Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria

Abstract

Previously, our international team proposed a 3-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification- A have well demarcated glands lacking destructive stromal invasion or lymphovascular invasion (lymphovascular invasion), Pattern Classification- B show localized, limited destructive invasion arising from A-type glands, and Pattern Classification- C have diffuse destructive stromal invasion, significant (filling a 4× field) confluence, or solid architecture. 24 Pattern Classification-A, 22 Pattern Classification-B, 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis (reference diagnosis) originally established. 1 H&E slide per case was reviewed by 7 gynecologic pathologists, 4 from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near complete (6 of 7) agreement in 50%. Overall concordance was 74%. Overall Kappa (agreement among pathologists) was .488 (moderate agreement). Pattern Classification- B has lowest kappa, and agreement is not improved by combining B+C. 6 of 7 reviewers had substantial agreement by weighted kappas (>.6), with one reviewer accounting for the majority of cases under or overcalled by 2 tiers. Confluence filling a 4× field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis- B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly applied by gynecologic pathologists. Further refinement of criteria should allow use of this powerful classification system to delineate which cervical adenocarcinomas can be safely treated conservatively.

Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification

“…49 Another study showed an overall concordance of 74% with kappa values of 0.54, 0.32 and 0.59 for patterns A, B and C, respectively. 56 Kappa values improved when comparing binarised patterns (A versus B and C). 49,51 This system is applicable to all resections, as invasion pattern on cones and loop electrosurgical excision procedures (LEEPs) can predict invasion pattern on a subsequent hysterectomy, particularly in patterns B and C tumours.…”

“…Several studies have demonstrated this 3‐tiered system to be reproducible among pathologists, with the reported kappa values ranging from fair to almost perfect ( k = 0.24–0.84) and moderate ( k = 0.65) . Another study showed an overall concordance of 74% with kappa values of 0.54, 0.32 and 0.59 for patterns A, B and C, respectively . Kappa values improved when comparing binarised patterns (A versus B and C) …”

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

“…Alternative classification systems incorporating stromal invasion pattern have been proposed for adenocarcinoma. [32][33][34] These systems remain to be validated for clinical use.…”

Metastases to the ovary arising from endometrial, cervical and fallopian tube cancer: recent advances

“…This principally subdivides EAC into prognostically relevant and reproducible HPV‐associated (HPVA) and non‐HPV associated (non‐HPVA) histological types . The second proposal, also of prognostic importance, is to replace the conventional, poorly defined grading systems that have low reproducibility with a pattern‐based classification . This only applies to HPVA EAC, as all non‐HPVA EAC fall into the poorest prognosis pattern C category.…”

“…[99][100][101] The second proposal, also of prognostic importance, is to replace the conventional, poorly defined grading systems that have low reproducibility with a pattern-based classification. [102][103][104] This only applies to HPVA EAC, as all non-HPVA EAC fall into the poorest prognosis pattern C category. The incorporation of these two approaches into clinical management algorithms requires development and prospective evaluation through international collaborative projects.…”