Non-Hodgkin lymphoma pathophysiology: Difference between revisions

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{{CMG}}; {{AE}}  
{{CMG}}; {{AE}}  
==Overview==
==Overview==
{{CMG}}; {{AE}}
==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==
==Pathophysiology==
===Physiology===
The normal physiology of [name of process] can be understood as follows:


*Non-Hodgkin's lymphoma is a group of heterogeneous tumors with varied clinical presentation and histological appearance.
===Pathogenesis===
*85%-90% of these lymphoid tumors are derived from B lymphocytes rest are from T lymphocytes, or natural killer cells.<ref name="pmid26980727">{{cite journal |vauthors=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES |title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms |journal=Blood |volume=127 |issue=20 |pages=2375–90 |date=May 2016 |pmid=26980727 |doi=10.1182/blood-2016-01-643569 |url=}}</ref>
*The exact pathogenesis of [disease name] is not completely understood.
*The 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>
OR
** Burkitt lymphoma
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
** Diffuse large B cell lymphoma
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
** Mantle cell lymphoma
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
** Small lymphocytic lymphoma
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
** Follicular lymphoma
*The progression to [disease name] usually involves the [molecular pathway].
** Extranodal marginal zone lymphoma
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
** Splenic marginal zone lymphoma
** Lymphoplasmacytic lymphoma
*Among these [[follicular lymphoma]] and [[diffuse large B cell lymphoma]] (DLBCL), account for about 65%
of all non-Hodgkin lymphomas.
 


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


OR


*These lymphoid tumors are derived from B lymphocytes, T lymphocytes, or natural killer cells which are the main immune cells in the body.<ref name="pmid21261680">{{cite journal| author=Farrell K, Jarrett RF| title=The molecular pathogenesis of Hodgkin lymphoma. | journal=Histopathology | year= 2011 | volume= 58 | issue= 1 | pages= 15-25 | pmid=21261680 | doi=10.1111/j.1365-2559.2010.03705.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21261680  }}</ref>
Genes involved in the pathogenesis of [disease name] include:
*[Gene1]
*[Gene2]
*[Gene3]


=== Pathogenesis ===
OR
*Lymphomas rise from different stages of B cell differentiation.


*The main mechanism of pathogenesis of NHL is recurrent balanced chromosomal translocation of key genes under the control of specific promoters and enhancers leading to oncogene activation.
The development of [disease name] is the result of multiple genetic mutations such as:
*Chromosomal translocations can be divided into two types:
*# When an intact oncogene (or intact coding region) is translocation with another gene, usually an antigen receptor gene. As a result, the oncogene becomes transcriptionally deregulated. Examples of this type include the t(8;14) in Burkitt lymphoma and the t(14;18) in follicular lymphoma.
*#Parts of two usually non–antigen receptor genes are disrupted and juxtaposed on each other, resulting in a fusion gene. Example of this type include the t(2;5) in anaplastic large cell lymphoma (ALCL).<ref name="pmid12946230">{{cite journal |vauthors=Vega F, Medeiros LJ |title=Chromosomal translocations involved in non-Hodgkin lymphomas |journal=Arch. Pathol. Lab. Med. |volume=127 |issue=9 |pages=1148–60 |date=September 2003 |pmid=12946230 |doi=10.1043/1543-2165(2003)127<1148:CTIINL>2.0.CO;2 |url=}}</ref>


*[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].


* The main pathogenesis mechanism of NHL is genetic mutations of the proto-oncogenes and tumor suppressor genes. It is activation of proto-oncogenes or inactivation of the tumor suppressor genes. 
==References==
* Unlike the solid tumors, the lymphomas do not have have microsatellite instability which is a DNA mismatch repair defect. Microsatellite instability is incorporated in the pathogenesis of many solid tumors. 
{{Reflist|2}}
* In NHL, there is mostly single or few chromosomal abnormalities in the genes causing lymphoma and it is caused by chromosomal translocation. The unbalanced translocations has been shown to be the cause of the disease progression.<ref name="pmid7579360">{{cite journal| author=Johansson B, Mertens F, Mitelman F| title=Cytogenetic evolution patterns in non-Hodgkin's lymphoma. | journal=Blood | year= 1995 | volume= 86 | issue= 10 | pages= 3905-14 | pmid=7579360 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7579360  }}</ref>
* 
* Different genetic alteration related to lymphoma:<ref name="pmid22216861">{{cite journal| author=Couronné L, Bastard C, Bernard OA| title=TET2 and DNMT3A mutations in human T-cell lymphoma. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 1 | pages= 95-6 | pmid=22216861 | doi=10.1056/NEJMc1111708 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22216861  }}</ref>
** Point mutation which result in changes in control of transcription genes as TET and DNMT3A mutations.
** Spliceosome mutations altering the process of translation.
* Deletion of p53 tumor suppresor gene is related to specific types of NHL as late stages of follicular lymphoma, CLL/SLL, and mantle cell lymphoma.<ref name="pmid2052620">{{cite journal| author=Gaidano G, Ballerini P, Gong JZ, Inghirami G, Neri A, Newcomb EW et al.| title=p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. | journal=Proc Natl Acad Sci U S A | year= 1991 | volume= 88 | issue= 12 | pages= 5413-7 | pmid=2052620 | doi= | pmc=51883 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2052620  }}</ref>
* The p53 gene inactivation is caused by point mutation in one allele and may be associated with consequent deletion of the second allele "second hit hypothesis". The deletion of the chromosome 6q is the frequent chromosomal deletion associated with lymphomas.<ref name="pmid1356511">{{cite journal| author=Gaidano G, Hauptschein RS, Parsa NZ, Offit K, Rao PH, Lenoir G et al.| title=Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma. | journal=Blood | year= 1992 | volume= 80 | issue= 7 | pages= 1781-7 | pmid=1356511 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1356511  }}</ref>


==== Chromosomal translocation ====
{{WH}}
*
{{WS}}
[[Category: (name of the system)]]


==Genetics==
==Genetics==

Revision as of 17:32, 12 December 2018

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

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; 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

Physiology

The normal physiology of [name of process] can be understood as follows:

Pathogenesis

  • The exact pathogenesis of [disease name] is not completely understood.

OR

  • It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
  • [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
  • Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
  • [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
  • The progression to [disease name] usually involves the [molecular pathway].
  • The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

[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

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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