# T-cell/histiocyte-rich large B-cell lymphoma
**T-cell/histiocyte-rich large B-cell lymphoma** (THRLBCL) is an aggressive [B-cell lymphoma](https://www.edgepedia.org/b-cell-lymphoma) in which fewer than 10% of the cells are large neoplastic B cells, scattered in a diffuse background rich in reactive T cells and histiocytes, with a virtual absence of small B cells.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) It is classified as a subtype of diffuse large B-cell lymphoma (DLBCL) and accounts for less than 10% of DLBCL cases.[2](https://ashpublications.org/blood/article/146/Supplement%201/898/555379/Outcomes-of-T-cell-histocyte-rich-large-B-cell) The disease typically affects younger male patients, usually presents as stage III–IV systemic disease with [B symptoms](https://www.edgepedia.org/b-symptoms), splenomegaly, or hepatomegaly, and was historically associated with poor survival.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma)
| Key fact | Detail |
|---|---|
| Definition | Aggressive B-cell lymphoma with <10% large neoplastic B cells in a diffuse background rich in T cells and histiocytes, with virtual absence of small B cells (WHO 5th edition)[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) |
| Frequency | Less than 10% of all DLBCL subtypes; one review places it below 5% of large B-cell lymphoma cases[2](https://ashpublications.org/blood/article/146/Supplement%201/898/555379/Outcomes-of-T-cell-histocyte-rich-large-B-cell) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) |
| Typical presentation | Younger male patients, stage III–IV systemic disease, B symptoms, splenomegaly, hepatomegaly[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) |
| Immunophenotype | CD20-positive neoplastic cells, CD15 negative, PD-1-positive T cells, PD-L1-positive macrophages surrounding neoplastic B cells[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) |
| Survival (NCDB cohort) | Unadjusted 5-year overall survival 65.9% for THRLBCL versus 54.1% for DLBCL-NOS; adjusted hazard ratio 0.80 (95% CI, 0.67–0.94; P=0.007)[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6928430/) |
| Microenvironment | Malignant B cells under 5% of total cells amid dense T-cell and macrophage infiltration; pronounced interferon-driven inflammation and PD-L1 signaling[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) |
| Relationship to NLPHL | A subset of cases shows marked clinical, immunophenotypic, and molecular overlap with nodular lymphocyte-predominant Hodgkin lymphoma[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) |
## Pathology and diagnosis
The defining histologic feature is the scarcity of the tumor itself. Large neoplastic B cells, which may resemble lymphocyte-predominant cells, centroblasts, or more pleomorphic Hodgkin-like cells, are scattered singly amid a dense infiltrate of small polyclonal T cells and non-epithelioid histiocytes.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) • [5](https://academic.oup.com/oncolo/article/11/4/384/6397057) [Immunohistochemistry](https://www.edgepedia.org/immunohistochemistry) identifies the malignant cells as CD20-positive B cells and shows the surrounding population: PD-1-positive T cells and PD-L1-positive macrophages encircling the neoplastic B cells.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) Genetic data associated with the entity include gains or amplifications of the CD274 (PD-L1) locus.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma)
**Classification history.** In 2001, the World Health Organization gave T/HRBCL formal recognition as a DLBCL morphologic variant, defined by an abundance of inflammatory cells surrounding neoplastic B cells that make up less than 10% of the lesion, and the 2008 edition classified it as a distinct DLBCL subtype.[5](https://academic.oup.com/oncolo/article/11/4/384/6397057) The term "histiocyte-rich B-cell lymphoma" was introduced in 1992 by Delabie and colleagues for cases dominated by histiocytes rather than T cells.[5](https://academic.oup.com/oncolo/article/11/4/384/6397057) In the WHO 5th edition, THRLBCL is listed among the mature B-cell neoplasms, with separate codes for de novo disease and for cases progressed from nodular lymphocyte-predominant [Hodgkin lymphoma](https://www.edgepedia.org/hodgkin-lymphoma).[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma)
## Relationship with nodular lymphocyte-predominant Hodgkin lymphoma
THRLBCL shares histologic features with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a germinal-center B-cell neoplasm that preferentially affects young to middle-aged men and usually behaves indolently, whereas de novo THRLBCL is frequently diagnosed at advanced stages.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/) Variants of NLPHL, especially the diffuse "THRLBCL-like" form, can closely mimic THRLBCL histologically.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/)
