Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020).

An updated World Health Organization (WHO) classification of female genital tumours was published in autumn 2020. We discuss the major new additions to and changes from the prior 2014 classification with a discussion of the reasons underlying these. A feature of the new classification is the greater emphasis on key molecular events with integration of morphological and molecular features. Most of the major changes from the prior classification pertain to uterine (corpus and cervix) and vulval tumours, but changes in all organs are covered.

The impact of the COVID-19 coronavirus pandemic on the surgical management of gynecological cancers: Analysis of the multicenter database of the French SCGP and the FRANCOGYN group.

INTRODUCTION: The coronavirus SARS-CoV-2 (COVID-19) pandemic has put tremendous pressure on the French healthcare system. Almost all hospital departments have had to profoundly modify their activity to cope with the crisis. In this context, the surgical management of cancers has been a topic of debate as care strategies were tailored to avoid any delay in treatment that could be detrimental to patient wellbeing while being careful not to overload intensive care units. The primary objective of this study was to observe changes in the surgical management of pelvic cancers during the COVID-19 pandemic in France. MATERIAL AND METHODS: This study analyzed data from the prospective multi-center cohort study conducted by the French Society for Pelvic and Gynecological Surgery (SCGP) with methodological support from the French (FRANCOGYN) Group. All members of the SCGP received by e-mail a link allowing them to include patients who were scheduled to undergo gynecological carcinologic surgery between March 16th 2020 and May 11th 2020. Demographic data, the characteristics of cancers and the impact of the crisis in terms of changes to the usual recommended coarse of care were collected. RESULTS: A total of 181 patients with a median age 63 years were included in the cohort. In total, 31 patients had cervical cancer, 76 patients had endometrial cancer, 52 patients had ovarian or tubal cancer, 5 patients had a borderline tumor of the ovary, and 17 patients had vulvar cancer. During the study period, the care strategy was changed for 49 (27%) patients with postponed for 35 (19.3%) patients, and canceled for 7 (3.9%) patients. Surgical treatment was maintained for 139 (76.8%) patients. Management with neoadjuvant chemotherapy was offered to 19 (10,5%) patients and a change in surgical choice was made for 5 (2,8%) patients. In total, 8 (4,4%) patients tested positive for COVID-19. Data also shows a greater number of therapeutic changes in cases of ovarian cancer as well as a cancelation of a lumbo-aortic lymphadenectomy in one patient with cervical cancer. Hospital consultants estimated a direct detrimental impact of the COVID-19 pandemic for 39 patients, representing 22% of gynecological cancers. CONCLUSION: This study provided observational data of the impact of the COVID-19 health crisis on the surgical management of gynecological cancers.

The incidence of unexpected gynaecological malignancies in hysterectomies carried out for benign indications.

The aim of the present study was to determine the incidence of unexpected gynaecological malignancies in patients undergoing hysterectomy for benign indications and to evaluate their clinical characteristics. Data from 6448 cases who had undergone hysterectomy for benign indications between the dates of 01.01.2008-01.01.2018 were recorded retrospectively from the database of the institution. The mean age of the cases with malignancy was 59.2 ± 9.66 (45-80) and 76,31% were (29/38) postmenopausal. The mean gravidity was 3.94 ± 1.73 and parity was 3.31 ± 1.45. Their mean BMI was 29.6 ± 4.26 kg/m2 (22.4-41.9 kg/m2 range). These patients were followed for a mean duration of 60.68 ± 37.66 months and during this period death associated with malignancy occurred in 4/38 (%10.52) cases, all of whom had leiomyosarcoma. The benign indications of procedure were as follows: myoma uteri (2675, 41.48%), abnormal uterine bleeding (1508, 23.38%), uterine prolapsus (793, 12.29%), ovarian cyst (619, 9.59%), endometriosis (303, 4.69%), endometrial polyp (264, 4.09%), pelvic pain (238, 3.69%) and other benign causes (48, 0.74%). Unexpected gynaecological malignancy was found in 20 cases (0.31%) with endometrial cancer, in eight cases (0.12%) with uterine sarcoma, in seven cases (0.10%) with ovarian cancer, in one case (0.01%) with tubal cancer and in two (0.03%) with cervical cancer. Gynaecological malignancy was found in 38 of 6648 cases who underwent hysterectomy for benign indications, yielding an incidence rate of 0.58%.IMPACT STATEMENTWhat is already known on this subject? Hysterectomy is the most common gynaecological surgery in the world and although most are performed for benign indications, unexpected gynaecological malignancy is possible in the final pathology results.Although there are available publications investigating unexpected gynaecological malignancy incidences after hysterectomies for benign reasons, the incidence is still not clear. We aimed to contribute to the existing literature with this study, which includes a large number of cases.What do the results of this study add? Our study adds new findings to the body of the knowledge on the incidence of unexpected gynaecological malignancies in hysterectomies for benign indications. Gynaecological malignancy was found in 38 of 6648 cases who underwent hysterectomy for benign indications, yielding an incidence rate of 0.58%.What are the implications of these findings for clinical practice and/or further research? There is an unexpected possibility of gynaecological malignancy even in cases where it is expected to be benign with current diagnostic methods. In cases that are expected to be benign, detailed preoperative evaluation should be performed in all patients to prevent unexpected gynaecological malignancies. More sensitive screening methods should be developed especially in the preoperative differential diagnosis of leiomyoma and leiomyosarcoma.

