Intravascular large B-cell lymphoma

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Intravascular Large B-cell Lymphoma.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). 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); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. 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)*

Kate Berry, MBBS, BBus (Hons), Pathology Queensland

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Mature B-cell neoplasms
Type Large B-cell lymphomas
Subtype(s) Intravascular large B-cell lymphoma

WHO Essential and Desirable Genetic Diagnostic Criteria

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WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

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Acceptable
Not Recommended

Gene Rearrangements

Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE: ABL1 EXAMPLE: BCR::ABL1 EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: Common (CML) EXAMPLE: D, P, T EXAMPLE: Yes (WHO, NCCN) 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). BCR::ABL1 is generally favorable in CML (add reference).

EXAMPLE: CIC EXAMPLE: CIC::DUX4 EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. EXAMPLE: t(4;19)(q25;q13) EXAMPLE: Common (CIC-rearranged sarcoma) EXAMPLE: D EXAMPLE:

DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).

EXAMPLE: ALK EXAMPLE: ELM4::ALK


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. EXAMPLE: N/A EXAMPLE: Rare (Lung adenocarcinoma) EXAMPLE: T EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

EXAMPLE: ABL1 EXAMPLE: N/A EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. EXAMPLE: N/A EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) EXAMPLE: D, P, T
editv4:Chromosomal Rearrangements (Gene Fusions)
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Due to limited data, the prevalence of chromosomal rearrangements in IVLBCL are incompletely described. However, multiple case reports and small series exist describing an array of gene fusions, many of which include the IgH gene, located at 14q32[1][2][3][4][5][6], rearrangements of which constitute a very common cytogenetic abnormality in DLBCL[7]. The t(14;19)(q32;q13) translocation, involving the BCL3 gene at 19q13, is a recurrent translocation in chronic lymphocytic leukaemia (CLL) and confers an adverse prognosis with a higher probability of requiring therapy and shorter overall survival[8]. However, in CLL the translocation is associated with over-expression of BCL3, which is involved in the regulation of the NF-κβ signalling pathway and is a suggested proto-oncogene. In one confirmed[1] and one possible [9] IVLBCL case with t(14;19)(q32;q13) in the literature, BCL3 overexpression was not identified by immunohistochemistry and Southern blot analysis, respectively, suggesting the role of a second oncogene at 19q13 in these tumours. In a karyotypic analysis of three cases of IVLBCL and a literature review, Khoury et al[4] described case reports of breakpoints involving BCL6, CMYC, PAX5, BCL1, BCL2 and BCL3, all gene loci which have been implicated in other haematological diseases, but more data is required to determine if IVLBCL harbours the same recurrent translocations as other B-cell malignancies.

There is insufficient data to comment on the prevalence of high-grade B-cell lymphoma (in which there are concurrent translocations of MYC as well as BCL2 and/or BCL6) amongst IVLBCL cases, but given that the vast majority of high-grade B-cell lymphomas are of germinal centre B-cell type[10][11], and small series have failed to identify MYC rearrangements by break-apart FISH[12] ,it can be assumed to be low.

End of V4 Section


editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)

Intravascular large B cell lymphoma is an aggressive disease, with median overall survival of 105 months and a 5 year survival rate of 46-84%[13][14][15]. Commonly used treatment regimens include R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) +/- high dose methotrexate, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), R-CODOX-M (rituximab, cyclophosphamide, cytarabine, doxorubicin, vincristine, methotrexate) and R-IVAC (rituximab, ifosfamide, cytarabine, etoposide)[16].Patients with the cutaneous variant have significantly longer overall survival, independent of their International Prognostic Index[17][12]. The effect of molecular aberrations on overall survival is difficult to define, both because of the limited data available and since a significant percentage of IVLBCL cases are diagnosed at a very advanced stage, or at autopsy. However in a small series of cases mutational status of MYD88 and CD79B did not significantly influence disease-specific overall survival, and were detected in patients with both the systemic and isolated cutaneous variants of the disease[12]. Several possible therapeutic targets exist amongst identified recurrent mutations. The high prevalence of PD-L2 and PD-L2 aberrations suggests a possible therapeutic role for immune checkpoint inhibitors [15] and the presence of MYD88 and CD79B mutations suggests that there may be a role for drugs targeting NFκβ signalling, such as ibrutinib[12]. TNFAIP3 loss has been shown to be associated with ibrutinib resistance in ABC-type DLBCL[18] and the implications of this mutation on treatment in IVLBCL requires further research. Finally, the most commonly detected MYD88 mutant, L265P, can form a stable protein signalling complex containing IRAK1, a serine/threonine protein kinase, providing a possible therapeutic target in the form of IRAK4 inhibitors[19].

