Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

Abstract

Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) and classical Hodgkin Lymphoma (CHL). This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

Figure 1

NLP-HL: HE section of a case of Nodular lymphocyte-predominant Hodgkin lymphoma, showing a typical lymphocyte-Predominant (LP) cell positive for CD20 (NLP-CD20) and surrounded by a rim of PD1-positive T cells (NLP-PD1). LR-CHL: HE section of a case of lymphocyte-Rich Classical Hodgkin lymphoma that highlights a typical Reed-Sternberg (R-S) cell with the characteristic phenotype (CD30+, LR-CD30) and surrounded by a rim of PD1-positive T cells (LR-PD1). The pattern is reminiscent of that found in the outer part of the germinal centre where PD1-positive cells surround large B blasts (see arrows in the immunofluorescence capture region of the outer zone of a reactive germinal centre).

Figure 2

The HRS cell and its cellular microenvironment. Significant interactions with impact in patients outcome are depicted. Increased Galectin1 and IL-10 secreted by HRS (Hodgkin and Reed-Sternberg) cells lead to decreased TCL (T cytotoxic) and Th1 responses, together with a Treg increase which, in turn, suppresses both Th2 and PD1+ T cell activity [–51]. PD1+CD4+ T cell activity is additionally suppressed by direct interations trough PD1-PD1L immunological synapse (T cell exhaustion) [52]. This leads to a decreased IFNγ production. Additionally, increased TAM (Tumor Associated Macrophages) contribute to T cell deletion trough STAT1 signaling pathway [53, 54].