Diffuse large B cell lymphoma pathophysiology: Difference between revisions
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*The presence of gene expression signatures commonly associated with [[macrophage]]s, T cells, and remodelling of the [[extracellular matrix]] seems to be associated with an improved prognosis and better overall survival.<ref name="Lenz2008" /><ref name="Linderoth2008">{{cite journal |doi=10.1111/j.1365-2141.2008.07037.x |pmid=18419622 |title=Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma |journal=British Journal of Haematology |volume=141 |issue=4 |pages=423–32 |year=2008 |last1=Linderoth |first1=Johan |last2=Edén |first2=Patrik |last3=Ehinger |first3=Mats |last4=Valcich |first4=Jeanette |last5=Jerkeman |first5=Mats |last6=Bendahl |first6=Pär-Ola |last7=Berglund |first7=Mattias |last8=Enblad |first8=Gunilla |last9=Erlanson |first9=Martin |last10=Roos |first10=Göran |last11=Cavallin-Ståhl |first11=Eva }}</ref> | *The presence of gene expression signatures commonly associated with [[macrophage]]s, T cells, and remodelling of the [[extracellular matrix]] seems to be associated with an improved prognosis and better overall survival.<ref name="Lenz2008" /><ref name="Linderoth2008">{{cite journal |doi=10.1111/j.1365-2141.2008.07037.x |pmid=18419622 |title=Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma |journal=British Journal of Haematology |volume=141 |issue=4 |pages=423–32 |year=2008 |last1=Linderoth |first1=Johan |last2=Edén |first2=Patrik |last3=Ehinger |first3=Mats |last4=Valcich |first4=Jeanette |last5=Jerkeman |first5=Mats |last6=Bendahl |first6=Pär-Ola |last7=Berglund |first7=Mattias |last8=Enblad |first8=Gunilla |last9=Erlanson |first9=Martin |last10=Roos |first10=Göran |last11=Cavallin-Ståhl |first11=Eva }}</ref> | ||
*Alternatively, expression of genes coding for [[Angiogenesis|pro-angiogenic]] factors is correlated with poorer survival.<ref name="Lenz2008" /> | *Alternatively, expression of genes coding for [[Angiogenesis|pro-angiogenic]] factors is correlated with poorer survival.<ref name="Lenz2008" /> | ||
Recently, it was described that short non-coding RNAs named microRNAs (miRNAs) have important functions in lymphoma biology. | Recently, it was described that short non-coding RNAs named microRNAs (miRNAs) have important functions in lymphoma biology. | ||
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*Production and class-switching of immunoglobulins.<ref name="pmid25541152">{{cite journal |doi=10.1038/leu.2014.351 |title=MicroRNAs in B-cell lymphomas: How a complex biology gets more complex |journal=Leukemia |year=2015 |last1=Musilova |first1=K |last2=Mraz |first2=M }}</ref> | *Production and class-switching of immunoglobulins.<ref name="pmid25541152">{{cite journal |doi=10.1038/leu.2014.351 |title=MicroRNAs in B-cell lymphomas: How a complex biology gets more complex |journal=Leukemia |year=2015 |last1=Musilova |first1=K |last2=Mraz |first2=M }}</ref> | ||
MiRNAs influence B cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and [[memory B cell]]s.<ref name="pmid25541152"/> | MiRNAs influence B cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and [[memory B cell]]s.<ref name="pmid25541152"/> | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
Revision as of 22:58, 20 August 2015
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Genetics
- Gene expression profiling studies have also attempted to distinguish heterogeneous groups of Diffuse large B cell lymphoma from each other.
- These studies examine thousands of genes simultaneously using a DNA microarray, looking for patterns which may help in grouping cases of Diffuse large B cell lymphoma.
- Many studies now suggest that cases of Diffuse large B cell lymphoma,not otherwise specified can be separated into two groups on the basis of their gene expression profiles
- Tumour cells in the Germinal centre B-cell-like subgroup resemble normal B cells in the germinal centre closely, and are generally associated with a favourable prognosis.[4][5]
- Activated B-cell-like tumour cells are associated with a poorer prognosis,[5] and derive their name from studies which show the continuous activation of certain pathways normally activated when B cells interact with an antigen.
- The NF-κB pathway, which is normally involved in transforming B cells into plasma cells, is an important example of one such pathway.[6]
MicroRNA expression
- Recent gene expression studies is the importance of the cells and microscopic structures interspersed between the malignant B cells within the Diffuse large B cell lymphoma tumor, an area commonly known as the tumour microenvironment.
- The presence of gene expression signatures commonly associated with macrophages, T cells, and remodelling of the extracellular matrix seems to be associated with an improved prognosis and better overall survival.[5][7]
- Alternatively, expression of genes coding for pro-angiogenic factors is correlated with poorer survival.[5]
Recently, it was described that short non-coding RNAs named microRNAs (miRNAs) have important functions in lymphoma biology. In malignant B cells miRNAs participate in pathways fundamental to B cell development like
- B cell receptor (BCR) signalling
- B cell migration/adhesion
- Cell-cell interactions in immune niches
- Production and class-switching of immunoglobulins.[8]
MiRNAs influence B cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and memory B cells.[8]
Microscopic Pathology
- Three variants are most commonly seen: centroblastic, immunoblastic, and anaplastic.
Centroblastic
- Most cases of are Diffuse large B cell lymphoma centroblastic, having the appearance of medium-to-large-sized lymphocytes with scanty cytoplasm.
- Oval or round nuclei containing fine chromatin are prominently visible, having two to four nucleoli within each nucleus.
