T-cell/histiocyte-rich large B-cell lymphoma: a heterogeneous entity with derivation from germinal center B cells

Am J Surg Pathol. 2002 Nov;26(11):1458-66. doi: 10.1097/00000478-200211000-00008.


T-cell/histiocyte-rich large B-cell non-Hodgkin's lymphoma (THRLBCL) is an unusual morphologic variant of diffuse large B-cell lymphoma. We reviewed 30 cases of THRLBCL to evaluate its heterogeneity based on morphologic, immunophenotypic, and genetic features. Cases were classified according to the appearance of the large neoplastic B cells into three morphologic variants: 1) lymphocytic and histiocytic (L&H-like) (resembling the L&H cells of nodular lymphocyte predominance Hodgkin's lymphoma (14 cases); 2) centroblast (or immunoblast)-like (10 cases), and 3) Reed-Sternberg cell-like (resembling the neoplastic cells of classic Hodgkin's lymphoma) (6 cases). We used a panel of immunohistochemical stains, including those with specificity for germinal center B cells: CD20, CD79a, CD30, CD15, epithelial membrane antigen, BCL-2, BCL-6, and CD10. The /JH polymerase chain reaction assay was further performed to investigate a relationship to follicular lymphoma. The results were correlated with Epstein-Barr virus status as determined by staining for latent membrane protein and EBER-1 in situ hybridization. All cases were of B-cell immunophenotype with strong surface CD20 reactivity in the neoplastic large lymphoid cells, although CD79a was more inconsistently and weakly expressed (10 of 17). Nuclear positivity for the BCL-6 protein was detected in the tumor cells in 26 of 29 (90%) cases. However, differences in expression of other antigens were encountered in the histologic subtypes. Epithelial membrane antigen positivity, a feature often seen in nodular lymphocyte predominance Hodgkin's lymphoma, was observed in 11 of 30 (37%) cases and was most commonly seen in cases with L&H cell morphology (8 of 14; 57%). CD30 expression was observed in 9 of 30 (30%) cases but was most frequent in cases with Reed-Sternberg-like morphology (3 of 6 [50%]). CD10 expression was infrequent overall (3 of 29; 10%), with 2 of 3 positive cases identified in the centroblastic group. The overall rarity of positivity for CD10, BCL-2 (3 of 22; 13%), and -2 JH rearrangement (1 of 28; 4%) indicates a lack of connection to follicular lymphoma for all subtypes. The three cases that were negative for BCL-6 protein were LMP-1 positive and EBER-1 positive by in situ hybridization, and 2 of 3 had neoplastic cells with Reed-Sternberg-like morphology. These results demonstrate that although a large proportion of THRLBCL represent tumors of germinal center B cell derivation, they exhibit a diversity of morphologic and immunophenotypic features. A subset of THRLBCL may be related to nodular lymphocyte predominance Hodgkin's lymphoma. A small percentage show features closely resembling classic Hodgkin's lymphoma and could be considered a variant of grey zone lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Biomarkers, Tumor / metabolism
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins / metabolism
  • Female
  • Germinal Center / metabolism
  • Germinal Center / pathology*
  • Histiocytes / metabolism
  • Histiocytes / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • Reed-Sternberg Cells / metabolism
  • Reed-Sternberg Cells / pathology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*
  • Transcription Factors / metabolism


  • Biomarkers, Tumor
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors