Lymphocyte Predominance Hodgkin's Disease

Abstract

Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms of lymphoma often requires immunohistochemistry (IHC). Most previously published recommended panels include markers to define the large neoplastic cells (for example, CD20, J chain, CD45) as well as the non-neoplastic background cells (CD21, CD45RO, CD57, TiA 1). In the present study we examine the practical use of a double IHC method designed to look simultaneously at two germinal center specific cell types: bcl6+ cells and [bc16+, CD57+] co-positive cells. All 10 nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells, including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell transformation contained numerous bcl6+ large cells both singly (in areas of typical LPHD) and in sheets (in foci of large cell transformation), many CD57+ small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of the five cases of florid progressive transformation of germinal centers were true rosettes seen, although all contained variable numbers of bcl6+ large cells and CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL). In the first, group "A," six of six cases had bc16- large cells and few CD57+ small cells, and none had significant numbers of [bcl6+, CD57+] co-positive cells. In the second, group "B," four of four cases had bcl6+ large cells with numerous CD57+ and [bcl6+, CD57+] co-positive cells. These findings not only show that LPHD can be distinguished from its morphologic mimics through identification of specific germinal center cell types, but also identifies a second group of TCRBCL (group "B") whose phenotype suggests it might be an architectural variant of nodular LPHD.

Nodular Lymphocyte Predominant Hodgkin Lymphoma and T Cell/Histiocyte Rich Large B Cell Lymphoma - Endpoints of a Spectrum of One Disease?

“…However, THRLBCL-like NLPHL was not included in the analysis, nor in other studies, which aimed to identify differentially expressed markers between the two entities [30] , [31] , [32] , [33] . So far, many commonly expressed genes in tumor cells of both entities were identified, such as BCL6, CD75, EMA, J-chain and PU.1, as well as a typical kappa light chain restriction [11] , [34] , [35] , [36] , [37] . The only investigations which clearly point to a distinct pathogenesis of both diseases are two comparative genomic hybridization studies, in which a higher number and different genomic aberrations were identified in NLPHL than in THRLBCL [38] , [39] .…”

Progressive Transformation of Germinal Centers

“…After double staining with these antibodies, the authors observed that in cases of LPNHD they observed bcl-6-positive large cells rimmed by a number of CD57+ cells including Bcl6+ and CD57+ copositive cells. This appearance was highly specific for NLPHD as in PTGC this appearance was not seen and on double staining few CD57+ cells with very rare double-positive cells were seen [15]. …”

Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

“…The characteristic lymphocyte-Predominant (LP) cells exhibit a GC phenotypic profile with expression of GC markers such as BCL6 [11, 21], GCET1 [22] and LMO2 [23], together with expression of transcription factors related to a sustained B cell program such as Oct-2 and BOB.1. Interestingly, the GC-related profile is seen not only in LP cells but also in the surrounding T cells, which characteristically create a rosette-like pattern typical of NLPHL (Figure 1).…”

“…Interestingly, the GC-related profile is seen not only in LP cells but also in the surrounding T cells, which characteristically create a rosette-like pattern typical of NLPHL (Figure 1). These rosetting T cells have a Follicular T cell phenotype with expression of CD3/CD4/CD57 [24], bcl6 [21], PD1 [20, 25] and, interestingly, CXCL13, a chemokine that is known to induce B cell homing to lymphoid follicles and that plays a role in the T cell-dependent B cell affinity maturation process [26]. These observations suggest that NLPHL is characterized by a GC phenotype in both LP and T cells.…”