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

Question: 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. The present study therefore aimed to find markers, which can be applied in the differential diagnosis between NLPHL and THRLBCL.

Methods: Gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL was performed. Immunohistochemical stainings of the tumor microenvironment were quantified in a blinded fashion.

Results: 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. 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 was more closely related to THRLBCL than NLPHL.

Conclusions: 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.