Non-Hodgkin lymphoma pathophysiology: Difference between revisions

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{{Non-Hodgkin lymphoma}}
{{Non-Hodgkin lymphoma}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{Preeti}}
==Overview==
==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.
Non Hodgkin's Lymphoma (NHL) 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. About 85% of NHL's are of B-cell origin and only 15% are derived from T/NK cells. Two specific lymphomas, follicular lymphoma and diffuse large B cell lymphoma, account for about 65% of all non-Hodgkin lymphomas.
 


==Pathophysiology==
==Pathophysiology==
 
*[[Lymphoma|Lymphomas]] can arise from different stages of [[B cell|B cell development]]:
==Pathogenesis==
 
*Lymphomas can arise from different stages of B cell development:
*[[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]]).
*[[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 cell|B cells]] encounter antigens via [[T cell|T cells]] and then undergo [[affinity maturation]] to produce [[Antibody|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.
*Somatically acquired genetic alterations ( mainly [[Chromosomal translocation|translocations]]) of these processes is probably the underlying cause of lymphomagenesis.<ref name="pmid25712152">{{cite journal |vauthors=Basso K, Dalla-Favera R |title=Germinal centres and B cell lymphomagenesis |journal=Nat. Rev. Immunol. |volume=15 |issue=3 |pages=172–84 |date=March 2015 |pmid=25712152 |doi=10.1038/nri3814 |url=}}</ref><ref name="pmid10648419">{{cite journal |vauthors=Nardini E, Aiello A, Giardini R, Colnaghi MI, Ménard S, Balsari A |title=Detection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas |journal=Blood |volume=95 |issue=3 |pages=1032–8 |date=February 2000 |pmid=10648419 |doi= |url=}}</ref><ref name="pmid18097447">{{cite journal |vauthors=Klein U, Dalla-Favera R |title=Germinal centres: role in B-cell physiology and malignancy |journal=Nat. Rev. Immunol. |volume=8 |issue=1 |pages=22–33 |date=January 2008 |pmid=18097447 |doi=10.1038/nri2217 |url=}}</ref>
*Somatically acquired genetic alterations ( mainly [[Chromosomal translocation|translocations]]) of these processes is probably the underlying cause of lymphomagenesis.


* 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 (NHL) include the following:
** Mature B-cell neoplasms:
** Mature B-cell neoplasms:
*** [[Diffuse large B cell lymphoma]]
*** [[Follicular lymphoma]]
*** [[Burkitt's lymphoma|Burkitt lymphoma]]  
*** [[Burkitt's lymphoma|Burkitt lymphoma]]  
*** [[Diffuse large B cell lymphoma]]  
*** [[Mantle cell lymphoma]]
*** Mantle cell lymphoma
*** [[Hairy cell leukemia]]
*** Small lymphocytic lymphoma
*** Follicular lymphoma
*** Extranodal marginal zone lymphoma
*** Extranodal marginal zone lymphoma
*** Splenic marginal zone lymphoma
*** [[Splenic marginal zone lymphoma]]
*** Lymphoplasmacytic lymphoma
*** [[Multiple myeloma|Plasma cell myeloma]]
** Mature T and NK neoplasms:
** Mature T and NK neoplasms:
*** Adult T-cell lymphoma
*** [[Adult T-cell leukemia|Adult T-cell lymphoma]]
*** Mycosis fungoides
*** [[Mycosis fungoides]]
*** Sezary syndrome
*** [[Sezary syndrome]]
*** Peripheral T cell lymphoma
*** [[Peripheral T cell lymphoma]]
 
