Compendium of Cancer Genome Aberrations

ALK-positive large B-cell lymphoma

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

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This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:ALK-Positive Large B-cell Lymphoma.

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Primary Author(s)*

Manando Nakasaki, MD, PhD (University of California, Irvine)

Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvine)

Cancer Category / Type

Mature B cell neoplasm

Cancer Sub-Classification / Subtype

Large B-cell lymphomas

Definition / Description of Disease

Diffuse, monomorphic neoplasm of large B-cells with a plasmablastic immunophenotype and ALK expression due to ALK rearrangement

Synonyms / Terminology

Not recommended: ALK-positive plasmablastic B-cell lymphoma; ALK-positive diffuse large B-cell lymphoma

Epidemiology / Prevalence

  • <1% of large B-cell lymphomas
    • ~ 200 cases reported in literature to date[1]
  • Range: 9-85 years; median: ~ 40 years[2][3]
  • Male to Female ratio: 3-4:1[4][5]

Clinical Features

Signs and Symptoms Asymptomatic lymphadenopathy

B-symptoms

Laboratory Findings Serum LDH elevation

Sites of Involvement

  • Lymph nodes are most commonly involved (~ 75%)
  • Extranodal sites: bone marrow, GI tract, liver, epidural space, ovaries, skeletal system, nasopharyngeal/nasal area, tongue, and brain[6][7][8]

Morphologic Features

  • Partial or diffuse effacement of lymph node architecture
  • Lymphoma cells infiltrate sinusoids[9][10]
  • Monomorphic infiltrate of large cells with abundant amphophilic or eosinophilic cytoplasm

Immunophenotype

Finding Marker
Positive (universal) ALK, CD138, VS38, IRF4/MUM1, BLIMP1, XBP1
Positive (subset) EMA (90%), Cytoplasmic Ig (90%), IgA (80%), CD45 (90%), CD30 (15%), CD4 (50%), CD57 (10%), CD43, Cytokeratin (10%)
Negative (universal) Pan-T cell antigens, CD8, B-cell antigens, CD10, BCL-6, Cyclin-D1, HHV8

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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).


editHAEM5 Conversion Notes
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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) ALK Immunostain Pattern Prevalence Notes
t(2;17)(p23;q23) CLTC::ALK Cytoplasmic; granular Most common [11]
t(2;5)(p23;q35) NPM::ALK Nuclear and cytoplasmic [12]
t(2;5)(p23;q35.3) SQSTM1::ALK Cytoplasmic; diffuse [13]
inv(2)(p23q13) or t(2;2)(p23;q13) RANBP2::ALK Nuclear membrane and perinuclear punctate [14]
inv(2)(p21p23) EML4::ALK Cytoplasmic; diffuse [15]
inv(2)(p21q31.1) or t(2;2)(p23;q31.1) GORASP2::ALK Cytoplasmic; diffuse [16]
Cryptic SEC31A::ALK Cytoplasmic; granular [17]

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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7:1- 159,335,973 [hg38]

EXAMPLE:

chr7

Yes 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).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8:1-145,138,636 [hg38]

EXAMPLE:

chr8

No No No EXAMPLE:

Common recurrent secondary finding for t(8;21) (add reference).

editHAEM5 Conversion Notes
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Gains or amplifications of MYC (~50% of cases)[18]

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)

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).

editHAEM5 Conversion Notes
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N/A

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.)

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.


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N/A

Epigenomic Alterations

N/A

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
ALK rearrangement; Activating fusions JAK/STAT, PI3K/AKT, MAPK/ERK and phospholipase C gamma 2 (PLCG2) pathways Transformation, increased growth and inhibition of apoptosis

Genetic Diagnostic Testing Methods

  • Detection of ALK rearrangement by NGS or FISH
  • Monoclonal IGH rearrangements by PCR

