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Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

ABSTRACT: 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.

SUBMITTER: Christgen M

PROVIDER: S-EPMC8822373 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Christgen Matthias M Kandt Leonie Donata LD Antonopoulos Wiebke W Bartels Stephan S Van Bockstal Mieke R MR Bredt Martin M Brito Maria Jose MJ Christgen Henriette H Colpaert Cecile C Cserni Bálint B Cserni Gábor G Daemmrich Maximilian E ME Danebrock Raihanatou R Dedeurwaerdere Franceska F van Deurzen Carolien Hm CH Erber Ramona R Fathke Christine C Feist Henning H Fiche Maryse M Gonzalez Claudia Aura CA Ter Hoeve Natalie D ND Kooreman Loes L Krech Till T Kristiansen Glen G Kulka Janina J Laenger Florian F Lafos Marcel M Lehmann Ulrich U Martin-Martinez Maria Dolores MD Mueller Sophie S Pelz Enrico E Raap Mieke M Ravarino Alberto A Reineke-Plaass Tanja T Schaumann Nora N Schelfhout Anne-Marie AM De Schepper Maxim M Schlue Jerome J Van de Vijver Koen K Waelput Wim W Wellmann Axel A Graeser Monika M Gluz Oleg O Kuemmel Sherko S Nitz Ulrike U Harbeck Nadia N Desmedt Christine C Floris Giuseppe G Derksen Patrick Wb PW van Diest Paul J PJ Vincent-Salomon Anne A Kreipe Hans H

The journal of pathology. Clinical research 20211210 2

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/eos ...[more]

PMID: 34889530

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Project description:BackgroundRecent developments in diagnostic techniques for malaria, particularly DNA probes and sero-immunology, have raised questions as to how these techniques might be used to facilitate malaria diagnosis at the most peripheral levels of the primary health care system. At present, malaria diagnosis is based on the standard microscopic examination of blood films in most field epidemiologic studies and is likely to remain so in the immediate future in Africa. The objective of this study was to assess inter-observer agreement for the examination of Giemsa-stained slides for Plasmodium falciparum parasites.MethodsChildren aged 0 to 10 years were enrolled yearly in Bancoumana village (West Africa), mainly during the transmission season (June to October). The blood smears obtained from the persistently negative children in June 1996, August 1996, October 1996 and March 1997 were systematically re-examined. A stratified random sample (10%) proportional to the following parasite density classes 1-100, 101-5000, and 5001 and over was taken from the slides collected. The kappa statistics and the intra-class correlation were used as measures of agreement the first and the second slide examinations.ResultsThe weighted kappa statistic, widely used as a chance-corrected measure for nominal agreement, showed excellent inter-observer agreement (κ(w)=0.7926; 95% CI [0.7588, 0.8263]; p=0.01). The intra-class correlation co-efficient had the same value of 0.7926 confirming the appropriateness of the weighted kappa statistic. Inter-observer agreement for slides read as negative by one observer, or as containing more than 100 parasites per μl, was excellent: 97% (493/506) and 92% (145/158), respectively. In contrast, the inter-observer agreement for slides read by one observer as containing 1-100 parasites/μl was poor, 36% (96/268).ConclusionsIn field conditions in Mali, there was a high reproducibility for slides reported as negative or as having more than 100 parasites per μl. However, smears with readings of 1-100 parasites per μl were less reproducible and should be re-examined carefully.

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Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Publications

Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

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