EBV-positive nodal T- and NK-cell lymphoma
Haematolymphoid Tumours (WHO Classification, 5th ed.)
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Primary Author(s)*
FNU Monika, MBBS; Andrew Siref, MD
Creighton University, Omaha, NE
WHO Classification of Disease
(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)
| Structure | Disease |
|---|---|
| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
Definition / Description of Disease
- EBV-positive nodal T- and NK-cell lymphoma is a rare EBV-positive lymphoma of cytotoxic T- or NK-cell lineage, primarily involving lymph nodes in adults.[1]
- Is a distinct entity in the Fifth WHO classification and as a provisional entity in the international consensus classification 2022.[2][3]
Synonyms / Terminology
nodal EBV+ cytotoxic T-cell lymphoma; nodal peripheral T-cell lymphoma, EBV-positive; primary nodal EBV-positive T/NK-cell lymphoma.[1]
Epidemiology / Prevalence
- Rare lymphoma
- Occurs mostly in eastern Asia
- Affects mainly older adults (median age: 61–64 years) although cases in younger adults have been reported
- The M:F ratio is 1.5–3.8:1 [1][4]
Clinical Features
| Signs and Symptoms[1][5][6][7] | Lymphadenopathy
Advanced clinical stage III/IV disease at diagnosis (86–88% of cases) B symptoms (72–80%) High or high/intermediate International Prognostic Index (IPI) score (64–87%) |
| Laboratory Findings | Anemia
Leukopenia Thrombocytopenia Elevated serum lactate dehydrogenase |
Sites of Involvement
- Primarily lymph nodes (most commonly cervical, inguinal, and axillary), although limited extranodal involvement can be seen[1]
- The liver and/or bone marrow (24–60% of cases); other extranodal sites, such as the skin and gastrointestinal tract, are less commonly involved[5][6][8]
- No nasal involvement has been reported[1]
Morphologic Features
- Architectural effacement of lymph node by a diffuse infiltrate of monotonous medium-sized to large lymphoid cells
- The neoplastic cells have centroblastic appearance with vesicular chromatin
- Less frequently, the neoplastic cells display large pleomorphic or mixed-cell morphology with abundant histiocytes and small lymphocytes in the background[1][9]
- Lacks classic morphological findings of angioinvasion and necrosis seen in extranodal positive T- and NK-cell lymphomas[5]
Immunophenotype
Based on T-cell receptor protein expression and/or clonal TR gene rearrangement, EBV-positive nodal T- and NK-cell lymphoma immunophenotype is more of a T-cell lineage rather than NK-cell (> 80% of cases)
| Finding | Marker |
|---|---|
| Positive (universal) | CD3, CD2, CD8 (63–72%) and CD56 (7–22%) cytotoxic molecules (TIA1, granzyme B, and perforin), EBER (ISH) |
| Positive (subset) | TCRβ (43–64%), TCRγ (0–13%), CD30[2] |
| Negative (universal) | CD4, CD5 |
| Negative (subset) | TCRβ and TCRγ (25%), CD4-/CD8- (21%), CD4+/CD8- (8%), CD4-/CD8+ (64%)[6] |
Chromosomal Rearrangements (Gene Fusions)
No chromosomal rearrangements are identified.
The combination of the 2 pieces of chromosome 9 formed the fusion of the promoter plus exon 1 of DOCK8 and exons 2-7 of PD-L1 (DOCK8/PD-L1 fusion). https://doi.org/10.1182/bloodadvances.2023012019
| 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 |
|---|---|---|---|---|---|---|---|
| NA | NA | NA | NA | NA | NA | NA | NA |
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)
| 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 |
|---|---|---|---|---|---|---|---|
| 3 | Loss | 3q26.1 | 3q26.1 | No | Yes | No | EXAMPLE:
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| 22q11.23 | Loss | 22q11.23 | 22q11.23 | No | No | No | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add reference). |
Characteristic Chromosomal Patterns
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| 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 |
EXAMPLE: Yes | EXAMPLE: No | EXAMPLE: 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)
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| 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: Yes | EXAMPLE: No | EXAMPLE: No | 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
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Genes and Main Pathways Involved
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| 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 |
Genetic Diagnostic Testing Methods
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Familial Forms
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Additional Information
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Links
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References
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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.
