title: Pattern-based classification of invasive endocervical adenocarcinoma, depth of invasion measurement and distinction from adenocarcinoma in situ: interobserver variation among gynecologic pathologists.
abstract: A pattern-based classification for invasive endocervical adenocarcinoma has been proposed as predictive of the risk of nodal metastases. We aimed to determine the reproducibility of such classification in the context of common diagnostic challenges: distinction between in situ and invasive adenocarcinoma and depth of invasion measurement. Nine gynecologic pathologists independently reviewed 96 cases of endocervical adenocarcinoma (two slides per case). They diagnosed each case as in situ or invasive carcinoma classifying the latter following the pattern-based classification as pattern A (non-destructive), B (focally destructive) or C (diffusely destructive). Depth of invasion, when applicable, was measured (mm). Overall, diagnostic reproducibility of pattern diagnosis was good (κ=0.65). Perfect agreement (9/9 reviewers) was seen in only 11 cases (11%), all destructively invasive (10 pattern C and 1 pattern B). In all, ≥5/9 reviewer concordance was achieved in 82/96 cases (85%). Distinction between in situ and invasive carcinoma, regardless of the pattern, showed only slight agreement (κ=0.37). Likewise, distinction restricted to in situ versus pattern A was poor (κ=0.23). Distinction between non-destructive (in situ+pattern A) and destructive (patterns B+C) carcinoma showed significantly higher agreement (κ=0.62). Estimation of depth of invasion showed excellent reproducibility (ICC=0.82). However, different measurements resulting in differing FIGO stages were common (from at least 1 reviewer in 79% cases). On the basis of interobserver agreement, the pattern-based classification is best at diagnosing destructive invasion, which carries a risk for nodal metastases. Agreement in diagnosing in situ versus invasive carcinoma, including pattern A, was poor. Given the nil risk of nodal spread in in situ and pattern A lesions, the term 'endocervical adenocarcinoma with non-destructive growth' can be considered when the distinction is difficult, after excluding destructive invasion. Depth of invasion measurement was highly reproducible among pathologists; thus, the pattern-based approach can complement, but should not replace, the depth of invasion metric.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Carlos
authors.identifier: 0000-0003-1420-7291
authors.initials: C
authors.lastname: Parra-Herran
authors.affiliation: Ottawa Hospital Research Institute and School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Taljaard
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Bojana
authors.initials: B
authors.lastname: Djordjevic
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Reyes
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Schwartz
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Schoolmeester
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Lastra
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Quick
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Laury
authors.affiliation: Department of Pathology, Toronto East General Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Golnar
authors.initials: G
authors.lastname: Rasty
authors.affiliation: Department of Pathology, Women's and Perinatal Pathology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.affiliation: Department of Pathology, Women's and Perinatal Pathology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Howitt
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000556:secondary*; D065311:Adenocarcinoma in Situ / Q000145:classification / Q000473:pathology*; D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015588:Observer Variation; D009864:Ontario; D000072142:Pathologists; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D009626:Terminology as Topic; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000145:classification / Q000473:pathology*