Non-Hodgkin lymphoma pathophysiology
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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
- Lymphomas can arise from different stages of B cell devevlopment:
- 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).
- 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.
- It supports rapid B-cell proliferation for immunoglobulin affinity maturation and production of antibody diversity through two processes know as somatic hypermutation (SHM) and immunoglobulin class switching.
- Both of these processes require rapid cell turnover and multiple double stranded DNA breaks, which is error-prone.
- Somatically acquired genetic alterations ( mainly translocations) of these processes is probably the underlying cause of lymphomagenesis.[1][2][3]
- The major subtypes of non-hodgkin lymphoma include the following:[4][5]
- Mature B-cell neoplasms:
- 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
- Mature T and NK neoplasms:
- Adult T-cell lymphoma
- Mycosis fungoides
- Sezary syndrome
- Peripheral T cell lymphoma
- Mature B-cell neoplasms:
Genetics
Different subtypes of non Hodgkin lymphoma and their genetic involvements::[6][7] These TCF3 and ID3 gene mutations in Burkitt's correspond to a cell survival pathway that may be found to be amenable to targeted therapy.[8]
| NHL Subtype | Translocations | Genes involves |
|---|---|---|
| Burkitt lymphoma | t(8;14) | c-myc, IgH (Ig heavy chain) |
| Diffuse large B cell lymphoma | t(3;16)(q27;p11)
t(11;14)(q13;q32) |
|
| 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
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ . doi:10.1182/blood-2016- 01-643569 Check
|doi=value (help). Missing or empty|title=(help) - ↑ Burkitt's Lymphoma. Wikibooks. https://en.wikibooks.org/wiki/Radiation_Oncology/NHL/Burkitt_lymphoma#Pathology Accessed on October,5 2015
- ↑ "NIH study shows Burkitt lymphoma is molecularly distinct from other lymphomas". National Cancer Institute.
- ↑ Staudt L, et al. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature. August 12, 2012 doi:10.1038/nature11378
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
- ↑ 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.