Federation Of Gynecology And Obstetrics Grade Research Articles

The Significance of International Federation of Gynecology and Obstetrics Grading in Microsatellite Instability-High and POLE-Mutant Endometrioid Endometrial Carcinoma

With the advancement of diagnostic molecular technology and the molecular classification of endometrial endometrioid carcinoma (EEC), it remains to be seen whether conventional International Federation of Gynecology and Obstetrics (FIGO) grading retains clinical significance in certain molecular subtypes of EECs. In this study, we explored the clinical significance of FIGO grading in microsatellite instability-high (MSI-H) and POLE-mutant EECs. A total of 162 cases of MSI-H EECs and 50 cases of POLE-mutant EECs were included in the analysis. Significant differences in tumor mutation burden (TMB), progression-free survival, and disease-specific survival were seen between the MSI-H and POLE-mutant cohorts. Within the MSI-H cohort, there were statistically significant differences in TMB and stage at presentation across FIGO grades, but not survival. Within the POLE-mutant cohort, there was significantly greater TMB with increasing FIGO grade, but there were no significant differences in stage or survival. In both the MSI-H and POLE-mutant cohorts, log-rank survival analysis showed no statistically significant difference in progression-free and disease-specific survival across FIGO grades. Similar findings were also seen when a binary grading system was utilized. Since FIGO grade was not associated with survival, we conclude that the intrinsic biology of these tumors, characterized by their molecular profile, may override the significance of FIGO grading.

Analysis of vanishing endometrial cancer by pathological types.

We asked why endometrial cancer sometimes vanishes. A total of 454 patients diagnosed with endometrioid-type endometrial cancer (EC) (via endometrial sampling) and treated in our clinic over the past 5 years were enrolled. The patients were divided into two groups: vanishing and residual, depending on whether a tumor was detected in the postoperative hysterectomy specimen. Patient age, numbers of pregnancies and deliveries, menopausal status, systemic disease status, hemogram parameters, International Federation of Gynecology and Obstetrics (FIGO) grade, and invasion status (evident on magnetic resonance imaging [MRI]) were compared between the groups. ECs vanished in 42 (9.25%) patients. The vanishing rates were 19.7% (37/187) in FIGO grade 1 patients, 2.1% (5/238) in grade 2 patients, and 0% (0/29) in grade 3 patients. The average age was lower in the vanishing than the residual group, but the premenopausal status and grade 1 tumor rates were higher (both p < 0.001). An absence of invasion (as revealed by MRI) was more common in the vanishing group (p < 0.001). No recurrence developed in the vanishing group, but recurrences were noted in 3.3% (14/412) of the residual group. There were no significant between-group differences in any of the numbers of pregnancies or births, systemic disease status, or hemogram parameters (all p > 0.05). Vanishing EC is more likely in premenopausal women with endometrioid grade 1 EC (as revealed by endometrial biopsy) who lack myometrial invasion on MRI.

The Association between Lower Uterine Segment Involvement in Corpus Located Endometrioid Adenocarcinoma with the (International Federation of Gynecology and Obstetrics) Grade and Stage

BACKGROUND: Although lower uterine segment (LUS) is regarded as an anatomically defined part that possess some histological differences, it is involvement by carcinoma have not been included in the criteria for definition in the staging system for endometrial carcinoma and there are few conflicting data focused on the effect of LUS involvement as a prognostic factor in endometrial cancer. AIM: To find the association between LUS involvement in corpus located endometrioid carcinoma with the grading and staging system established by the international federation of gynecology and obstetrics (FIGO). METHODS: This was a retrospective study involving data collected from achieves of histopathology departments of teaching laboratories within successive 4 years period in Medical City complex at Bagdad. Pathological analysis of 70 hysterectomy specimens of corpus located endometriod adenocarcinoma was done, histological sections from each case of endometrioid adenocarcinoma carcinoma were microscopically reviewed for appropriate grading and staging, in addition, meticulous search was applied for histological finding consistent with LUS involvement. The statistical comparison between the results was done using either independent sample t-test (for continuous data; mean ± SD) or Chi-square test at a significant p &lt; 0.05. RESULTS: The study enrolled 70 histological samples of endometrioid adenocarcinoma, the majority of the samples were of low grade and stage at presentation. Of total sample, 46 (65.71%) showed LUS involvement by tumor cells. There was a significant statistical relationship between LUS involvement and FIGO stage while a non-significant statistical association with FIGO grade was found. CONCLUSION: LUS involvement by corpus located endometrioid adenocarcinoma is associated with an advanced FIGO stage at presentation while non-significant relationship was found between patient age and tumor grade.

