Difference between revisions of "HAEM5:High grade B-cell lymphoma with 11q aberrations"

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{{DISPLAYTITLE:High grade B-cell lymphoma with 11q aberrations}}
 
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<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
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<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
  
 
==Primary Author(s)*==
 
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==Definition / Description of Disease==
 
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==Synonyms / Terminology==
 
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==Immunophenotype==
 
==Immunophenotype==
  
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Revision as of 19:19, 3 September 2024

Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Burkitt-Like Lymphoma with 11q Aberration.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Lauren Shealy, MD, Medical University of South Carolina

Daynna Wolff, PhD, Medical University of South Carolina

Cancer Category / Type

Mature B-cell lymphoma

Cancer Sub-Classification / Subtype

Put your text here

Definition / Description of Disease

Put your text here (Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories referring to the specific WHO book pages, diagnostic criteria if applicable, and differential diagnosis if applicable)

Synonyms / Terminology

Put your text here (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)

Epidemiology / Prevalence

  • Males>females, with estimated ratio of 2.75:1 in one cohort[1]
  • Seems to have no racial predilection
  • Increased incidence in post-transplant/immunodeficient individuals[2], but never EBV-associated[1] [3]
  • Immunodeficiency can be congenital, HIV-associated, or iatrogenic in setting of transplant[3] [4]
  • Age range: 4[1]-82[5]
    • median age: 13.9 in a study limited to pediatric patient cohort [6], 49.5[7]
    • mean age: 15[8],15.5[1]

Clinical Features

Signs and Symptoms Small, localized lymphadenopathy (most common) [8]bulky tumors (>7-20 cm) possible, mostly abdominal [9]

1/3 of pediatric patients B-symptoms (weight loss, fever, night sweats) [6]

Laboratory Findings LDH elevation possible, generally below 500 [9] [6]

Sites of Involvement

  • Nodal involvement [8]
    • cervical and abdominal lymphadenopathy predominant, with axillary, inguinal, tonsillar, and submandibular less commonly reported [3] [1] [2] [8] [9]
    • less common sites such as testes, parotid reported in association with immunodeficient patients [3]
  • Rare bone marrow involvement[10]
  • CNS involvement is rare [3] [1] [2] [8] [9]

Morphologic Features

  • Medium to large sheets of B-cells frequently with starry-sky background
  • Diverse, having been morphologically classified as the following: [6] [8]
    • BLL, including atypical
    • HGBCL, NOS
    • DLBCL
  • Course and increased number of apoptotic bodies (5-9) per macrophage[7]
  • Cytologic features often more blastoid [8]

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table)

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4


editv4:Immunophenotype
The content below was from the previous version of the page. Please incorporate above.
Flow Findings Marker
Positive (universal) CD10, CD20, CD19, CD22, BCL6 [9]
Positive (subset) CD16/CD56 (present in 60%), CD8 (present in 40%) [9]
Negative (universal) CD5, CD11C, CD23, CD200, BCL2 [9]
Negative (subset) CD38 bright (absent 90%) [9]

Statistically significant differences in flow cytometry of BLL11q as compared to myc-positive Burkitt Lymphoma:[9]

  • less frequent CD45 depression [9]
  • less frequent CD38 bright expression (10% as opposed to 91% in myc-postive BL) [9]
  • CD16/CD56 (NK differentiation) positivity (60% of time as opposed to 0% in myc-positive BL) [9]
  • CD 8 expression (40% as opposed to 4% in myc-positive BL) [9]

Immunohistochemistry:

  • Ki67 usually >90% [6] [9][8] [1] [7]
  • LMO2 expression (46% to 70% as compared to 0% in myc-positive BL)[8][9]
  • MYC may be positive if using a 40% MYC[8]

Chromosomal Rearrangements (Gene Fusions)

BLL-11q has no known gene fusions at this time.

