Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens

Anja Mottok, George Wright, Andreas Rosenwald, German Ott, Colleen Ramsower, Elias Campo, Rita M. Braziel, Jan Delabie, Dennis D. Weisenburger, Joo Y. Song, Wing C. Chan, James R. Cook, Kai Fu, Tim Greiner, Erlend Smeland, Harald Holte, Kerry J. Savage, Betty J. Glinsmann-Gibson, Randy D. Gascoyne, Louis M. StaudtElaine S. Jaffe, Joseph M. Connors, David W. Scott, Christian Steidl, Lisa M. Rimsza

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the diagnosis relies on consensus of histopathology, clinical variables, and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures. However, requirement of fresh-frozen biopsy material has precluded the transfer of gene expression–based assays to the clinic. Here, we developed a robust and accurate molecular classification assay (Lymph3Cx) for the distinction of PMBCL from DLBCL subtypes based on gene expression measurements in formalin-fixed, paraffin-embedded tissue. A probabilistic model accounting for classification error, comprising 58 gene features, was trained on 68 cases of PMBCL and DLBCL. Performance of the model was subsequently evaluated in an independent validation cohort of 158 cases and showed high agreement of the Lymph3Cx molecular classification with the clinicopathological diagnosis of an expert panel (frank misclassification rate, 3.8%). Furthermore, we demonstrate reproducibility of the assay with 100% concordance of subtype assignments at 2 independent laboratories. Future studies will determine Lymph3Cx’s utility for routine diagnostic purposes and therapeutic decision making.

Original languageEnglish (US)
Pages (from-to)2401-2405
Number of pages5
Issue number22
StatePublished - Nov 29 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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