Abstract
Endometrial carcinoma is the most common gynaecological cancer in developed countries. Most cases are low-volume/low-grade tumour at presentation; however, high-grade subtypes may present with locally advanced disease with higher propensity for spread outside of the pelvis. MRI has a role in local staging of the tumour and helping the clinicians in treatment decision making. This pictorial essay gives examples of endometrial carcinoma at different stages with histological correlation. It also explores the potential limitations and pitfalls of imaging in this context.
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MRI plays an important role in staging endometrial carcinoma particularly in the evaluation of depth of invasion into the myometrium.
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Factors such as large intracavitary tumour, cornual tumour location, variable tumour appearance, adenomyosis and fibroid can affect the MRI accuracy in assessing the depth of myometrial invasion.
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Measurement of depth of invasion is best performed on oblique axial post-contrast sequence—paralleling the pathologists’ histological assessment.
Background
Endometrial cancer is the most common gynaecological cancer in developed countries [1, 2]. It predominantly affects post-menopausal women; however, younger cases can be seen in association with diabetes, obesity and Lynch syndrome, for example. Magnetic resonance imaging (MRI) has emerged as an informative imaging modality for local staging of endometrial cancer. This review aims to demonstrate the correlative radiological and pathological findings of endometrial carcinoma in various FIGO (International Federation of Gynecology and Obstetrics) stages as well as give examples of potential pitfalls where MR imaging is limited.
Histopathology and clinical factors
Endometrial cancer can be broadly divided into two types: Type I and Type II (Fig. 1). The most common Type 1 endometrial cancer is endometrioid adenocarcinoma, which accounts for 75–80% of endometrial cancers [3] and often arises on a background of atypical hyperplasia. Type II is less oestrogen dependent and shows a more aggressive behaviour with tendency to deeper myometrial invasion. Serous, clear-cell and undifferentiated carcinoma makes up the common histological subtypes of the Type II cancer.
The specific histology subtype of the endometrial carcinoma can influence the prognosis as well as the pattern of extra-uterine spread. Endometrioid subtype tends to spread by direct extension and nodal disease initially. In contrast, serous and clear-cell endometrial carcinoma is more aggressive with increased lymphovascular invasion, peritoneal and extra-abdominal spread [3].
The prognosis of endometrial cancer is dependent on histological subtype, histological grade, lymphovascular invasion and FIGO staging [4, 5]. Tumours are at higher risk of lymph node metastases with higher grades or deeper myometrial invasion. In these patients, additional surgical staging with lymphadenectomy or sentinel node biopsy may be performed [5,6,7]. Lymphadenectomy does not confer survival advantage but allows nodal staging that identify patients that require further adjuvant therapy following surgery.
FIGO staging was last updated in 2009 [8] (Table 1). The majority of patients with endometrial carcinoma present at early stage. Over two-thirds (69%) of the women present with stage I disease at diagnosis, whilst other stages are less common (stage II 7%; stage III 10%; stage IV 7%; stage unknown 7%) (10). There has been a recent proposal for updating the staging. The proposal incorporates the histopathologic grade into the definition of stage 1 and eliminates the cervical involvement from the staging [9].
MRI technique
The MRI protocol for the imaging of endometrial carcinoma as well as the value of the individual sequences is detailed in Table 2. High-resolution T2 imaging helps to delineate the anatomy of the uterus and its relationship to adjacent organs. DWI is sensitive for tumour which shows diffusion restriction but has low spatial resolution. Dynamic contrast-enhanced (DCE) sequences with arterial phase allow visualisation of the normal early sub-endometrial myometrial enhancement. Contrast-enhanced sequence is the most reliable in differentiating between the tumour and the myometrium and optimal for the measurement of the depth of tumour invasion.
Radiology–pathology correlation
Endometrial carcinoma is intermediate in signal intensity on T2-weighted imaging and hyperintense compared to the myometrium. The tumour is hypoenhancing relative to the background myometrium on the contrast-enhanced sequences—a useful feature in evaluating the depth of myometrium invasion. Normal endometrium, in contrast, shows delayed enhancement similar to the myometrium. The tumour has signal restriction on diffusion weighted imaging (DWI) due to the increased cellularity. DWI findings help to identify the tumour when small. The tumour can be quite variable in its growth pattern. It may have a large polypoidal intracavitary component, diffuse thickening of the endometrium or minimal intracavitary component with bulk of the tumour growing into the myometrium.
