# Nodular lymphocyte predominant Hodgkin lymphoma
**Nodular lymphocyte predominant Hodgkin lymphoma** (NLPHL) is a rare type of [Hodgkin lymphoma](https://www.edgepedia.org/hodgkin-lymphoma), a cancer of the immune system, marked by the presence of lymphocyte-predominant (LP) cells, once called popcorn cells, which differ from the Reed-Sternberg cells of classic Hodgkin lymphoma.[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nodular-lymphocyte-predominant-hodgkin-lymphoma) It accounts for roughly 5% of all Hodgkin lymphoma cases[2](https://www.sciencedirect.com/science/article/pii/S0360301615001790) and behaves clinically more like an indolent [B-cell lymphoma](https://www.edgepedia.org/b-cell-lymphoma) than like classic Hodgkin lymphoma, with most patients presenting at an early stage and surviving long term.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11532684/)
| Key fact | Detail |
|---|---|
| Frequency | Approximately 5% of all Hodgkin lymphoma cases[2](https://www.sciencedirect.com/science/article/pii/S0360301615001790) |
| Defining cells | LP cells, formerly called L&H or popcorn cells, with multilobulated nuclei and a germinal center B-cell phenotype[4](https://haematologica.org/article/view/10248) |
| Immunophenotype | CD20 positive, CD15 negative, CD30 negative, CD45 positive; classic Hodgkin lymphoma is typically the reverse[5](https://pubmed.ncbi.nlm.nih.gov/27496311/) • [6](https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq) |
| Who it affects | Typically young men aged 30 to 50 years, with a 3:1 male predominance and cervical, axillary, or inguinal node involvement[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) • [8](https://academic.oup.com/oncolo/article/14/7/739/6397951) |
| Stage at presentation | 70% to 80% of patients present with stage I or II disease[8](https://academic.oup.com/oncolo/article/14/7/739/6397951) |
| Survival | 5- and 10-year overall survival of 91% and 83%, versus 81% and 74% for classic Hodgkin lymphoma in a SEER analysis of 1,162 NLPHL patients[2](https://www.sciencedirect.com/science/article/pii/S0360301615001790) |
| Main risk | Transformation to diffuse large B-cell lymphoma, at roughly 1% of patients per year[4](https://haematologica.org/article/view/10248) |
## Classification and naming
NLPHL was initially classified as a subtype of Hodgkin lymphoma, but its biological, pathological, and clinical features differ from classic Hodgkin lymphoma (cHL). Because of these differences and the entity's close relationship with [T-cell/histiocyte-rich large B-cell lymphoma](https://www.edgepedia.org/t-cell-histiocyte-rich-large-b-cell-lymphoma), the 2022 International Consensus Classification (ICC) proposed renaming it nodular lymphocyte predominant B-cell lymphoma (NLPBL) and moved it among the large B-cell lymphomas.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC11232355/) The fifth edition of the World Health Organization classification retains the term NLPHL to align with ongoing trials and research while recognizing NLPBL as an acceptable alternative.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11532684/) The disease was first described as a clinicopathological entity, Hodgkin's paragranuloma, by Jackson and Parker in 1944, who noted its indolent course; the WHO renamed the disease NLPHL in 2001.[4](https://haematologica.org/article/view/10248) • [8](https://academic.oup.com/oncolo/article/14/7/739/6397951)
## Pathology and cell of origin
The hallmark histologic feature is scattered malignant LP cells embedded within a nodular infiltrate of small lymphocytes, supported by a background of follicular dendritic cells and abundant reactive small B cells.[8](https://academic.oup.com/oncolo/article/14/7/739/6397951) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) LP cells were initially termed L&H cells, for their morphological resemblance to lymphocytes and histiocytes, and have multilobulated nuclei, indistinct nucleoli, and a germinal center B-cell phenotype and genotype, in contrast to the Reed-Sternberg cells of cHL.[4](https://haematologica.org/article/view/10248) Both LP cells and the Hodgkin/Reed-Sternberg cells of cHL derive from germinal-center B cells, but LP cells retain their B-cell phenotype while cHL cells largely lose it.[10](https://www.annualreviews.org/content/journals/10.1146/annurev.pathol.4.110807.092209)