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

High Tumor Infiltrating Lymphocytes Are Associated with Overall Survival and Good Prognostic Parameters in Endometrial Endometrioid Carcinoma Patients.

The mortality incidence of endometrial carcinomas (ECs) has increased in recent years. Therefore, recent studies have focused on the cellular and microenvironmental properties of ECs. Tumor-infiltrating lymphocytes (TILs), a component of the microenvironment, have been found to be associated with the prognosis in many tumors. Although TILs were mostly evaluated by immunohistochemical studies in ECs, in our study, the evaluation was done with a light microscope as a practical approach, and we aimed to determine the prognostic importance of TILs in endometrioid ECs. 104 patients were included in the study. TILs in the stromal area (sTILs) were evaluated on hematoxylin and eosin (HE) stained-sections at X200 objective. The presence of TILs was evaluated as follows; 0-10% as low, 20-40% as moderate, and 50-90% as intense. Then TILs were grouped as low and high. Tumors with high TILs were more prone to have FIGO (International Federation of Gynecology and Obstetrics) grade 1 tumors, low nuclear grade, early pathological stage, smaller size, no lymphovascular invasion, myometrial invasion below 50%, and no cervical involvement. In the presence of high TILs, the overall survival showed significant increase but no significant correlation was found with disease-free survival. Interest in the molecular properties of ECs has increased in recent years. TIL, which can be easily evaluated in HE sections, is an important parameter in patient selection for molecular tests and determining the prognosis of patients.

Immunohistochemical Expression of “HE4” in Endometrial Hyperplasia versus Endometrial Endometrioid Carcinoma

Aim &#x0D; Endometrial cancer is the most common cancer of the female genital tract. No effective biomarkers currently exist to allow for an efficient risk classification of endometrial carcinoma. Human epididymis protein 4 (HE4) overexpression is first observed in ovarian cancer tissue and subsequent research has shown that the HE4 overexpression has also been observed in patients with endometrial carcinoma. To our knowledge, this marker was evaluated in small number of research studies in cases of endometrial carcinoma versus hyperplasia. This has inspired us to test for immunohistochemical expression of HE4 in endometrial endometrioid carcinoma and hyperplastic endometria and to correlate HE4 expression with various prognostic pathological parameters including International Federation of Gynecology and Obstetrics (FIGO) grading and staging.&#x0D; Methods &#x0D; Immunohistochemical staining for HE4 was performed on paraffin-embedded sections of forty cases of endometrial endometrioid carcinoma and thirty cases of endometrial hyperplasia: including 15 cases of non-atypical hyperplasia and 15 cases of atypical hyperplasia. A histochemical score was used to evaluate HE4 expression by the tumor cells.&#x0D; Results&#x0D; In this study, HE4 overexpression level was significantly higher in endometrial endometrioid carcinoma than endometrial hyperplasia and significantly higher than non-atypical endometrial hyperplasia (P&lt;0.05). HE4 strong expression was detected in 20% of atypical endometrial hyperplasia, but no statistical significance was detected between atypical hyperplasia and endometrial carcinoma. HE4 overexpression showed statistically significant positive correlation with FIGO grading, FIGO staging, and depth of myometrial invasion.&#x0D; Conclusion:&#x0D; During interpretation of endometrial biopsies of atypical hyperplasia, HE4 strong expression might raise the possibility of the presence of coexisting adenocarcinoma not biopsied or even warning of a near future malignant transformation. Also, strong expression of HE4 by tissue biopsy of adenocarcinoma should be reported as this might predict higher grade and stage of the tumor, a point that should be considered by surgeons while performing hysterectomy. These results should be further confirmed by extending the study on a large scale, correlation of HE4 expression with the molecular classification of Tumor Cancer Genome Atlas and long term follow up are required to establish the prognostic significance of HE4 expression in endometrial carcinoma and atypical hyperplasia.&#x0D; Keywords: Endometrial carcinoma, Endometrial hyperplasia, HE4, Immunohistochemistry.

