Document Type : Original Research Article
Authors
- Arvin Arian 1
- Masume Giti 1
- Azamosadat Moosavi 2
- Setare Akhavan 3
- Arash Azhideh 4
- Mehran Arab-Ahmadi 1
1 Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Gynecologist Oncologist, Tehran University of Medical Science, Iran
3 Gynecology Ward, Vali-e Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Radiology Department, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Background & Objective: Endometrial cancer is the most frequent genitourinary tract malignancy in women. Women with endometrial cancer mostly refer at early stages of the disease which leads to good prognosis. Magnetic resonance imaging (MRI) has a crucial role in staging of the cancer. As there are little studies regarding the correlation between histopathology and International Federation of Gynecology and Obstetrics (FIGO) staging in Iranian women with endometrial cancer, we designed this study to assess the relationship between histopathology and FIGO staging with MRI in Iranian women with endometrial cancer.
Materials & Methods: This retrospective study was conducted in Imam Khomeini hospital complex between January 2015 and January 2018. All MRIs were performed on a 3T system. All imaging was done in Imam Hospital under observation of attending Radiologists with 10 and 20 years of work experience in women’s imaging who conducted this research. Obtained surgical specimens were assessed by an expert pathologist in the field of cancer and type of cancers were determined.
Results: Thirty two women with proved endometrial cancer (D&C or endometrial biopsy) were enrolled. Mean age was 55.2±10.7 years and all women referred to our clinic with vaginal bleeding. The most common FIGO staging was IA (14, 43.75%) and the most frequent pathology was endometrioid type adenocarcinoma (30, 93.7%) (60% well differentiated, 13.3% moderately differentiated, and 26.6% poorly differentiated). Most cases with endometrioid type poorly differentiated referred with IIIC1 stage of cancer, most patients with endometrioid type well differentiated referred with stage IA, a patient with clear cell cancer referred with stage IIIB, and patients with sarcoma referred with stages IB, and IV.
Conclusion: Patients with poor differentiated endometrial cancer referred with higher stages of the cancer.
Keywords
Main Subjects
Endometrial cancer is the most frequent genitourinary tract malignancy in women which accounts the sixth malignancy in females and is the cause of death in near 90000 in 2018 (1). The incidence of the cancer is two-fold in Caucasians compared to African Americans (2). Advanced age, obesity, diabetes mellitus, nulliparity, estrogen therapy, tamoxifen regimen, physical inactivity and hypertension are among common risk factors (3,4).
The histopathological classification is made, based on microscopic features.
According to WHO, endometrial cancer classification is as following (5):
| Endometrioid adenocarcinoma, usual type |
| • Endometrioid adenocarcinoma, variant types |
| − With squamous differentiation |
| − With secretory differentiation |
| − Villoglandular |
| − With mucinous differentiation |
| − Ciliated cell type |
| • Mucinous carcinoma |
| Serous endometrial intraepithelial carcinoma |
| • Serous adenocarcinoma |
| • Clear cell adenocarcinoma |
| • Neuroendocrine carcinoma |
| − Low-grade neuroendocrine tumor/carcinoid tumor |
| − High-grade neuroendocrine carcinoma |
| • Small cell neuroendocrine carcinoma |
| • Large cell neuroendocrine carcinoma |
| • Mixed carcinomas |
| • Undifferentiated carcinoma |
| • Dedifferentiated carcinoma |
Nowadays, based on clinic-pathological and molecular parameters, two types of endometrial carcinomas are introduced. Type I, consists of 80-90% of all endometrial cancers, which is a low stage at diagnosis with satisfactory clinical progression (6). It mostly occurs in peri- and postmenopausal period (6). Histologically, they are endometrioid type of endometrial adenocarcinomas (grade 1 and 2) and mucinous carcinomas (6).
Type II carcinomas are high grade at diagnosis with poor outcome and histologic compatible with serous carcinoma as well as clear cell, undifferentiated carcinomas and a group of endometrioid type of endometrial adenocarcinomas (grade 3) (6).
International Federation of Gynecology and Obstetrics (FIGO) staging system is used worldwide for endometrial cancer staging which was revised in 2009 (7) and is useful for clinical management. As the primary treatment of endometrial cancer is hysterectomy which is based on surgery and histology (8) accurate FIGO staging could be helpful.