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


Individual Region Genomic Gain / Loss / LOH

The table below represents the smallest reported minimal lost region and smallest reported minimal gain region. Other larger MGR and MLR have been reported.[10] [11]

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
11 Loss[12] chr11: 128,177,670-134,931,948[12] 11q24.4q25[12] Yes unknown unknown
11 Gain[12] chr11: 117,815,640-119,275,901 [12] 11q23.3[12] Yes unknown unknown
11 minimal duplication

region, 11.95 Mbp[12]

ch11: 109,285,414-121,236,822 [12] 11q22.3q24.1[12] Yes unknown unknown Minimal duplication region contained PAFAH1B2, USP2, and CBL oncogenes.[12]

Characteristic Chromosomal Patterns

  • Research up until this point has revealed no conservative breakpoints. [12]
Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
proximal 11q duplications range in size
  • often >50 Mbp or <20 Mbp and most often involving the 11q22.2.-23.2 [12]
  • can be as proximal as 11q13.3 [12]
  • often with inversion [12]
 yes unknown unknown The characteristic gains combined with the terminal deletions can occur in the context of myc-positive BL and other myc-negative HGBCLs. The absence of a MYC translocation/amplification in association with this chromosomal pattern is critical to the provisional diagnosis of BLL-11q and may have prognostic and therapeutic implications, which are further discussed below. At least one case has been identified with only proximal gains in the context of UPD.[12]
terminal 11q deletions range in size
  • most often 11q24.1-24.3 [12]
  • noted to be as proximal as 11q23.3q25[12]
 yes unknown unknown
5q21.3q32 gain and 6q12.1-q21 loss [13][8] unknown unknown unknown Noted to be recurrently concomitantly present with the characteristic proximal duplications and deletions that define BLL, 11q.[13]

Notably, no 1q21 abnormalities were found in myc-negative, 11q positive cases. [7][8]

Gene Mutations (SNV / INDEL)

  • Studies suggest an overall unique mutational profile, with little to no overlap with commonly mutated genes in DLCBL and BL, respectively. Notably, recurrent mutations in BL such as ID3, TCF3, and CCND3 were not present. [8] [14]
  • Mutations listed below where noted to be recurrent in BLL-11q cases. Bold genes have also been found recurrently mutated in DLCBL.
    • DDX3X[8][14]
    • ETS1 coding mutations located a DNA-binding domain, combined with lower RNA expression in BLL-11q cases [8]
    • 7/15 cases showed mutations in GNA13[14]
    • FOXO1[14]
    • 3/15 cases showed a Y641 mutational hotspot mutation of EZH2 [14]
    • TTN[14]

Recurrently mutated genes in BLL-11q with known mechanisms that may contribute to pathogenesis.

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
BTG2; variable potential LOF mutations


three missense mutations, 1 splice site deletion mutation [8]


tumor suppressor gene via inhibition of CCND1 via pRb[8] 4/11 cases[8]


none known none known unknown unknown unknown
NFRKB **located in region of terminal deletion


3/4 were stop-gain mutations[14]

gene associated with INO80 complex[14] 4/15 cases[14] none known none known unknown unknown unknown NFRKB is within the terminal deletion region, so these mutations would result in a biallelic loss. [14]


See main pathway involvement below.

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

  • KMT2A has been found to be duplicated and occasionally amplified in numerous cases of BLL-11q[12]
    • functions to methylate histones[15]
  • Found to have mutations in EP300, HIST1H1D, HIST1H2BC, CREBBP, KMT2C, EZH2, ARID1A, KMT2D[8]

Genes and Main Pathways Involved

  • Given the notable variations in size of the duplicated and deleted regions of BLL-11q, pathogenesis appears to be complex and remains to be elucidated. Still, it is presumed to be a a product of dosage effects produced by the more varied proximal duplications and more consistent terminal deletions.[12]
  • Genes found recurrently in minimal duplication region: IL10RA; TMPRSS4; SCN4B; AMICA1; MPZL3; CD3E; CD3D; UBE4A; ATP5L; KMT2A; TTC36, TMEM25, IFT46; ARCN1 [10] [12]
  • Genes found recurrently in terminal deleted region: ETS1; FLT1; KCNJ5; C11orf45; TP53AIP1 [10] [12]
    • ETS1 and FLT1 are candidate tumor supressor genes thought to be involved in the pathogenesis of DLBCL [10] [16]


GENES with PROPOSED/KNOWN CANCER ASSOCIATIONS

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
IL10RA; Duplication insulin receptor substrate-2/PI 3-kinase/AKT pathway[17] increase survival of progenitor myeloid cells[17]
KMT2A; Duplication methylation of histones (turns off genes)[15] amplification noted to be associated with bulky BLL-11q tumors >20 cm, mainly located in the retroperitoneum[12]
USP2; duplication (found 1x) [12] deubiquitinase known to target proteins such as MDM2 (udiquinates p53), MDM4, and CCND1[18] increased degradation of p53 (less tumor suppressor) and more CCND1-->increased movement from G1 to synthesis[18]
NFRKB; deleted[14] encodes a nuclear factor involved with the INO80 complex[14] altered transcriptional regulation [14]

