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Created page with "==Primary Author(s)*== Kapitolina Semenova, MD, Jack Reid, MD, Fabiola Quintero-Rivera, MD Departments of Pathology, Laboratory Medicine, and *Pediatrics, Division of Geneti..."

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==Primary Author(s)*==

Kapitolina Semenova, MD, Jack Reid, MD, Fabiola Quintero-Rivera, MD

Departments of Pathology, Laboratory Medicine, and *Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine (UCI)

__TOC__

==Cancer Category/Type==

Low-grade mature B-cell neoplasm<ref name=":0">Vardiman JW, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification 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, p232-235</ref><ref name=":2">{{Cite journal|last=Varettoni|first=Marzia|last2=Boveri|first2=Emanuela|last3=Zibellini|first3=Silvia|last4=Tedeschi|first4=Alessandra|last5=Candido|first5=Chiara|last6=Ferretti|first6=Virginia Valeria|last7=Rizzo|first7=Ettore|last8=Doni|first8=Elisa|last9=Merli|first9=Michele|date=2019-11|title=Clinical and molecular characteristics of lymphoplasmacytic lymphoma not associated with an IgM monoclonal protein: A multicentric study of the Rete Ematologica Lombarda (REL) network|url=https://pubmed.ncbi.nlm.nih.gov/31378966|journal=American Journal of Hematology|volume=94|issue=11|pages=1193–1199|doi=10.1002/ajh.25600|issn=1096-8652|pmid=31378966}}</ref>

==Cancer Sub-Classification / Subtype==

Non-Hodgkin small B-cell lymphoma<ref name=":0" /><ref>{{Cite journal|last=Vajdic|first=Claire M.|last2=Landgren|first2=Ola|last3=McMaster|first3=Mary L.|last4=Slager|first4=Susan L.|last5=Brooks-Wilson|first5=Angela|last6=Smith|first6=Alex|last7=Staines|first7=Anthony|last8=Dogan|first8=Ahmet|last9=Ansell|first9=Stephen M.|date=2014-08|title=Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project|url=https://pubmed.ncbi.nlm.nih.gov/25174029|journal=Journal of the National Cancer Institute. Monographs|volume=2014|issue=48|pages=87–97|doi=10.1093/jncimonographs/lgu002|issn=1745-6614|pmc=4155457|pmid=25174029}}</ref>

==Definition / Description of Disease==

*Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B lymphocytes, plasmacytoid lymphocytes, and plasma cells, usually involving bone marrow and spleen, which does not fulfil the criteria for any of the other small B-cell lymphoid neoplasms, that can have plasmacytic differentiation. <ref name=":0" />
*Based on the presence of the bone marrow involvement and the presence of paraprotein, LPL is categorized into [[Waldenstrom Macroglobulinemia|Waldenström macroglobulinemia]] and LPL of non-Waldenström macroglobulinemia. <ref name=":1">{{Cite journal|last=Wang|first=Wei|last2=Lin|first2=Pei|date=2020-01|title=Lymphoplasmacytic lymphoma and Waldenström macroglobulinaemia: clinicopathological features and differential diagnosis|url=https://pubmed.ncbi.nlm.nih.gov/31767130|journal=Pathology|volume=52|issue=1|pages=6–14|doi=10.1016/j.pathol.2019.09.009|issn=1465-3931|pmid=31767130}}</ref>
*The majority of cases of LPL lymphoma are associated with IgM paraprotein secretion (Waldenström macroglobulinemia), with less than 5% of cases attributed to IgA, IgG, and nonsecreting cases of LPL. <ref>{{Cite journal|last=Hunter|first=Zachary R.|last2=Yang|first2=Guang|last3=Xu|first3=Lian|last4=Liu|first4=Xia|last5=Castillo|first5=Jorge J.|last6=Treon|first6=Steven P.|date=2017-03-20|title=Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia|url=https://pubmed.ncbi.nlm.nih.gov/28294689|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=35|issue=9|pages=994–1001|doi=10.1200/JCO.2016.71.0814|issn=1527-7755|pmid=28294689}}</ref>

==Synonyms / Terminology==

Malignant lymphoma, lymphoplasmacytoid lymphoma.<ref name=":0" />

==Epidemiology / Prevalence==

*Lymphoplasmacytic lymphoma, in approximately 95% of cases, occurs in patients of Caucasian descent. <ref name=":1" />
*The median age is in the seventh decade of life. <ref name=":0" /><ref name=":1" />
*Approximately 1000-1500 new cases are diagnosed yearly in the United States.
*LPL associated with IgM ([[Waldenstrom Macroglobulinemia|Waldenström macroglobulinemia]]) is more commonly occurs in male patients, while LPL with a non-IgM is reported more frequently in females. <ref name=":2" />

==Clinical Features<ref name=":0" /><ref name=":1" />==
{| class="wikitable"
|'''Signs and Symptoms'''
|Weakness (usually related to anemia)
Fatigue

Hyperviscosity (in 30% of cases)

Lymphadenopathy and splenomegaly (in 10-20% of patient at time of diagnosis)

Paraprotein deposition in tissues with organ-specific dysfunction:

*Neuropathy (minority of patients; may be related to the IgM paraprotein with myelin sheath antigens)

*Diarrhea (rare, due to paraprotein deposition in gastrointestinal tract)

*Coagulopathy (may be cause by IgM binding to clotting factors)
*Bullae or papules in the skin
*Proteinuria and renal failure
|-
|'''Laboratory Findings'''
|IgM paraprotein

