Non-Hodgkin lymphoma pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==


===Pathogenesis==
==Pathogenesis==


*Lymphomas can arise from different stages of B cell devevlopment:
*Lymphomas can arise from different stages of B cell development:
*[[B cell development]] starts in the primary lymphoid tissue, the bone marrow and subsequent maturation takes place in secondary lymphoid tissue (spleen and lymph nodes).
*[[B cell|B cell development]] starts in the primary lymphoid tissue, the [[bone marrow]] and subsequent maturation takes place in secondary [[Lymphatic system|lymphoid tissue]] ([[spleen]] and [[Lymph node|lymph nodes]]).
*At the [[germinal centers]] of secondary lymphoid tissue B cells encounter antigens via T cells and then undergo affinity maturation to produce immunoglobulins of high affinity.
*At the [[germinal centers]] of secondary lymphoid tissue [[B cell|B cells]] encounter antigens via [[T cell|T cells]] and then undergo [[affinity maturation]] to produce [[Antibody|immunoglobulins]] of high affinity.
*It supports rapid B-cell proliferation for [[immunoglobulin]] affinity maturation and production of antibody diversity through two processes know as [[somatic hypermutation]] (SHM) and [[Class switching|immunoglobulin class switching]].
*It supports rapid B-cell proliferation for [[immunoglobulin]] affinity maturation and production of antibody diversity through two processes know as [[somatic hypermutation]] (SHM) and [[Class switching|immunoglobulin class switching]].
*Both of these processes require  rapid cell turnover and multiple double stranded [[DNA]] breaks, which is error-prone.
*Both of these processes require  rapid cell turnover and multiple double stranded [[DNA]] breaks, which is error-prone.
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* The major subtypes of non-hodgkin lymphoma include the following:<ref name="pmid21261684">{{cite journal| author=Coupland SE| title=The challenge of the microenvironment in B-cell lymphomas. | journal=Histopathology | year= 2011 | volume= 58 | issue= 1 | pages= 69-80 | pmid=21261684 | doi=10.1111/j.1365-2559.2010.03706.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21261684  }}</ref><ref>{{cite journal|doi=10.1182/blood-2016- 01-643569}}</ref>
* The major subtypes of non-hodgkin lymphoma include the following:<ref name="pmid21261684">{{cite journal| author=Coupland SE| title=The challenge of the microenvironment in B-cell lymphomas. | journal=Histopathology | year= 2011 | volume= 58 | issue= 1 | pages= 69-80 | pmid=21261684 | doi=10.1111/j.1365-2559.2010.03706.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21261684  }}</ref><ref>{{cite journal|doi=10.1182/blood-2016- 01-643569}}</ref>
** Mature B-cell neoplasms:
** Mature B-cell neoplasms:
*** Burkitt lymphoma  
*** [[Burkitt's lymphoma|Burkitt lymphoma]]
*** Diffuse large B cell lymphoma  
*** [[Diffuse large B cell lymphoma]]
*** Mantle cell lymphoma
*** Mantle cell lymphoma
*** Small lymphocytic lymphoma
*** Small lymphocytic lymphoma
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==Genetics==
==Genetics==


Different subtypes of non Hodgkin lymphoma and their genetic involvements::<ref> Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015</ref><ref>{{cite web|title=NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas|url=http://cancer.gov/newscenter/newsfromnci/2012/BurkittReleaseStaudt|publisher=National Cancer Institute}}</ref> These ''TCF3'' and ''[[ID3 (gene)|ID3]]'' gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to [[targeted therapy]].<ref>Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 {{DOI|10.1038/nature11378}}</ref>
Different subtypes of non Hodgkin lymphoma and their genetic involvements::<ref>Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015</ref><ref>{{cite web|title=NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas|url=http://cancer.gov/newscenter/newsfromnci/2012/BurkittReleaseStaudt|publisher=National Cancer Institute}}</ref><ref>Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 {{DOI|10.1038/nature11378}}</ref>


{| class="wikitable"
{| class="wikitable"
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!Genes involves
!Genes involves
|-
|-
|Burkitt lymphoma
|[[Burkitt's lymphoma|Burkitt lymphoma]]
|t(8;14)  
|t(8;14)
t(2;8)
 
t(8;22)  


|c-myc, IgH (Ig heavy chain)
|c-myc, IgH (Ig heavy chain)
kappa light chain, c-myc
c-myc, lambda light chain
|-
|-
|Diffuse large B cell lymphoma
|Diffuse large B cell lymphoma
|t(3;16)(q27;p11)
|t(3;v)(q27;v)
t(14;18)(q32;q21)
 
t(8;v)(q24;v)
 
inv(3q)
 
t(6;v)(p25.3;v)
 
t(14;16)(q32;q24.1)
 
t(5;14)(q33;q32)
 
t(14;17)(q32;p13.1)
 
t(9;14)(p13;q32)
|BCL6 and variable partners; Ig heavy chain most common
 
Ig heavy chain and BCL2
 
MYC and variable partners; Ig heavy chain most common ; kappa and lambda light chain< 10%
 
