International Endocervical Adenocarcinoma Criteria and Classification: Validation and interobserver reproducibility Journal Article


Authors: Hodgson, A.; Park, K. J.; Djordjevic, B.; Howitt, B. E.; Nucci, M. R.; Oliva, E.; Stolnicu, S.; Xu, B.; Soslow, R. A.; Parra-Herran, C.
Article Title: International Endocervical Adenocarcinoma Criteria and Classification: Validation and interobserver reproducibility
Abstract: The current World Health Organization (WHO) classification for endocervical adenocarcinoma (EA) is based on descriptive morphologic characteristics; however, it does not fully reflect our current knowledge of the diverse pathogenesis of cervical glandular neoplasia. A novel classification system, the International Endocervical Adenocarcinoma Criteria and Classification (IECC), which incorporates etiology and biological behavior into the morphologic scheme, has been recently proposed. We aimed to validate the IECC by assessing its interobserver reproducibility in comparison to the WHO system. A cohort of 75 EAs was reviewed independently by 7 gynecologic pathologists and categorized following IECC and WHO criteria based on hematoxylin and eosin material alone and after immunohistochemistry results for p16, PR, p53, Napsin-A, vimentin, CDX2, and GATA3 were provided. Human papillomavirus (HPV) in situ hybridization and polymerase chain reaction results were compared with consensus diagnoses. IECC was superior to WHO in terms of interobserver agreement with κ=0.46 versus 0.3, respectively, on hematoxylin and eosin review and κ=0.51 versus 0.33, respectively, with immunohistochemistry. Under the IECC, 73 (97%) of EAs had majority agreement (≥4 reviewers in agreement) whereas 42 (56%) had perfect agreement (7/7 reviewers in agreement). Conversely, WHO showed majority agreement in 56 (75%) and perfect agreement in only 7 (10%) EAs. Reproducibility was poor in HPV-related WHO types (usual κ=0.36, mucinous not otherwise specified κ=0.13, intestinal κ=0.31, villoglandular κ=0.21) and good in major HPV-unrelated categories (gastric type κ=0.63, clear cell κ=0.81, mesonephric κ=0.5). Classification as per the IECC had excellent correlation with HPV status (by RNA in situ hybridization or polymerase chain reaction). We have shown that the IECC has superior interobserver agreement compared with the WHO classification system, and that distinction between HPV-related and HPV-unrelated EA can be made with good reproducibility and excellent prediction of HPV status. WHO morphologic variants of HPV-related EA are poorly reproducible. Conversely, agreement is high among important high-risk HPV-unrelated subtypes. Thus, our results further support replacing the current WHO classification with the IECC. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: reproducibility; clear cell carcinoma; gastric adenocarcinoma; hpv; interobserver agreement; endocervical adenocarcinoma; iecc; mesonephric carcinoma; stratified mucin-producing carcinoma; villoglandular carcinoma
Journal Title: American Journal of Surgical Pathology
Volume: 43
Issue: 1
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2019-01-01
Start Page: 75
End Page: 83
Language: English
DOI: 10.1097/pas.0000000000001095
PUBMED: 29877920
PROVIDER: scopus
PMCID: PMC6281796
DOI/URL:
Notes: Export Date: 1 February 2019 -- Source: Scopus
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MSK Authors
  1. Kay Jung Park
    289 Park
  2. Robert Soslow
    790 Soslow