**Molecular features.** BCL6 rearrangements have been observed in 50% of NLPHL cases, and recurrent mutations have been described in DUSP2, JUNB, SGK1, JAK2, STAT6, and SOCS1, genes shared with T-cell/histiocyte-rich large B-cell lymphoma.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) Common mutations in NLPHL tumor cells involve signaling pathways such as JAK/STAT.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11532684/) One line of research suggests antigenic drive: recombinantly expressed B-cell receptors from microdissected LP cells of IgD-positive cases bind bacterial antigens from [Moraxella](https://www.edgepedia.org/moraxella) species, and [Moraxella catarrhalis](https://www.edgepedia.org/moraxella-catarrhalis) is associated with common childhood infections.[4](https://haematologica.org/article/view/10248)
## Clinical presentation
The condition typically affects the cervical, axillary, and inguinal lymph nodes of young men aged 30 to 50 years; involvement of mediastinal or abdominal lymph nodes is very rare.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) Compared with cHL, NLPHL shows a slightly older median age at presentation (30 to 40 years), a 3:1 male predominance, mediastinal involvement in fewer than 15% of cases, and fewer classical risk factors such as [B symptoms](https://www.edgepedia.org/b-symptoms), which occur in only 5% to 10% of patients.[8](https://academic.oup.com/oncolo/article/14/7/739/6397951) Nodal spread is discontiguous, unlike the contiguous spread of cHL, and B symptoms are uncommon.[8](https://academic.oup.com/oncolo/article/14/7/739/6397951) Most patients present with early-stage disease and generally have an indolent course, though a minority behave more aggressively and transform to large B-cell lymphoma.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/)
## Prognosis and transformation
Survival in NLPHL exceeds that of classic Hodgkin lymphoma even after adjustment for stage and baseline characteristics. In a SEER population-based analysis of 1,162 NLPHL and 29,083 cHL patients diagnosed between 1988 and 2010, 5- and 10-year overall survival was 91% and 83% for NLPHL versus 81% and 74% for cHL, with multivariate hazard ratios of 0.62 for overall survival and 0.48 for disease-specific survival favoring NLPHL.[2](https://www.sciencedirect.com/science/article/pii/S0360301615001790) A Dutch population-based cohort reported a 10-year overall survival of 94.0% and 10-year progression-free survival of 75.8%.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC4742486/)
Transformation is the principal clinical risk. The disease transforms into diffuse large B-cell lymphoma (DLBCL) in approximately 1% of patients per year, which is associated with shorter survival and is the major indication for treatment.[4](https://haematologica.org/article/view/10248) Transformation risk varies with histological pattern: it has been recognized in 8.5% of tumors with pattern E but only 1.7% of other histological patterns, and appears to occur mainly in older patients and IgD-negative tumors.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) Studies suggest that DLBCL transformed from NLPHL tends to have a better prognosis than de novo DLBCL.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) Molecular work on paired samples has found that initial biopsies from cases that later transformed were IgD-negative, lacked the characteristic LP-cell IGHV3/IGHD3/IGHJ6 rearrangement, showed high repertoire clonality, and came from older patients, indicating that high B-cell repertoire clonality with dominant intraclonal diversification at diagnosis predicts subsequent transformation.[4](https://haematologica.org/article/view/10248) Because relapses can be late and transformation requires tissue diagnosis, long-term follow-up with rebiopsy at relapse is emphasized.[6](https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq)
