Non-Hodgkin lymphoma pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
*Non-Hodgkin's lymphoma is a group of | *Non-Hodgkin's lymphoma is a group of heterogeneous tumors with varied clinical presentation and histological appearance. | ||
*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> | |||
*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> | *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> | ||
** Burkitt lymphoma | ** Burkitt lymphoma | ||
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==== Chromosomal translocation ==== | ==== Chromosomal translocation ==== | ||
* | * | ||
==Genetics== | ==Genetics== |
Revision as of 20:41, 11 December 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
- Non-Hodgkin's lymphoma is a group of heterogeneous tumors with varied clinical presentation and histological appearance.
- These lymphoid tumors are derived from B lymphocytes, T lymphocytes, or natural killer cells which are the main immune cells in the body.[1]
- The subtypes of non-hodgkin lymphoma include the following:[2]
- Burkitt lymphoma
- Diffuse large B cell lymphoma
- Mantle cell lymphoma
- Small lymphocytic lymphoma
- Follicular lymphoma
- Extranodal marginal zone lymphoma
- Splenic marginal zone lymphoma
- Lymphoplasmacytic lymphoma
Pathogenesis
- 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.
- 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.
- 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.[3]
- Different genetic alteration related to lymphoma:[4]
- 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.[5]
- 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.[6]
Chromosomal translocation
Genetics
The development of Non-Hodgkin lymphoma is the result of multiple genetic mutations such as:[7][8]
- Mutations of the B-cell receptor genes and NFKB pathway
- RNA splicing mutations in the small lymphocytic lymphoma
- Genetic mutations in histone formation:[9]
- 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
- ↑ Farrell K, Jarrett RF (2011). "The molecular pathogenesis of Hodgkin lymphoma". Histopathology. 58 (1): 15–25. doi:10.1111/j.1365-2559.2010.03705.x. PMID 21261680.
- ↑ 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.
- ↑ Johansson B, Mertens F, Mitelman F (1995). "Cytogenetic evolution patterns in non-Hodgkin's lymphoma". Blood. 86 (10): 3905–14. PMID 7579360.
- ↑ Couronné L, Bastard C, Bernard OA (2012). "TET2 and DNMT3A mutations in human T-cell lymphoma". N Engl J Med. 366 (1): 95–6. doi:10.1056/NEJMc1111708. PMID 22216861.
- ↑ Gaidano G, Ballerini P, Gong JZ, Inghirami G, Neri A, Newcomb EW; et al. (1991). "p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia". Proc Natl Acad Sci U S A. 88 (12): 5413–7. PMC 51883. PMID 2052620.
- ↑ Gaidano G, Hauptschein RS, Parsa NZ, Offit K, Rao PH, Lenoir G; et al. (1992). "Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma". Blood. 80 (7): 1781–7. PMID 1356511.
- ↑ 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.
- ↑ 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.
- ↑ 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.