Placenta Accreta Spectrum: Correlation between FIGO Clinical Classification and Histopathologic Findings.

Placenta accreta spectrum (PAS) covers a wide spectrum of placental adherence/invasion with varied clinical significance. Histopathologic examination is considered the confirmatory gold standard, but is only obtained sometime after definitive treatment. The International Federation of Gynecology and Obstetrics (FIGO) has published a new clinical classification that can be assigned at delivery, and we aimed to investigate the association between this new FIGO classification and histopathology and also to assess its correlation with maternal outcomes. We studied a retrospective cohort of 185 patients with histopathologically proven PAS managed at our referral center between September 2012 and January 2019. Two experienced surgeons retrospectively reviewed charts and assigned the FIGO grading based on findings reported at delivery. A third experienced reviewer adjudicated to determine the classification used for final analysis. Categorical outcomes were compared with the use of chi-squared and the Fisher exact test, as appropriate. A multivariate model was designed to adjust outcomes in different FIGO groups for the involvement of a formal multidisciplinary management team. Among 185 patients, there were 41 (22%) placenta accreta, 44 (24%) placenta increta, and 100 (54%) placenta percreta on histopathology. The inter-rater reliability was found to be substantial with Kappa = 0.661 (p < 0.001), and 95% confidence interval (CI): 0.449-0.872. There was a significant association between all histopathology groupings and the FIGO clinical classification (p < 0.001). However, we found no association between FIGO classifications and maternal complications. The new FIGO clinical classification is strongly associated with histopathologic findings. A better understanding of the depth and extent of invasion as afforded by the clinical classification system will help standardize reporting and future research. · PAS includes a wide spectrum of placental invasion with varied clinical significance.. · Histopathological examination is considered the confirmatory gold standard.. · The new FIGO clinical classification is strongly associated with histopathologic findings..

Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer - mass spectrometry analysis.

IntroductionDue to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III–IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer.Material and methodsA total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS.ResultsPlasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging (p = 0.001, p = 0.024 and p = 0.005), and grading (p = 0.021, p = 0.021 and p = 0.033).ConclusionsPlasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.

Mixed Endometrioid Adenocarcinoma and Müllerian Adenosarcoma of the Uterus and Ovary: Clinicopathologic Characterization With Emphasis on its Distinction From Carcinosarcoma.

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas.

Dynamic contrast‐enhanced ultrasound improves diagnostic performance in endometrial cancer staging

