The lymph node architecture is effaced by an atypical mottled nodular lymphoproliferation comprising nodules replete with small lymphocytes. At higher power, singly scattered mononuclear variants as well as mummified variants of Hodgkin/Reed-Sternberg cells are seen admixed with the lymphocytes within the nodules.

The nodular area is a rich in small B cells, highlighted by CD20 and Pax-5 immunostains. In addition, there are a fair number of T cells admixed in the background but notably, the Hodgkin cells are negative for CD20 and express weak Pax-5 in keeping with down regulation of the B-cell program within the neoplastic cells in classical Hodgkin lymphoma. On the Pax-5 immunostain, as detected below, a corona of Pax-5 negative small lymphocytes are seen to intervene in between the Hodgkin cells and the surrounding Pax-5 positive B-cells. This corona/rosette comprise CD3 + T-cells which express PD-1 (programmed death-1). More recent studies have indicated that Hodgkin cells frequently express the ligand for PD-1, i.e. PD-L1; as a result of the cognate interaction of PD-L1 with the PD-1 positive background T-cells, there is resulting T-cell exhaustion and suboptimal immune response to the Hodgkin lymphoma cells. Hence, there is ongoing trials involving targeted therapy which are being tested in classical Hodgkin lymphoma directed towards PD-L1 and PD-1 with promising responses.