By Alexandra Samborski, MD
Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY
SYNOPSIS: In women without abnormal uterine bleeding undergoing transvaginal ultrasound, endometrial intraepithelial neoplasia or endometrial cancer was associated with a thicker endometrium, heterogenous echotexture, more frequent endometrial cysts, and increased vascularity.
SOURCE: Heremans R, Van den Bosch T, Valentin L, et al. Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: Results from the International Endometrial Tumor Analysis study (IETA3). Ultrasound Obstet Gynecol 2022;60:243-255.
Transvaginal ultrasound has been used to evaluate patients with abnormal uterine bleeding and to help triage which patients need endometrial sampling. The focus of most studies has been on the thickness of the endometrium in patients with postmenopausal bleeding, but less is known about ultrasound features in patients without abnormal bleeding. The aim of this study was to assess ultrasound features in women with intracavitary pathology without abnormal uterine bleeding, to compare these findings to women with abnormal uterine bleeding, and to specifically assess patients with endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN).
This study was a prospective, observational, multicenter study conducted over eight years by the International Endometrial Tumor Analysis (IETA) consortium. Patients (both premenopausal and postmenopausal) without abnormal bleeding in the prior year were recruited; these patients were undergoing ultrasound for routine gynecologic assessment, follow-up of non-endometrial pathology, workup for infertility, assessment of ovarian pathology, or prior to treatment for uterine prolapse.
Transvaginal ultrasound was performed with assessment of the uterine cavity and endometrium per the IETA guidelines. Endometrial sampling was performed after the ultrasound and examined by nonblinded pathologists for a histologic diagnosis. Endometrial sampling included endometrial biopsy, dilation and curettage, hysteroscopy with guided biopsy, or hysterectomy. Histologic endpoints included endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, leiomyoma, EIN, or endometrial cancer. Patients without a histologic diagnosis were included if they had at least one year of follow-up and had no signs of endometrial malignancy at clinical and ultrasound follow-up. Descriptive statistics were used to assess the sonographic features of each histologic endpoint.
Initially, 2,206 women were recruited for the study, and after assessment for whether they met inclusion criteria, 1,745 patients were included. Nearly 90% of patients had a histologic diagnosis. EC or EIN was noted in 1.7% of patients, endometrial polyps in 58.9% of patients, intracavitary myomas in 3.8% of patients, proliferative or secretory changes or hyperplasia without atypia in 8.3% of patients, and endometrial atrophy in 15.2% of patients. A majority of malignancies were grade 1 endometrioid adenocarcinomas. These patients were older, had a higher body mass index, and were more likely to be postmenopausal.
Patients with premalignant or malignant pathology had a higher mean endometrial thickness than patients with the benign pathologies (11.3 mm vs. 8.8 mm), were more likely to have a non-uniform echogenicity (75% vs. 54%), and were more likely to have endometrial cysts (35% vs. 22%). Increased vascularity was noted in 31% of patients with a premalignant or malignant lesion compared with 13% of those with benign pathology, but a single dominant vessel was more likely with benign pathology (48% vs. 38%). The majority of endometrial polyps showed a single dominant vessel, a bright edge, and a regular endometrial-myometrial junction, and, specifically for postmenopausal patients with polyps, their endometrial thickness was a mean of 2 mm thinner than those with EIN/EC (9 mm vs. 11 mm).
In comparison to women who presented with abnormal uterine bleeding, those without abnormal bleeding had more favorable grade of differentiation, lower stage at diagnosis, and more frequent endometrioid histology. Patients with EC without abnormal bleeding also had a thinner endometrium, a more regular endometrial-myometrial junction, and less vascularization on ultrasound than patients with abnormal uterine bleeding.
COMMENTARY
Currently, we have well-established guidelines for endometrial sampling for patients with abnormal uterine bleeding or postmenopausal bleeding with the purpose of catching those with a premalignant or malignant lesion.1 These guidelines are based on patients’ symptomatology, risk factors, and ultrasound findings — most notably, the endometrial thickness in postmenopausal patients. Less is known for asymptomatic patients, since these are a minority of patients diagnosed with EIN or EC. Widespread screening for EC in asymptomatic patients at average risk is unlikely to be of benefit, since so many already are caught at an early stage and have a favorable prognosis, but being able to use information from testing performed for other reasons to identify these lesions may be of value to our patients.
Another study has shown similar sonographic findings for EIN. These patients had a thicker endometrium with a poorly defined endometrial-myometrial junction and higher rates of cysts and vascularity.2 Although these findings on an ultrasound for a patient with abnormal uterine bleeding should prompt further evaluation, consideration for further workup should be given to asymptomatic patients with these findings as well. Given that this study only included patients who went on to have endometrial sampling or long-term monitoring, the actual prevalence of patients with these sonographic features and EIN or EC likely is higher in the general population.
Although a minority of patients with EC do not present with vaginal bleeding, since endometrial cancer is the most common gynecologic malignancy, a large number of patients may fall into this category.3 These patients usually are early stage at the time of diagnosis, as demonstrated in this study.
Another study demonstrated that symptoms correlated with tumor invasion into the myometrium and cervical stroma, although stage or histology did not significantly affect symptomatology.4 Since patients diagnosed with early stage disease have an excellent prognosis, with a five-year survival rate of 90%, it is unclear whether identifying these patients prior to the development of symptoms would change the clinical outcome.5 A prior study showed no difference in prognosis between patients who were symptomatic and asymptomatic.6
What could be of more value would be ultrasound findings useful in the prediction of type II ECs or non-endometrial uterine malignancies, since these can be more aggressive and would benefit from early detection. Another area where these findings could have a stronger effect would be when evaluating patients who are at high risk for EC (such as patients with Lynch syndrome), since the prevalence of the disease is higher. For patients who are poor surgical candidates or desire future fertility, this earlier diagnosis also may have greater clinical implications, since they could attempt medical management sooner.
The sonographic findings noted earlier that are associated with EIN or EC are things to keep in mind when assessing a patient’s imaging, particularly for patients with risk factors for type I ECs, since it may prompt earlier endometrial sampling or closer follow-up. Although these findings are not necessarily included in the radiology reports, some of these can be identified by personal review of the images by the provider. Being mindful of these findings and having a discussion with patients regarding possible outcomes may lead to a lower threshold for endometrial sampling in these patients. Although EIN and EC are rare in asymptomatic patients, the patients who can be diagnosed early would greatly appreciate it.
REFERENCES
- Committee on Practice Bulletins—Gynecology. Practice bulletin no. 128: Diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 2012;120:197-206.
- Levine D, Gupta SC, Kwan C, et al. The sonographic appearance of endometrial intraepithelial neoplasia. J Ultrasound Med 2022;41:1723-1737.
- [No authors listed]. ACOG Committee Opinion No. 734: The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol 2018;131:e124-e129.
- Vinklerová P, Bednaríková M, Minár L, et al. Tumor characteristic
variations between symptomatic and asymptomatic endometrial cancer. Healthcare (Basel) 2021;9:902.
- [No authors listed]. Practice Bulletin No. 149: Endometrial cancer. Obstet Gynecol 2015;125:1006-1026.
- Vinklerová P, Ovesná P, Bednaríková M, et al. Does an endometrial cancer diagnosis among asymptomatic patients improve prognosis? Cancers (Basel) 2021;14:115.
