# Lymphocyte-depleted Hodgkin lymphoma
Lymphocyte-depleted Hodgkin lymphoma (LDHL) is the rarest subtype of classical [Hodgkin lymphoma](https://www.edgepedia.org/hodgkin-lymphoma), defined microscopically by abundant Reed–Sternberg cells against a background of depleted lymphocytes and often extensive fibrosis. It accounts for under 1% to about 1.5% of classical Hodgkin lymphoma cases in Western countries, depending on the series.[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) • [2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) The subtype is overrepresented in people with HIV and in older adults, and it tends to present at an advanced stage with [B symptoms](https://www.edgepedia.org/b-symptoms).[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/)
| Fact | Value |
|---|---|
| Share of classical Hodgkin lymphoma | <1% of 10,019 centrally reviewed trial patients (84 cases); 1–1.5% in Western countries[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) • [2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) |
| Median age at diagnosis | 55 years vs 38 years for other subtypes (SEER, 2000–2022)[4](https://www.nature.com/articles/s41598-026-54391-6) |
| EBV association | LMP1-positive in up to 60–72% of cases; near-universal in HIV-associated disease[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/) |
| HIV association | About 15% of patients have HIV infection[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) |
| Advanced stage at diagnosis | 64% stage III–IV; 35% stage IV in SEER[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) • [4](https://www.nature.com/articles/s41598-026-54391-6) |
| 5-year overall survival | 51.2% (SEER population cohort); 83% (German trial cohort)[4](https://www.nature.com/articles/s41598-026-54391-6) • [1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) |
| Strongest prognostic variables | Age (importance 0.31) and chemotherapy receipt (0.10)[4](https://www.nature.com/articles/s41598-026-54391-6) |
## Pathology and differential diagnosis
LDHL is defined by a predominance of Reed–Sternberg cells (the large, often multinucleated malignant B-derived cells of Hodgkin lymphoma) and scarce background lymphocytes. Two morphological patterns are recognized. The diffuse fibrosis pattern shows a hypocellular background with abundant disordered, nonbirefringent fibroblastic stroma, numerous histiocytes, scattered Reed–Sternberg cells, scant lymphocytes, and a lack of plasma cells or eosinophils. The reticular pattern contains sheets of Reed–Sternberg cells with anaplastic, pleomorphic, or sarcomatous features; capsular and perinodal infiltration is common in this pattern, and cells may show multilobated nuclei with eosinophilic inclusion-like nucleoli, coagulative necrosis, and sinusoidal invasion.[5](https://www.pathologyoutlines.com/topic/lymphomanonBlymphocytedepleted.html) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/)
The immunophenotype is that of classical Hodgkin lymphoma: CD30 positive in almost all cases, CD15 in a subset, weak PAX5, and EBER positivity; CD20 is positive in about 20% of cases, and the cells are negative for CD45, OCT2, BOB1, CD3, CD79a, and ALK1.[5](https://www.pathologyoutlines.com/topic/lymphomanonBlymphocytedepleted.html) • [2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) [Diagnosis](https://www.edgepedia.org/diagnosis) requires an excisional lymph node biopsy; fine-needle aspiration is inadequate to establish it.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/)
The reticular pattern, with its sheets of pleomorphic large cells, invites several misdiagnoses. Anaplastic large cell lymphoma expresses T-cell markers such as CD43, CD4, and cytotoxic markers and is negative for CD15 and PAX5, the opposite of the Hodgkin phenotype. [Diffuse large B-cell lymphoma](https://www.edgepedia.org/diffuse-large-b-cell-lymphoma) is a further pitfall, as is [T-cell/histiocyte-rich large B-cell lymphoma](https://www.edgepedia.org/t-cell-histiocyte-rich-large-b-cell-lymphoma), which shows scattered large CD20-positive B cells typically negative for CD15 and CD30. Gray-zone lymphoma is distinguished by a disconnect between Reed–Sternberg morphology and strong, homogeneous expression of multiple B-cell markers; uniform CD20 expression in an otherwise typical nodular sclerosis tumor alone should not prompt a gray-zone diagnosis.[5](https://www.pathologyoutlines.com/topic/lymphomanonBlymphocytedepleted.html) • [6](https://www.pathologyoutlines.com/topic/lymphomanonbclassic.html) The subtype can be misdiagnosed as aggressive B-cell or T-cell lymphomas.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/)
## HIV, older age, and who gets it
The epidemiology differs sharply from other classical subtypes. In SEER data covering 2000 to 2022, patients with LDHL had a median age of 55 years (interquartile range 37–72) compared with 38 years (25–58) for other subtypes, and 61% were male versus 54%.[4](https://www.nature.com/articles/s41598-026-54391-6) About 40% of cases are diagnosed in patients aged 60 or older and 28% in those aged 18 to 39.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) [Sex ratio](https://www.edgepedia.org/sex-ratio) estimates differ between sources: StatPearls reports a 2:1 male predominance,[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) while a review of classical Hodgkin lymphoma biology reports 4:1.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/)
