Classic Hodgkin lymphoma
Haematolymphoid Tumours (WHO Classification, 5th ed.)
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editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Lymphocyte-Rich Classic Hodgkin Lymphoma.Other relevent pages include: HAEM4:Nodular Sclerosis Classic Hodgkin Lymphoma
Note: author needs to merge Nodular Sclerosis Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma, Mixed Cellularity Classic Hodgkin Lymphoma, Lymphocyte-Depleted Classic Hodgkin Lymphoma
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Primary Author(s)*
Patricia V. Hernandez, M.D., Washington University School of Medicine
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | B-cell lymphoid proliferations and lymphomas |
| Family | Hodgkin lymphoma |
| Type | N/A |
| Subtype(s) | Classic Hodgkin lymphoma |
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
N/A
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
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) |
Yes | No | Yes | EXAMPLE:
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 |
|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
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
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
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 (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
N/A
Genes and Main Pathways Involved
N/A
| 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
N/A
Familial Forms
N/A
Additional Information
N/A
Links
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References
- ↑ 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) - ↑ 2.0 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) - ↑ 3.0 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) - ↑ 4.0 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.
- ↑ 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.
- ↑ 6.00 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) - ↑ 7.0 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.
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Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
*Citation of this Page: “Classic Hodgkin lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Classic_Hodgkin_lymphoma.