PMID- 36849712
OWN - NLM
STAT- MEDLINE
DCOM- 20230517
LR  - 20230517
IS  - 1365-2559 (Electronic)
IS  - 0309-0167 (Linking)
VI  - 82
IP  - 7
DP  - 2023 Jun
TI  - Lack of reproducibility of histopathological features in MYC-rearranged large B 
      cell lymphoma using digital whole slide images: a study from the Lunenburg 
      lymphoma biomarker consortium.
PG  - 1105-1111
LID - 10.1111/his.14896 [doi]
AB  - AIMS: Subclassification of large B cell lymphoma (LBCL) is challenging due to the 
      overlap in histopathological, immunophenotypical and genetic data. In particular, 
      the criteria to separate diffuse large B cell lymphoma (DLBCL) and high-grade B 
      cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma 
      Biomarker Consortium previously reported a cohort of over 5000 LBCL that included 
      fluorescence in-situ hybridisation (FISH) data. This cohort contained 209 cases 
      with MYC rearrangement that were available for a validation study by a panel of 
      eight expert haematopathologists of how various histopathological features are 
      used. METHODS AND RESULTS: Digital whole slide images of haematoxylin and 
      eosin-stained sections allowed the pathologists to visually score cases 
      independently as well as participate in virtual joint review conferences. 
      Standardised consensus guidelines were formulated for scoring histopathological 
      features and included overall architecture/growth pattern, presence or absence of 
      a starry-sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a 
      range of cytological characteristics. Despite the use of consensus guidelines, 
      the results show a high degree of discordance among the eight expert 
      pathologists. Approximately 50% of the cases lacked a majority score, and this 
      discordance spanned all six histopathological features. Moreover, none of the 
      histological variables aided in prediction of MYC single versus double/triple-hit 
      or immunoglobulin-partner FISH-based designations or clinical outcome measures. 
      CONCLUSIONS: Our findings indicate that there are no specific conventional 
      morphological parameters that help to subclassify MYC-rearranged LBCL or select 
      cases for FISH analysis, and that incorporation of FISH data is essential for 
      accurate classification and prognostication.
CI  - (c) 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
FAU - Natkunam, Yasodha
AU  - Natkunam Y
AUID- ORCID: 0000-0002-9816-1018
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - de Jong, Daphne
AU  - de Jong D
AD  - Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije 
      Universiteit Amsterdam, Amsterdam, the Netherlands.
FAU - Farinha, Pedro
AU  - Farinha P
AD  - BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, 
      Canada.
FAU - Gaulard, Philippe
AU  - Gaulard P
AD  - Department of Pathology, Henri Mondor University Hospital, APHP, INSERM U955, 
      Universite Paris-Est, Creteil, France.
FAU - Klapper, Wolfram
AU  - Klapper W
AUID- ORCID: 0000-0001-7208-4117
AD  - Institute of Pathology, University of Schleswig-Holstein Kiel, Kiel, Germany.
FAU - Rosenwald, Andreas
AU  - Rosenwald A
AD  - Comprehensive Cancer Center Mainfranken, Institute of Pathology, University of 
      Wurzburg, Wurzburg, Germany.
FAU - Sander, Birgitta
AU  - Sander B
AD  - Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet 
      and Karolinska University Hospital, Stockholm, Sweden.
FAU - Tooze, Reuben
AU  - Tooze R
AD  - Division of Haematology and Immunology, Leeds Institute of Medical Research, 
      University of Leeds, Leeds, UK.
FAU - Advani, Ranjana
AU  - Advani R
AD  - Department of Medicine, Division of Oncology, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Burton, Catherine
AU  - Burton C
AD  - Haematological Malignancy Diagnostic Service, St James's University Hospital, 
      Leeds, UK.
FAU - Gribben, John G
AU  - Gribben JG
AD  - Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of 
      London, London, UK.
FAU - Kersten, Marie-Jose
AU  - Kersten MJ
AD  - Department of Haematology, Cancer Center Amsterdam, Amsterdam UMC, Location 
      University of Amsterdam, Amsterdam, the Netherlands.
FAU - Kimby, Eva
AU  - Kimby E
AD  - Department of Medicine, Division of Hematology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Lenz, Georg
AU  - Lenz G
AD  - Medical Department A for Haematology, Oncology, and Pneumology, University 
      Hospital Munster, Munster, Germany.
FAU - Molina, Thierry
AU  - Molina T
AD  - Department of Pathology, Universite Paris Cite, AP-HP, Necker and Robert Debre 
      Hospitals, Paris, France.
FAU - Morschhauser, Franck
AU  - Morschhauser F
AD  - Department of Hematology, CHU Lille, Univ. Lille, ULR 7365 - GRITA - Groupe de 
      Recherche sur les formes Injectables et les Technologies Associees, Lille, 
      France.
FAU - Scott, David
AU  - Scott D
AD  - BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, 
      Canada.
FAU - Sehn, Laurie
AU  - Sehn L
AD  - BC Cancer Centre for Lymphoid Cancer, University of British Columbia, Vancouver, 
      Canada.
FAU - Stevens, Wendy
AU  - Stevens W
AD  - Department of Hematology, Radboud UMC Nijmegen, Nijmegen, the Netherlands.
FAU - Clear, Andrew
AU  - Clear A
AD  - Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of 
      London, London, UK.
FAU - Baia, Maryse
AU  - Baia M
AD  - Department of Pathology, Henri Mondor University Hospital, APHP, INSERM U955, 
      Universite Paris-Est, Creteil, France.
FAU - Habi, Abdelmalek
AU  - Habi A
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Elsensohn, Mad-Helenie
AU  - Elsensohn MH
AD  - Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, Pole Sante 
      Publique, Lyon, France.
FAU - Langlois-Jacques, Carole
AU  - Langlois-Jacques C
AD  - Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, Pole Sante 
      Publique, Lyon, France.
FAU - Maucort-Boulch, Delphine
AU  - Maucort-Boulch D
AD  - Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, Pole Sante 
      Publique, Lyon, France.
FAU - Calaminici, Maria
AU  - Calaminici M
AD  - Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of 
      London, London, UK.
LA  - eng
PT  - Journal Article
DEP - 20230320
PL  - England
TA  - Histopathology
JT  - Histopathology
JID - 7704136
RN  - 0 (Biomarkers)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
SB  - IM
MH  - Humans
MH  - Reproducibility of Results
MH  - *Lymphoma, Large B-Cell, Diffuse/diagnosis/genetics/pathology
MH  - Biomarkers
MH  - Proto-Oncogene Proteins c-myc/genetics
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
MH  - Proto-Oncogene Proteins c-bcl-6/genetics
MH  - Gene Rearrangement
OTO - NOTNLM
OT  - FISH
OT  - MYC-rearrangement
OT  - diffuse large B cell lymphoma
OT  - digital whole slide image
OT  - high-grade B cell lymphoma
EDAT- 2023/03/01 06:00
MHDA- 2023/05/17 06:42
CRDT- 2023/02/28 00:11
PHST- 2023/01/16 00:00 [revised]
PHST- 2022/08/09 00:00 [received]
PHST- 2023/02/22 00:00 [accepted]
PHST- 2023/05/17 06:42 [medline]
PHST- 2023/03/01 06:00 [pubmed]
PHST- 2023/02/28 00:11 [entrez]
AID - 10.1111/his.14896 [doi]
PST - ppublish
SO  - Histopathology. 2023 Jun;82(7):1105-1111. doi: 10.1111/his.14896. Epub 2023 Mar 
      20.