Stage I
Myometrial invasion
Most of the endometrial carcinoma presents at Stage 1. Stage IA and stage IB are differentiated by invasion greater than 50% of the myometrium (Figs. 2, 3). Whilst the volume of disease has been reported to be a potential prognostic factor, deep myometrial invasion is more important in prognosis indication and staging [10]. With deeper myometrial invasion, there is increased propensity for spread of cancer beyond the uterus, particularly to pelvic lymph nodes. Measurement of the depth of myometrial invasion is therefore critical in local staging of endometrial carcinoma.
The measurement on histology is based on low-field microscopy and is defined as tumour invasion into myometrial smooth muscle, relative to the estimated depth of the entire myometrium at that point (Fig. 4) [11, 12]. The radiological measurement is best performed on short-axis oblique post-contrast sequence through the uterus [4,5,6, 13, 14]. The measurement, however, can be difficult on both imaging and pathology, and the potential pitfalls are listed in Table 3 (Figs. 3, 5, 6, 7, 8, 9, 10)[15].
The endometrium/myometrium interface is an important landmark, but it can be irregular or distorted due to fibroids or background adenomyosis. Identifying normal physiological enhancement of the subendometrial myometrium (junction zone) on the early DCE sequences is important to exclude myometrial invasion. However, it is not always present due to either timing of the scan or tumour involvement. It can also occasionally be mimicked by the early enhancement at the pushing front of the tumour. The latter tends to be irregular, thick and associated with large tumours.
Large tumour volume may also distend the endometrial cavity. The intracavitary component of the large tumour may be erroneously included as part of the tumour depth into the myometrium leading to overestimation of the depth of invasion.
Atypical appearance of the tumour can be seen particularly in relation to T2 signal. Occasionally, tumour may be isointense to the myometrium or contain T2 hyperintense mucinous components. In those cases, the contrast-enhanced sequences are more reliable in marking out the extent of the tumour.
Stage II
Cervical stromal invasion
The invasion of the cervical stroma denotes stage II (Fig. 11). Cervical stroma is differentiated from the myometrium based on the type of supporting stroma on histology. Whilst the uterus has smooth muscle bundles, the cervix has dense fibrocollagenous tissue. On MRI, the cervical stroma has lower T2 signal reflective of the dense stroma. Cervical stromal invasion is seen on delayed contrast-enhanced images as disruption of normal cervical enhancement by hypoenhancing tumour. Tumour involvement of only the surface mucosa or glandular epithelium of the cervix without stromal involvement remains stage I. Tumour extending into the endocervical canal without actual disruption of the low T2 signal of the cervical stroma should not be considered cervical stromal invasion. Cervical stromal involvement can be due to contiguous involvement or may be distant from the tumour as a so-called drop metastasis.
Stage IIIA
Serosal involvement
Involvement of the serosa (stage IIIA) on MRI is characterised by full thickness tumour signal replacement of the myometrium with irregularity at the uterine outer surface (Fig. 12). This correlates with histological finding of extension of tumour beyond the myometrium and into the serosal layer. This can be seen on microscopic examination and sometimes on macroscopic examination as well (Fig. 12).
Ovarian involvement
Ovarian involvement (stage IIIA) can occur with contiguous spread of the primary tumour with engulfment of the normal ovarian tissue (Fig. 13). It can also occur as part of the peritoneal spread process on the ovarian serosa (Figs. 13, 14). It is important to be aware that synchronous ovarian tumour either benign or malignant can occur in conjunction with endometrial carcinoma. Not all ovarian lesions are due to metastases. A primary endometrial and secondary ovarian metastasis are more likely when there is a large volume endometrial tumour, high tumour grade and/or deep myometrial invasion in combination with a small ovarian lesion or when there is bilateral ovarian involvement [16].
Stage IIIB
Vaginal involvement
Vaginal involvement at time of initial diagnosis is rare. Vaginal involvement commonly is due to drop metastasis (Fig. 15) and is separate from the primary tumour. Direct contiguous involvement of the vagina is very uncommon. Involvement of the vagina (stage IIIB) is readily apparent on clinical examination and can be difficult to identify on MRI when the drop metastasis is small, and the vaginal vault is collapsed. Review of the entire genital tract down to the level of the vaginal introitus on the MRI is helpful to ensure that larger drop metastases are not missed.