HIV infection is a defining association. Approximately 15% of patients with LDHL have HIV infection.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) HIV-infected individuals, especially those with AIDS, have up to a 10-fold increased incidence of classical Hodgkin lymphoma, and the subtype is usually mixed cellularity or lymphocyte-depleted, advanced in stage, and has a near-universal association with EBV.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/) The proposed mechanism is chronic B-cell activation through interaction with CD40-ligand-bearing virions and HIV proteins, combined with impaired immune eradication of EBV-infected B cells.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) HIV-associated LDHL frequently presents with extranodal and bone marrow involvement, marked B symptoms, and stage III–IV disease.[7](https://cancerfax.com/conditions/classical-hodgkin-lymphoma-lymphocyte-depleted)
## Clinical presentation and prognosis
Most patients present with B symptoms, defined as unexplained fever above 38 °C, drenching night sweats, or unexplained loss of more than 10% of body weight over six months, with a predilection for retroperitoneal nodes and bone marrow.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/) In the German Hodgkin Study Group (GHSG) trials HD4 to HD15, LDHL patients presented more often with advanced disease (74% vs 42%) and B symptoms (76% vs 41%) than other subtypes.[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) Population data are less extreme but in the same direction: 35% had stage IV disease versus 15% of other subtypes, and B symptoms occurred in 67.8% versus 54.5%.[4](https://www.nature.com/articles/s41598-026-54391-6)
Survival figures depend heavily on the cohort. In the SEER population-based analysis of 451 LDHL patients against 42,130 patients with other subtypes, 5-year overall survival was 51.2% (95% CI 46.7–56.2) versus 81.1% (95% CI 80.7–81.5).[4](https://www.nature.com/articles/s41598-026-54391-6) In the GHSG trial cohort, by contrast, 5-year overall survival was 83% versus 92% and progression-free survival 71% versus 85%.[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) Within LDHL, survival falls steeply with age: 5-year overall survival was 78.5% under age 40, 43.3% at ages 40 to 60, and 15.6% over age 60; lymphoma-specific survival was correspondingly 88.9%, 84.3%, and 60.5%.[4](https://www.nature.com/articles/s41598-026-54391-6)
Whether the subtype itself, rather than its risk profile, drives these outcomes is contested. In the GHSG data, LDHL patients treated with intensified or dose-dense BEACOPP chemotherapy had outcomes similar to other subtypes (n = 39 vs 3,564; P = .61), suggesting the subtype stops predicting outcome once risk-appropriate treatment is given.[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) The SEER analysis reached a different conclusion: even among chemotherapy-treated patients, LDHL remained associated with inferior survival, with [random survival forest](https://www.edgepedia.org/random-survival-forest) analysis ranking age (variable importance 0.31) and chemotherapy receipt (0.10) as the strongest prognostic variables.[4](https://www.nature.com/articles/s41598-026-54391-6) Part of the registry gap may reflect under-treatment: only 71% of LDHL patients received chemotherapy versus 83% of other subtypes.[4](https://www.nature.com/articles/s41598-026-54391-6)
## By the numbers
Several figures carry cohort caveats worth keeping in mind.
- **Rarity.** 84 of 10,019 centrally reviewed GHSG patients (<1%); 1–1.5% of classical Hodgkin lymphoma in Western countries per StatPearls.[1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703) • [2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/)
- **Cohort sizes.** 451 SEER patients versus 42,130 with other subtypes.[4](https://www.nature.com/articles/s41598-026-54391-6)
- **Survival contrast.** 5-year overall survival of 51.2% in SEER all-comers versus 83% in the GHSG trial cohort, which enrolled centrally reviewed patients treated on standardized protocols.[4](https://www.nature.com/articles/s41598-026-54391-6) • [1](https://ascopubs.org/doi/10.1200/JCO.2011.36.4703)
- **Age gradient.** 78.5%, 43.3%, and 15.6% 5-year survival for ages under 40, 40–60, and over 60.[4](https://www.nature.com/articles/s41598-026-54391-6)
- **EBV.** 60–72% of cases are LMP1-positive.[2](https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/)
## References
1. Lymphocyte-Depleted Classical Hodgkin's Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group. Journal of Clinical Oncology. https://ascopubs.org/doi/10.1200/JCO.2011.36.4703
2. Lymphocyte Depleted Hodgkin Lymphoma. StatPearls, NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/sites/books/NBK556042/
3. Hodgkin Lymphoma: An Update on Its Biology with Newer Insights into Classification. https://pmc.ncbi.nlm.nih.gov/articles/PMC2806063/
4. Clinical features, outcomes, and prognostic factors of lymphocyte-depleted classical Hodgkin lymphoma: a population-based SEER analysis. Scientific Reports. https://www.nature.com/articles/s41598-026-54391-6
5. CHL lymphocyte depleted. Pathology Outlines. https://www.pathologyoutlines.com/topic/lymphomanonBlymphocytedepleted.html
6. Classic Hodgkin lymphoma. Pathology Outlines. https://www.pathologyoutlines.com/topic/lymphomanonbclassic.html
7. Lymphocyte-Depleted Classical Hodgkin Lymphoma (LD-cHL). CancerFax. https://cancerfax.com/conditions/classical-hodgkin-lymphoma-lymphocyte-depleted
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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 › Classical Hodgkin lymphoma, lymphocyte-depleted type*
*Initially written Sep 17, 2026 · Edited: Oct 11, 2026; Oct 15, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license