By means of FIGO staging, myometrial and uterine serosa invasion, adenexal involvement, cytology of peritoneum, and lymph node involvements should be considered (9) which are used for prognosis determination (10).
Magnetic Resonance Imaging (MRI) can be used as the sole diagnostic method of evaluation before surgical interventions with accuracy reported between 83-92% (11, 12). Myometrial invasion, cervical, vaginal and nodal involvement could be assessed which will help treatment option selection.
As there are little studies regarding the correlation between histopathology and FIGO staging in Iranian women with endometrial cancer, we designed this study to assess the relationship between histopathology on FIGO staging of endometrial cancer in Iranian women.
This retrospective study was conducted in Imam Khomeini hospital complex affiliated hospital with Tehran University of medical sciences (TUMS) between January 2015 and January 2018.
Inclusion criteria were: confirmed endometrial cancer diagnosis based on D&C or endometrial biopsy.
All MRIs were performed on a 3T system (Siemens MAGNETOM TRIO, ATim system 3T eco) which has a six-channel body coil. The gradient strength is 45mTper meter. The patients were placed in supine position and the head was pointing toward the magnet, the spine coils were placed and body coils were placed over abdomen and pelvic. The body coils were tightened to prevent respiratory artifacts. We put the laser beam localizer over the iliac crest and registered the cases in the system. T 1-weighted turbo spin-echo images were obtained in axial plane (FOV:300×220 MM, TE: 12 ms, TR:800 ms, slice thickness 3 mm, slice gap: 1 mm, matrix:256×186).
T2-weighted turbo-spin echo were achieved in sagittal and oblique axial planes FOV:220×165 MM, TE: 101 ms, TR:5000 ms, slice thickness 3 mm, slice gap: 0.3 mm, matrix:256×186), oblique coronal plane (FOV:240×240, matrix:320×310).
The oblique, axial and coronal planes were placed in relation to the minor/major axis of the uterine body orthogonal with endometrial line. Diffusion-weighted images were obtained with echo-planner technique with body background suppression (FOV:350×265 mm, TE:85 ms, TR:6100 ms, slice thickness:4 mm, b value of 50, 400 ,1000). Contrast-enahnced fat-suppressed T1-weighted imaging sagittal images were aslso performed by the following characteristics: (FOV:320×240MM, TE:2.1 ms; slice thickness: 3 mm, TR:4.3, matrix: 265×196, dynamic techniques in phases including 30, 90, 180 second), axial : (FOV:300×220 mm, TE:1.5 ms, TR:2.59 ms, slice thickness: 3mm, matrix: 256×192, dynamic technique in phase including 4 Minute).
We staged our cases by FIGO staging. The reference standard was the revised FIGO staging system (2009) (13). Obtained surgical specimens were assessed by an expert pathologist in the field of cancer and type of cancers were determined.
SPSS version 24 (SPSS Inc., Chicago, IL., USA) was used for data analysis. Data was shown in mean ± SD for continuous and frequencies for categorical variables.
Thirty-two women were enrolled. Mean age was 55.2±10.7 years and all women referred to Imam Hospital with vaginal bleeding.
The most common FIGO staging was IA (14, 43, 7%) and the most frequent pathology was endometroid type adenocarcinoma (93.7%) (Table 1).
Most cases with endometroid type poorly differentiated referred with IIIC1 stage of cancer, most patients with endometroid type well differentiated referred with stage IA, and patients with sarcoma referred with stages IB, and IV (Table2 and 3).