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Siok-Bian Ng, et al. EBV-positive nodal T- and NK-cell lymphoma. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2024 [cited 2024 Oct 6]. (WHO classification of tumors series, 5th ed.; vol. 11). Available from: BlueBooksOnline (who.int)
- ↑ 2.0 2.1 Yu, Fang; et al. (2024-04). "EBV-positive Nodal T-Cell and NK-Cell Lymphoma: A Study of 26 Cases Including a Subset With Strong CD30 Expression Mimicking Anaplastic Large Cell Lymphoma". American Journal of Surgical Pathology. 48 (4): 406–416. doi:10.1097/PAS.0000000000002184. ISSN 0147-5185. Check date values in:
|date=(help) - ↑ Kato, Seiichi; et al. (2024-05-14). "EBV+ nodal T/NK-cell lymphoma associated with clonal hematopoiesis and structural variations of the viral genome". Blood Advances. 8 (9): 2138–2147. doi:10.1182/bloodadvances.2023012019. ISSN 2473-9529. PMC PMC11068532 Check
|pmc=value (help). PMID 38429084 Check|pmid=value (help).CS1 maint: PMC format (link) - ↑ Ha, Sang Yun; et al. (2013-07-01). "Epstein–Barr virus-positive nodal peripheral T cell lymphomas: Clinicopathologic and gene expression profiling study". Pathology - Research and Practice. 209 (7): 448–454. doi:10.1016/j.prp.2013.04.013. ISSN 0344-0338.
- ↑ 5.0 5.1 5.2 Jeon, Yoon Kyung; et al. (2015-07). "Epstein-Barr virus–positive nodal T/NK-cell lymphoma: an analysis of 15 cases with distinct clinicopathological features". Human Pathology. 46 (7): 981–990. doi:10.1016/j.humpath.2015.03.002. Check date values in:
|date=(help) - ↑ 6.0 6.1 6.2 Kato, Seiichi; et al. (2015-04). "T-cell Receptor (TCR) Phenotype of Nodal Epstein-Barr Virus (EBV)-positive Cytotoxic T-cell Lymphoma (CTL): A Clinicopathologic Study of 39 Cases". American Journal of Surgical Pathology. 39 (4): 462–471. doi:10.1097/PAS.0000000000000323. ISSN 0147-5185. Check date values in:
|date=(help) - ↑ Yu, Fang; et al. (2024-04). "EBV-positive Nodal T-Cell and NK-Cell Lymphoma: A Study of 26 Cases Including a Subset With Strong CD30 Expression Mimicking Anaplastic Large Cell Lymphoma". American Journal of Surgical Pathology. 48 (4): 406–416. doi:10.1097/PAS.0000000000002184. ISSN 0147-5185. Check date values in:
|date=(help) - ↑ Yamashita, Daisuke; et al. (2018-08). "Reappraisal of nodal Epstein‐Barr Virus‐negative cytotoxic T‐cell lymphoma: Identification of indolent CD 5 + diseases". Cancer Science. 109 (8): 2599–2610. doi:10.1111/cas.13652. ISSN 1347-9032. PMC 6113510. PMID 29845715. Check date values in:
|date=(help)CS1 maint: PMC format (link) - ↑ Attygalle, Ayoma D; et al. (2014-01). "Peripheral T‐cell and NK ‐cell lymphomas and their mimics; taking a step forward – report on the lymphoma workshop of the XVI th meeting of the European Association for Haematopathology and the Society for Hematopathology". Histopathology. 64 (2): 171–199. doi:10.1111/his.12251. ISSN 0309-0167. PMC 6364972. PMID 24128129. Check date values in:
|date=(help)CS1 maint: PMC format (link)