Familial Forms

N/A

Additional Information

N/A

Links

N/A

References

  1. ↑ Castillo, Jorge J.; et al. (2021-12). "Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management". Leukemia & Lymphoma. 62 (12): 2845–2853. doi:10.1080/10428194.2021.1941929. ISSN 1029-2403. PMID 34151703 Check |pmid= value (help). Check date values in: |date= (help)
  2. ↑ Pan, Zenggang; et al. (2017-01). "ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature". The American Journal of Surgical Pathology. 41 (1): 25–38. doi:10.1097/PAS.0000000000000753. ISSN 1532-0979. PMID 27740969. Check date values in: |date= (help)
  3. ↑ Castillo, Jorge J.; et al. (2021-12). "Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management". Leukemia & Lymphoma. 62 (12): 2845–2853. doi:10.1080/10428194.2021.1941929. ISSN 1029-2403. PMID 34151703 Check |pmid= value (help). Check date values in: |date= (help)
  4. ↑ Sukswai, Narittee; et al. (2020-01). "Diffuse large B-cell lymphoma variants: an update". Pathology. 52 (1): 53–67. doi:10.1016/j.pathol.2019.08.013. ISSN 1465-3931. PMID 31735345. Check date values in: |date= (help)
  5. ↑ Castillo, Jorge J.; et al. (2021-12). "Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management". Leukemia & Lymphoma. 62 (12): 2845–2853. doi:10.1080/10428194.2021.1941929. ISSN 1029-2403. PMID 34151703 Check |pmid= value (help). Check date values in: |date= (help)
  6. ↑ Morgan, Elizabeth A.; et al. (2012). "Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma". Advances in Hematology. 2012: 529572. doi:10.1155/2012/529572. ISSN 1687-9112. PMC 3299366. PMID 22474449.
  7. ↑ Pan, Zenggang; et al. (2017-01). "ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature". The American Journal of Surgical Pathology. 41 (1): 25–38. doi:10.1097/PAS.0000000000000753. ISSN 1532-0979. PMID 27740969. Check date values in: |date= (help)
  8. ↑ Laurent, Camille; et al. (2009-09-01). "Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 27 (25): 4211–4216. doi:10.1200/JCO.2008.21.5020. ISSN 1527-7755. PMID 19636007.
  9. ↑ Pan, Zenggang; et al. (2017-01). "ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature". The American Journal of Surgical Pathology. 41 (1): 25–38. doi:10.1097/PAS.0000000000000753. ISSN 1532-0979. PMID 27740969. Check date values in: |date= (help)
  10. ↑ Sukswai, Narittee; et al. (2020-01). "Diffuse large B-cell lymphoma variants: an update". Pathology. 52 (1): 53–67. doi:10.1016/j.pathol.2019.08.013. ISSN 1465-3931. PMID 31735345. Check date values in: |date= (help)
  11. ↑ Gascoyne, Randy D.; et al. (2003-10-01). "ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases". Blood. 102 (7): 2568–2573. doi:10.1182/blood-2003-03-0786. ISSN 0006-4971. PMID 12763927.
  12. ↑ Onciu, Mihaela; et al. (2003-10-01). "ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases". Blood. 102 (7): 2642–2644. doi:10.1182/blood-2003-04-1095. ISSN 0006-4971. PMID 12816858.
  13. ↑ Takeuchi, Kengo; et al. (2011-03). "Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma". Haematologica. 96 (3): 464–467. doi:10.3324/haematol.2010.033514. ISSN 1592-8721. PMC 3046280. PMID 21134980. Check date values in: |date= (help)
  14. ↑ Lee, Seung Eun; et al. (2014-12). "Identification of RANBP2-ALK fusion in ALK positive diffuse large B-cell lymphoma". Hematological Oncology. 32 (4): 221–224. doi:10.1002/hon.2125. ISSN 1099-1069. PMID 24470379. Check date values in: |date= (help)
  15. ↑ Sakamoto, Kana; et al. (2016-04). "ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern". International Journal of Hematology. 103 (4): 399–408. doi:10.1007/s12185-016-1934-1. ISSN 1865-3774. PMID 26781614. Check date values in: |date= (help)
  16. ↑ Ise, Mikiko; et al. (2019-02). "Identification of a novel GORASP2-ALK fusion in an ALK-positive large B-cell lymphoma". Leukemia & Lymphoma. 60 (2): 493–497. doi:10.1080/10428194.2018.1493731. ISSN 1029-2403. PMID 30187817. Check date values in: |date= (help)
  17. ↑ Bedwell, Clare; et al. (2011-02). "Cytogenetically complex SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas". Haematologica. 96 (2): 343–346. doi:10.3324/haematol.2010.031484. ISSN 1592-8721. PMC 3031708. PMID 21109691. Check date values in: |date= (help)
  18. ↑ Valera, Alexandra; et al. (2013-10). "ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 26 (10): 1329–1337. doi:10.1038/modpathol.2013.73. ISSN 1530-0285. PMC 6368829. PMID 23599149. Check date values in: |date= (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: “ALK-positive large B-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/1/2024, https://ccga.io/index.php/HAEM5:ALK-positive_large_B-cell_lymphoma.

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