Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers

Abstract

CD200, an immunoglobulin superfamily membrane glycoprotein, is expressed in a number of B cell lymphoproliferative disorders, including primary mediastinal large B cell lymphoma, but not diffuse large B cell lymphoma, based on a preliminary study. Here, we compare the expression of CD200 with other markers of primary mediastinal large B cell lymphoma, including MAL and CD23, in formalin-fixed, paraffin-embedded histologic sections from a series of 35 cases of primary mediastinal large B cell lymphoma and 30 cases of diffuse large B cell lymphoma. CD200 exhibits the greatest staining sensitivity of the markers studied: 94%, compared with CD23 (69%), MAL (86%), TRAF (86%), and REL (77%). It exhibits staining specificity of 93%, similar to that of CD23 (93%) and MAL (97%), and greater than that of TRAF (77%) and REL (83%). We conclude that CD200 is a practical and useful marker for the diagnosis of primary mediastinal large B cell lymphoma.

PDCD1LG2 (PD‐L2) RNA in situ hybridization is a sensitive, specific, and practical marker of primary mediastinal large B‐cell lymphoma

“…The MAL antibody, which has been reported to be the most specific marker of PMLBCL is not currently commercially available (Copie-Bergman et al, 2002;Johnson & Davies, 2008). CD200, which has been reported to show the highest sensitivity for PMLBCL in the literature has been adopted for flow cytometry by several groups, but CD200 IHC has not been well characterized to date (Dorfman et al, 2012). As shown in this report, PDCD1LG2 RNA expression offers a sensitivity and specificity for PMLBCL similar to other markers in the prior literature.…”

“…The sensitivity and specificity reported for these immunohistochemical stains range from 69-94% and 77-97%, correspondence respectively (Martelli et al, 2008;Dorfman et al, 2012). The application of these markers into routine clinical practice has been limited to date.…”

“…Gene expression profiling studies have confirmed a distinct signature in PMLBCL that differs from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and partially overlaps with that found in classical Hodgkin lymphoma (Savage et al, 2003;Bea et al, 2005). In routine clinical practice, however, distinguishing between PMLBCL and DLBCL, NOS is frequently difficult, due partly to a paucity of sensitive and specific biomarkers (Martelli et al, 2008;Dorfman et al, 2012). Recent studies have shown that PMLBCL shows frequent copy number alterations or translocations involving the CD274 (PD-L1) or PDCD1LG2 (PD-L2) genes at chromosome 9p24.1, leading to overexpression of CD274 (PD-L1) and, especially, PDCD1LG (PD-L2) proteins (Shi et al, 2014;Twa & Steidl, 2015).…”

Primary mediastinal large B-cell lymphoma

“…The major differential diagnosis of a mediastinal lymphoma include Hodgkin's lymphoma, mediastinal gray-zone lymphoma (discussed in detail in a recent review) [42], systemic DLBCL and T-cell acute lymphoblastic lymphoma [20,43]. The following immunophenotypic markers are highly expressed in PMBCL, as compared to DLBCL: CD200, CD23, MAL, TRAF and REL [44]. In a gene expression profile study, higher expression of the PDL2 gene best discriminated PMBCL from DLBCL [22].…”

Update in large cell lymphoma: understanding the pathology report

“…Among the proposed useful markers are expression of MAL, PDL2, and CD200, and coexpression of cytoplasmic TRAF1 and nuclear cREL. 14,[35][36][37] Given the current lack of suitable commercially available MAL and PDL2 antibodies and difficulties in cREL staining (as well as reported modest diagnostic sensitivity of 53% for cREL and TRAF1 coexpression), CD200 may be more promising but requires verification in other centers. Of note, we are currently evaluating the performance of a commercially available MAL antibody for use in identifying PMBL.…”