End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE: 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 references).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE:

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

EXAMPLE:

17

EXAMPLE: Amp EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

EXAMPLE:

ERBB2

EXAMPLE: D, P, T EXAMPLE:

Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

editv4:Genomic Gain/Loss/LOH
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IVLBCL cases in the literature with available cytogenetic information have invariably complex karyotypes, comprising both numerical and structural changes with a median of 10 aberrations per case [4][5][20]. The most commonly detected cytogenetic abnormalities are 6q deletions, rearrangements of 8p, chromosome 1 aberrations and deletions or duplication of chromosome 18[20][4][21]. Recurrent cytogenetic abnormalities involving chromosomes 1, 6q and 18 occur in more than 50% of cases[5] .The majority of chromosome 6 deletions involve the long arm, in particular 6q21-q23[4][5], a region which has been implicated in a number of other mature B-cell neoplasms, including diffuse large b-cell lymphoma(DLBCL)[22]. Gains of chromosome 18 are common in DLBCL, mantle zone lymphoma and follicular lymphoma and, frequently, the amplified region involves the BCL2 oncogene at 18q21.3[4]. Whether 18q gain is associated with BCL2 protein overexpression in IVLBCL requires further analysis. Furthermore, loss of chromosome 18 has been shown to be associated with inactivation of the DCC tumour suppressor gene, located at 18q21[23]. One of the most frequently involved chromosome 1 loci, 1p13, contains the NOTCH2 gene[5], a gene essential for the transition of B-cells towards marginal zone maturation[24], mutations in which have been implicated in a number of mature B-cell lymphomas.

Structural variations or copy-number gains in the PD-L1 and PD-L2 encoding genes (CD274 and PDCD1LG2) occur in up to 48% of cases, primarily involving truncation of the 3'UTR sequence which leads to increased expression of PD-L1 transcripts, facilitating immune invasion[15].Small series have confirmed an association between PD-L1 overexpression on IHC and tumours with 9p mutations including amplifications and structural variations[15]. Deish et al[20] postulated that amplification of the MLL or KMTD2 gene, seen in AML and myelodysplastic disorders, may also be a recurrent abnormality in IVLBCL, based on a case they identified with tandem triplication of 11q21-23 leading to three copies of the gene, and three other reported cases in the literature, one with a segmental 11q23 duplication[2] and two with a gain of chromosome 11[25][2].

Chromosome Number Gain/Loss/Amp/LOH Region
1[4] Loss whole chromosome
3[4][3] Loss q21-qter
6[15][4] Loss q21-q23; q11-qter
8[4] Loss p21-qter
9[4] Loss p21-pter; p22-qter
15[4] Loss whole chromosome
18[4][15] Gain whole chromosome, 11q13→qter region
18[4] Loss q23
21 Amp q
22[4] Loss q21-q23
End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T

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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:EGFR


EXAMPLE: Exon 18-21 activating mutations EXAMPLE: Oncogene EXAMPLE: Common (lung cancer) EXAMPLE: T EXAMPLE: Yes (NCCN) EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations


EXAMPLE: Variable LOF mutations EXAMPLE: Tumor Supressor Gene EXAMPLE: Common (breast cancer) EXAMPLE: P EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations EXAMPLE: Activating mutations EXAMPLE: Oncogene EXAMPLE: Common (melanoma) EXAMPLE: T

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

editv4:Gene Mutations (SNV/INDEL)
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Due to the rarity of IVLBCL, only small series describing recurrent gene mutations are currently available. However, several studies have identified recurrent mutations in multiple genes with known aberrations in both nodal DLBCL and other extranodal lymphomas. These include driver mutations in genes involved in the B-cell receptor/NF-κβ signalling pathways (CD79B, MYD88, IRF4, ITPKB, NFKBIE and TNFAIP3), genes targeted by Activation Induced Deaminase (PIM1 and IGLL5), genes affecting B-cell development (PRDM1 and TOX) and histone modification factors (SETD1B, KMT2D and EP300)[15]. Although the mutational landscape of IVLBCL tends to be similar to that of ABC type nodal DLBCL, there is a higher frequency of mutations in several genes including MYD88, CD79B, TBL1XR1 and SETD1B[15].

