Mediastinal involvement is considered essential for the diagnosis of primary mediastinal large B-cell lymphoma (PMBL). However, we have observed cases of diffuse large B-cell lymphoma (DLBCL) with features of PMBL but without detectable mediastinal involvement. The goal was to assess our previously established gene expression profiling (GEP) signature for PMBL in classifying these cases. In a large series of DLBCL cases, we identified 24 cases with a GEP signature of PMBL, including 9 cases with a submission diagnosis of DLBCL consistent with PMBL (G-PMBL-P) and 15 cases with a submission diagnosis of DLBCL. The pathology reviewers agreed with the diagnosis in the 9 G-PMBL-P cases. Among the other 15 DLBCL cases, 11 were considered to be PMBL or DLBCL consistent with PMBL, 3 were considered to be DLBCL, and 1 case was a gray-zone lymphoma with features intermediate between DLBCL and classical Hodgkin lymphoma. All 9 G-PMBL-P and 9 of the 15 DLBCL cases (G-PMBL-M) had demonstrated mediastinal involvement at presentation. Interestingly, 6 of the 15 DLBCL cases (G-PMBL-NM) had no clinical or radiologic evidence of mediastinal involvement. The 3 subgroups of PMBL had otherwise similar clinical characteristics, and there were no significant differences in overall survival. Genetic alterations of CIITA and PDL1/2 were detected in 26% and 40% of cases, respectively, including 1 G-PMBL-NM case with gain of PDL1/2. In conclusion, PMBL can present as a nonmediastinal tumor without evidence of mediastinal involvement, and GEP offers a more precise diagnosis of PMBL.
*Department of Pathology and Microbiology
¶Department of Biostatistics, College of Public Health
##Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE
**Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD
∥Department of Pathology, City of Hope National Medical Center, Duarte, CA
#Department of Pathology, University of Arizona, Tucson, AZ
§§Department of Clinical Pathology, Oregon Health and Science University, Portland, OR
∥∥Department of Molecular Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH
‡Institute of Pathology, Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg
¶¶Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
§British Columbia Cancer Agency, Centre for Lymphoid Cancer, University of British Columbia, Vancouver, BC, Canada
††Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
‡‡Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway
Partly supported by National Institutes of Health grant UO1CA157581 to W.C.C.
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Correspondence: Wing C. Chan, MD, Department of Pathology, City of Hope National Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010 (e-mail: email@example.com).