Current Practices in the Processing, Diagnosis, and Reporting of Endometrial Carcinoma: Results of a Web-based Survey by the International Society of Gynecological Pathologists (ISGyP)

There have been significant advances in our understanding of the biology and classification of endometrial carcinoma, over the last few years, and the new prediction models proposed for prognostication. To accurately diagnose and stage tumors and apply these prediction models, it is necessary that there be standardized processing of specimens, and a common understanding and usage of the diagnostic terminology of endometrial carcinoma. The International Society of Gynecological Pathologists embarked on an ambitious project to achieve this goal in 2015. An early step in the process was to collect baseline information on existing practices with regard to the processing, diagnosis, and reporting of endometrial carcinomas among the members of the society. This was carried out using a web-based survey comprising 112 questions. The results are presented herein and reveal areas of uniformity but also areas of substantial variation among pathologists. The results of the survey assisted in developing the subsequent recommendations that follow as separate articles in this issue of the journal with regard to processing, diagnosis, and reporting of endometrial carcinomas

The International Society of Gynecological Pathologists (ISGyP) Endometrial Carcinoma Project

Endometrial carcinoma is the commonest gynecological malignancy in developed countries, and the various aspects of the pathology report are critical for patient management. There are many areas of controversy with regard to the handling of resection specimens and the pathologic reporting of endometrial carcinomas. These controversies include those related to sampling, diagnosis, reporting of parameters important for staging, and the undertaking of ancillary studies. These controversies stimulated the International Society of Gynecological Pathologists (ISGyP) endometrial carcinoma project. The project was devised at the ISGyP Board of Directors meeting in March 2015 under the Presidency of Richard Zaino. An organizing committee was selected from the members of the Board of Directors and the education committee of the ISGyP. The organizing committee (comprising the 5 authors of this editorial), as a first step, devised a comprehensive survey, which was emailed to all members of the ISGyP; the survey covered all aspects of endometrial cancer reporting, including specimen dissection and sampling, diagnosis, staging, prognostic factors, and ancillary studies

Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists

This article provides practical recommendations developed from the International Society of Gynecological Pathologists Endometrial Carcinoma Project to address 4 issues that may arise in the diagnosis of uterine corpus low-grade endometrioid carcinoma: (1) The distinction between atypical hyperplasia and low-grade endometrioid carcinoma. (2) The distinction between low-grade endometrioid carcinoma and serous carcinoma. (3) The distinction between corded and hyalinized or spindle cell variants of low-grade endometrioid carcinoma and carcinosarcoma. (4) The diagnostic criteria for mixed endometrial carcinomas, a rare entity that should be diagnosed only after exclusion of a spectrum of tumors including morphologic variants of endometrioid carcinoma, dedifferentiated endometrial carcinoma, carcinosarcoma, and endometrial carcinomas with ambiguous morphology

Endometrial carcinoma, grossing and processing issues: recommendations of the International Society of Gynecologic Pathologists.

Endometrial cancer is the most common gynecologic neoplasm in developed countries; however, updated universal guidelines are currently not available to handle specimens obtained during the surgical treatment of patients affected by this disease. This article presents recommendations on how to gross and submit sections for microscopic examination of hysterectomy specimens and other tissues removed during the surgical management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and lymph node dissection-including sentinel lymph nodes. In addition, the intraoperative assessment of some of these specimens is addressed. These recommendations are based on a review of the literature, grossing manuals from various institutions, and a collaborative effort by a subgroup of the Endometrial Cancer Task Force of the International Society of Gynecological Pathologists. The aim of these recommendations is to standardize the processing of endometrial cancer specimens which is vital for adequate pathological reporting and will ultimately improve our understanding of this disease

High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations

This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation

Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade)

