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 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).
- 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][8][9][10][11][12][13][14]
| NHL Subtype | Translocations | Genes involves |
|---|---|---|
| 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) 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 | 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
- ↑ 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
- ↑ 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 (July 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.
- ↑ 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 (January 2016). "Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma". Oncotarget. 7 (3): 2401–16. doi:10.18632/oncotarget.6262. PMC 4823044. PMID 26573234.
- ↑ Nguyen L, Papenhausen P, Shao H (April 2017). "The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects". Genes (Basel). 8 (4). doi:10.3390/genes8040116. PMC 5406863. PMID 28379189.
- ↑ Offit, Kenneth; Coco, Francesco Lo; Louie, Diane C.; Parsa, Nasser Z.; Leung, Denis; Portlock, Carol; Ye, Bihui H.; Lista, Florigio; Filippa, Daniel A.; Rosenbaum, Ayala; Ladanyi, Marc; Jhanwar, Suresh; Dalla-Favera, Riccardo; Chaganti, R.S.K. (1994). "Rearrangement of the bcl-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma". New England Journal of Medicine. 331 (2): 74–80. doi:10.1056/NEJM199407143310202. ISSN 0028-4793.
- ↑ Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM (November 1998). "Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma". Blood. 92 (9): 3152–62. PMID 9787151.
- ↑ 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 (2013). "CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma". Blood. 121 (8): 1394–1402. doi:10.1182/blood-2012-08-452284. PMID 23255553. Unknown parameter
|month=ignored (help)
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.