title: Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.
abstract: Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
authors.affiliation: Bács-Kiskun County Teaching Hospital, Nyiri ut 38, Kecskemét, 6000, Hungary. cserni@freemail.hu.|Department of Pathology, University of Szeged, Allomás u. 2, Szeged, 6720, Hungary. cserni@freemail.hu.
authors.forename: G
authors.initials: G
authors.lastname: Cserni
authors.affiliation: Department of Pathology, University College London, Level 2, Rockefeller Building, 21, University Street, London, WC1E 6JJ, UK.
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authors.initials: CA
authors.lastname: Wells
authors.affiliation: School of Medicine, Department of Pathology, Marmara University, Istanbul, Turkey.
authors.forename: H
authors.initials: H
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authors.affiliation: Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, 8036, Graz, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Regitnig
authors.affiliation: Department of Medical Sciences, University of Torino, Italy, Via Santena, 7, 10120, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven-University of Leuven, Herestraat 49, 3000, Leuven, Belgium.|Department of Pathology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Floris
authors.affiliation: German Breast-Screening Program, Reference Centres Berlin and Muenster, Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestraße 30, 17036, Neubrandenburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Decker
authors.affiliation: Anatomic Pathology, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bellaria Hospital, Via Altura 3, 40137, Bologna, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Foschini
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
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authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Sölvegatan 25, 221 85, Lund, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Grabau
authors.affiliation: Pathologisch-Bakteriologisches Institut, Donauspital am SMZO, Langobardenstraße 122, Vienna, Austria.
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authors.affiliation: Department of Pathology, Mater Dei Hospital, Tal-Qroqq, Msida, MSD 2090, Malta.
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authors.affiliation: Department of Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
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authors.initials: E
authors.lastname: Chmielik
authors.affiliation: Department of Pathology, Complejo Hospitalario de Navarra, Irunlarrea 3, 31008, Pamplona, Navarra, Spain.
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authors.initials: A
authors.lastname: Cordoba
authors.affiliation: Department of Pathology. Corporació Sanitària Parc Taulí, University Autònoma Barcelona, 08202, Sabadell, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Andreu
authors.affiliation: Department of Pathology, Medical School, University of Patras, 26504, Patras, Rion, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Zolota
authors.affiliation: CRCM, Molecular Oncology "Equipe labellisée Ligue Contre le Cancer", Inserm, U1068, 13009, Marseille, France.|Institut Paoli-Calmettes, 13009, Marseille, France.|Aix-Marseille Université, 13284, Marseille, France.|Centre National de la Recherche Scientifique, UMR7258, 13009, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: The Fingerland Department of Pathology, Charles University Medical Faculty and University Hospital, Sokolska 581, 50005, Hradec Kralove, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Ryska
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zürich, Switzerland.
authors.forename: Z
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Department of Pathology, Strasbourg University Hospitals, Hôpital de Hautepierre, 1 avenue Molière, 67100, Strasbourg Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Weingertner
authors.affiliation: Department of Pathology, Strasbourg University Hospitals, Hôpital de Hautepierre, 1 avenue Molière, 67100, Strasbourg Cedex, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Bellocq
authors.affiliation: Pathology Centre, Riga East Clinical University Hospital, Hipokrata St 2, Riga, LV-1038, Latvia.
authors.forename: I
authors.initials: I
authors.lastname: Liepniece-Karele
authors.affiliation: Discipline of Pathology, NUI Galway, Clinical Sciences Institute, Costello Road, Galway, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Callagy
authors.affiliation: 2nd Department of Pathology, Semmelweis University Budapest, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Kulka
authors.affiliation: Institute of Pathology, Breast Cancer Center Paderborn, Husener Str.46a, 33098, Paderborn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bürger
authors.affiliation: Laboratório de Anatomia Patológica, Instituto Portugues de Oncologia de Coimbra FG, Av Bissaia Barreto 98, 3000-075, Coimbra, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Figueiredo
authors.affiliation: Divisions of Diagnostic Oncology & Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Laboratório de Anatomia Patológica, Centro Hospitalar de São João e IPATIMUP, 4440-563, Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Amendoeira
authors.affiliation: CMP-Cerba European Labs, 45A avenue Wybran, 1070, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Faverly
authors.affiliation: Department of Histopathology, St. Vincent's University Hospital, Dublin 4, Dublin, Ireland.
authors.forename: C M
authors.initials: CM
authors.lastname: Quinn
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, AOU Careggi, Largo G. A. Brambilla 3, 50134, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bianchi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D015588:Observer Variation; D010338:Pathology, Clinical / Q000379:methods / Q000592:standards
chemical_list: D014408:Biomarkers, Tumor
keywords: Immunohistochemistry; In situ carcinoma; Microinvasion; Myoepithelium; Reproducibility
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