[Gene expression profiling](https://www.edgepedia.org/gene-expression-profiling) of microdissected tumor cells from NLPHL, THRLBCL-like NLPHL, and THRLBCL found that the lymphomas did not cluster by entity, and supervised analyses identified only a few moderately differentially expressed transcripts; the study concluded there are no clear and consistent gene expression differences among the tumor cells of the three entities.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/) The same work identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/) The main differences lie in the microenvironment: the cellular composition of T-cell and histiocyte infiltrates differs significantly between typical NLPHL and THRLBCL, and the authors proposed that NLPHL and THRLBCL may represent a spectrum of the same disease, with clinical behavior shaped by the microenvironment.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/) The 2017 WHO classification designated NLPHL cases that progress to a diffuse T-cell-rich pattern as "THRLBCL-like transformation of NLPHL".[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC6763378/)
## Tumor microenvironment and immune evasion
The THRLBCL microenvironment is immunosuppressive despite its abundance of immune cells. Malignant B cells constitute fewer than 5% of total cells, surrounded by reactive T lymphocytes and macrophages, a composition that hinders conventional chemotherapy.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) Gene [coexpression network analysis](https://www.edgepedia.org/coexpression-network-analysis) shows a pronounced interferon-driven inflammatory pathway and PD-L1 signaling, with upregulation of PD-1, PD-L1, CTLA-4, and LAG3, indicating T-cell exhaustion and immune evasion.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) The PD-1/PD-L1 pathway has been described as a key driver of immune escape in this subtype, with PD-L1 gene alterations such as copy gains and high PD-L1 expression on malignant B cells often surrounded by PD-L1-expressing macrophages and PD-1-positive T cells.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC11792173/)
## Treatment and outcomes
Frontline treatment has centered on rituximab-containing chemotherapy, typically R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for localized disease, and recent studies suggest newly diagnosed patients may benefit from higher-intensity regimens such as those combining R-CHOP with R-ICE.[9](https://www.cancer.gov/types/lymphoma/hp/aggressive-b-cell-lymphoma-treatment-pdq) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) Optimal frontline treatment remains unclear, with some studies advocating intensive regimens.[2](https://ashpublications.org/blood/article/146/Supplement%201/898/555379/Outcomes-of-T-cell-histocyte-rich-large-B-cell)
**Survival relative to DLBCL-NOS.** In an analysis of the US National Cancer Data Base, median overall survival was not reached, and unadjusted 5-year overall survival was 65.9% (95% CI, 60.2–70.9) for THRLBCL versus 54.1% (95% CI, 53.7–54.6) for DLBCL-NOS.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6928430/) After adjustment for age, sex, race, stage, B symptoms, extranodal site, comorbidities, income, and hospital type, THRLBCL remained associated with better overall survival (adjusted hazard ratio, 0.80; 95% CI, 0.67–0.94; P=0.007), a result consistent across academic and community hospitals and in models restricted to stage III/IV disease or multi-agent chemotherapy.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6928430/)
**Immunotherapy and CAR T cells.** The PD-L1-rich microenvironment motivated interest in immune checkpoint inhibitors, but CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown limited efficacy, often limited by primary resistance and early relapse.