Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has traditionally been recognized as having two morphologic patterns, nodular and diffuse, and the current WHO definition of NLPHL requires at least a partial nodular pattern. Variant patterns have not been well documented. We analyzed retrospectively the morphologic and immunophenotypic patterns of NLPHL from 118 patients (total of 137 biopsy samples). Histology plus antibodies directed against CD20, CD3, and CD21 were used to evaluate the immunoarchitecture. We identified six distinct immunoarchitectural patterns in our cases of NLPHL: "classic" (B-cell-rich) nodular, serpiginous/interconnected nodular, nodular with prominent extranodular L&H cells, T-cell-rich nodular, diffuse with a T-cell-rich background (T-cell-rich B-cell lymphoma [TCRBCL]-like), and a (diffuse) B-cell-rich pattern. Small germinal centers within neoplastic nodules were found in approximately 15% of cases, a finding not previously emphasized in NLPHL. Prominent sclerosis was identified in approximately 20% of cases and was frequently seen in recurrent disease. Clinical follow-up was obtained on 56 patients, including 26 patients who had not had recurrence of disease and 30 patients who had recurrence. The follow-up period was 5 months to 16 years (median 2.5 years). The presence of a diffuse (TCRBCL-like) pattern was significantly more common in patients with recurrent disease than those without recurrence. Furthermore, the presence of a diffuse pattern (TCRBCL-like) was shown to be an independent predictor of recurrent disease (P = 0.00324). In addition, there is a tendency for progression to an increasingly more diffuse pattern over time. Analysis of sequential biopsies from patients with recurrent disease suggests that the presence of prominent extranodular L&H cells might represent early evolution to a diffuse (TCRBCL-like) pattern. We also report three patients who presented initially with diffuse large B-cell lymphoma and later developed NLPHL.

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