To compare the sensitivity and specificity of conventional two-dimensional transvaginal ultrasound/power Doppler (2D-TVU/PD) alone and 2D-TVU/PD combined with dynamic contrast-enhanced ultrasound (DCE-US) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) in women with endometrial cancer (EC), and to assess the association of DCE-US semiquantitative and qualitative variables with International Federation of Gynecology and Obstetrics (FIGO) Stage ≥ IB and 'high-risk' cancer. This was a prospective study of 101 consecutive women with biopsy-confirmed EC, undergoing expert ultrasound examination at Karolinska University Hospital, a tertiary referral center. All consenting women underwent DCE-US using a 1.5-2.5-mL intravenous bolus of SonoVue contrast agent, as well as conventional 2D-TVU/PD examination. DCE-US videoclips were analyzed with regard to filling (global or focal), wash-in (prior, simultaneous or after) and wash-out (global or focal) patterns of the contrast agent in the tumor compared with the surrounding tissue, as well as semiquantitative DCE-US parameters (wash-in slope, time-to-peak, peak intensity and area under the time-intensity curve (TIC)) obtained from a TIC. The study cohort was compared with a control cohort of women with EC examined at our center according to the International Endometrial Tumor Analysis protocol using 2D-TVU/PD only, matched at a ratio of 3:1 for FIGO stage and grade. The sensitivity and specificity of 2D-TVU/PD alone in the control cohort and in combination with DCE-US in the study cohort in the diagnosis of deep MI, CSI and high-risk cancer (defined as FIGO Stage ≥ IB and/or Grade 3 endometrioid and/or non-endometrioid histology) were compared, using pathological evaluation after hysterectomy as the 'gold standard'. After exclusions, 93 women were included in the study cohort and were matched to 279 women in the control cohort. The prevalence of FIGO Stage IA, Grade 1-2 EC was 52% in both cohorts. The sensitivity of 2D-TVU/PD with DCE-US in the study cohort was higher than that of 2D-TVU/PD alone in the control cohort in diagnosing both deep MI (0.74 vs 0.62; P = 0.036) and CSI (0.75 vs 0.51; P < 0.001), whereas the specificity was not significantly different (0.87 vs 0.85 and 0.96 vs 0.95, respectively). Compared with 2D-TVU/PD alone, the specificity of 2D-TVU/PD with DCE-US was higher in detecting high-risk cancer (0.94 vs 0.85; P = 0.024) but the sensitivity did not differ (0.73 vs 0.71). High-risk cancer and FIGO Stage ≥ IB were characterized by a 'focal' filling pattern, with a 'prior' wash-in pattern and a 'focal' wash-out pattern on subjective assessment of DCE-US videoclips. All semiquantitative DCE-US parameters were significantly predictive of FIGO Stage ≥ IB but not of high-risk cancer, despite a clear trend. Compared with 2D-TVU/PD alone, combining 2D-TVU/PD with DCE-US can significantly improve the detection of deep MI and CSI in women with EC, without increasing the false-positive rate. It can also improve the correct classification of high-risk disease, mainly by increasing specificity, thereby possibly reducing the number of unnecessarily extensive surgeries by almost 10%. Semiquantitative DCE-US parameters, as well as a 'focal' filling pattern, endometrial wash-in prior to the myometrium and a 'focal' wash-out pattern, are all associated with more advanced disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14months. Patients' mean age was 56.3 ± 10.8years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

Histological grading of ovarian mucinous carcinoma-an outcome-based analysis of traditional and novel systems.

Grading of primary ovarian mucinous carcinoma (OMC) is inconsistent among practices. The International Collaboration on Cancer Reporting recommends grading OMC using the International Federation of Gynecology and Obstetrics (FIGO) system for endometrial endometrioid carcinoma, when needed. The growth pattern (expansile versus infiltrative), a known prognostic variable in OMC, is not considered in any grading system. We herein analysed the prognostic value of various grading methods in a well-annotated cohort of OMC. Institutional OMCs underwent review and grading by the Silverberg and FIGO schemes and a novel system, growth-based grading (GBG), defined as G1 (expansile growth or infiltrative invasion in ≤10%) and G2 (infiltrative growth >10% of tumour). Of 46 OMCs included, 80% were FIGO stage I, 11% stage II and 9% stage III. On follow-up (mean= 52 months, range=1-190), five patients (11%) had adverse events (three recurrences and four deaths). On univariate analysis, stage (P=0.01, Cox proportional analysis), Silverberg grade (P=0.01), GBG grade (P=0.001) and percentage of infiltrative growth (P<0.001), but not FIGO grade, correlated with disease-free survival. Log-rank analysis showed increased survival in patients with Silverberg grade 1 versus 2 (P<0.001) and those with GBG G1 versus G2 (P<0.001). None of the parameters evaluated was significant on multivariate analysis (restricted due to the low number of adverse events). Silverberg and the new GBG system appear to be prognostically significant in OMC. Pattern-based grading allows for a binary stratification into low- and high-grade categories, which may be more appropriate for patient risk stratification. Despite current practices and recommendations to utilise FIGO grading in OMC, our study shows no prognostic significance of this system and we advise against its use.

