COO remains a major and independent factor in relapsed/refractory DLBCL, with a better response to R-DHAP in GCB-like DLBCL. This needs confirmation by a prospective study.

IntroductionNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for 6.5% of cases in the German Hodgkin lymphoma study. It is characterized by a nodular, or a nodular and diffuse proliferation of scattered large neoplastic cells (lymphocytic and/or histiocytic [L&H] cells or "popcorn" cells) in large spherical meshworks of follicular dendritic cells (FDCs) filled with nonneoplastic small lymphocytes, mainly of B-cell type. 1 There have been doubts whether a purely diffuse lymphocyte-predominant Hodgkin lymphoma (LPHL) really exists. 2,3 NLPHL has recently been distinguished from the nodular lymphocyte-rich variant of classical Hodgkin lymphoma (cHL), based on immunophenotype. In contrast to cHL, tumor cells of NLPHL do not express CD30 and CD15, but they are positive for B-cell markers (CD20, CD79a), immunoglobulins, J chain, and epithelial membrane antigen. 1 The B-cell phenotype and genetic features of NLPHL, exhibiting clonally rearranged immunoglobulin genes with ongoing mutations, 4,5 indicate its close relationship to B-cell non-Hodgkin lymphomas. 2,6 Among B-cell non-Hodgkin lymphomas, T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) represents a variant of diffuse large B-cell lymphoma (DLBCL) in which neoplastic CD20 ϩ B cells, accounting for less than 10% of the infiltrate, are scattered among the majority of nonneoplastic T cells with or without histiocytes. 2 Nevertheless, T/HRBCL seems heterogeneous, comprising several subgroups. The tumor cells may resemble centroblasts, immunoblasts, Reed-Sternberg (RS) cells, or L&H cells. 2,[7][8][9][10][11] The clinical presentation and treatment strategies of NLPHL and T/HRBCL are different. 12,13 NLPHL presents at a localized clinical stage and pursues an indolent course, 2 while T/HRBCL presents typically at a high stage and its outcome is worse. 7,9,[13][14][15][16][17] According to morphologic, immunophenotypic, molecular-genetic, and clinical data gathered over several past years, there exists a substantial overlap-a gray zone-between NLPHL and T/HRBCL. 2,6,13,18 Both diseases may occur as composite lymphomas in the same lymph node or in subsequent biopsies, as well as in members of the same family. 13,19 In addition, a diffuse pattern in NLPHL may represent a morphologic tumor progression and transition to T/HRBCL. The tumor cells of NLPHL and T/HRBCL are alike not only morphologically, but also immunophenotypically. 20 Only PU.1, a transcription factor essential for B-cell development, has been described as being expressed more often in NLPHL than in T/HRBCL, albeit in a small number of cases. 21 For personal use only. on May 10, 2018. by guest www.bloodjournal.org From However, differences in the background composition and growth pattern do exist. 2,13,20,22 To choose treatment and to include patients in clinical studies, it is essential to distinguish NLPHL from T/HRBCL.The differential diagnosis is not settled for cases sharing architectural and immunomorphologic features of both NLPHL and T/HRBCL. We compared pathologic and clinical pro...