Genetic Diagnostic Testing Methods

  • Conventional cytogenetics (karyotyping) + FISH using MYC break-apart probe to rule out MYC translocation [13] [3]
  • Chromosomal microarray analysis [8] [3]

Familial Forms

  • None known

Additional Information

Put your text here

Links

HAEM5:Burkitt lymphoma

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Wagener, Rabea; et al. (2019-02-28). "The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma". Blood. 133 (9): 962–966. doi:10.1182/blood-2018-07-864025. ISSN 0006-4971. PMC 6396176. PMID 30567752.CS1 maint: PMC format (link)
  2. ↑ 2.0 2.1 2.2 Wang, Jing; et al. (2021-03-16). "Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review". Open Medicine. 16 (1): 428–434. doi:10.1515/med-2021-0246. ISSN 2391-5463. PMC PMC7967281 Check |pmc= value (help). PMID 33763601 Check |pmid= value (help).CS1 maint: PMC format (link)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Kim, Jee Ah; et al. (2021-11-01). "A Case of Burkitt-Like Lymphoma With 11q Aberration With HIV Infection in East Asia and Literature Review". Annals of Laboratory Medicine. 41 (6): 593–597. doi:10.3343/alm.2021.41.6.593. PMC PMC8203433 Check |pmc= value (help). PMID 34108287 Check |pmid= value (help).CS1 maint: PMC format (link)
  4. ↑ Wang, Jing; et al. (2021-01-01). "Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review". Open Medicine. 16 (1): 428–434. doi:10.1515/med-2021-0246. ISSN 2391-5463. PMC PMC7967281 Check |pmc= value (help). PMID 33763601 Check |pmid= value (help).CS1 maint: PMC format (link)
  5. ↑ Moshref Razavi, Habib; et al. (2019-01-24). "Unusual presentation of Burkitt-like lymphoma with 11q aberration in an elderly patient". Blood. 133 (4): 381–381. doi:10.1182/blood-2018-08-864728. ISSN 0006-4971.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Au‐Yeung, Rex K. H.; et al. (2020-09). "Experience with provisional WHO‐entities large B‐cell lymphoma with IRF4 ‐rearrangement and Burkitt‐like lymphoma with 11q aberration in paediatric patients of the NHL‐BFM group". British Journal of Haematology. 190 (5): 753–763. doi:10.1111/bjh.16578. ISSN 0007-1048. Check date values in: |date= (help)
  7. ↑ 7.0 7.1 7.2 7.3 7.4 Horn, Heike; et al. (2021-03). "A Diagnostic Approach to the Identification of Burkitt-like Lymphoma With 11q Aberration in Aggressive B-Cell Lymphomas". American Journal of Surgical Pathology. 45 (3): 356–364. doi:10.1097/PAS.0000000000001613. ISSN 0147-5185. Check date values in: |date= (help)
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 Gonzalez-Farre, Blanca; et al. (2019-09). "Burkitt-like lymphoma with 11q aberration: a germinal center-derived lymphoma genetically unrelated to Burkitt lymphoma". Haematologica. 104 (9): 1822–1829. doi:10.3324/haematol.2018.207928. ISSN 0390-6078. PMC 6717587. PMID 30733272. Check date values in: |date= (help)CS1 maint: PMC format (link)
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 Rymkiewicz, Grzegorz; et al. (2018-05). "A comprehensive flow-cytometry-based immunophenotypic characterization of Burkitt-like lymphoma with 11q aberration". Modern Pathology. 31 (5): 732–743. doi:10.1038/modpathol.2017.186. ISSN 0893-3952. Check date values in: |date= (help)
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Salaverria, Itziar; et al. (2014-02-20). "A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma". Blood. 123 (8): 1187–1198. doi:10.1182/blood-2013-06-507996. ISSN 0006-4971. PMC 3931189. PMID 24398325.CS1 maint: PMC format (link)
  11. ↑ Ferreiro, J. F.; et al. (2015-07-01). "Post-transplant molecularly defined Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern". Haematologica. 100 (7): e275–e279. doi:10.3324/haematol.2015.124305. ISSN 0390-6078. PMC 4486241. PMID 25795716.CS1 maint: PMC format (link)
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 12.11 12.12 12.13 12.14 12.15 12.16 12.17 12.18 12.19 12.20 12.21 12.22 Grygalewicz, Beata; et al. (2018-01-01). "The 11q-Gain/Loss Aberration Occurs Recurrently in MYC-Negative Burkitt-like Lymphoma With 11q Aberration, as Well as MYC-Positive Burkitt Lymphoma and MYC-Positive High-Grade B-Cell Lymphoma, NOS". American Journal of Clinical Pathology. 149 (1): 17–28. doi:10.1093/ajcp/aqx139. ISSN 0002-9173. PMC 5848380. PMID 29272887.CS1 maint: PMC format (link)
  13. ↑ 13.0 13.1 13.2 Asadbeigi, Sepideh N.; et al. (2020-09-08). "Burkitt-Like Lymphoma with 11q Aberration: A Case Report and Review of a Rare Entity". Case Reports in Hematology. 2020: e8896322. doi:10.1155/2020/8896322. ISSN 2090-6560. PMC PMC7495152 Check |pmc= value (help). PMID 32963851 Check |pmid= value (help).CS1 maint: PMC format (link)
  14. ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 Wagener, Rabea; et al. (2019-02-28). "The mutational landscape of Burkitt-like lymphoma with 11q aberration is distinct from that of Burkitt lymphoma". Blood. 133 (9): 962–966. doi:10.1182/blood-2018-07-864025. ISSN 0006-4971. PMC 6396176. PMID 30567752.CS1 maint: PMC format (link)
  15. ↑ 15.0 15.1 https://www.genecards.org/cgi-bin/carddisp.pl?gene=KMT2A. Missing or empty |title= (help)
  16. ↑ Bonetti, Paola; et al. (2013-09-26). "Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma". Blood. 122 (13): 2233–2241. doi:10.1182/blood-2013-01-475772. ISSN 0006-4971.
  17. ↑ 17.0 17.1 https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL10RA. Missing or empty |title= (help)
  18. ↑ 18.0 18.1 https://www.genecards.org/cgi-bin/carddisp.pl?gene=USP2. Missing or empty |title= (help)



