Diagnostic workup for endometrioid borderline ovarian tumors (eBOT) requires histopathological evaluation of the uterus

BACKGROUND For young borderline ovarian tumor (BOT) patients, preservation of the uterus was incorporated as an accepted option into treatment guidelines. For the endometrioid subtype (eBOT) however, adequate histological evaluation is challenging and might be associated with synchronous endometrial disorders or misinterpreted as spread from uterine primaries. CASE PRESENTATION We report the cases of two young patients with eBOT who underwent treatment according to current guidelines. In both cases, unexpected findings of invasive uterine carcinomas were established in final histopathological evaluation. CONCLUSIONS This constellation highlights the challenging diagnostic workup of BOT and underlines that uterine curettage is indispensable for eBOT to exclude uterine primary tumors when fertility preservation is planned. Accordingly, we suggest to include this procedure into recommendations for diagnostic workup and to state the potential risk in treatment guidelines

Clinical and demographic factors in endometrial and ovary carcinoma: Synchronous carcinoma vs stage IIIA endometrial carcinoma

Objective: To compare pre-surgical demographic and clinical factors and preoperative serum tumor marker values of patients with endometrial and ovarian synchronous carcinoma with those diagnosed with endometrial carcinoma with metastatic ovarian involvement (FIGO stage IIIA). Methods: A retrospective observational study including patients with endometrial and ovarian malignant tumors that were treated at Miguel Servet University Hospital, Zaragoza, Spain, since January 2000 to June 2020. All pathologic specimens were reviewed by two pathologists specialized in gynecological oncology. Results: Overall, 51 patients were included. 24 cases of them, were endometrial and ovarian synchronous primary carcinomas and the remaining 27 cases were endometrial tumors with adnexa. Parity, personal and family oncological history, arterial hypertension, diabetes, dyslipidemia, obesity and the prior use of hormone replacement therapy did not show significant differences between both groups. Age (p = 0.002), menopausal status (p = 0.029), abnormal uterine bleeding (p = 0.001), Ca 12.5 preoperative serum level (p = 0.038) and Ca 19.9 preoperative serum level (0.028) were factors with significant differences between both groups. In multivariate analysis, only abnormal uterine bleeding and Ca 19.9 values were independents factors. Conclusions: The presence of abnormal uterine bleeding and Ca 19.9 preoperative serum level could guide the clinician in the preoperative differential diagnosis between endometrial cancer with ovarian involvement and endometrial and ovarian synchronous carcinoma. © 2021 The Author(s)

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for patients with peritoneal metastases from endometrial cancer

Background: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. Results: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3–35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan–Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. Conclusions: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma

FIGO staging of endometrial cancer: 2023

INTRODUCTION: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. METHODS: The FIGO Women\u27s Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. RESULTS: Based on the existing evidence, the substages were defined as follows: SUMMARY: The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data

Ovarian Cancer Genetics: Subtypes and Risk Factors

The genetics of ovarian cancer are a complex, ever evolving concept that presents hurdles in classification, diagnosis, and treatment in the clinic. Instead of common driver mutations, genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. In high-grade serous ovarian cancer, the most common subtype, TP53 is mutated in over 90% of all patients while the next most common mutation is less than 20%. However, next-generation sequencing and biological statistics have shown that mutations within DNA repair pathways, including BRCA1 and BRCA2, are common in about 50% of all high-grade serous patients leading to the development of a breakthrough therapy of poly ADP ribose polymerase (PARP) inhibitors. This is just one example of how a better understanding of the complex genetic background of ovarian cancer can improve clinical treatment. A thorough review of ovarian cancer genetics and the effect it has on disease development, diagnosis, progression, and treatment will enhance the understanding of how to better research and treat ovarian cancer

Cancer of the Uterine Endometrium

The book Cancer of the Uterine Endometrium - Advances and Controversies brings together an international collaboration of authors who share their contributions for the management of endometrial carcinoma. The scope of the text is not basic, but rather aims to provide a comprehensive and updated source of advances in the diagnosis and therapeutic strategies in this field of gynecologic cancer. Each section in the book attempts to provide the most relevant evidence-based information in the biology and genetics, modern imaging, surgery and staging, and therapies for endometrial cancer. It is hoped that future editions will bring additional authors to contribute to this endeavor. To this end, it is our patients who will benefit from this work