TCGA molecular subgroups and FIGO grade in endometrial endometrioid carcinoma.

International Federation of Gynecology and Obstetrics (FIGO) grade is a crucial factor in the current system for the risk stratification of endometrial endometrioid carcinoma (EC). The Cancer Genome Atlas (TCGA) demonstrated four molecular prognostic subgroups for EC: POLE (good prognosis), microsatellite-instable (MSI, intermediate prognosis), copy-number-high (CNH, poor prognosis), and copy-number-low (CNL, variable prognosis). To assess how the prevalence of the TCGA molecular subgroups changes from low-grade (G1-2) to high-grade (G3) EC, to understand how it may affect the current risk-assessment system. A systematic review and meta-analysis was carried out by searching seven electronic databases from January 2013 to September 2019 for studies assessing the TCGA classification G1-2 and G3 EC. Pooled prevalence of the TCGA subgroups was calculated in EC. The association of each subgroup with grade was assessed using odds ratio (OR), with a significant p value < 0.05. Nine studies with 3185 patients were included. G3 EC showed significantly higher prevalence of the POLE subgroup (12.1% vs 6.2%; OR = 2.13; p = 0.0001), of the MSI subgroup (39.7% vs 24.7%; OR = 2.15; p = 0.0003) and of the CNH subgroup (21.3% vs 4.7%; OR = 5.25; p < 0.00001), and significantly lower prevalence of the CNL subgroup (28% vs 63.5%; OR = 0.2; p < 0.00001) than G1-2 EC. The prevalence of the TCGA subgroups is not in accordance with the prognostic value of FIGO grade, indicating that the current risk stratification of EC will be heavily affected by molecular signature.

588: Placenta accreta spectrum FIGO clinical classification in association with histopathological findings

Placenta accreta spectrum (PAS) covers a wide spectrum of placental adherence/ invasion with varied clinical significance. Histopathological examination is considered the confirmatory gold standard but is only obtained sometime after definitive treatment. The International Federation of Gynecology and Obstetrics (FIGO) has recently published a new clinical classification that can be assigned at delivery, and we aimed to investigate the association between this new FIGO classification and histopathology. We studied a retrospective cohort of 185 subjects with histopathology proven PAS managed at our referral center between September 2012 and January 2019. Two experienced surgeons retrospectively reviewed charts and assigned the FIGO grading based on findings reported at delivery. A third experienced reviewer adjudicated to determine classification used for final analysis. Subjects were further subcategorized into accreta/increta vs. percreta and FIGO grade 2-3 vs. grade 4-6 since FIGO grading above 4 represents invasion through the uterine serosa correlating with placenta percreta. Among 185 subjects, there were 41 (22%) placenta accrete, 44 (24%) increta, and 100 (54%) percreta on histopathology. FIGO grades included 72 (39%) grade 2-3, and 113 (61%) grade 4-6. The interrater reliability was found to be substantial with Kappa = 0.661 (p < 0.001), 95% CI (0.449, 0.872). There was a significant association between all histopathology groupings and the FIGO clinical classification, P< 0.001, in particular, percreta was associated with FIGO clinical classification 4-6 (P< 0.001), as 95 (84%) of subjects with FIGO clinical classification 4 and above had placenta percreta. The new FIGO clinical classification is strongly associated with histopathologic findings. We have demonstrated that with robust documentation and detailed record review, and bring mindful of the inherent limitations, retrospective assignment of FIGO class may be feasible. Reporting of FIGO Classification at the time of delivery may be important in reducing bias in future clinical studies.

Prenatal ultrasound staging system for placenta accreta spectrum disorders.

To develop a prenatal ultrasound staging system for placenta accreta spectrum (PAS) disorders in women with placenta previa and to evaluate its association with surgical outcome, placental invasion and the clinical staging system for PAS disorders proposed by the International Federation of Gynecology and Obstetrics (FIGO). This was a secondary retrospective analysis of prospectively collected data from women with placenta previa. We classified women according to the following staging system for PAS disorders, based upon the presence of ultrasound signs of PAS in women with placenta previa: PAS0, placenta previa with no ultrasound signs of invasion or with placental lacunae but no evidence of abnormal uterus-bladder interface; PAS1, presence of at least two of placental lacunae, loss of the clear zone or bladder wall interruption; PAS2, PAS1 plus uterovescical hypervascularity; PAS3, PAS1 or PAS2 plus evidence of increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region. We explored whether this ultrasound staging system correlates with surgical outcome (estimated blood loss (EBL, mL), units of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets (PLT) transfused, operation time (min), surgical complications defined as the occurrence of any damage to the bladder, ureters or bowel, length of hospital stay (days) and admission to intensive care unit (ICU)) and depth of placental invasion. The correlation between the present ultrasound staging system and the clinical grading system proposed by FIGO was assessed. Prenatal and surgical management were not based on the proposed prenatal ultrasound staging system. Linear and multiple regression models were used. Two-hundred and fifty-nine women were included in the analysis. Mean EBL was 516 ± 151 mL in women with PAS0, 609 ± 146 mL in those with PAS1, 950 ± 190 mL in those with PAS2 and 1323 ± 533 mL in those with PAS3, and increased significantly with increasing severity of PAS ultrasound stage. Mean units of PRBC transfused were 0.05 ± 0.21 in PAS0, 0.10 ± 0.45 in PAS1, 1.19 ± 1.11 in PAS2 and 4.48 ± 2.06 in PAS3, and increased significantly with PAS stage. Similarly, there was a progressive increase in the mean units of FFP transfused from PAS1 to PAS3 (0.0 ± 0.0 in PAS1, 0.25 ± 1.0 in PAS2 and 3.63 ± 2.67 in PAS3). Women presenting with PAS3 on ultrasound had significantly more units of PLT transfused (2.37 ± 2.40) compared with those with PAS0 (0.03 ± 0.18), PAS1 (0.0 ± 0.0) or PAS2 (0.0 ± 0.0). Mean operation time was longer in women with PAS3 (184 ± 32 min) compared with those with PAS1 (153 ± 38 min) or PAS2 (161 ± 28 min). Similarly, women with PAS3 had longer hospital stay (7.4 ± 2.1 days) compared with those with PAS0 (3.4 ± 0.6 days), PAS1 (6.4 ± 1.3 days) or PAS2 (5.9 ± 0.8 days). On linear regression analysis, after adjusting for all potential confounders, higher PAS stage was associated independently with a significant increase in EBL (314 (95% CI, 230-399) mL per one-stage increase; P < 0.001), units of PRBC transfused (1.74 (95% CI, 1.33-2.15) per one-stage increase; P < 0.001), units of FFP transfused (1.19 (95% CI, 0.61-1.77) per one-stage increase; P < 0.001), units of PLT transfused (1.03 (95% CI, 0.59-1.47) per one-stage increase; P < 0.001), operation time (38.8 (95% CI, 31.6-46.1) min per one-stage increase; P < 0.001) and length of hospital stay (0.83 (95% CI, 0.46-1.27) days per one-stage increase; P < 0.001). On logistic regression analysis, increased severity of PAS was associated independently with surgical complications (odds ratio, 3.14 (95% CI, 1.36-7.25); P = 0.007), while only PAS3 was associated with admission to the ICU (P < 0.001). All women with PAS0 on ultrasound were classified as having Grade-1 PAS disorder according to the FIGO grading system. Conversely, of the women presenting with PAS1 on ultrasound, 64.1% (95% CI, 48.4-77.3%) were classified as having Grade-3, while 35.9% (95% CI, 22.7-51.6%) were classified as having Grade-4 PAS disorder, according to the FIGO grading system. All women with PAS2 were categorized as having Grade-5 and all those with PAS3 as having Grade-6 PAS disorder according to the FIGO system. Ultrasound staging of PAS disorders is feasible and correlates with surgical outcome, depth of invasion and the FIGO clinical grading system. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