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) In a multicenter study of CD19-directed CAR T therapy in THRLBCL, poor performance status before CAR T infusion was associated with higher mortality (hazard ratio, 2.35; 95% CI, 1.02–5.5).[10](https://pubmed.ncbi.nlm.nih.gov/38985302/) Proposed strategies to improve results include combining [CAR T-cell therapy](https://www.edgepedia.org/car-t-cell-therapy) with immune checkpoint inhibitors and Bruton tyrosine kinase inhibitors, and developing CAR constructs targeting multiple antigens to counter antigen escape.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/) THRLBCL patients remain underrepresented in pivotal trials of bispecific antibodies, tafasitamab-lenalidomide, and antibody-drug conjugates developed for relapsed or refractory DLBCL.[11](https://www.tandfonline.com/doi/full/10.1080/10428194.2025.2607549)
## Epidemiology
THRLBCL is rare, accounting for less than 10% of DLBCL, with a male predominance and a primary age range reported as 12 to 61 years in registry data.[1](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma) • [2](https://ashpublications.org/blood/article/146/Supplement%201/898/555379/Outcomes-of-T-cell-histocyte-rich-large-B-cell) Because of the abundant T cells and overlapping features, a proportion of cases have been misdiagnosed as T-cell lymphomas or NLPHL.[12](https://www.researchgate.net/profile/Gaurav-Goyal-11/publication/325449603_T_cellhistiocyte-rich_large_B_cell_lymphoma_Incidence_demographic_disparities_and_long-term_outcomes/links/5b571bae0f7e9b240f021c04/T-cell-histiocyte-rich-large-B-cell-lymphoma-Incidence-demographic-disparities-and-long-term-outcomes.pdf)
## References
1. [SEER Hematopoietic and Lymphoid Neoplasm Database: T-cell/histiocyte-rich large B-cell lymphoma](https://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a1/?q=diffuse+large+cell+lymphoma)
2. [Outcomes of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL): An international LEO/MER and NiHiL collaborative study, Blood](https://ashpublications.org/blood/article/146/Supplement%201/898/555379/Outcomes-of-T-cell-histocyte-rich-large-B-cell)
3. [Immune checkpoint blockade and CAR T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma: Challenges and opportunities, Heliyon (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11425163/)
4. [Clinical features and survival of patients with T-cell/histiocyte-rich large B-cell lymphoma: analysis of the National Cancer Data Base](https://pmc.ncbi.nlm.nih.gov/articles/PMC6928430/)
5. [T-Cell/Histiocyte-Rich B-Cell Lymphoma: Biology, Diagnosis, and Management, The Oncologist](https://academic.oup.com/oncolo/article/11/4/384/6397057)
6. [Nodular Lymphocyte Predominant Hodgkin Lymphoma and T Cell/Histiocyte Rich Large B Cell Lymphoma: Endpoints of a Spectrum of One Disease?](https://pmc.ncbi.nlm.nih.gov/articles/PMC3823948/)
7. [Update on the classification of T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms](https://pmc.ncbi.nlm.nih.gov/articles/PMC6763378/)
8. [Chimeric antigen receptor T-cell therapy outcomes in T-cell/histiocyte-rich large B-cell lymphoma and subsequent treatment strategies after disease progression: A GELTAMO/GETH study](https://pmc.ncbi.nlm.nih.gov/articles/PMC11792173/)
9. [Aggressive B-Cell Non-Hodgkin Lymphoma Treatment (PDQ®), National Cancer Institute](https://www.cancer.gov/types/lymphoma/hp/aggressive-b-cell-lymphoma-treatment-pdq)
10. [CD19-directed CAR T therapy for T-cell/histiocyte-rich large B-cell lymphoma, Blood Advances (2024)](https://pubmed.ncbi.nlm.nih.gov/38985302/)
11. [T-cell/histiocyte-rich large B-cell lymphoma, insights into prognosis and treatment complexity in the context of immunotherapeutics, Leukemia & Lymphoma](https://www.tandfonline.com/doi/full/10.1080/10428194.2025.2607549)
12. [T cell/histiocyte-rich large B cell lymphoma: incidence, demographic disparities, and long-term outcomes](https://www.researchgate.net/profile/Gaurav-Goyal-11/publication/325449603_T_cellhistiocyte-rich_large_B_cell_lymphoma_Incidence_demographic_disparities_and_long-term_outcomes/links/5b571bae0f7e9b240f021c04/T-cell-histiocyte-rich-large-B-cell-lymphoma-Incidence-demographic-disparities-and-long-term-outcomes.pdf)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Cardiovascular and blood conditions › Blood disorders (hematologic conditions) › Lymphomas › B-cell non-Hodgkin lymphomas › DLBCL variants and related entities*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license