Second Opinion Expert Pathology in Endometrial Cancer: Potential Clinical Implications

Grevenkamp, Friederike; Kommoss, Felix K.F.; Kommoss, Friedrich; Lax, Sigurd; Fend, Falko; Wallwiener, D.; Schönfisch, Birgitt; Krämer, B.; Brucker, Sara Y.; Taran, Florin‐Andrei; Staebler, Annette; Kommoss, Stefan

doi:10.1097/igc.0000000000000870

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…It was shown that using a World Health Organization (WHO) two-tier classification with two diagnostic categories, hyperplasia without atypia and endometrial hyperplasia/endometrioid intra-epithelial neoplasia, improved reproducibility ( Kendall et al , 1998 ; Bergeron et al , 1999 ; Trimble et al , 2006 ; Ordi et al , 2014 ). The distinction between atypical endometrial hyperplasia and well-differentiated endometrial carcinoma showed poor intra-observer and inter-observer agreement ( Grevenkamp et al , 2017 ). Moreover, poor inter-observer agreement exists when evaluating the grade of endometrial carcinomas specifically in curettage material ( Lax et al , 2000 ; Scholten et al , 2004 ).…”

Section: Resultsmentioning

confidence: 99%

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma,

Rodolakis

Scambia

Acién

et al. 2022

Human Reproduction Open

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STUDY QUESTION How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN, SIZE, DURATION A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS, SETTING, METHODS ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS, REASONS FOR CAUTION Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTEREST(S) All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

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Section: Resultsmentioning

confidence: 99%

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma,

Rodolakis

Scambia

Acién

et al. 2022

Human Reproduction Open

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“…Finally, the core strength of this study was its comprehensive analysis of DFF40 and DFF45 expression and BCL2 expression in ECs. As previous studies have reported discrepancies regarding the pathological classifications of different types of ECs, all the specimens included herein were independently re-evaluated by two experienced pathologists to confirm their diagnoses and classifications [ 48 ]. Additionally, the relatively large size of the cohort, as well as the well-defined clinical characteristics of the specimens included herein, allowed us to analyze the relationships between DFF40, DFF45, and BCL2 expression and the clinical characteristics, including OS and DFS.…”

Section: Discussionmentioning

confidence: 99%

Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) underexpression

et al. 2018

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BackgroundThe expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS).MethodsImmunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student’s t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox’s proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics.ResultsDFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS.ConclusionsCompared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs.

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“…The importance of histological revision in expert centers has been seen in many neoplasms, with an impact on clinical decisions ranging between 7.5 and 23.3% [18][19][20][21][22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…In detail, a surgical/ endoscopic resection was proposed in 4.6% of the revised cases and a change in medical treatment in 21.7%. In an additional 21.1% of patients, the histopathological reassessment led to the need for further diagnostic tests, such as an additional 18 FDG-PET/CT for complete staging of patients with G3 NEN. According to the literature for other neoplasms, the original histological report is changed by a second evaluation in expert centers in 18.0-33.3% of cases, and in our study a similar rate of significant discordance was observed (36.0%).…”

Section: Discussionmentioning

confidence: 99%

Histopathological Revision for Gastroenteropancreatic Neuroendocrine Neoplasms in Expert Centers: Does It Make the Difference?

et al. 2020

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Background: The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. Objectives: To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. Methods: Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. Results: 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. Conclusions: Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.

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Second Opinion Expert Pathology in Endometrial Cancer: Potential Clinical Implications

Cited by 20 publications

References 34 publications

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma,

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma,

Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) underexpression

Histopathological Revision for Gastroenteropancreatic Neuroendocrine Neoplasms in Expert Centers: Does It Make the Difference?

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