Objective:To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer.Material and Methods:Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman’s rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis.Results:Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis.Conclusion:Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

66 Interobserver Variability of Uterine Carcinoma Regarding FIGO Grade, Myometrial Invasion, and Tumor Subtype

Disease prognosis of endometrial carcinoma varies significantly depending on the International Federation of Gynecology and Obstetrics (FIGO) grade, extent of the myometrial invasion, and tumor type. However, assessment of these tumor characteristics can be difficult and subjective. Therefore, the interobserver variability would play a major role in the credibility of the consensus guidelines. Institutional review board approval was obtained. Five pathologists independently evaluated one representative section of a total of 90 cases of uterine carcinoma for tumor FIGO grade, myometrial invasion, and tumor subtypes. The 90 cases included 73 endometrioid adenocarcinoma, two mixed endometrioid and serous carcinoma, seven carcinosarcoma, six serous carcinoma, and two clear cell carcinoma. For the FIGO grades, only 22/90 cases were agreed on by all five pathologists, 49/90 cases were agreed on by 4/5 pathologists, and 88/90 cases were agreed on by 3/5 pathologists. If the FIGO grades 1 and 2 were together denoted as low grade, and FIGO 3 denoted as high grade, all five pathologists agreed on 70/90 cases. For myometrial invasion (<1/2 vs >1/2), all five pathologists agreed on 65/75 cases, and 4/5 pathologists agreed on 72/75 cases. For carcinoma subtypes, none of the 10 cases of clear cell or serous carcinoma was agreed by all five pathologists based on morphology. Two-tier FIGO grading (low grade vs high grade) appears better than the three-tier classification system, but the group consensus diagnosis seems to be the best system for FIGO grading. Evaluation of myometrial invasion (<1/2 vs >1/2) appears to be very reliable among the practicing pathologists. Identification of the serous or clear cell component based on pure morphology is not reliable, and immunohistochemistry should be routinely applied.

Association between Morphological Patterns of Myometrial Invasion and Cancer Stem Cell Markers in Endometrial Endometrioid Carcinoma.

In endometrial endometrioid adenocarcinoma (EEC), the depth of myometrial invasion (MI) is an important parameter for determining whether additional treatment is warranted. The present study investigated the association between MI patterns, cancer stem cell (CSC) phenotypes, and their clinicopathological significance in EEC. A total of 73 cases of EEC with MI were examined in this study. Haematoxylin and eosin-stained tissue specimens were analysed for MI pattern, which was categorised as infiltrating; expansile; adenomyosis (AM)-like; or microcystic, elongated, and fragmented (MELF)-type. The expression of CSC markers such as cluster of differentiation (CD)44, CD133, and Nanog1, as well as oestrogen receptor (ER) and progesterone receptor (PR) was examined by immunohistochemistry. Clinicopathological features including age, DOI, MI pattern, LVI, lymph node (LN) metastasis, disease progression, and survival outcome were recorded. Most examined cases (45/73) were International Federation of Gynecology and Obstetrics (FIGO) stage I. MI showed infiltrating (49.3%), AM-like (26.3%), MELF (15.1%), and expansile (9.6%) patterns. Tumours with the infiltrating pattern were associated with high FIGO grade (P=0.002), reduced ER and PR, and CD44 expression (P=0.014, 0.026, and 0.030, respectively); those with a MELF pattern showed LN metastasis (P<0.001), lymphovascular invasion (P=0.011), and reduced ER, CD44, and CD133 expression (P=0.036, 0.006, and 0.016, respectively). EEC with infiltrating/MELF patterns of MI is associated with worse prognosis. These results suggest that CSC expression profiles are an unfavourable indicator of EEC.

