Lymphoma & related disorders

Mature B cell neoplasms

Large B cell lymphomas-special subtypes

T cell / histiocyte rich

Last author update: 1 July 2017
Last staff update: 30 May 2023 (update in progress)

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PubMed Search: T cell / histiocyte rich large B cell lymphoma

Rumina Musani, M.D.
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Cite this page: Chan K, Musani R. T cell / histiocyte rich. website. Accessed June 7th, 2023.
Definition / general
  • Diffuse large B cell lymphoma subtype with abundant nonneoplastic T cells and histiocytes, that may obscure tumor cells
Essential features
  • Must differentiate from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL): has different microenvironment (cytotoxic T cells vs B cells / follicular dendritic (FD) meshwork); also requires clinical correlation (THRLBCL is advanced stage vs. NLPHL is indolent)
  • Sample lymph node thoroughly to find typical areas of NLPHL in order to rule out THRLBCL
  • Caution when diagnosing THRLBCL in a small biopsy: if there is history of NLPHL, describe as "THRLBCL-like transformation" of NLPHL
  • Evidence exists that NLPHL and THRLBCL represent different spectrum of the same pathobiological entity
Diagrams / tables

Contributed by Konrad Chan, M.D.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) versus T cell / histiocyte rich B cell lymphoma (THRLBCL)

Clinical features
  • Rare morphological variant of diffuse large B cell lymphoma (DLBCL); 1 - 3% of all B cell lymphomas
  • Usually middle age adults, often with advanced stage (Ann Arbor III / IV) and involvement of lymph nodes, spleen, bone marrow
  • Clinical presentation: fever, malaise, splenomegaly or hepatomegaly
  • Same treatment protocol as DLBCL, NOS but lower complete remission rate
Case reports
Gross images

Case #317

Axillary node of
37 year old man

Microscopic (histologic) description
  • Diffuse or vaguely nodular pattern
  • Scattered single neoplastic large B cells ( < 10% of all cells) amongst small reactive T cells and histiocytes
  • Near absence of B lymphocytes in the background; no remnants of B follicles or clusters of small B lymphocytes
  • Diverse morphologic and immunophenotypic features (Am J Surg Pathol 2002;26:1458)
    • LP-like (lymphocyte predominant-like): pale and indistinct cytoplasm, lobated and vesicular nuclei resembling popcorn cells with small central nucleoli; background of small lymphocytes and often histiocytes, no granulomas
    • Centroblast-like: pale eosinophilic cytoplasm, oval / round nuclei with vesicular chromatin and without nuclear atypia, small basophilic nucleoli adjacent to nuclear membrane
    • HRS-like (Hodgkin Reed-Sternberg cell-like): large multinucleated cells with abundant amphophilic cytoplasm, pleomorphic nuclei with prominent eosinophilic or amphophilic round / central nucleoli
  • Neoplastic B cells are surrounded by clusters of bland nonepithelioid histiocytes
Microscopic (histologic) images

Contributed by Drs. Asmaa Gaber Abdou and Nancy Youssef Asaad

Case #317

Various images





Images hosted on other servers:

Low power view: retroperitoneal lymph node

Large cell population

Scattered eosinophils


T cell component of NHL


Positive stains
  • Large B cells:
    • Pan B markers and transcription factors (CD20, CD79a, PAX5, Oct2 / BOB.1)
    • BCL6 (50 - 91%), EMA (~30%, associated with lymphocyte rich/LR-like cells), BCL2 (40%)
    • Rarely positive for CD30 (8 - 30%, usually stains HRS-like cells) and CD10 (10%)
  • Reactive T cells: CD3+, CD5+, CD8+, TIA1+ (cytotoxic T cells)
  • Reactive histiocytes: CD68+, CD163+
Negative stains
  • Large B cells: CD15, CD30, CD138, IgD
  • Background small lymphocytes: IgD (mantle cell marker)
  • No FDC meshwork (CD21, CD23, CD35)
  • (Rarely) T cell rosetting around tumor cells
  • EBV (otherwise defined as EBV+ DLBCL)
Molecular / cytogenetics description
  • PAX5 / IgH gene rearrangement by FISH
Differential diagnosis
  • Classic Hodgkin lymphoma (cHL): neoplastic B cells are CD15+ / CD30+ (strong) / MUM1+ (strong); different microenvironment (see below)
  • Immunodeficiency related lymphoproliferative disorder (ID-LPD): clinical history (primary immune disorder, posttransplant, immunosuppressive therapy); polymorphous (including plasma cells), EBER+
  • Nodular lymphocyte predominant - Hodgkin lymphoma (NLPHL):
    1. Neoplastic B cells:
      • BCL6- / MUM1+ favors THRLBCL
      • IgD+ favors NLPHL
    2. Different microenvironments (see diagrams and tables)
      • NLPHL has residual IgD positive mantle cells and CD21+ follicular dendritic cell meshwork (not present in THRLBCL)
  • Peripheral T cell lymphoma such as angioimmunoblastic T cell lymphoma (large B cells are nonneoplastic): prominent infiltration of eosinophils, plasma cells and increased vascularity; CD10+ in T cells (TFH cells)
  • Reactive conditions (drugs, viral infection, autoimmune diseases): preserved architecture; heterogeneous cytological appearance of immunoblasts; CD15- immunoblasts; EBER+ in both large and small lymphocytes (infectious mononucleosis)

  • Relationship between T cell / histiocyte rich B cell lymphoma (THRLBCL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL):
    • Classical NLPHL has indolent clinical course, while THRLBCL is an advance stage, aggressive disease
    • Cases of NLPHL are known to have morphologically transformed into THRLBCL
    • There are cases of NLPHL with diffuse T cell rich, "THRLBCL-like" pattern which behaves less aggressively than de novo THRLBCL
    • Evidence suggests these two entities may represent different spectrum of the same pathobiology
      • Evidence suggesting similarity between both diseases:
        1. Neoplastic B cells show similar immunophenotypical profile
        2. Gene expression profiling (GEP) shows no clearly distinct gene expression pattern between the two diseases (PLoS One 2013;8:e78812)
        3. Comparative genomic hybridization (CGH) shows similar unique aberrations (REL locus) (Br J Haematol 2015;169:415)
      • Evidence suggesting tumor microenvironment may affect manifestation of the disease:
        1. CD4+ T cells less frequent in THRLBCL than NLPHL
        2. CD163+ histiocytes more frequent in THRLBCL than NLPHL (Haematologica 2010;95:440)
Board review style question #1
Which one of the following statements regarding T cell / histiocyte rich large B cell lymphoma (TCHRLBCL) is FALSE?

  1. Differential diagnosis of TCHRLBCL include viral infection, peripheral T cell lymphoma and classic Hodgkin lymphoma
  2. TCHRLBCL and NLPHL show different clinical presentation and organ involvement
  3. The large cell component of both TCHRLBCL and NLPHL are CD20+, OCT2+, BCL6+ and EBV+
  4. The peritumoral environment of TCHRLBCL contains abundant CD8+ / TIA1+ cells
  5. 35 year old man presents with cervical and supraclavicular lymphadenopathy. Core biopsy shows scattered LP ("popcorn") cells in a background mostly of T lymphocytes and histiocytes and scarce B lymphocytes. The diagnosis is "nodular lymphocyte predominant Hodgkin lymphoma with T cell / histiocyte rich large B cell lymphoma-like pattern"
Board review style answer #1
C. is false: the large B cells are generally EBV negative

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