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: “High grade B-cell lymphoma with 11q aberrations”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/3/2024, https://ccga.io/index.php/HAEM5:High_grade_B-cell_lymphoma_with_11q_aberrations.

Other Sections

Cancer Sub-Classification/Subtype


Burkitt-like lymphoma with 11q aberration


Definition/Description of Disease


Rare aggressive mature B-cell lymphoma


Synonyms/Terminology


myc-negative Burkitt-like lymphoma (mnBLL, 11q)[1]

non-myc Burkitt-like lymphoma (nmBLL)

BLL, 11q [2]

BLL-11q[3]HAEM5:Burkitt lymphoma


Clinical Implications


  • Look for 11q aberration if Myc negative lymphoma with morphology reminiscent of BL, DLBCL, or HGBCL [3]
  • Attend to associated chromosomal and mutational abnormalities of other aggressive B-cell lymphomas, ensuring their absence before diagnosis of BLL-11q, since BLL-11q may represent [2] [4] [5]
  • BLL-11q patients treated with R-CHOP (DLBCL treatment) have a higher risk of relapse than those treated with traditional BL treatment [6] [7]

Tentatively appears to portend a better prognosis with high likelihood of years of remission [3] [8] [6][2]

  • 100% 2 year event free survival in pediatric cohort[9]
  1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :1
  2. ↑ 2.0 2.1 2.2 Cite error: Invalid <ref> tag; no text was provided for refs named :3
  3. ↑ 3.0 3.1 3.2 Cite error: Invalid <ref> tag; no text was provided for refs named :6
  4. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :8
  5. ↑ Grygalewicz, Beata; et al. (2020-07-01). "Genetic progression of post-transplant Burkitt-like lymphoma case with 11q-Gain/Loss and MYC amplification". Cancer Genetics. 245: 1–5. doi:10.1016/j.cancergen.2020.05.001. ISSN 2210-7762. PMID 32531723 Check |pmid= value (help).
  6. ↑ 6.0 6.1 Cite error: Invalid <ref> tag; no text was provided for refs named :5
  7. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :0
  8. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :9
  9. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :4
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