Collated, comprehensive gene mutation prevalence data is not currently available, however the table below summarises the most common gene mutations identified from a number of recent studies[12][26][15][27]:

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
IGLL5 Not fully characterised 90% (19/21)
PIM1 Oncogene GOF 83% (25/30)
SET1B Not fully characterised 57% (12/21)
CD79B Oncogene GOF; Driver 49% (26/53)
MYD88 L265P Oncogene GOF; Driver 45% (29/65)
PRDM1 Tumour suppressor LOF 43% (13/30)
IRF4 Oncogene GOF 38% (8/21)
TOX3 Not fully characterised 33% (7/21)
TNFAIP3 Tumour suppressor LOF 24% (5/21)
KMT2D Tumour suppressor LOF 24% (5/21)
BTG2 Tumour suppressor LOF 22% (2/9)
ITPKB Tumour suppressor LOF 14% (3/21)
NFKBIE Tumour suppressor LOF 14% (3/21)
EP300 Oncogene GOF 14% (3/21)
End of V4 Section

Epigenomic Alterations

Although the role of epigenomics in IVLBCL specifically has been incompletely described, several of the genes most frequently mutated in IVLBCL have been shown to be epigenetic determinants in DLBCL, including KMT2D and EP300.

KMT2D mutants promote lymphomagenesis in part by impeding H3K4 methylation, driving enhanced proliferation in germinal centres, and impeding terminal differentiation of B-cells[28]. The extent to which KMT2D inactivation promotes lymphomagenesis appears to be affected by dysregulation of the expression of a number of other genes, including BCL2 and AICDA. KMT2D loss, in combination with increased BCL2 expression, has been shown in mouse models to increase lymphoma incidence from that of mice with wild type KMT2D, and the effect is greater for those with homozygous deletions[28][29]. AICDA encodes activation-induced cytidine deaminase (AID), an enzyme involved in somatic hypermutation, class switch recombination and gene conversion in the process of immunoglobulin diversification. Overexpression of AICDA has been shown in mice models, in combination with KMT2D inactivation, to be associated with increased lymphoma incidence and also with more aggressive phenotypes than tumours with KMT2D deletion alone[28].

In DLBCL, mutations in EP300, a histone acetyltransferase, have been shown to inhibit H3K27 acetylation and activate the NOTCH signalling pathway, possibly through inhibition of FBXW7 expression, which acts as a NOTCH suppressor[30]. The NOTCH pathway plays a critical role in normal B-cell development and dysregulation of NOTCH signalling has been implicated in a wide array of mature B-cell malignancies, including DLBCL[31]. Additionally, mutations in EP300 have been shown to promote tumour-associated macrophage (TAM) activation, as evidenced by increased macrophages in the tumour microenvironment, which promote tumour progression by inhibiting T-cell immunity[30]. Notably, patients with mutations in EP300 and CREBBP, a closely related chromatin-modifying gene, have been shown to have significantly lower 3-year progression-free and overall survival rates than patients with wild-type EP300/CREBBP[30]

