measurement of endometrial thickness in the presence of a localized endometrial lesion and intracavitary fluid: the lesion must be measured at its thickest point and this measurement added to the maximum thickness of the opposite endometrial layer.
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Figure 2. Diagram and ultrasound image showing measurement of endometrial thickness in the case of a localized lesion in the supraisthmic part of the endometrium: this endometrial line must be measured at its thickest part in a sagittal plane.
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- Patients and methods
Our results confirm that it is very unusual for endometrial malignancy to have an endometrial thickness < 5 mm. Indeed, in 12 of the 13 women with endometrial malignancy recorded in our database to have an endometrial thickness < 5 mm, there was some problem with this measurement: in nine, it had been made inappropriately after endometrial sampling; in two, there were focal lesions noted at ultrasound that in error were not included in the endometrial thickness measurement; and in one, a measurement was taken and noted in our database despite the whole endometrium not being visible. In only one case (breast cancer metastases in the endometrium) was the endometrium correctly measured to be < 5 mm.
Prior diagnostic D&C within 3 months before sonography does not allow relevant endometrial measurement because a substantial amount of endometrial tissue is removed. Office endometrial sampling also disrupts sonographic evaluation of the endometrium8. In order to obtain reliable and reproducible endometrial thickness measurements, it is mandatory to perform the ultrasound examination before proceeding with office sampling or D&C. The median endometrial thickness was about 5 mm less in the group of women who had undergone a D&C compared with in those who had not. This value implies removal of roughly 20% of the endometrium. One might have expected a larger difference in endometrial thickness between these groups, because, depending on the sampling technique, a larger proportion of the endometrium might be removed. However, unlike in the surgical evacuation of retained products of conception, most clinicians aim to obtain a representative tissue sample instead of achieving almost complete removal of the endometrium. Moreover, after sampling, bleeding may occur inside the endometrium as well as in the uterine cavity, leading to an apparent thickening of the endometrium at ultrasound8. Finally, endometrial tissue, especially if it is malignant, may grow quite rapidly after D&C.
In three of our cases, the endometrial thickness was recorded incorrectly in the database. The total endometrial thickness is the thickest solid area of the endometrium in a sagittal plane, including any area of focal thickening (cf. Case 4). The maximum thickness in a sagittal plane is not necessarily found in the fundus of the uterus (cf. Case 8). It is also important to visualize the totality of the endometrium from the cervical canal to the fundus of the uterus and from cornu to cornu (Case 12). If the endometrium cannot be evaluated properly this must be recorded and the endometrium considered abnormal. Three of our patients were recorded to have an immeasurable endometrium. Goldstein9 emphasizes that the endometrium cannot be assessed adequately in a substantial number of patients and that such cases may benefit from saline infusion hydrosonography to enhance the diagnostic accuracy.
To be considered as ‘normal’, not only must the endometrium be thinner than 5 mm, but also the endometrial lining must be regular and clearly visible over the totality of the uterine cavity. Any focal thickening seen or even suspected on ultrasound must be considered abnormal, independently of the measured endometrial thickness. We propose recording the maximum sagittal diameter at the level of the focal thickening if it exceeds the maximum thickness of the remaining endometrial lining. In the case of an irregular endometrial lining and in the case of suspicion of a focal lesion, we advocate proceeding with hydrosonography to confirm the diagnosis. If a focal lesion is seen on hydrosonography, we propose that the lesion as well as the endometrium are measured opposite the lesion in a sagittal plane and that the sum of these measurements is recorded. Epstein et al.10 reported that the majority of pathological lesions in their series of women with postmenopausal bleeding manifested a focal growth pattern. In focal lesions, hysteroscopically directed resection is superior to D&C for obtaining a representative endometrial sample.