## Treatment
Because of the disease's rarity, the optimal management is not settled, and opinion differs on whether treatment should follow cHL paradigms or those of indolent B-cell lymphomas.[5](https://pubmed.ncbi.nlm.nih.gov/27496311/) For early-stage disease, involved-field radiotherapy at 30 to 36 Gy has been described as standard treatment, with response rates to primary therapy exceeding 90%.[8](https://academic.oup.com/oncolo/article/14/7/739/6397951) [Radiation](https://www.edgepedia.org/radiation) use declined by 40% among NLPHL patients from 1988 to 2010 in the SEER analysis, and active surveillance is an option for some patients given the indolent course.[2](https://www.sciencedirect.com/science/article/pii/S0360301615001790) • [4](https://haematologica.org/article/view/10248) Patient-facing guidance describes options that include surgery followed by radiotherapy, chemotherapy combined with rituximab, or active monitoring when the lymphoma is not causing symptoms that affect daily life.[12](https://lymphoma-action.org.uk/sites/default/files/media/documents/2024-03/LA_Hodgkin%20Lymphoma%20MAR%2024_1.pdf)
**Rituximab.** Because NLPHL expresses CD20, the monoclonal antibody rituximab, which targets CD20, has been incorporated into management; rituximab-containing regimens commonly used in indolent B-cell non-Hodgkin lymphoma have shown activity, with evaluated response rates of 94% to 100%.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/) • [13](https://arua-ncd.org/wp-content/uploads/2022/10/National-treatment-Protocols-2019.pdf) Advanced-stage disease is treated with upfront chemotherapy, with regimens used in cHL, such as ABVD, and rituximab-containing combinations such as R-CHOP applied in practice.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC11532684/) • [14](https://glowconsortium.org/wp-content/uploads/2024/03/2022-Lo-Leukemia-Lymphoma_Practice-patterns-for-the-management-of-NLPHL.pdf) Approaches applied in cHL result in very good outcomes with only limited excess mortality compared with the general population.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/)
## References
1. [Nodular lymphocyte-predominant Hodgkin lymphoma, NCI Dictionary of Cancer Terms](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nodular-lymphocyte-predominant-hodgkin-lymphoma)
2. [Characteristics and Outcomes of Patients With NLPHL Versus Those With Classical Hodgkin Lymphoma: A Population-Based Analysis, Int J Radiat Oncol Biol Phys (2015)](https://www.sciencedirect.com/science/article/pii/S0360301615001790)
3. [Nodular lymphocyte-predominant Hodgkin lymphoma: advances in disease biology, risk stratification, and treatment, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11532684/)
4. [Straus DJ. Progress in understanding the biology of nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica (2021)](https://haematologica.org/article/view/10248)
5. [Savage KJ, Mottok A, Fanale M. Nodular lymphocyte-predominant Hodgkin lymphoma, Semin Hematol (2016)](https://pubmed.ncbi.nlm.nih.gov/27496311/)
6. [Hodgkin Lymphoma Treatment (PDQ®), Health Professional Version, NCI](https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq)
7. [Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Update on Biology and Treatment, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12167645/)
8. [Lee AI, LaCasce AS. Nodular Lymphocyte Predominant Hodgkin Lymphoma, The Oncologist (2009)](https://academic.oup.com/oncolo/article/14/7/739/6397951)
9. [Mature B, T and NK-cell, plasma cell and histiocytic/dendritic cell neoplasms: classification according to WHO and ICC, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11232355/)
10. [Pathogenesis of Classical and Lymphocyte-Predominant Hodgkin Lymphoma, Annual Review of Pathology](https://www.annualreviews.org/content/journals/10.1146/annurev.pathol.4.110807.092209)
11. [A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of NLPHL, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4742486/)
12. [Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), Lymphoma Action](https://lymphoma-action.org.uk/sites/default/files/media/documents/2024-03/LA_Hodgkin%20Lymphoma%20MAR%2024_1.pdf)
13. [Treatment of Nodular Lymphocyte Predominant Hodgkin's Lymphoma, Kenya National Cancer Treatment Protocols](https://arua-ncd.org/wp-content/uploads/2022/10/National-treatment-Protocols-2019.pdf)
14. [Practice patterns for the management of NLPHL, Leukemia & Lymphoma (2022), GLOW Consortium](https://glowconsortium.org/wp-content/uploads/2024/03/2022-Lo-Leukemia-Lymphoma_Practice-patterns-for-the-management-of-NLPHL.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 › Hodgkin lymphoma › Nodular lymphocyte-predominant Hodgkin lymphoma*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; 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