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
editv4:Genes and Main Pathways Involved
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One of the most widely studied genes in IVLBCL is MYD88 with 45% of patients found to have a somatic MYD88 mutation, 86% of these being L265P mutations. This mutation is commonly associated with lymphoplasmacytic lymphoma and Waldenstrom macroglobulinaemia (WM), being present in >90% of WM cases and 54% of IgM MGUS patients[32]. MYD L265P mutations have also been found in 29% of activated B-cell (ABC) type DLBCL[19], and can be seen in primary cutaneous DLBCL, testicular and primary CNS DLBCL and DLBCL of leg type[33]. Overall, the mutational profile of IVLBCL is more similar to these entities than to DLBCL, NOS[15]. Ngo et al[19] demonstrated that in ABC-type DLBCL L265P functions as a gain-of-function driver mutation which promotes cell survival through the promotion of NF-κβ and JAK-STAT3 signalling. Given that IVLBCL is overwhelmingly of ABC type, the role of MYD L265P as a driver mutation in IVLBCL should be considered. Some studies have also shown that TNFAIP3 loss (observed in approximately 24% of IVLBCL) acts synergistically with MYD88 L265P to drive upregulation of anti-apoptotic signalling in DLBCL[18]. Loss of TNFAIP3 occurs in around 55% of DLBCL and also contributes to higher baseline phosphorylation of NF-κβ and STAT3 as well as p38 which, in association with NF-κβ, causes upregulation of BCL2 and MYC[18]. IGLL5 located at 22q11, which is mutated in around 90% of IVLBCL, is a recurrently mutated gene in DLBCL and multiple myeloma, in which mutations confer an increased risk of disease progression[34].

End of V4 Section

Genetic Diagnostic Testing Methods

Due to its non-specific clinical presentation and frequent lack of characteristic radiological findings, such as lymphadenopathy, IVLBCL often poses a diagnostic challenge. When IVLBCL is suspected clinically, random skin biopsy is easy to perform and frequently diagnostic[27], with tumour cells often observed in subcutaneous tissues, even in the absence of macroscopic lesions[35]. However, as the lymphoma cells are most commonly found within the subcutaneous adipose tissues, rather than the dermis, inadequate hypodermic sampling may lead to false negative results[13]. Although intrasinusoidal infiltration of the bone marrow is considered to be characteristic of IVLBCL, nodular and interstitial infiltration are often also seen, making it difficult on bone marrow biopsy alone to distinguish it from splenic and primary bone marrow DLBCL which show many common clinical features and immunohistochemical findings[13].

The use of plasma- and serum-derived cell-free DNA (cfDNA) is emerging as a potential non-invasive means of obtaining tumour material for both diagnosis and genetic testing. A 2021 study by Shimada et al[15] showed the yield of cfDNA to be ten times higher in patients with IVLBCL than diffuse large B-cell lymphoma, and significantly higher than that from healthy controls. Furthermore, cfDNA levels were significantly correlated with serum lactate dehydrogenase level and the status of bone marrow invasion, and rapidly decreased after commencing chemotherapy, whilst being elevated in the refractory phase. This not only suggests that cfDNA is mainly derived from lymphoma cells, but that lactate dehydrogenase level is a reliable surrogate marker for monitoring disease progression and response to treatment. When using whole-exome sequencing to compare mutations detected in plasma-derived cf-DNA to those in bone marrow samples, not only did the mutations observed in cf-DNA have substantially higher variant allele frequencies (a marker of intratumoural heterogeneity), suggesting that tumour-derived DNA is significantly enriched in cfDNA, but many mutations detected in cfDNA were not found in the corresponding bone marrow samples, suggesting improved sensitivity with the use of cf-DNA over bone marrow samples[15]. Variant allele frequency has also been shown to be significantly higher in cfDNA than tissue-derived DNA samples, with increased sensitivity[27]. In patients with an L265P MYD88 mutation, monitoring of cfDNA has been shown in small-scale longitudinal analysis to be of potential diagnostic utility, with detectable L265P MYD88 in cfDNA from one patient 117 days prior to definitive diagnosis, at a time in which bone marrow biopsy was negative, and in three patients prior to a definite diagnosis of disease relapse[27].

In a study in 1997, DiGiuseppe et al.[36] detected monoclonal B-cell populations by IgH gene rearrangement studies in the bone marrow of 5/5 cases of IVLBCL studied, all of whom had histologically non-involved marrow, suggesting both that marrow involvement may be under-recognised in IVLBCL, and that bone marrow biopsy may be a useful diagnostic tool to provide material for genetic testing, even when disease cannot be visualised histologically within the bone marrow.

Familial Forms

No known familial association exists.