==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><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><ref name="pmid21804550">{{cite journal |vauthors=Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R |title=Analysis of the coding genome of diffuse large B-cell lymphoma |journal=Nat. Genet. |volume=43 |issue=9 |pages=830–7 |date=July 2011 |pmid=21804550 |pmc=3297422 |doi=10.1038/ng.892 |url=}}</ref><ref name="pmid26573234">{{cite journal |vauthors=Ye Q, Xu-Monette ZY, Tzankov A, Deng L, Wang X, Manyam GC, Visco C, Montes-Moreno S, Zhang L, Dybkær K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WW, van Krieken JH, Huh J, Ponzoni M, Ferreri AJ, Parsons BM, Møller MB, Piris MA, Winter JN, Medeiros LJ, Hu S, Young KH |title=Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma |journal=Oncotarget |volume=7 |issue=3 |pages=2401–16 |date=January 2016 |pmid=26573234 |pmc=4823044 |doi=10.18632/oncotarget.6262 |url=}}</ref><ref name="pmid28379189">{{cite journal |vauthors=Nguyen L, Papenhausen P, Shao H |title=The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects |journal=Genes (Basel) |volume=8 |issue=4 |pages= |date=April 2017 |pmid=28379189 |pmc=5406863 |doi=10.3390/genes8040116 |url=}}</ref><ref name="OffitCoco1994">{{cite journal|last1=Offit|first1=Kenneth|last2=Coco|first2=Francesco Lo|last3=Louie|first3=Diane C.|last4=Parsa|first4=Nasser Z.|last5=Leung|first5=Denis|last6=Portlock|first6=Carol|last7=Ye|first7=Bihui H.|last8=Lista|first8=Florigio|last9=Filippa|first9=Daniel A.|last10=Rosenbaum|first10=Ayala|last11=Ladanyi|first11=Marc|last12=Jhanwar|first12=Suresh|last13=Dalla-Favera|first13=Riccardo|last14=Chaganti|first14=R.S.K.|title=Rearrangement of the bcl-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma|journal=New England Journal of Medicine|volume=331|issue=2|year=1994|pages=74–80|issn=0028-4793|doi=10.1056/NEJM199407143310202}}</ref><ref name="pmid9787151">{{cite journal |vauthors=Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM |title=Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma |journal=Blood |volume=92 |issue=9 |pages=3152–62 |date=November 1998 |pmid=9787151 |doi= |url=}}</ref><ref>{{Cite journal
| author = [[Itziar Salaverria]], [[Cristina Royo]], [[Alejandra Carvajal-Cuenca]], [[Guillem Clot]], [[Alba Navarro]], [[Alejandra Valera]], [[Joo Y. Song]], [[Renata Woroniecka]], [[Grzegorz Rymkiewicz]], [[Wolfram Klapper]], [[Elena M. Hartmann]], [[Pierre Sujobert]], [[Iwona Wlodarska]], [[Judith A. Ferry]], [[Philippe Gaulard]], [[German Ott]], [[Andreas Rosenwald]], [[Armando Lopez-Guillermo]], [[Leticia Quintanilla-Martinez]], [[Nancy L. Harris]], [[Elaine S. Jaffe]], [[Reiner Siebert]], [[Elias Campo]] & [[Silvia Bea]]
| title = CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma
| journal = [[Blood]]
| volume = 121
| issue = 8
| pages = 1394–1402
| year = 2013
| month = February
| doi = 10.1182/blood-2012-08-452284
| pmid = 23255553
}}</ref>
 
{| class="wikitable"
|+
!NHL Subtype
!Translocations
!Genes involves
|-
|[[Burkitt's lymphoma|Burkitt lymphoma]]
|t(8;14)
t(2;8)
 
t(8;22)
 
|c-myc and IgH (Ig heavy chain)
kappa light chain and c-myc
 
c-myc and 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)
*About 85% of NHLs are of B-cell origin and only 15% are derived from T/NK cells.<ref name="pmid15992695">{{cite journal| author=Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS et al.| title=Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. | journal=Lancet Oncol | year= 2005 | volume= 6 | issue= 7 | pages= 469-76 | pmid=15992695 | doi=10.1016/S1470-2045(05)70214-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15992695  }} </ref>
 
*The small remainder stems from [[macrophages]].
t(14;17)(q32;p13.1)
*These [[tumors]] are characterized by the level of [[differentiation]], the size of the [[cell]] of origin, the origin cell's rate of [[proliferation]], and the histological pattern of growth.
 
*[[Lymphomas]] of small [[lymphocytes]] generally have a more indolent course than those of large [[lymphocytes]], which may have intermediate-grade or high-grade aggressiveness.
t(9;14)(p13;q32)
*Two specific lymphomas, [[follicular lymphoma]] and [[diffuse large B cell lymphoma]], account for about 65% of all non-Hodgkin lymphomas.
|BCL6 and variable partners; Ig heavy chain most common
*The gene-expression profiles of almost all non-Hodgkin lymphomas are a reflection of the equivalent healthy cell of origin from which the [[lymphoma]] is derived.<ref name="pmid15992695">{{cite journal| author=Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS et al.| title=Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. | journal=Lancet Oncol | year= 2005 | volume= 6 | issue= 7 | pages= 469-76 | pmid=15992695 | doi=10.1016/S1470-2045(05)70214-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15992695  }} </ref>
 