Role of immunohistochemistry in gynec oncopathology including specific diagnostic scenarios with associated treatment implications.

Over the years, immunohistochemistry has emerged as a powerful tool for a more precise diagnosis of certain tumors in gynecologic oncopathology and resolving certain diagnostic dilemmas with significant treatment implications. Certain specific immunohistochemical (IHC) markers have been useful in the more correct identification of rare tumors, characterized by specific molecular signatures. Immunohistochemistry has also been useful in the identification of underlying genetic events, characterizing various tumors, as well as precancerous lesions. This review will focus upon the judicious application of various IHC antibody markers in gynec oncopathology, including authors' experience during "sign-outs" and especially during interaction with other oncology colleagues within the institutional disease management group. The updated references were retrieved from PubMed.

Revising the WHO classification: female genital tract tumours.

The upcoming revision of the World Health Organisation (WHO) classification of tumours of the female genital tract is scheduled for release in the second quarter of 2020. It will feature significant changes compared to earlier editions. In this review, we outline the process of revising this important reference source for those diagnosing tumours or engaged in cancer research and describe the significant changes. The WHO classification of tumours is increasingly evidence-based, with a clear update cycle, improved quality of illustrations and content, led by an editorial board comprised mainly of pathologists, but increasingly incorporating input from other disciplines. The advent of the new website allows the use of whole-slide images and hyperlinks to evidence or external bodies that produce guidance on staging or reporting.

Evaluation of pathology review at gynaecological oncology multidisciplinary team meetings: a 5-year prospective analysis of cases with major diagnostic discordance.

Multidisciplinary team meetings (MDTs) play an essential role in the management of patients with newly diagnosed and recurrent cancers, and often include review of pathology specimens that were initially assessed in external departments. Many studies have demonstrated a low but significant rate of diagnostic disagreement following such review but the pathological findings have seldom been detailed. We present a prospective 5-year study of all external cases reviewed at the Western Australian Gynaecological Oncology MDT focusing upon those cases with major diagnostic discordance likely to impact patient management. In total, 1275 cases were reviewed of which 132 (10.4%) were considered discordant including 48 (3.8%) with major discordance. Different interpretation of the presence and/or extent of tumour invasion accounted for a significant proportion of cases and in particular some adenocarcinoma and squamous carcinoma variants were initially reported to show only in situ or minimally invasive disease. Endometrial high-grade serous carcinoma was under-recognised and on occasion reassignment of tumour origin including metastasis to the gynaecological tract was facilitated by additional clinical information and supported by appropriate immunohistochemistry. This study supports the role of pathology review at MDTs and highlights problematic lesions that may merit a low threshold for additional opinion and ancillary studies.

Scope and Epidemiology of Gynecologic Cancers: An Overview.

OBJECTIVE: To provide a current overview of the scope and epidemiology of gynecologic cancers. DATA SOURCES: A review of articles dated 2005-2018 from PubMed, as well as data from The Centers for Disease Control and Prevention, National Cervical Cancer Coalition, and the American Cancer Society. CONCLUSION: Gynecologic cancers include any cancer that originates in a woman's reproductive system; cervical, ovarian, uterine, vaginal, vulvar, and fallopian tube (which is very rare), each named for the body part in which the cancer commences. The overall incidence of these cancers has decreased with time, except for vulvar and endometrial cancers, but racial disparities still exist. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a significant role in educating patients on the importance of preventative measures and modifiable lifestyles and behaviors. Likewise, nurses are in a unique position to help coordinate patients' care, thereby improving patient satisfaction. Nurses can participate and contribute to gynecologic research and influence political change to benefit those affected by gynecologic cancers.

New and Novel Therapies for Gynecologic Cancers.

