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

Abstract

In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/ BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.

Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis

“…Pairwise supervised comparisons also demonstrated very few differentially expressed genes, and it is speculated that the composition of the microenvironment defines these entities, which may in turn reflect the host immune status. 21 In our analysis, there was an excess of lymphoma relapses in NLPHL compared with CHL using ABVD-like chemotherapy which, in some instances, resembled THRLBCL. Further pathologic studies are needed to define which NLPHL patients may be better suited for aggressive lymphoma therapies.…”

“…Gene expression studies support a close relatedness of NLPHL with CHL but also with THRLBCL, highlighting its unique biology. 20 A more recent study by Hartmann et al 21 compared the gene expression profile of microdissected tumor cells from NLPHL, THRLBCL-like NLPHL (defined as having at least one typical NLPHL nodule), and THRLBCL and found significant molecular overlap between these entities. Pairwise supervised comparisons also demonstrated very few differentially expressed genes, and it is speculated that the composition of the microenvironment defines these entities, which may in turn reflect the host immune status.…”

The 2016 revision of the World Health Organization classification of lymphoid neoplasms

“…Recent data indicate that progression to a process with features of THRLBCL is associated with a more aggressive clinical course, and requires different management, such that the term NLPHL in this setting may not be sufficient. 147,148 However, cases with only focal diffuse areas are not considered transformation. It is also of interest that aside from their immunomorphologic appearance, GEP and array comparative genomic hybridization studies have shown similarities between NLPHL and THRLBCL, suggesting a relationship to each other, in spite of other major differences.…”

“…It is also of interest that aside from their immunomorphologic appearance, GEP and array comparative genomic hybridization studies have shown similarities between NLPHL and THRLBCL, suggesting a relationship to each other, in spite of other major differences. 147,149 The revision will also acknowledge that lymphocyterich CHL has some features that are intermediate between other CHL and NLPHL. 150 …”

Thomas Hodgkin and Hodgkin lymphoma

“…In T cell/ histiocyte-rich large B cell lymphoma, the background cells are almost all T cells with hardly any small B cells. T cell/ histiocyte-rich large B cell lymphoma is reported to have a higher proportion of CD8+ T cells and TIA1+ T cells than NLPHL in some studies [10,30].T cell/histiocyte-rich large B cell lymphoma is also reported to have a lower proportion of CD4+ T cells and of T cells with a T follicular helper cell phenotype than NLPHL [31]. Staining for the T follicular helper cell marker PD1 may be helpful, as PD1+ T cells do not form rosettes around large neoplastic B cells in typical cases of T cell/histiocyte-rich large B cell lymphoma [19].…”