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August 27, 2019; 93 (9) Article

Idiopathic inflammatory myopathy

Interrater variability in muscle biopsy reading

Pieter A. Olivier, View ORCID ProfileBoel De Paepe, Eleonora Aronica, Florieke Berfelo, View ORCID ProfileRoos Colman, Anthony Amato, Dalia Dimitri, Eduard Gallardo, Romain Gherardi, Hans-Hilmar Goebel, David Hilton-Jones, Monika Hofer, Janice Holton, View ORCID ProfileHenrik daa Schrøder, Duygu Selcen, Werner Stenzel, Marianne de Visser, Jan L. De Bleecker
First published July 29, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008005
Pieter A. Olivier
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Boel De Paepe
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Eleonora Aronica
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Florieke Berfelo
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Roos Colman
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Anthony Amato
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Dalia Dimitri
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Eduard Gallardo
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Romain Gherardi
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Hans-Hilmar Goebel
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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David Hilton-Jones
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Monika Hofer
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Janice Holton
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Henrik daa Schrøder
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Duygu Selcen
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Werner Stenzel
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Marianne de Visser
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Jan L. De Bleecker
From Ghent University Hospital (P.A.O., B.D.P., R.C., J.L.D.B.), Belgium; Academic Medical Centre (E.A., F.B., M.d.V.), University of Amsterdam, the Netherlands; Harvard Medical School (A.A.), Boston, MA; CHU Henri Mondor (D.D.), Créteil, France; Hospital Santa Creu i Sant Pau (E.G.), Barcelona, Spain; Université Paris Est-Créteil (R.G.), France; Charité–Universitätsmedizin Berlin (H.-H.G., W.S.), Germany; John Radcliffe Hospital (D.H.-J.); Oxford University Hospitals (M.H.); UCL Institute of Neurology (J.H.), London, UK; Syddansk Universitet (H.d.S.), Odense, Denmark; and Mayo Clinic (D.S.), Rochester, MN.
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Citation
Idiopathic inflammatory myopathy
Interrater variability in muscle biopsy reading
Pieter A. Olivier, Boel De Paepe, Eleonora Aronica, Florieke Berfelo, Roos Colman, Anthony Amato, Dalia Dimitri, Eduard Gallardo, Romain Gherardi, Hans-Hilmar Goebel, David Hilton-Jones, Monika Hofer, Janice Holton, Henrik daa Schrøder, Duygu Selcen, Werner Stenzel, Marianne de Visser, Jan L. De Bleecker
Neurology Aug 2019, 93 (9) e889-e894; DOI: 10.1212/WNL.0000000000008005

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Abstract

Objective To determine interrater variability in diagnosing individual muscle biopsy abnormalities and diagnosis.

Methods We developed a scoring tool to analyze consensus in muscle biopsy reading of an ad hoc workgroup of international experts. Twenty-four samples from patients with suspected idiopathic inflammatory myopathy (IIM) were randomly selected, providing sections that were stained with standard histologic and immunohistochemical methods. Sections were made available on an online platform, and experts were queried about myopathologic features within 4 pathologic domains: muscle fibers, inflammation, connective tissue, and vasculature. A short clinical presentation of cases was included, and experts were asked to give a tentative diagnosis of polymyositis, dermatomyositis, inclusion-body myositis, antisynthetase syndrome–related myositis, immune-mediated necrotizing myopathy, nonspecific myositis, or other disease. Fleiss κ values, scoring interrater variability, showed the highest agreement within the muscle fiber and connective tissue domains.

Results Despite overall low κ values, moderate agreement was achieved for tentative diagnosis, supporting the idea of using holistic muscle biopsy interpretation rather than adding up individual features.

Conclusion The assessment of individual pathologic features needs to be standardized and harmonized and should be measured for sensitivity and specificity for subgroup classification. Standardizing the process of diagnostic muscle biopsy reading would allow identification of more homogeneous patient cohorts for upcoming treatment trials.

Glossary

ENMC=
European Neuromuscular Centre;
IBM=
inclusion-body myositis;
IIM=
idiopathic inflammatory myopathy;
IMNM=
immune-mediated necrotizing myopathy;
NSM=
nonspecific myositis

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • CME Course: NPub.org/cmelist

  • Received September 25, 2018.
  • Accepted in final form April 4, 2019.
  • © 2019 American Academy of Neurology
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