OBJECTIVE: To review recent therapies approved by the US Food and Drug Administration for the treatment of gynecologic malignancies. DATA SOURCES: PubMed, FDA.gov, ASCO.org. CONCLUSION: The landscape for treating gynecologic malignancies is rapidly changing. Maintenance therapy now exists for women with advanced ovarian cancer after completing chemotherapy for both newly diagnosed and platinum-sensitive recurrent ovarian cancer. Anti-angiogenic therapy has many applications in gynecologic malignancies. Immunotherapy can be used in certain situations for women with gynecologic malignancies. IMPLICATIONS FOR NURSING PRACTICE: Biologic agents and immunotherapy have distinct side-effect profiles that nurses need to be aware of to optimize patient care and outcomes.

TNM classification of gynaecological malignant tumours, eighth edition: changes between the seventh and eighth editions.

The staging classification of gynaecological malignancies has been revised by the International Federation of Gynecology and Obstetrics (FIGO) and has been subsequently reviewed by the FIGO Committee on Gynecologic Oncology, the International Union for Cancer Control TNM Committee and the American Joint Committee on Cancer. The major change in the eighth edition of TNM classification of gynaecological malignant tumours is integrated staging for ovarian, fallopian tube and primary peritoneal carcinoma, whereas the seventh edition distinguished 'ovary and primary peritoneal carcinoma' and 'Fallopian tube carcinoma'. Furthermore, the new edition describes a prognostic factor grid for vulvar, cervical, endometrial and ovarian, fallopian tube and primary peritoneal carcinoma. If these factors contribute strongly to the prognosis, they may be incorporated into future staging classifications. This paper reviews the staging system for gynaecological malignancies, how it was developed, and current problems to be resolved.

Potential for Mitochondrial DNA Sequencing in the Differential Diagnosis of Gynaecological Malignancies.

In the event of multiple synchronous gynecological lesions, a fundamental piece of information to determine patient management, prognosis, and therapeutic regimen choice is whether the simultaneous malignancies arise independently or as a result of metastatic dissemination. An example of synchronous primary tumors of the female genital tract most frequently described are ovarian and endometrial cancers. Surgical findings and histopathological examination aimed at resolving this conundrum may be aided by molecular analyses, although they are too often inconclusive. High mitochondrial DNA (mtDNA) variability and its propensity to accumulate mutations has been proposed by our group as a tool to define clonality. We showed mtDNA sequencing to be informative in synchronous primary ovarian and endometrial cancer, detecting tumor-specific mutations in both lesions, ruling out independence of the two neoplasms, and indicating clonality. Furthermore, we tested this method in another frequent simultaneously detected gynecological lesion type, borderline ovarian cancer and their peritoneal implants, which may be monoclonal extra-ovarian metastases or polyclonal independent masses. The purpose of this review is to provide an update on the potential use of mtDNA sequencing in distinguishing independent and metastatic lesions in gynecological cancers, and to compare the efficiency of molecular analyses currently in use with this novel method.

Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration.

The discovery of circulating tumour DNA molecules created a paradigm shift in tumour biomarkers as predictors of recurrence. Non-invasive prenatal testing (NIPT) to detect circulating cell-free foetal DNA in maternal plasma is increasingly recognised as a valuable substitute to perceive foetal copy number variation (CNV). This study aimed to determine whether the copy number detection in plasma samples using NIPT platform could be used as a prognostic biomarker in patients with gynaecological cancer. We conducted a prospective study using samples containing preoperative plasma from 100 women with gynaecological cancers. Samples were randomly rearranged and blindly sequenced using a low-coverage whole-genome sequencing plasma DNA, NIPT platform. The NIPT pipeline identified copy number alterations (CNAs) were counted in plasma as a gain or loss if they exceeded 10 Mb from the expected diploid coverage. Progression-free survival (PFS) and overall survival (OS) were analysed according to the presence of CNA in plasma using Kaplan-Meier analyses. The NIPT pipeline detected 19/100 cases of all gynaecological cancers, including 6/36 ovarian cancers, 3/11 cervical cancers, and 10/53 endometrial cancers. Patients with CNA in plasma had a significantly poorer prognosis in all stages concerning PFS and OS. Therefore, low-coverage sequencing NIPT platform could serve as a predictive marker of patient outcome.

Metastatic gynecologic malignancies: advances in treatment and management.