TBL1XR1-TP63
 
IRF4 with Ig; usually Ig heavy chain but rarely  kappa and lambda light chain
 
Ig heavy chain and IRF8
 
EBF1 and  Ig heavy chain
 
Ig heavy chain and TNFRSF13


t(11;14)(q13;q32)
PAX5 and  Ig heavy chain
|
|-
|-
|Mantle cell lymphoma
|Mantle cell lymphoma

Revision as of 17:24, 13 December 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Non Hodgkin's Lymphoma represents a heterogeneous group of diseases with varied clinical presentation and histological appearance.It arises from cell of the lymphoid system, tumors are mainly derived from B lymphocytes, but are also from T lymphocytes, or natural killer cells. Lymphomas rise from different stages of B and T cell differentiation. Aberrations in the tightly controlled steps of B cell development can lead to oncogenesis. These aberrations are mainly seen in form of chromosomal translocation.


Pathophysiology

Pathogenesis

  • The major subtypes of non-hodgkin lymphoma include the following:[4][5]
    • Mature B-cell neoplasms:
    • Mature T and NK neoplasms:
      • Adult T-cell lymphoma
      • Mycosis fungoides
      • Sezary syndrome
      • Peripheral T cell lymphoma

Genetics

Different subtypes of non Hodgkin lymphoma and their genetic involvements::[6][7][8]

NHL Subtype Translocations Genes involves
Burkitt lymphoma t(8;14)

t(2;8)

t(8;22)

c-myc, IgH (Ig heavy chain)

kappa light chain, c-myc

c-myc, lambda light chain

Diffuse large B cell lymphoma t(3;v)(q27;v)

t(14;18)(q32;q21)

t(8;v)(q24;v)

inv(3q)

t(6;v)(p25.3;v)

t(14;16)(q32;q24.1)

t(5;14)(q33;q32)

t(14;17)(q32;p13.1)

t(9;14)(p13;q32)

BCL6 and variable partners; Ig heavy chain most common

Ig heavy chain and BCL2

MYC and variable partners; Ig heavy chain most common ; kappa and lambda light chain< 10%

TBL1XR1-TP63

IRF4 with Ig; usually Ig heavy chain but rarely kappa and lambda light chain

Ig heavy chain and IRF8

EBF1 and Ig heavy chain

Ig heavy chain and TNFRSF13

PAX5 and Ig heavy chain

Mantle cell lymphoma
Small lymphocytic lymphoma
Follicular lymphoma
Extranodal marginal zone lymphoma
Splenic marginal zone lymphoma
Lymphoplasmacytic lymphoma

[Disease name] is transmitted in [mode of genetic transmission] pattern.

OR

Genes involved in the pathogenesis of [disease name] include:

  • [Gene1]
  • [Gene2]
  • [Gene3]

OR

The development of [disease name] is the result of multiple genetic mutations such as:

  • [Mutation 1]
  • [Mutation 2]
  • [Mutation 3]

Associated Conditions

Conditions associated with [disease name] include:

  • [Condition 1]
  • [Condition 2]
  • [Condition 3]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. ↑ Basso K, Dalla-Favera R (March 2015). "Germinal centres and B cell lymphomagenesis". Nat. Rev. Immunol. 15 (3): 172–84. doi:10.1038/nri3814. PMID 25712152.
  2. ↑ Nardini E, Aiello A, Giardini R, Colnaghi MI, Ménard S, Balsari A (February 2000). "Detection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas". Blood. 95 (3): 1032–8. PMID 10648419.
  3. ↑ Klein U, Dalla-Favera R (January 2008). "Germinal centres: role in B-cell physiology and malignancy". Nat. Rev. Immunol. 8 (1): 22–33. doi:10.1038/nri2217. PMID 18097447.
  4. ↑ Coupland SE (2011). "The challenge of the microenvironment in B-cell lymphomas". Histopathology. 58 (1): 69–80. doi:10.1111/j.1365-2559.2010.03706.x. PMID 21261684.
  5. ↑ . doi:10.1182/blood-2016- 01-643569 Check |doi= value (help). Missing or empty |title= (help)
  6. ↑ Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015
  7. ↑ "NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas". National Cancer Institute.
  8. ↑ Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 doi:10.1038/nature11378

Template:WH Template:WS

Genetics

The development of Non-Hodgkin lymphoma is the result of multiple genetic mutations such as:[1][2]

  • Mutations of the B-cell receptor genes and NFKB pathway
  • RNA splicing mutations in the small lymphocytic lymphoma
  • Genetic mutations in histone formation:[3]
    • MLL2
    • MEF2B
    • EZH2
    • CREBBP
    • EP300
    • MLL2

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. ↑ Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A; et al. (2011). "Analysis of the coding genome of diffuse large B-cell lymphoma". Nat Genet. 43 (9): 830–7. doi:10.1038/ng.892. PMC 3297422. PMID 21804550.
  2. ↑ Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C; et al. (2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing". Proc Natl Acad Sci U S A. 109 (10): 3879–84. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.
  3. ↑ Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL; et al. (2013). "Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma". Blood. 121 (9): 1604–11. doi:10.1182/blood-2012-09-457283. PMC 3587323. PMID 23297126.


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