Although endometrial carcinoma (EC) is generally considered to have a good prognosis, over 20% of women with EC die of their disease, with a projected increase in both incidence and mortality over the next few decades. The aim of accurate prognostication is to ensure that patients receive optimal treatment and are neither overtreated nor undertreated, thereby improving patient outcomes overall. Patients with EC can be categorized into prognostic risk groups based on clinicopathologic findings. Other than tumor type and grade, groupings and recommended management algorithms may take into account age, body mass index, stage, and presence of lymphovascular space invasion. The molecular classification of EC that has emerged from the Cancer Genome Atlas (TCGA) study provides additional, potentially superior, prognostic information to traditional histologic typing and grading. This classifier does not, however, replace clinicopathologic risk assessment based on parameters other than histotype and grade. It is envisaged that molecular and clinicopathologic prognostic grouping systems will work better together than either alone. Thus, while tumor typing and grading may be superseded by a classification based on underlying genomic abnormalities, accurate assessment of other pathologic parameters will continue to be key to patient management. These include those factors related to staging, such as depth of myometrial invasion, cervical, vaginal, serosal surface, adnexal and parametrial invasion, and those independent of stage such as lymphovascular space invasion. Other prognostic parameters will also be discussed. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project

International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project : Guidelines From the Special Techniques and Ancillary Studies Group:Guidelines From the Special Techniques and Ancillary Studies Group

The aim of this article is to propose guidelines and recommendations in problematic areas in pathologic reporting of endometrial carcinoma (EC) regarding special techniques and ancillary studies. An organizing committee designed a comprehensive survey with different questions related to pathologic features, diagnosis, and prognosis of EC that was sent to all members of the International Society of Gynecological Pathologists. The special techniques/ancillary studies group received 4 different questions to be addressed. Five members of the group reviewed the literature and came up with recommendations and an accompanying text which were discussed and agreed upon by all members of the group. Twelve different recommendations are made. They address the value of immunohistochemistry, ploidy, and molecular analysis for assessing prognosis in EC, the value of steroid hormone receptor analysis to predict response to hormone therapy, and parameters regarding applying immunohistochemistry and molecular tests for assessing mismatch deficiency in EC

p53 aberrations in low grade endometrioid carcinoma of the endometrium with nodal metastases: possible insights on pathogenesis discerned from immunohistochemistry

Abstract Background TP53 mutations are rarely identified in low grade endometrioid carcinoma of the endometrium, and their pathogenic significance in such tumors is evidenced by the fact that TP53 aberrations have been associated with reduced recurrence-free survival in this subset of tumors. However, TP53 aberrations may not always represent a driving molecular event in a given endometrial cancer with a mutation. In this case study, the immunophenotype of a distinctive low grade endometrioid adenocarcinoma with an unusual pattern of lymph node metastases is used to explore the possible roles for underlying TP53-related molecular events in its pathogenesis. Case presentation A low grade endometrioid carcinoma, 9 cm in greatest dimension, with 35% invasion of the myometrial wall thickness, focal lymphovascular invasion, and metastases to 2 of 16 pelvic lymph nodes, was diagnosed in a 52-year-old woman. The endometrial tumor showed a p53-mutation (aberrant)-type immunohistochemical pattern in 40% of the tumor, but the rest of the tumor, as well as the foci of myometrial and lymphovascular invasion, were p53-wild type. Both lymph nodes with metastatic disease showed a distinct biphasic pattern, comprised of both p53-wild type and p53-aberrant areas in tumoral foci that were spatially apposed but not intermixed. Most p53-aberrant areas (at both the lymph nodes and the endometrium) showed a higher mitotic index and increased atypia as compared to the p53-wild type areas; both showed squamous differentiation. The p53-aberrant areas at both locations were also p16-diffusely positive, vimentin-positive, and estrogen/progesterone receptor-positive, whereas the p53-wild type areas showed an identical immunophenotype with the exception of being p16-mosaic positive. All components of the tumor at both the primary and metastatic sites showed loss of MSH2 and MSH6 and retained MLH/PMS2 expression. Conclusions The presence of p53-mutant and wild-type areas in multiple lymph nodes, coupled with the absence of a p53-aberrant immunophenotype in the myometrium-invasive or lymphovascular-invasive portions of the tumor, argues against the possibility that the TP53 mutation in this tumor is a driving event in its pathogenesis, at least regarding the metastatic process. This case illustrates how routine immunohistochemistry can provide important insights into underlying molecular events in cancers, exemplifies an uncommon co-existence of DNA mismatch repair protein deficiency and p53-aberrant immunophenotype in low-grade endometrioid carcinoma, illustrates morphologic differences between p53-aberrant and p53-wild type areas within in the same tumor, and is an exemplar of the emerging theory that lymph node metastases of endometrial cancer may be comprised of different subclones of the primary tumor