Table 3 gives a review of the literature on the occurrence of endometrial cancer in patients with an endometrium thickness < 5 mm on ultrasound11–21. Two papers reporting endometrial cancer cases with an endometrial thickness < 6 mm were excluded from the table22, 23. The quality of these papers is highly variable and in most articles only scanty information is given on the sonographic features of the cancer cases with a thin endometrium. However, in the series of Ferrazzi et al.4, two of the four cancer cases reportedly had a typical thin and regular endometrium. In our series, the only case of a truly regular thin endometrium was associated with a diffuse metastatic disease in a woman with breast cancer (Case 13). In their series, Dørum et al.24 found one case of malignant lymphoma with an endometrial thickness of 3 mm. Although these cases cannot truly be categorized as ‘endometrial’ malignancies, they illustrate the (albeit infrequent) occurrence of other malignancies involving the uterine cavity in women with abnormal uterine bleeding. In six of the nine studies reported in Tabor's meta-analysis6, no woman with endometrial malignancy had an endometrial thickness below 5 mm1, 2, 24–27. Of the other three series which reported malignant cases with endometrial thickness < 5 mm4, 28, 29, one was a retrospective series29 and one was a multicenter study performed by sonographers with different levels of expertise4. We hypothesize that the rigorous use of standardized endometrial thickness measurements by experienced sonographers could enhance diagnostic accuracy. Nevertheless, incidental cases in which endometrial thickness measurements fail to indicate malignancy might occur even in experienced hands.
Table 3. Literature review of patients with endometrial cancer and an endometrial thickness (ET) < 5 mm on transvaginal ultrasound
|Reference||Total patients (n)||Cancer cases (n (%))||Cancer cases with ET < 5 mm (n (%))||Comments|
|Rudelstorfer et al.11 (1990)||106||13 (12.3)||1 (7.7)||Stage Ia and endometrium obscured by myoma|
|Abu Hmeidan et al.12 (1992)||571||88 (15.4)||5 (5.7)|| |
|Dørum et al.24 (1993)||100||15 (15.0)||3 (20)||1 CA: malignant lymphoma (3 mm)|
| ||1 CA: Stage 1B (2 mm)|
| ||1 CA: Stage 1C (3 mm)|
|Conoscenti et al.29 (1995)||149||16 (10.7)||3 (18.7)||1 CA < 4 mm|
| ||2 CA < 5 mm|
|Schramm et al.13 (1995)||195||29 (14.9)||6 (20.7)|| |
|Ferrazzi et al.4 (1996)||930||107 (11.5)||4 (3.7)||2 CA ≤ 4 mm (‘typical thin, regular endometrium’)|
| ||2 CA ≤ 5 mm|
| ||All CA > 3.5 mm|
|Kufahl et al.14 (1997)||181||16 (8.8)||1 (6.2)|| |
|Tsuda et al.28 (1997)||300||8 (2.7)||2 (25.0)||1 CA < 3 mm|
| ||1 CA: 3–4mm|
|Weber et al.15 (1998)||159||62 (39.0)||1 (1.6)||Lesion not included in the measurement|
|Büyük et al.16 (1999)||54||9 (16.7)||3 (33.3)||3 CA: 3 mm|
|Gerber et al.17 (1999)||879||154 (17.5)||6 (3.9)||Retrospective|
|Gull et al.18 (2000)||361||38 (10.5)||1 (2.6)||1 CA: 3 mm|
|Amit et al.19 (2000)||60||11 (18.3)||3 (27.3)|| |
|Randelzhofer et al.20 (2002)||321||95 (29.6)||2 (2.1)|| |
|Phillip et al.21 (2004)||75||8 (10.7)||4 (50.0)||4 CA 3–4 mm|
| ||No CA < 3 mm|
We conclude that the finding of a thin and regular endometrium at ultrasound is very reliable to exclude endometrial malignancy, provided no recent endometrial sampling has been performed before the examination and provided meticulous evaluation of the entire endometrium is performed by dedicated sonographers, with attention being paid to focal alterations.
Even if a thin endometrium has been visualized at initial evaluation, a prudent clinician should maintain a certain degree of suspicion, especially in high-risk patients or in cases of recurrent vaginal bleeding30, 31.