IgM and IgG paraprotein (minority of patients)

Cold agglutinins

Cryoglobulinemia
|}

==Sites of Involvement==

*Bone marrow (most of cases), lymph nodes, spleen, liver, and other extranodal sites. The peripheral blood may also be involved.
*Rare involvement of CNS associated with Waldenström macroglobulinemia (known as [[Bing-Neel syndrome]]). Lymphoplasmacytic lymphoma may occur at sites typically involved by extranodal marginal zone lymphoma (MZL) of mucosal-associated lymphoid tissue (MALT lymphoma), such as the ocular adnexa. <ref name=":0" /><ref name=":1" />
*Patients with non-IgM LPL are more likely to present with extramedullary involvement such as lymphadenopathy, splenomegaly, or extranodal disease. <ref name=":2" />
*Bone marrow involvement is more common in patients with IgM-associated LPL ([[Waldenstrom Macroglobulinemia|Waldenström macroglobulinemia]]) when compared to non-IgM LPL. <ref name=":2" />

==Morphologic Features==

*Bone marrow involvement is characterized by diffuse, interstitial, and nodular infiltration patterns. Paratrabecular can also be present; however, it has been observed more frequently in cases of [[marginal zone lymphoma.]]
*The infiltrate is characterized by small monotonous lymphocytes admixed with a variable amount of plasmacytoid lymphocytes and plasma cells. Although nonspecific, variable amount of reactive mast cell and hemosiderin deposits are frequently observed. Dutcher bodies (nuclear vacuoles containing IgM protein) and Russell bodies (cytoplasmic inclusion) are often seen similarly in multiple myeloma cases. <ref name=":0" />

*Peripheral blood often demonstrates lymphoma cells with similar morphology. Leukocytosis is not typically observed. Peripheral blood may also demonstrate a rouleaux formation due to increased IgM paraprotein.

==Immunophenotype<ref name=":1" />==

Put your text here and fill in the table

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (subset)
|IgM
|-
|Positive (subset)
|IgG
|-
|Positive (subset)
|IgA
|-
|Positive (universal)||CD19
|-
|Positive (universal)||CD20
|-
|Positive (universal)||CD22 (dim)
|-
|Positive (universal)||CD25
|-
|Positive (universal)
|CD79a
|-
|Positive (universal)
|CD45
|-
|Positive (variable)
|CD38
|-
|Positive (universal)
|PAX5
|-
|Positive (subset)
|CD5
|-
|Positive (subset)
|CD10
|-
|Positive (subset)
|TCL1
|-
|Negative (universal)
|Cyclin D1
|-
|Negative (universal)
|LEF1
|-
|Negative (universal)
|EBV stain
|-
|Negative (universal)
|CD56
|-
|Negative (universal)
|CD117
|}

==Chromosomal Rearrangements (Gene Fusions)<ref name=":0" /><ref name=":1" />==

No specific chromosomal abnormalities are identified in LPL.

{| class="wikitable sortable"
|-
!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
|-
|t(9:14)(p13:q32)||IGH/PAX5|| ||rare
|Yes
|No
|No
|
|}

==Individual Region Genomic Gain/Loss/LOH==

{| class="wikitable sortable"
|-
!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
|
|
|
|
|
|
|
|}
==Characteristic Chromosomal Patterns==

Put your text here

{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE

<br />
|
|
|
|
|}
==Gene Mutations (SNV/INDEL)==

<br />

{| class="wikitable sortable"
|-
!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
|-
|MYD88 L265; Activating mutation
|
|>90%
|
|
|Yes
|Yes
|Yes
|This is also seen in some non-germinal centre subtype DLBCL, NOS, primary cutaneous DLBCL, leg type, and primary CNS and testicular DLBCL cases.

Cases lacking MYDBB L265P mutation are reported to have an adverse prognosis and a lower response to ibrutinib.<br />
|-
|CXCR4 S338X or or frameshift mutations
|
|30%
|
|
|Yes
|
|Yes
|Cases with nonsense mutations, has been associated with more symptomatic/active disease, other clinical and laboratory findings, and greater resistance to ibrutinib and possibly other therapeutic agents.

Mutations are similar to those seen in the syndrome of warts, hypogammaglobulinaemia, immunodeficiency, and myelokathexis (WHIM syndrome).

Mutations in this gene are also present in a very small proportion of other small B-cell lymphomas.
|-
|ARID1A
|
|17%
|
|
|
|
|
|
|}
Less commonly, other somatic mutations, such as mutations of TP53, CD79B, KMT20 (previously designated MLL2), and MYBBP1A

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==

Put your text here

==Genes and Main Pathways Involved==

Put your text here and fill in the table
{| class="wikitable sortable"
|-
!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==

Put your text here

==Familial Forms==

Put your text here

==Additional Information==

Put your text here

==Links==

Put your text placeholder here (use "Link" icon at top of page)

==References==
<references />
(use "Cite" icon at top of page
==Notes==
<nowiki>*</nowiki>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.

HAEM4Backup:Lymphoplasmacytic Lymphoma - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== Kapitolina Semenova, MD, Jack Reid, MD, Fabiola Quintero-Rivera, MD Departments of Pathology, Laboratory Medicine, and *Pediatrics, Division of Geneti..."

Bailey.Glen: Created page with "==Primary Author(s)== Kapitolina Semenova, MD, Jack Reid, MD, Fabiola Quintero-Rivera, MD Departments of Pathology, Laboratory Medicine, and Pediatrics, Division of Geneti..."