The ISGyP Endocervical Adenocarcinoma Project: Master Plan Summary, Acknowledgment of Participants, and Participant Responses to Final Recommendations of the Expert Panels

The International Society of Gynecological Pathologists carried out a multifaceted project with the broad aim of improving the pathological reporting of endocervical adenocarcinoma (EAC). The intentions were to promote and align practices with the WHO 2020 classification, which endorses HPV status-based classification of EAC and the Silva pattern-based assessment of HPV-associated EAC, to promote uniformity in applying the recent FIGO staging revisions on cervical carcinoma, and to provide best practice guidelines on all aspects of EAC pathology reporting. To facilitate the use of the new WHO/IECC classification and the Silva system, two online educational portals were set up with training and test sets of scanned slides; these remain available to society members on the ISGyP educational website. In addition, a large international collaborative individual data collection project is ongoing, aiming to ascertain the prognostic value of EAC categories, and to provide a database with the potential to address unanswered questions. A single on-site meeting was held on February 29, 2020 in Los Angeles, in advance of the USCAP Annual Meeting; all other correspondence was by email and through electronic surveys. Project participants were invited to vote and comment on the recommendations contained within the practice guideline articles. The project received an enthusiastic response from pathologists across the world. This report includes an overview and summary of all aspects of the project, a list of participants and the results of polling on practice recommendations.


BACKGROUND
In 2019, under the leadership of its President, Dr Esther Oliva, the International Society of Gynecological Pathologists (ISGyP) embarked on a multifaceted project on endocervical adenocarcinoma (EAC), in part to synchronize with recent updates introduced by the revised FIGO 2018 staging for cervical carcinoma, the fifth edition of the World Health Organization classification of tumors of the female genital tract and the International Collaboration on Cancer Reporting for cervical cancers. In order to develop, promote and facilitate a uniform and standardized approach to pathologic reporting, the ISGyP EAC project engaged the ISGyP members and convened an expert panel to survey current practices to identify areas of discordance, construct an online training portal using scanned slides, develop best practice guidelines with recommendations for pathology reporting, assess ISGyP members response to the final recommendations via polling, and conduct an international multicenter outcome study. Herein we document the mechanics and timeline of these various project components and acknowledge the ISGyP members who contributed time, effort, and creative input to one or more of them.

Project Aims
The overarching aim of the project was to improve the pathologic reporting of EAC. The specific goals are: To understand the spectrum of current global practices in the pathologic evaluation (gross specimen management, diagnosis, classification) and reporting (invasiveness, staging, margins) of endocervical cancer.
To improve the global reproducibility of EAC classification and pathological reporting by: Developing online self-education modules for applying the new International Endocervical Adenocarcinoma Criteria and Classification (IECC) system and Silva classification system of tumor invasiveness. Developing evidence-based best practice guidelines for gross specimen management, tumor classification, staging and reporting, as well as managing problematic and controversial issues. To assess the prognostic significance of WHO/ IECC EAC classification and Silva patternbased classification of HPV-associated adenocarcinomas by conducting an international outcome study.

Project Components
An overview of the project components is illustrated in Figure 1.
(1) Development of expert panel recommendations.
A systematic approach to developing the recommendations was implemented, incorporating efforts to identify areas of problems and  11. Invasive adenocarcinoma: in the absence of destructive growth, the following diagnoses should be considered: either adenocarcinoma in situ: in the absence of destructive growth, draw attention to the gland distribution and density; if these are within the confines of the normal endocervix, diagnosis of adenocarcinoma in situ is warranted. Comparison with the uninvolved/normal endocervical gland architecture is helpful. OR pattern-A (nondestructive) adenocarcinoma: if a nondestructive lesion exceeds the size and distribution expected for AIS, or such determination cannot be made, the diagnosis of pattern-A adenocarcinoma (with nondestructive growth) is warranted. It is recommended for now to separate these lesions from frankly invasive adenocarcinoma, as their behavior is largely indolent. It is currently not recommended to classify them as AIS until new evidence on their risk of ovarian spread is available. Reporting size, stage, and margin status is still warranted in this category 84 5 4 7 12. Distinction between in situ and invasive gastric type endocervical adenocarcinoma: in the absence of destructive growth, the following diagnoses should be considered: (i) AIS: gland distribution and density similar and within the confines of the normal endocervix. Comparison with the uninvolved/normal endocervical mucosa is helpful. (ii) Atypical lobular endocervical glandular hyperplasia: floret-like arrangements with small, acini-like glands surrounding a central duct and nuclear atypia. Invasive gastric type adenocarcinoma, minimal deviation type: haphazard distribution of glands with involvement of the deep cervical stroma, lack of lobular organization, minimal to absent nuclear atypia    6. Depth of invasion should be reported as measured on each specimen but for final staging purposes, the deepest invasion in any single specimen should be used 20. Tumor involving the anterior or posterior paracervical tissue, including extension to bladder or bowel WITHOUT mucosal involvement, should be staged as IIB (as this is clinically treated as parametrial involvement)    The study was designed to evaluate patients with EAC for whom a minimum of 2 yr of follow-up is available and to correlate outcome with the IECC system and Silva system for tumor invasiveness. Assessment of the IECC tumor classification and Silva pattern of invasiveness was performed locally by the contributing institution. Each participating institution was requested to contribute a minimum of 15 consecutive cases with complete data. The project received sponsorship from Queen Mary University of London on December 2, 2019, and ethical approval from the South West-Frenchay Research Ethics Committee on February 26, 2020 (IRAS 273971; REC ref 20/S/0008). Data accrual was closed in October, 2020. Due to delays as a result of the pandemic, completion of paperwork, data cleaning and analysis are currently ongoing and preliminary results are expected in 2021.

Acknowledgement of Project Participants
The success of the ISGyP EAC Project is a result of more than 250 pathologists across the globe who have dedicated time, effort, and creative input to various components of the project. These pathologists are acknowledged in Table 7. Gratitude is also extended to several pathologists who preferred to remain anonymous. All contributors from each Centre participating in the outcome study will be acknowledged in the publication(s) arising from the data; only the pathologists from these Centres are listed in Table 7. 80. Lymph node specimens: Intraoperative evaluation of SLN should be performed only if the surgeon is prepared to alter the intraoperative plan based on the results and is aware of the limitations to diagnostic sensitivity

CONCLUSIONS
The ISGyP EAC Project has now concluded, with the exception of the analysis of the results of the international outcome study. The extensive contributions of pathologists all across the world has enabled the Project to be a success and is a testament to the value of global collaboration. As co-Chairs of the ISGyP Education Committee, the authors take this opportunity to express their gratitude to all participants, whether or not included in the participant list, for making this endeavor a success in the hope that it will contribute to improving the standard of pathology reporting in EAC and thereby improving the clinical outcomes of our patients. S123 THE ISGYP ENDOCERVICAL ADENOCARCINOMA PROJECT