Parametrial involvement
Radiologically, parametrial involvement occurs in the context of tumour involvement of the cervix. The involvement of the parametrium can be identified on MRI as loss of the full thickness low T2 cervical stroma signal with irregular interface at the adjacent parametrial fat or frank tumour extension into the fat (Fig. 16). On histology, this correlates with tumour cells with surrounding adipose tissue either by direct (continuous) or metastatic (discontinuous) spread [12].
Lymph nodes
The evaluation of the para-aortic nodes is easier on CT unless additional large field of view sequences are obtained through the abdomen. The evaluation of the pelvic nodes on MRI is still based on the short-axis dimension with a short-axis diameter cut-off of > 8 mm for pelvic lymph nodes and > 10 mm for para-aortic lymph nodes [6, 13]. Whilst occasionally, heterogeneity with tumour signal may be helpful to indicate involvement, this is not sensitive or specific [4,5,6, 13]. Benign and malignant nodes both show diffusion restriction. Tumour deposits may be microscopic, i.e. < 2 mm (N1mi) with no extra-capsular extension (Fig. 17). Inguinal nodes are considered to be stage IV with the other pelvic nodes considered to be stage IIIC.
Stage IV
Pelvic organ involvement
Whilst rare, endometrial cancer can invade adjacent pelvic organs such as bladder and bowel (Fig. 18). This would occur in late presentation of the disease. Such pattern of advance pelvic invasion is more commonly seen with cervical carcinoma.
The high-resolution T2 sequences are optimal for the assessing the relationship of the tumour to the adjacent organs. The local invasion on MRI shows tumour signal that disrupts the adjacent organs such as bowel or bladder. Bladder involvement requires extension to the bladder urothelium. Isolated detrusor muscle involvement is not considered to be stage IV disease. Often, involvement of the urinary bladder detrusor muscle leads to an oedematous mucosa (bullous oedema) in the bladder which can be seen on MRI or cystoscopy. Protuberant tumour in the bladder lumen with acute angle relative to the bladder inner layer would be highly concerning for urothelial involvement. The finding of a utero-vesical fistula also invariably infers the presence of bladder involvement.
Conclusion
Endometrial carcinoma is the most common gynaecological cancer. Whilst most cases are low grade with low-volume disease, it can also present with higher grade and more advanced disease with higher risk of nodal spread. MRI can assist in the local staging of the endometrial carcinoma preoperatively and guide the surgical and management decisions. MRI can assess the depth of myometrial invasion and distinguish between stage 1A and stage 1B disease. Its accuracy can, however, be affected by factors such as fibroids, adenomyosis, atrophic myometrium, bulky tumour, indistinct or variegated endometrium/myometrium junction and atypical tumour appearance on MRI. Understanding these potential pitfalls would help the reporter to improve the accuracy in detection of deep myometrial invasion. MRI with its higher tissue contrast resolution also has a role in identifying the extra-uterine pelvic disease. The extra-uterine disease can be due to different patterns of spread including contiguous, drop metastases, transcoelomic and lymphatic nodal spread. We present in this paper the radiology–pathology correlation at the different FIGO stages to help reporting radiologists to have a better understanding of the local spread of endometrial carcinoma and its imaging appearance.
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Abbreviations
- DCE:
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Dynamic contrast enhanced
- FIGO:
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The International Federation of Gynecology and Obstetrics
- MRI:
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Magnetic resonance imaging
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We thank Dr. Tristan Rutland for the supply of whole mount histopathology images.
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ED was a major contributor in writing the manuscript. LA contributed the histology images and the manuscript section on pathology. SC contributed the radiology images. VCH contributed to the radiology section on manuscript. KML contributed to the radiology section of the manuscript. SS contributed to the clinical section of the manuscript. YXK was a major contributor in writing the manuscript and overseeing the project. All authors read and approved the final manuscript.
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Dokter, E., Anderson, L., Cho, SM. et al. Radiology–pathology correlation of endometrial carcinoma assessment on magnetic resonance imaging. Insights Imaging 13, 80 (2022). https://doi.org/10.1186/s13244-022-01218-3
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DOI: https://doi.org/10.1186/s13244-022-01218-3