T-Cell–Rich Hodgkin Lymphoma With Features of Classic Hodgkin Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma

The median age of patients with lymphocyterich CHL is similar to that of patients with NLPHL and is significantly older than that observed in patients with nodular sclerosis CHL.1 The clinical features of lymphocyterich CHL and NLPHL are similar, as most patients with lymphocyte-rich CHL present with stage I or II disease and rarely have B-type symptoms.7 Furthermore, unlike NLPHL patients, those with lymphocyte-rich CHL relapse less frequently.7 Nevertheless, the overall survival rates in both entities are outstanding. Cases of NLPHL demonstrating nodular sclerosis–like features prior to therapy resembling nodular sclerosis CHL have been described.3,8 Furthermore, a striking resemblance between cases of NLPHL and lymphocyte-rich CHL has been previously acknowledged,1,7,9–11 leading some to conceptualize lymphocyte-rich CHL as an intermediate state between CHL and NLPHL.11 In fact, the nodules of lymphocyte-rich CHL resemble those of NLPHL, with Hodgkin and Reed-Sternberg (HRS) cells, predominantly found within B-cell-rich nodules with features of mantle zone B cells (positive for immunoglobulin [Ig] M and IgD), with scant or absent eosinophils and/or neutrophils.10 In addition, similar to NLPHL, the expression of B-cell transcription factors octamer binding protein 2 (OCT2) and B-cell–specific octamer binding protein-1 (BOB1) has been found to be more frequent in the HRS cells of lymphocyte-rich CHL than in other CHL types.11 Rosettes with a T follicular helper (TFH) cell immunophenotype (programmed death-1 (PD-1)/CD279þ, CD57/þ) surrounding the neoplastic cells are also present in up to 50% of lymphocyte-rich CHL cases.11 One distinguishing feature is the presence of eccentrically located, small germinal centers in lymphocyte-rich CHL, which are uncommon in NLPHL (about 15% of cases).3 Although these morphologic features may be misleading, performing immunohistochemical studies and using an adequate battery of antibodies such as CD15, CD20, CD30, and paired box 5 (PAX5), as well as in situ hybridization for EpsteinBarr virus (EBV)encoded small RNA (EBER), are helpful in successfully distinguishing these 2 entities most of the time.9 We have encountered cases of Hodgkin lymphoma (HL) with overlapping features between T-cell–rich NLPHL (pattern D) and T-cell–rich CHL in which a clear distinction was challenging even after thorough morphologic examination of excisional biopsy specimens with extensive immunohistochemical characterization. Immunophenotyping a