Lymphocyte-Rich Classic Hodgkin Lymphoma

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Primary Author(s)*

Patricia V. Hernandez, M.D., Washington University School of Medicine

Cancer Category/Type

Hodgkin's lymphoma

Cancer Sub-Classification / Subtype


Definition / Description of Disease

Variant of classical Hodgkin's lymphoma rich in lymphocytes, with expanded mantle zones, atrophic germinal centers, small number of Reed-Stenberg cells and classical Hodgkin's lymphoma immonophenotype [1][2].

Synonyms / Terminology


Epidemiology / Prevalence

It was the last subtype of classical Hodgkin lymphoma to be described and presents a low frequency, accounting for 3-5% of classical Hodgkin lymphomas [3]. Because of its rarity, the literature is limited on this type of lymphoma.

Clinical Features

The main clinical features are listed below [2][4][5].

Signs and Symptoms Older in age

Presentation at early stages are common

Infrequent B symptoms (weight loss, fever, night sweats)

Infrequent mediastinal involvement and bulky disease

Usually good prognosis

Laboratory Findings There is no characteristic finding in this condition. It can present with anemia, lymphocytopenia as a common condition of Hodgkin's lymphoma

Sites of Involvement

Nodal disease with involvement of cervical lymph nodes. Mediastinal mass are rarely seen.

Morphologic Features

Lymphocyte-rich subtype presents intermediate characteristics between those of classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma [1][3]. The main feature is the predominance of small-lymphocytes in the background resembling nodular sclerosis classical Hodgkin Lymphoma,[6] but with T-cell populations surrounding the germinal centers [1]. Classic Reed Sternberg cells are found adjacent to germinal centers in approximately 89.5% of cases although they account for only a small fraction of the cells [4]. There are three growth patterns, the most frequent is the nodular pattern, with intact or atrophic germinal centers composed of small lymphoid cells displaying round nuclei [4] . Other growth patterns are interfollicular, composed of neoplastic cells forming small nodules with expansion to interfollicular areas and infiltration to adjacent mantle zones, and more rarely a diffuse growth pattern in which a germinal center is not seen [4].


Immunophenotype of lymphoma-rich classical Hodgkin lymphoma is shown in the table below [1][4].

Finding Marker
Positive (universal) CD30 [1], MUM-1 [1], TRA-1 [1]
Positive (subset) CD15 (56%) [1], EBER (31%) [1], CD20 (31%) [1], CD79a (13%) [4], OCT.1 (50%) [1], OCT.2 (56%) [1], BOB.1 (62%) [1], Pax-5 (94%) [1], KLHL6 (69%) [1], P-50 (73%) [1]
Negative (universal) GCET-1 [1], J-chain [4]
Negative (subset) CD20 (68%) [4], EBER (53%) [4], BCL6 (64%) [1], C-REL (75%) [1], REL-B (88%) [1], IgD (94%) [1], Blimp-1 (25%) [1]

Chromosomal Rearrangements (Gene Fusions)

No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE t(9;22)(q34;q11.2) EXAMPLE 3'ABL1 / 5'BCR EXAMPLE der(22) EXAMPLE 20% (COSMIC)

EXAMPLE 30% (add reference)


The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

Individual Region Genomic Gain/Loss/LOH

There is no typical findings for lymphocyte-rich classical Hodgkin's lymphoma, the main features are also seen in other classical Hodgkin's lymphoma subtypes.

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
2p [6][7] Gain chr2 Unknown Unknown Unknown It can result in REL (2p16), CD40 (20q13) [6]
9p [6][7] Gain chr9 Unknown Unknown Unknown It can result in JAK2, CD274 (PDL1) and PDCD1LG2 (PDL2) mutations. The amplification of 9p24.1 is critical to CD274/PDCD1LG2 gain of function[6]
17q [6][7] Gain chr17 Unknown Unknown Unknown it can result in MAP3K14 (17q21) mutation[6]
19q [6][7] Gain chr19 Unknown Unknown Unknown It can result in RELB (19q13) mutation[6]
20q [6][7] Gain chr20 Unknown Unknown Unknown CD40 is the lesion of 20q13[6]
6q [6][7] Loss chr6 Unknown Unknown Unknown
13q [6][7] Loss chr13 Unknown Unknown Unknown

Characteristic Chromosomal Patterns

No characteristic chromosomal patterns have been reported for lymphocyte-rich classical Hodgkin's lymphoma.

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes

Co-deletion of 1p and 18q


See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV/INDEL)

No characteristic gene mutations have been reported for lymphocyte-rich classical Hodgkin's lymphoma.

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations


EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations


EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (, COSMIC (, ICGC ( and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations


Genes and Main Pathways Involved


Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program
REL (2p16), RELB (19q13), CD40 (20q13) and MAP3K14 (17q21) nuclear factor (NF)-κB signalling
JAK2 amplification PD-L1 protein expression/ JAK/STAT pathway

Genetic Diagnostic Testing Methods


Familial Forms


Additional Information



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  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 Nam-Cha, Syong H.; et al. (2009-08). "Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 22 (8): 1006–1015. doi:10.1038/modpathol.2009.54. ISSN 1530-0285. PMID 19465900. Check date values in: |date= (help)
  2. 2.0 2.1 Diehl, V.; et al. (1999-03). "Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 17 (3): 776–783. doi:10.1200/JCO.1999.17.3.776. ISSN 0732-183X. PMID 10071266. Check date values in: |date= (help)
  3. 3.0 3.1 Jiang, Manli; et al. (2017-03). "Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms". Expert Review of Hematology. 10 (3): 239–249. doi:10.1080/17474086.2017.1281122. ISSN 1747-4094. PMC 5514564. PMID 28133975. Check date values in: |date= (help)
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Anagnostopoulos, I.; et al. (2000-09-01). "European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes". Blood. 96 (5): 1889–1899. ISSN 0006-4971. PMID 10961891.
  5. Shimabukuro-Vornhagen, Alexander; et al. (2005-08-20). "Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 23 (24): 5739–5745. doi:10.1200/JCO.2005.17.970. ISSN 0732-183X. PMID 16009944.
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 Wang, Hao-Wei; et al. (2019-01). "Diagnosis of Hodgkin lymphoma in the modern era". British Journal of Haematology. 184 (1): 45–59. doi:10.1111/bjh.15614. ISSN 1365-2141. PMC 6310079. PMID 30407610. Check date values in: |date= (help)
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Steidl, Christian; et al. (2010-07-22). "Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome". Blood. 116 (3): 418–427. doi:10.1182/blood-2009-12-257345. ISSN 1528-0020. PMID 20339089.

(use "Cite" icon at top of page)


  1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.


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