Gynecologic cancers comprise of mostly uterine, ovarian, and cervical malignancies and are responsible for 95,000 new cases annually in the United States. Uterine cancer is the most common and the number of new cases and mortality has been increasing. Cervical cancer has decreased due to screening, early detection, and treatment of pre-invasive cancers. However, ovarian cancer remains the most lethal because of advanced stage at diagnosis and drug resistance. The metastatic spread pattern differs amongst these cancers, with uterine and cervical cancer found mostly in the primary organ and ovarian cancer disseminating throughout the peritoneum and upper abdomen at presentation. The primary treatment of ovarian cancer typically involves surgery followed by systemic therapy for more advanced disease. Previously, systemic chemotherapy with platinums, taxanes, doxorubicin, topotecan, and gemcitabine has been the standard in either upfront or recurrent setting. With molecular and genetic breakthroughs, we now have over eight new indications and five novel biologic therapies including antiangiogenics, poly ADP ribose polymerase inhibitors, and immunotherapies approved over the last 3 years. In this review, we will examine the biology of gynecologic cancer metastasis and focus on new treatment options for these cancers with a focus on ovarian cancer.

Is there a revision needed of the current FIGO staging system?

The FIGO staging system has undergone many modifications since it first appeared in about the middle of the previous century. Due to the use of modern diagnostic tools, namely computed tomography, magnetic resonance imaging, positron emission tomography, sentinel lymph node biopsy and neoadjuvant chemotherapy, certain gynecological cancer cases cannot be allocated to a specific stage if one wishes to adhere strictly to FIGO requirements. In these circumstances such cases actually remain unstaged. This should prompt appropriate modifications of the current FIGO staging system so that it fulfills its aims.

Genetics of gynaecological disorders.

From genomic imbalances associated with developmental abnormalities of the female genital tract to the molecular mechanisms underpinning endometriosis and uterine leiomyomatosis, new technologies have allowed the exploration of the genetic contribution and mapping the molecular pathways underpinning common and rare gynaecological conditions. While some of these conditions have historically been considered sporadic, recent research has demonstrated their potentially heritable nature linked to single genes or copy number variants. The phenotypic variability including non-penetrance indicates their multifactorial, complex aetiology encompassing genetic, epigenetic and environmental influences. Although genetic tests are not routinely conducted in gynaecological practice, there is an increasing body of evidence suggesting that, in appropriate cases, molecular investigations such as array CGH analysis may be an important part of the diagnostic algorithm. The subtlety of clinical features, especially in the context of syndromic diagnoses, requires the practitioner to become familiar with those conditions and the approach to diagnostic investigations. This chapter combines the recent research output related to gynaecological disorders with a clinical genetics approach aiming to highlight the multisystem character of some of these conditions, their implications for management, reproductive risks and options, and the importance of genetic counselling.

Genetics of gynaecological cancers.

Gynaecological cancers accounted for 16.3% of all cancers and 13.9% of all cancer deaths in women globally in 2012. Cancer of the cervix is the most common gynaecological cancer, followed by cancers of the uterus and the ovary. Although cervical cancer is almost exclusively triggered by human papilloma virus infection, approximately 5% of all uterine cancers and 20% of all ovarian cancers are caused by germline mutations in cancer predisposition genes. A number of genetic syndromes are associated with rarer gynaecological tumours. This review focuses on the epidemiology and pathology of inherited gynaecological cancer predisposition syndromes arising because of germline mutations.

Robot-assisted Surgery in Gynecologic Cancers.

Robotic-assisted surgery is a technological advancement that facilitates the application of minimally invasive techniques for complex operations in gynecologic oncology. The objective of this article was to review the literature regarding the role of robotic-assisted surgery to treat women with gynecologic cancers. The majority of publications on robotic surgery are still retrospective or descriptive in nature; however, the data for managing patients with a robotic-assisted approach show comparable, and at times improved, outcomes compared with both laparoscopy (2-dimensional) and laparotomy approaches. Robotic-assisted surgery has been used for patients with endometrial cancer and resulted in the increased use of minimally invasive surgery with improved outcomes compared with laparotomy and partially with laparoscopy. This has been shown in large cohorts of patients as well as in obese patients in whom the complication rates have significantly decreased. For early cervical cancer, robotic radical hysterectomy seems to be safe and feasible and to be preferable to laparotomy with seemingly comparable oncologic outcomes. Robotic-assisted surgery and conventional laparoscopy to stage women with early-stage ovarian cancer seem to have similar surgical and oncologic outcomes, with a shorter learning curve for robotic-assisted surgery. However, robotic-assisted surgery appears to be more expensive than laparotomy and traditional laparoscopy. In conclusion, robotic-assisted surgery appears to facilitate the surgical approach for complex operations to treat women with gynecologic cancers. Although randomized controlled trials are lacking to further elucidate the equivalence of robot-assisted surgery with conventional methods in terms of oncologic outcome and patients' quality of life, the technology appears to be safe and effective and could offer a minimally invasive approach to a much larger group of patients.