A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification

Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) clas-sification. Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, kappa) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analy-sis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). Results: On WHO classification, H&E staining exhibited 'fair agreement' (kappa= 0.21) with a 47.0% agreement rate. Simple clas-sifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agree-ment rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (kappa= 0.16) ex-hibited lower agreement compared to the non-EPC/SPC subgroup (kappa= 0.35) with WHO classification, which was similar to the results of any other classification systems. Conclusions: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.