Is Tumor Size Really Important for Prediction of Lymphatic Dissemination in Grade 1 Endometrial Carcinoma With Superficial Myometrial Invasion?

Selection of patients with endometrioid endometrial cancer (EEC), in whom systematic lymph node dissection (LND) is indicated, is an important part of management to maintain optimal oncological outcomes, while avoiding unnecessary morbidities. According to the current approach, LND is recommended for the patients with International Federation of Gynecology and Obstetrics (FIGO) grade 1 to 2 tumors and a primary tumor diameter (PTD) greater than 2 cm, even with myometrial invasion (MMI) of less than 50%. We aimed to determine incidence of LN metastasis in this particular group of patients with grade 1 tumors, superficial MMI, and a PTD greater than 2 cm. This study only focused on women with FIGO grade 1 EEC having less than 50% MMI. Therefore, women with grade 2 or 3 tumors were excluded, as well as patients with 50% or greater MMI. We also excluded women with macroscopic extrauterine disease, as well as patients with cervical stromal involvement. Patients were divided into subgroups with regard to PTD; group 1 was composed of patients with PTD of 20 mm or less, whereas group 2 was composed of patients with PTD greater than 20 mm. All clinical and pathological variables were compared between the groups. Final pathology reports of 484 women with EEC who underwent surgical staging were analyzed. Among these women, there were 123 women in group 1 (PTD ≤ 20 mm) and 120 women in group 2 (PTD > 20 mm), with FIGO grade 1 tumors and superficial MMI. The median number of total LNs removed was 54 (range, 20-151). There were no women with pelvic and/or para-aortic LN metastasis in group 2, as well as in group 1. Our results suggest that lymphadenectomy may be omitted in women with FIGO grade 1 EEC having superficial MMI regardless of PTD. Deferral of systematic LND in this subgroup of patients may lead to reductions in costs and surgical morbidity.

Agreement Between Preoperative Endometrial Sampling and Surgical Specimen Findings in Endometrial Carcinoma.

The aims of the study were to evaluate agreement between preoperative endometrial samples and surgical specimens in endometrial carcinoma and to correlate this agreement with sample and patient characteristics. Patients who received primary surgical treatment for endometrial carcinoma at a tertiary care center and had undergone preoperative endometrial sampling were included. Medical records were reviewed to collect information from pathology reports and data on patient characteristics. The study sample comprised 166 patients (mean age, 64.6 years). The histological results of the biopsies were the following: endometrioid cancer (n = 118), nonendometrioid tumor (n = 38), and hyperplasia (n = 10). The agreement rates were 93.2% for endometrioid and 68.9% for nonendometrioid tumors, with a κ coefficient of 0.73 for tumor cell type. Tumor International Federation of Gynecology and Obstetrics (FIGO) grade was distributed as follows: 37.1% G1, 35.7% G2, and 27.1% G3, with agreement rates of 61.5%, 56%, and 78.9%, respectively. The overall κ coefficient for FIGO grading was 0.46. Only 1.9% of the tumors originally classified as G1 were upgraded to G3, whereas 16% of G2 lesions were upgraded. There was no significant difference in agreement rates for tumor cell type and FIGO grade in relation to any of the studied variables, except that biopsy specimens weighing more than 3 g had significantly better agreement in FIGO grading (P = 0.040). Preoperative biopsy has suboptimal accuracy for prediction of characteristics in the definitive surgical specimen. Caution must be taken when using preoperative information to determine extent of surgical resection, due to the risk of understaging. Additional information must be combined with the biopsy data to help in the decision-making process.