Additional Information

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Links

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References

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  1. ↑ Jump up to: 1.0 1.1 Kobayashi, Taishi; et al. (2011). "Intravascular Large B-Cell Lymphoma Associated with t(14;19)(q32;q13) Translocation". Internal Medicine. 50 (18): 2007–2010. doi:10.2169/internalmedicine.50.5706. ISSN 0918-2918.
  2. ↑ Jump up to: 2.0 2.1 2.2 Murase, Takuhei; et al. (2000-12). "An Asian variant of intravascular large B-cell lymphoma: clinical, pathological and cytogenetic approaches to diffuse large B-cell lymphoma associated with haemophagocytic syndrome". British Journal of Haematology. 111 (3): 826–834. doi:10.1111/j.1365-2141.2000.02426.x. ISSN 0007-1048. Check date values in: |date= (help)
  3. ↑ Jump up to: 3.0 3.1 Rashid, Rumana; et al. (2006-12). "Intravascular large B-cell lymphoma associated with a near-tetraploid karyotype, rearrangement of BCL6, and a t(11;14)(q13;q32)". Cancer Genetics and Cytogenetics. 171 (2): 101–104. doi:10.1016/j.cancergencyto.2006.07.018. Check date values in: |date= (help)
  4. ↑ Jump up to: 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 Khoury, Haytham; et al. (2003-07). "Multicolor Karyotyping and Clinicopathological Analysis of Three Intravascular Lymphoma Cases". Modern Pathology. 16 (7): 716–724. doi:10.1097/01.MP.0000077515.68734.85. ISSN 0893-3952. Check date values in: |date= (help)
  5. ↑ Jump up to: 5.0 5.1 5.2 5.3 5.4 Klairmont, Matthew M; et al. (2018-05-31). "Recurrent Cytogenetic Abnormalities in Intravascular Large B-Cell Lymphoma". American Journal of Clinical Pathology. 150 (1): 18–26. doi:10.1093/ajcp/aqy023. ISSN 0002-9173.
  6. ↑ Cui, Jing; et al. (2014-03). "An intravascular large B-cell lymphoma with a t(3;14)(q27;q32) translocation". Journal of Clinical Pathology. 67 (3): 279–281. doi:10.1136/jclinpath-2013-201980. ISSN 0021-9746. Check date values in: |date= (help)
  7. ↑ Cigudosa, Juan C.; et al. (1999-06). <123::aid-gcc8>3.0.co;2-4 "Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas". Genes, Chromosomes and Cancer. 25 (2): 123–133. doi:10.1002/(sici)1098-2264(199906)25:2<123::aid-gcc8>3.0.co;2-4. ISSN 1045-2257. Check date values in: |date= (help)
  8. ↑ Fang, Hong; et al. (2019-03). "IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes". American Journal of Hematology. 94 (3): 338–345. doi:10.1002/ajh.25385. PMC 6625355. PMID 30575108. Check date values in: |date= (help)CS1 maint: PMC format (link)
  9. ↑ Yamamoto, Katsuya; et al. (2001-10). "Translocation (14;19)(q32;q13) detected by spectral karyotyping and lack of BCL3 rearrangement in CD5-positive B-cell lymphoma associated with hemophagocytic syndrome". Cancer Genetics and Cytogenetics. 130 (1): 38–41. doi:10.1016/S0165-4608(01)00466-6. Check date values in: |date= (help)
  10. ↑ Akyurek, Nalan; et al. (2012-09-01). "Prognostic significance of MYC , BCL2 , and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab: MYC , BCL2 , BCL6 Rearrangements in DLBCL". Cancer. 118 (17): 4173–4183. doi:10.1002/cncr.27396.
  11. ↑ Copie-Bergman, Christiane; et al. (2015-11-26). "MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study". Blood. 126 (22): 2466–2474. doi:10.1182/blood-2015-05-647602. ISSN 0006-4971.
  12. ↑ Jump up to: 12.0 12.1 12.2 12.3 12.4 Schrader, Anne M. R.; et al. (2018-05-03). "High prevalence of MYD88 and CD79B mutations in intravascular large B-cell lymphoma". Blood. 131 (18): 2086–2089. doi:10.1182/blood-2017-12-822817. ISSN 0006-4971.
