Open AccessInter‐observer agreement for the histological diagnosis of invasive lobular breast carcinoma
Author(s) -
Christgen Matthias,
Kandt Leonie Donata,
Antonopoulos Wiebke,
Bartels Stephan,
Bockstal Mieke R,
Bredt Martin,
Brito Maria Jose,
Christgen Henriette,
Colpaert Cecile,
Cserni Bálint,
Cserni Gábor,
Daemmrich Maximilian E,
Danebrock Raihanatou,
Dedeurwaerdere Franceska,
Deurzen Carolien HM,
Erber Ramona,
Fathke Christine,
Feist Henning,
Fiche Maryse,
Gonzalez Claudia Aura,
Hoeve Natalie D,
Kooreman Loes,
Krech Till,
Kristiansen Glen,
Kulka Janina,
Laenger Florian,
Lafos Marcel,
Lehmann Ulrich,
MartinMartinez Maria Dolores,
Mueller Sophie,
Pelz Enrico,
Raap Mieke,
Ravarino Alberto,
ReinekePlaass Tanja,
Schaumann Nora,
Schelfhout AnneMarie,
Schepper Maxim,
Schlue Jerome,
Van de Vijver Koen,
Waelput Wim,
Wellmann Axel,
Graeser Monika,
Gluz Oleg,
Kuemmel Sherko,
Nitz Ulrike,
Harbeck Nadia,
Desmedt Christine,
Floris Giuseppe,
Derksen Patrick WB,
Diest Paul J,
VincentSalomon Anne,
Kreipe Hans
Publication year - 2022
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.253
Subject(s) - kappa , medicine , interquartile range , cdh1 , invasive lobular carcinoma , breast cancer , pathology , lobular carcinoma , immunohistochemistry , gastroenterology , invasive ductal carcinoma , radiology , cancer , cadherin , ductal carcinoma , biology , mathematics , genetics , geometry , cell
Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E‐cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)‐positive/HER2‐negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)‐stained sections. In set B (62 cases), participants were provided with HE‐stained sections and E‐cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non‐lobular BC versus mixed BC versus ILC. Pairwise inter‐observer agreement and agreement with a pre‐defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1 /E‐cadherin mutation status. Thirty‐five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter‐observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48–0.66) and substantial in set B (median κ = 0.75, IQR: 0.56–0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57–0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73–0.93, p < 0.001). The median frequency of CDH1 /E‐cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56–72%) and 73% in set B (IQR: 65–75%, p < 0.001). Cases with variable subtype calls included E‐cadherin‐positive ILCs harboring CDH1 missense mutations, and E‐cadherin‐negative ILCs with tubular elements and focal P‐cadherin expression. ILCs with trabecular growth pattern were often misclassified as non‐lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre‐defined reference standard, if assessment is supported by E‐cadherin IHC. CDH1 missense mutations associated with preserved E‐cadherin protein expression, E‐ to P‐cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.