*[[Follicular lymphoma]] most commonly results from the t(14;18)(q32;q21) [[translocation]]; this [[translocation]] places BCL2 (which encodes B-cell CLL/lymphoma 2) under control of the IGH enhancer element, leading to constitutive BCL2 expression.<ref name="pmid25174027">{{cite journal| author=Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM et al.| title=Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 66-75 | pmid=25174027 | doi=10.1093/jncimonographs/lgu012 | pmc=4155466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174027  }} </ref>
Ig heavy chain and BCL2
*BCL-2 is an anti-apoptotic protein, and the t(14;18)(q32;q21) translocation results in markedly elevated expression of BCL-2, which blocks the healthy germinal center default program of apoptotic cell death and represents a defining pathogenic feature of [[follicular lymphoma]].<ref name="pmid25174027">{{cite journal| author=Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM et al.| title=Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 66-75 | pmid=25174027 | doi=10.1093/jncimonographs/lgu012 | pmc=4155466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174027  }} </ref><ref name="pmid25174034">{{cite journal| author=Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF et al.| title=Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 130-44 | pmid=25174034 | doi=10.1093/jncimonographs/lgu013 | pmc=4155467 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174034  }} </ref>
 
*Similarly, [[mantle cell lymphoma]] is characterised by the t(11;14)(q13;q32) translocation, which leads to the deregulated expression of [[cyclin D1]].<ref name="pmid28978864">{{cite journal| author=Tamaru JI| title=2016 revision of the WHO classification of lymphoid neoplasms. | journal=Rinsho Ketsueki | year= 2017 | volume= 58 | issue= 10 | pages= 2188-2193 | pmid=28978864 | doi=10.11406/rinketsu.58.2188 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28978864  }} </ref>
MYC and variable partners; Ig heavy chain most common ; kappa and lambda light chain< 10%
*Moreover, [[burkitt lymphoma]] overexpresses MYC as a result of the t(8;14)(q24;q32) [[translocation]] or variants.
 
*Recurrent [[translocations]] are less common in [[peripheral T-cell lymphomas]] than in other types of lymphoma, and examples include the characteristic t(2;5) (p23;q35) [[translocation]] seen in [[anaplastic lymphoma kinase]] (ALK)-positive [[anaplastic T-cell lymphoma]] and the t(5;9)(q33;q22) translocation associated with [[Follicular lymphoma|follicular T-cell lymphoma]].<ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727  }} </ref>
TBL1XR1-TP63
*Recurrent translocations including t(6;7) (p25;q32) and recurrent gene fusions involving the tumour-suppressor gene [[TP63]] are characteristic of ALK-negative [[anaplastic T-cell lymphoma]].<ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727  }} </ref><ref name="pmid29741263">{{cite journal| author=Matutes E| title=The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms. | journal=Int J Lab Hematol | year= 2018 | volume= 40 Suppl 1 | issue=  | pages= 97-103 | pmid=29741263 | doi=10.1111/ijlh.12817 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29741263  }} </ref><br />
 
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
|t(11;14)(q13;q32)
|CCDN1 (cyclin D1) and immunoglobulin heavy chain
|-
|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==
{{Reflist|2}}
 
{{WH}}
{{WS}}
[[Category: (name of the system)]]


==Genetics==
==Genetics==
The development of Non-Hodgkin lymphoma is the result of multiple genetic mutations such as:<ref name="pmid21804550">{{cite journal| author=Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A et al.| title=Analysis of the coding genome of diffuse large B-cell lymphoma. | journal=Nat Genet | year= 2011 | volume= 43 | issue= 9 | pages= 830-7 | pmid=21804550 | doi=10.1038/ng.892 | pmc=3297422 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21804550  }}</ref><ref name="pmid22343534">{{cite journal| author=Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C et al.| title=Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 10 | pages= 3879-84 | pmid=22343534 | doi=10.1073/pnas.1121343109 | pmc=3309757 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22343534  }}</ref>
The development of non-Hodgkin lymphoma is the result of multiple genetic mutations such as:<ref name="pmid21804550">{{cite journal| author=Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A et al.| title=Analysis of the coding genome of diffuse large B-cell lymphoma. | journal=Nat Genet | year= 2011 | volume= 43 | issue= 9 | pages= 830-7 | pmid=21804550 | doi=10.1038/ng.892 | pmc=3297422 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21804550  }}</ref><ref name="pmid22343534">{{cite journal| author=Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C et al.| title=Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 10 | pages= 3879-84 | pmid=22343534 | doi=10.1073/pnas.1121343109 | pmc=3309757 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22343534  }}</ref>
*[[Mutations]] of the [[B-cell]] receptor genes and [[NFKB]] pathway.
*[[RNA splicing]] [[mutations]] in the [[small lymphocytic lymphoma]].
*[[Genetic mutations]] in histone formation:<ref name="pmid23297126">{{cite journal| author=Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL et al.| title=Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. | journal=Blood | year= 2013 | volume= 121 | issue= 9 | pages= 1604-11 | pmid=23297126 | doi=10.1182/blood-2012-09-457283 | pmc=3587323 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23297126  }}</ref>
**[[MLL2]]
**[[MEF2B]]
**[[EZH2]]
**CREBBP
**[[EP300]]
**[[MLL2]]
**[[KMT2D]]
*Mutations in [[CDKN2A]] alters cell cycle control and affects JAK–STAT signalling.
*Upregulation of key signalling pathways such as [[CD79B]], [[MYD88]], [[CARD11]].
*Block to terminal differentiation such as [[BCL6]] translocations and loss of [[PRDM1]].