  13. ↑ Jump up to: 13.0 13.1 13.2 Matsue, Kosei; et al. (2019-11). "Diagnosis of intravascular large B cell lymphoma: novel insights into clinicopathological features from 42 patients at a single institution over 20 years". British Journal of Haematology. 187 (3): 328–336. doi:10.1111/bjh.16081. ISSN 0007-1048. PMC 6900202. PMID 31267524. Check date values in: |date= (help)CS1 maint: PMC format (link)
  14. ↑ Rajyaguru, Devalkumar J.; et al. (2017-09-02). "Intravascular large B-cell lymphoma in the United States (US): a population-based study using Surveillance, Epidemiology, and End Results program and National Cancer Database*". Leukemia & Lymphoma. 58 (9): 2080–2088. doi:10.1080/10428194.2017.1287363. ISSN 1042-8194.
  15. ↑ Jump up to: 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 Shimada, Kazuyuki; et al. (2021-03-18). "Frequent genetic alterations in immune checkpoint–related genes in intravascular large B-cell lymphoma". Blood. 137 (11): 1491–1502. doi:10.1182/blood.2020007245. ISSN 0006-4971. PMC PMC7976508 Check |pmc= value (help). PMID 33512416 Check |pmid= value (help).CS1 maint: PMC format (link)
  16. ↑ Geer, Marcus; et al. (2019-05). "Multicentre retrospective study of intravascular large B‐cell lymphoma treated at academic institutions within the United States". British Journal of Haematology: bjh.15923. doi:10.1111/bjh.15923. ISSN 0007-1048. Check date values in: |date= (help)
  17. ↑ Ponzoni, Maurilio; et al. (2007-07-20). "Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting". Journal of Clinical Oncology. 25 (21): 3168–3173. doi:10.1200/JCO.2006.08.2313. ISSN 0732-183X.
  18. ↑ Jump up to: 18.0 18.1 18.2 Wenzl, Kerstin; et al. (2018-10-09). "Loss of TNFAIP3 enhances MYD88L265P-driven signaling in non-Hodgkin lymphoma". Blood Cancer Journal. 8 (10): 97. doi:10.1038/s41408-018-0130-3. ISSN 2044-5385. PMC 6177394. PMID 30301877.
  19. ↑ Jump up to: 19.0 19.1 19.2 Ngo, Vu N.; et al. (2011-02). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–119. doi:10.1038/nature09671. ISSN 0028-0836. PMC 5024568. PMID 21179087. Check date values in: |date= (help)CS1 maint: PMC format (link)
  20. ↑ Jump up to: 20.0 20.1 20.2 Deisch, Jeremy; et al. (2009-09-01). "Segmental Tandem Triplication of the MLL Gene in an Intravascular Large B-Cell Lymphoma With Multisystem Involvement: A Comprehensive Morphologic, Immunophenotypic, Cytogenetic, and Molecular Cytogenetic Antemortem Study". Archives of Pathology & Laboratory Medicine. 133 (9): 1477–1482. doi:10.5858/133.9.1477. ISSN 1543-2165.
  21. ↑ Murase, Takuhei; et al. (2007-01-15). "Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5". Blood. 109 (2): 478–485. doi:10.1182/blood-2006-01-021253. ISSN 0006-4971.
  22. ↑ Thelander, Emma Flordal; et al. (2008-01). "Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia". Leukemia & Lymphoma. 49 (3): 477–487. doi:10.1080/10428190701817282. ISSN 1042-8194. Check date values in: |date= (help)
  23. ↑ Porfiri, E; et al. (1993-05-15). "DCC tumor suppressor gene is inactivated in hematologic malignancies showing monosomy 18". Blood. 81 (10): 2696–2701. doi:10.1182/blood.v81.10.2696.bloodjournal81102696. ISSN 0006-4971.
  24. ↑ Arruga, Francesca; et al. (2018). "The NOTCH Pathway and Its Mutations in Mature B Cell Malignancies". Frontiers in Oncology. 8: 550. doi:10.3389/fonc.2018.00550. ISSN 2234-943X. PMC 6275466. PMID 30534535.