Primary malignant mixed Müllerian tumor arising from the mesorectum with a synchronous ovarian cancer: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Extragenital malignant mixed Müllerian tumor is an extremely rare presentation of malignant mixed Müllerian tumor, especially when combined with a synchronous ovarian cancer.</p> <p>Case presentation</p> <p>We report the clinical course and pathologic findings of a case of mesorectal malignant mixed Müllerian tumor with synchronous ovarian cancer, in a 50-year-old, gravida 0, para 0, Han Chinese woman with regular menstruation. This is the sixteenth case in the English literature of extragenital malignant mixed Müllerian tumor combined with synchronous or metachronous malignancy reported.</p> <p>Conclusion</p> <p>Although extragenital malignant mixed Müllerian tumor is very rare and has a poor prognososis, a longer survival time might be achieved with treatment by cytoreductive surgery, radiotherapy and chemotherapy.</p

Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression

Analyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors’ evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decisionWe thank all those at the Translational Research Laboratory of the MD Anderson Cancer Center Madrid for their invaluable help with this study. Tissue samples were obtained with the support of the MD Anderson Foundation Biobank (recordnumber B.0000745, ISCIII National Biobank Record), the “Xarxa Catalana de Bancs de Tumors” and “Plataforma de Biobancos” ISCIII (PT13/0010/0014, B.000609). This study has been supported by the Spanish Ministry of Economy and Innovation (PID2019-104644RB-I00 (GMB), the Instituto de Salud Carlos III (ISCIII, CIBERONC, CB16/12/00295 - GMB-, CB16/12/00328 -EC, AGM- and CB16/12/00231 -XMG- [all partly supported by FEDER funds]) and by the AECC Scientific Foundation (FC_AECC PROYE19036MOR -GMB- and Coordinated groups 2018 -XMG, AGM, GMB-). SO is funded by an AECC-postdoctoral grant (2020). JSR-F and BW are funded in part by the Breast Cancer Research Foundation and in part by the NIH/ NCI P50 CA247749 01 grant. Research reported in this publication was supported in part by a Cancer Center Support Grant of the NIH/NCI (Grant No. P30CA008748; MSK). We thank the Eurofins Megalab laboratory for helping us to perform the analysis of DNA HPV detection

Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression

Endometrial cancer; Clonal evolution; MutationCáncer endometrial; Evolución clonal; MutaciónCàncer d'endometri; Evolució clonal; MutacióAnalyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors’ evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decision.We thank all those at the Translational Research Laboratory of the MD Anderson Cancer Center Madrid for their invaluable help with this study. Tissue samples were obtained with the support of the MD Anderson Foundation Biobank (record number B.0000745, ISCIII National Biobank Record), the “Xarxa Catalana de Bancs de Tumors” and “Plataforma de Biobancos” ISCIII (PT13/0010/0014, B.000609). This study has been supported by the Spanish Ministry of Economy and Innovation (PID2019-104644RB-I00 (GMB), the Instituto de Salud Carlos III (ISCIII, CIBERONC, CB16/12/00295 - GMB-, CB16/12/00328 -EC, AGM- and CB16/12/00231 -XMG- [all partly supported by FEDER funds]) and by the AECC Scientific Foundation (FC_AECC PROYE19036MOR -GMB- and Coordinated groups 2018 -XMG, AGM, GMB-). SO is funded by an AECC-postdoctoral grant (2020). JSR-F and BW are funded in part by the Breast Cancer Research Foundation and in part by the NIH/NCI P50 CA247749 01 grant. Research reported in this publication was supported in part by a Cancer Center Support Grant of the NIH/NCI (Grant No. P30CA008748; MSK). We thank the Eurofins Megalab laboratory for helping us to perform the analysis of DNA HPV detection

Controversies in the Management of Endometrial Carcinoma

Endometrial carcinoma is the most common type of female genital tract malignancy. Although endometrial carcinoma is a low grade curable malignancy, the condition of the disease can range from excellent prognosis with high curability to aggressive disease with poor outcome. During the last 10 years many researches have provided some new valuable data of optimal treatments for endometrial carcinoma. Progression in diagnostic imaging, radiation delivery systems, and systemic therapies potentially can improve outcomes while minimizing morbidity. Firstly, total hysterectomy and bilateral salphingo-oophorectomy is the primary operative procedure. Pelvic lymhadenectomy is performed in most centers on therapeutic and prognostic grounds and to individualize adjuvant treatment. Women with endometrial carcinoma can be readily segregated intraoperatively into “low-risk” and “high-risk” groups to better identify those women who will most likely benefit from thorough lymphadenectomy. Secondly, adjuvant therapies have been proposed for women with endometrial carcinoma postoperatively. Postoperative irradiation is used to reduce pelvic and vaginal recurrences in high risk cases. Chemotherapy is emerging as an important treatment modality in advanced endometrial carcinoma. Meanwhile the availability of new hormonal and biological agents presents new opportunities for therapy