*Mutations of the B-cell receptor genes and NFKB pathway
== Associated Conditions ==
*RNA splicing mutations in the small lymphocytic lymphoma
* Several conditions are associated with non-Hodgkin's lymphoma depending on the type. However, [[Epstein Barr virus]], [[Human Immunodeficiency Virus|human immunodeficiency virus]], and [[hepatitis C]] infection are commonly present.
*Genetic mutations in histone formation:<ref name="pmid23297126">{{cite journal| author=Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL et al.| title=Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. | journal=Blood | year= 2013 | volume= 121 | issue= 9 | pages= 1604-11 | pmid=23297126 | doi=10.1182/blood-2012-09-457283 | pmc=3587323 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23297126  }}</ref>
**MLL2
**MEF2B
**EZH2
**CREBBP
**EP300
**MLL2


==Gross Pathology==
== Gross Pathology ==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*For information on gross pathology findings of [[Follicular lymphoma]], [[Follicular lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Mantle cell lymphoma]], [[Mantel cell lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Hairy cell leukemia]], [[hairy cell leukemia pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Splenic marginal zone lymphoma]], [[Splenic marginal zone lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Mycosis fungoides]], [[Mycosis fungoides pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Peripheral T cell lymphoma]], [[Peripheral T cell lymphoma pathophysiology#Gross Pathology|click here]].


==Microscopic Pathology==
== Microscopy Pathology ==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*For information on microscopic pathology findings of [[Follicular lymphoma]], [[Follicular lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Mantle cell lymphoma]], [[Mantel cell lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Hairy cell leukemia]], [[hairy cell leukemia pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Splenic marginal zone lymphoma]], [[Splenic marginal zone lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Mycosis fungoides]], [[Mycosis fungoides pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Peripheral T cell lymphoma]], [[Peripheral T cell lymphoma pathophysiology#Microscopic Pathology|click here]].


==References==
==References==

Latest revision as of 20:27, 21 January 2019

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Differentiating Non-Hodgkin's Lymphoma

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Differentiating Types of Non-Hodgkin's Lymphoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]

Overview

Non Hodgkin's Lymphoma (NHL) 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. About 85% of NHL's are of B-cell origin and only 15% are derived from T/NK cells. Two specific lymphomas, follicular lymphoma and diffuse large B cell lymphoma, account for about 65% of all non-Hodgkin lymphomas.

Pathophysiology

Genetics

The development of non-Hodgkin lymphoma is the result of multiple genetic mutations such as:[7][8]

Associated Conditions

Gross Pathology

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References

  1. ↑ 1.0 1.1 Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS; et al. (2005). "Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis". Lancet Oncol. 6 (7): 469–76. doi:10.1016/S1470-2045(05)70214-X. PMID 15992695.
  2. ↑ 2.0 2.1 Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM; et al. (2014). "Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 66–75. doi:10.1093/jncimonographs/lgu012. PMC 4155466. PMID 25174027.
  3. ↑ Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF; et al. (2014). "Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 130–44. doi:10.1093/jncimonographs/lgu013. PMC 4155467. PMID 25174034.
  4. ↑ Tamaru JI (2017). "2016 revision of the WHO classification of lymphoid neoplasms". Rinsho Ketsueki. 58 (10): 2188–2193. doi:10.11406/rinketsu.58.2188. PMID 28978864.
  5. ↑ 5.0 5.1 Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.
  6. ↑ Matutes E (2018). "The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms". Int J Lab Hematol. 40 Suppl 1: 97–103. doi:10.1111/ijlh.12817. PMID 29741263.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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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