  25. ↑ Molina, Arturo; et al. (1990-08-01). <474::aid-cncr2820660313>3.0.co;2-p "Immunohistochemical and cytogenetic studies indicate that malignant angioendotheliomatosis is a primary intravascular (angiotropic) lymphoma". Cancer. 66 (3): 474–479. doi:10.1002/1097-0142(19900801)66:3<474::aid-cncr2820660313>3.0.co;2-p. ISSN 0008-543X.
  26. ↑ Zhang, D. D.; et al. (2021-03-08). "[Clinicopathological features and MYD88 L265P mutation status of intravascular large B cell lymphoma]". Zhonghua Bing Li Xue Za Zhi = Chinese Journal of Pathology. 50 (3): 217–221. doi:10.3760/cma.j.cn112151-20200513-00383. ISSN 0529-5807. PMID 33677885 Check |pmid= value (help).
  27. ↑ Jump up to: 27.0 27.1 27.2 27.3 Suehara, Yasuhito; et al. (2018-06). "Liquid biopsy for the identification of intravascular large B-cell lymphoma". Haematologica. 103 (6): e241–e244. doi:10.3324/haematol.2017.178830. ISSN 0390-6078. PMC 6058794. PMID 29472348. Check date values in: |date= (help)CS1 maint: PMC format (link)
  28. ↑ Jump up to: 28.0 28.1 28.2 Ortega-Molina, Ana; et al. (2015-10). "The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development". Nature medicine. 21 (10): 1199–1208. doi:10.1038/nm.3943. ISSN 1078-8956. PMC 4676270. PMID 26366710. Check date values in: |date= (help)
  29. ↑ Zhang, Jiyuan; et al. (2015-10). "Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis". Nature Medicine. 21 (10): 1190–1198. doi:10.1038/nm.3940. ISSN 1078-8956. PMC 5145002. PMID 26366712. Check date values in: |date= (help)CS1 maint: PMC format (link)
  30. ↑ Jump up to: 30.0 30.1 30.2 Huang, Yao-Hui; et al. (2021-12). "CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis". Signal Transduction and Targeted Therapy. 6 (1): 10. doi:10.1038/s41392-020-00437-8. ISSN 2059-3635. PMC PMC7801454 Check |pmc= value (help). PMID 33431788 Check |pmid= value (help). Check date values in: |date= (help)CS1 maint: PMC format (link)
  31. ↑ Arruga, Francesca; et al. (2018-11-26). "The NOTCH Pathway and Its Mutations in Mature B Cell Malignancies". Frontiers in Oncology. 8: 550. doi:10.3389/fonc.2018.00550. ISSN 2234-943X. PMC 6275466. PMID 30534535.CS1 maint: PMC format (link)
  32. ↑ Xu, Lian; et al. (2013-03-14). "MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction". Blood. 121 (11): 2051–2058. doi:10.1182/blood-2012-09-454355. ISSN 0006-4971. PMC 3596964. PMID 23321251.CS1 maint: PMC format (link)
  33. ↑ Swerdlow SH, et al,, (2017). Lymphoplasmacytic lymphoma, in World Health Organisation Classificaiton 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, p330-334.
  34. ↑ White, Brian S.; et al. (2018-03-21). "A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5". Blood Cancer Journal. 8 (3): 35. doi:10.1038/s41408-018-0062-y. ISSN 2044-5385. PMC 5862875. PMID 29563506.
  35. ↑ Matsue, Kosei; et al. (2011-04). "Random skin biopsy and bone marrow biopsy for diagnosis of intravascular large B cell lymphoma". Annals of Hematology. 90 (4): 417–421. doi:10.1007/s00277-010-1101-3. ISSN 1432-0584. PMID 20957365. Check date values in: |date= (help)
  36. ↑ DiGiuseppe, J. A.; et al. (1997-01). "Molecular detection of bone marrow involvement in intravascular lymphomatosis". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 10 (1): 33–37. ISSN 0893-3952. PMID 9021724. Check date values in: |date= (help)


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*Citation of this Page: “Intravascular large B-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/11/2025, https://ccga.io/index.php/HAEM5:Intravascular_large_B-cell_lymphoma.

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