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. 2015 Oct;39(10):1322-30.
doi: 10.1097/PAS.0000000000000473.

Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling

Ji Yuan  1 , George Wright, Andreas Rosenwald, Christian Steidl, Randy D Gascoyne, Joseph M Connors, Anja Mottok, Dennis D Weisenburger, Timothy C Greiner, Kai Fu, Lynette Smith, Lisa M Rimsza, Elaine S Jaffe, Elias Campo, Antonio Martinez, Jan Delabie, Rita M Braziel, James R Cook, German Ott, Julie M Vose, Louis M Staudt, Wing C Chan; Lymphoma Leukemia Molecular Profiling Project (LLMPP)
Affiliations

Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling

Ji Yuan et al. Am J Surg Pathol. 2015 Oct.

Abstract

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.

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Conflict of interest statement

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.

Figures

FIGURE 1.
FIGURE 1.
Representative interphase FISH analysis for detection of chromosomal rearrangement, gain, or amplification involving CIITA (A and C) and PDL1/2 (B and D). Detection of separate red and green signals indicates a chromosomal breakpoint affecting the CIITA locus at 16p13.13 (A) or the PDL1/2 locus at 9p24.1 (B). Multiple fused green and red signals indicate amplification of CIITA (C) and PDL1/2 (D).
FIGURE 2.
FIGURE 2.
A representative G-PMBL-P case with PDL1/PDL2 genetic alterations showing large atypical cells with pale cytoplasm in a background of fibrosis (H&E stain) (A) and intense membranous staining for PDL2 (B).
FIGURE 3.
FIGURE 3.
OS (A) and EFS (B) of patients with PMBL (G-PMBL-P), DLBCL with mediastinal involvement (G-PMBL-M), and DLBCL without mediastinal involvement (G-PMBL-NM). OS (C) and EFS (D) of patients with mediastinal involvement (G-PMBL-P and G-PMBL-M) and those without mediastinal involvement (G-PMBL-NM).
FIGURE 4.
FIGURE 4.
OS (A) and EFS (B) of patients with or without CIITA and/or PDL1/2 genetic alterations.
See this image and copyright information in PMC

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