Lymph node architecture effaced by vaguely nodular lymphoid infitlrate. The expansile nodular structures contain predominantly lymphocytes with scattered large cells at high power with the classic "popcorn" cytomorphology of the so called Lymphocytic and Histiocytic (L&H)/ lymphocyte predominant (LP) cells. These cells have convoluted and deeply folded nuclear contours with indistinct nucleoli in contrast to the Hodgkin/Reed Sternberg cell of classical Hodgkin lymphoma. The term 'L&H' comes from the close proximity of the neoplastic cells to lymphocytes and histiocytes within the nodules.

CD20, Pax5 and Oct-2 (latter two are nuclear markers) are all B-cell lineage markers. The nodular structures show numerous CD20+ small B-cells (evident in the immunostain). The L&H/LP ("Popcorn") cells within the nodules express strong CD20, Pax5 and Oct-2 (depicted at higher power) with a rosette of lymphocytes which are positive for CD3 indicating the presence of T-cell rosettes around the neoplastic cells. CD21 immunostain (a marker of dendritic cells) highlights expanded disrupted meshworks within the nodules.

Numerous CD57 positive lymphocytes are typically noted in NLPHL lesions, a finding of diagnostic use in discriminating NLPHL from the similar looking T-cell/histiocyte rich large B-cell lymphoma wherein the numbers of CD57+ lymphoid cells in the background are much reduced to absent. CD30 is negative in the neoplastic cells allowing exclusion of classical Hodgkin lymphoma.