Table 1. Frequency of FIGO staging and pathology in all recruited cases
| FIGO staging | Frequency (%) |
| IA IB II IIIA IIIB IIIC1 IIIC2 IV |
14(43.7%) 5(15.6%) 2(6.25%) - - 8(25.0%) 2(6.25%) 1(3.1%) |
| Pathology | Frequency (%) |
| Endometroid adenocarcinoma Poor differentiated Moderately differentiated Well differentiated Sarcoma |
30(93.7%) 8(26.6%) 4(13.3%) 18(60%) 2(6.3%) |
Table 2. Pathology findings and staging of the cancer
| Stage | Endometroid type poor differentiated | Endometroid type well differentiated | Endometroid type moderately differentiated | Sarcoma | P-value <0.001 |
| IA | 1(3.125%) | 12(37.5%) | 1(3.125%) | 0 | |
| IB | 0 | 3(9.4%) | 1(3.125%) | 1(3.125%) | |
| II | 2(6.25%) | 0 | 0 | 0 | |
| IIIA | 0 | 0 | 0 | 0 | |
| IIIB | 0 | 0 | 0 | 0 | |
| IIIC1 | 4(12.5%) | 3(9.4%) | 1(3.125%) | 0 | |
| IIIC2 | 1(3.125%) | 0 | 1(3.125%) | ||
| IV A | 0 | 0 | 0 | 1(3.125%) |
Table 3. FIGO staging and types of the cancer
| Staging | Type I N=22 |
Type II N=15 |
P-value |
|---|---|---|---|
| IA | 12(60%) | 5(29.4%) | 0.3 |
| IB | 3(15%) | 2(11.8%) | |
| II | 1(4.5%) | 2(11.8%) | |
| IIIA | 0 | 1(5.9%) | |
| IIIB | 0 | 1(5.9%) | |
| IIIC1 | 4(20%) | 4(23.5%) | |
| IIIC2 | 1(5%) | 1(5.9%) | |
| IV | 0 | 1(5.9%) |
The result of current study showed that poorly differentiated endometroid type cancers refer to the physicians in higher stages while well-differentiated cases refer with lower stages. The results also showed that patients with sarcomas refer with higher stage of the cancer. We also found that most common type of the cancer was endometroid adenocarcinoma and more than half of patients referred with lower stages (IA, IB).
In a previous study which was conducted by Tanaka et al., the most common stage of endometrial cancer was IA followed by IB (14) and in Zamani et al. study the most frequent type of cancer was endometroid type (15) which is in line with our results.
Uterine sarcomas consisted of 8% of uterine malignancies which present as pelvic masses, vaginal bleeding and abdominopelvic pain (16). Our results showed that patients with uterine sarcoma refer with different staging’s (IA, IB, IV).
Endometrial cancer mostly presents at early stages which has good prognosis (17). Between 3 and 13% of endometrial cancers invade other organs or extent outside the uterus (17). Survival of patients with stage IV is estimated to be 10-20% (17). Near 80% of endometrial cancers are adenocarcinomas of which 60–65% of them are endometrioid cancers (17). Endometroid type-cancers could be well differentiated (grade1), moderately differentiated (grade2) and poorly differentiated (grade3) (9).
Endometrial cancer could be regarded as type I and type II. Type I represents 75% of all endometrial cancers and endometrioid is the most common histology while clear cell and papillary serous are considered as subgroups of type II cancers (17). Type II cancers arise in post-menopausal women and have poorer prognosis.
The preoperative assessment includes MRI which provides information regarding myometrial invasion, cervical, vaginal and nodal involvement (9). MRI will help to determine the plan of treatment.
Obesity is a risk factor for endometrial cancer through different pathways such as insulin resistance, hyperglycaemia and hyperinsulinaemia which leads to increase of bioavailability of insulin growth factor (IGF) (17,18). IGF promotes endometrial proliferation and finally, endometrial cancer development. Estrogen exposure could be exogenous (hormone replacement therapy) or endogenous (excessive obesity and anovulation) (17). The treatment includes surgery, adjuvant radiotherapy, hormonal and target agent therapy (9).
This study had some limitations. First, it was conducted in a tertiary center. Second, the sample size was limited. Larger multi-centric studies are recommended.
Patients with poor differentiated endometrial cancer referred with higher stages. FIGO staging of endometrial cancer by MRI with superior soft tissue resolution is well correlated with histopathology of endometrial cancer. In current study the patients with type I endometrial cancer (mainly well differentiated endometroid type) referred at lower stages, while the patients with type II (mainly poor differentiated type) referred at higher stages.
The authors would like to express their gratitude towards all who helped in the improvement of this paper.
The authors declared that there are no conflicts of interest.
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