- Sometimes the tumour may be monomorphic, composed almost entirely of centroblasts.
- However, most cases are polymorphic, with a mixture of centroblastic and immunoblastic cells.
Immunoblastic
- Immunoblasts have significant basophilic cytoplasm and a central nucleolus.
- A tumour can be classified as immunoblastic if greater than 90% of its cells are immunoblasts. This distinction can be problematic, however, because hematopathologists reviewing the microscope slides may often disagree on whether a collection of cells is best characterized as centroblasts or immunoblasts.[9] Such disagreement indicates poor inter-rater reliability.
Anaplastic
- The third morphologic variant, anaplastic, consists of tumour cells which appear very differently from their normal B cell counterparts.
- The cells are generally very large with a round, oval, or polygonal shape and pleomorphic nuclei, and may resemble Hodgkin cells or Reed-Sternberg cells.
References
- ↑ Shipp, Margaret A.; Ross, Ken N.; Tamayo, Pablo; Weng, Andrew P.; Kutok, Jeffery L.; Aguiar, Ricardo C.T.; Gaasenbeek, Michelle; Angelo, Michael; Reich, Michael; Pinkus, Geraldine S.; Ray, Tane S.; Koval, Margaret A.; Last, Kim W.; Norton, Andrew; Lister, T. Andrew; Mesirov, Jill; Neuberg, Donna S.; Lander, Eric S.; Aster, Jon C.; Golub, Todd R. (2002). "Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning". Nature Medicine. 8 (1): 68–74. doi:10.1038/nm0102-68. PMID 11786909.
- ↑ Rosenwald, Andreas; Wright, George; Chan, Wing C.; Connors, Joseph M.; Campo, Elias; Fisher, Richard I.; Gascoyne, Randy D.; Muller-Hermelink, H. Konrad; Smeland, Erlend B.; Giltnane, Jena M.; Hurt, Elaine M.; Zhao, Hong; Averett, Lauren; Yang, Liming; Wilson, Wyndham H.; Jaffe, Elaine S.; Simon, Richard; Klausner, Richard D.; Powell, John; Duffey, Patricia L.; Longo, Dan L.; Greiner, Timothy C.; Weisenburger, Dennis D.; Sanger, Warren G.; Dave, Bhavana J.; Lynch, James C.; Vose, Julie; Armitage, James O.; Montserrat, Emilio; et al. (2002). "The Use of Molecular Profiling to Predict Survival after Chemotherapy for Diffuse Large-B-Cell Lymphoma". New England Journal of Medicine. 346 (25): 1937–47. doi:10.1056/NEJMoa012914. PMID 12075054.
- ↑ Wright, G.; Tan, B.; Rosenwald, A.; Hurt, E. H.; Wiestner, A.; Staudt, L. M. (2003). "A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma". Proceedings of the National Academy of Sciences. 100 (17): 9991–6. Bibcode:2003PNAS..100.9991W. doi:10.1073/pnas.1732008100. JSTOR 3147650. PMC 187912. PMID 12900505.
- ↑ Gutierrez-Garcia, G.; Cardesa-Salzmann, T.; Climent, F.; Gonzalez-Barca, E.; Mercadal, S.; Mate, J. L.; Sancho, J. M.; Arenillas, L.; Serrano, S.; Escoda, L.; Martinez, S.; Valera, A.; Martinez, A.; Jares, P.; Pinyol, M.; Garcia-Herrera, A.; Martinez-Trillos, A.; Gine, E.; Villamor, N.; Campo, E.; Colomo, L.; Lopez-Guillermo, A.; Grup per l'Estudi dels Limfomes de Catalunya I Balears (GELCAB) (2011). "Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy". Blood. 117 (18): 4836–43. doi:10.1182/blood-2010-12-322362. PMID 21441466.
- ↑ 5.0 5.1 5.2 5.3 Lenz, G.; Wright, G.; Dave, S.S.; Xiao, W.; Powell, J.; Zhao, H.; Xu, W.; Tan, B.; Goldschmidt, N.; Iqbal, J.; Vose, J.; Bast, M.; Fu, K.; Weisenburger, D.D.; Greiner, T.C.; Armitage, J.O.; Kyle, A.; May, L.; Gascoyne, R.D.; Connors, J.M.; Troen, G.; Holte, H.; Kvaloy, S.; Dierickx, D.; Verhoef, G.; Delabie, J.; Smeland, E.B.; Jares, P.; Martinez, A.; et al. (2008). "Stromal Gene Signatures in Large-B-Cell Lymphomas". New England Journal of Medicine. 359 (22): 2313–23. doi:10.1056/NEJMoa0802885. PMID 19038878.
- ↑ Schwartz, Robert S.; Lenz, Georg; Staudt, Louis M. (2010). "Aggressive Lymphomas". New England Journal of Medicine. 362 (15): 1417–29. doi:10.1056/NEJMra0807082. PMID 20393178.
- ↑ Linderoth, Johan; Edén, Patrik; Ehinger, Mats; Valcich, Jeanette; Jerkeman, Mats; Bendahl, Pär-Ola; Berglund, Mattias; Enblad, Gunilla; Erlanson, Martin; Roos, Göran; Cavallin-Ståhl, Eva (2008). "Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma". British Journal of Haematology. 141 (4): 423–32. doi:10.1111/j.1365-2141.2008.07037.x. PMID 18419622.
- ↑ 8.0 8.1 Musilova, K; Mraz, M (2015). "MicroRNAs in B-cell lymphomas: How a complex biology gets more complex". Leukemia. doi:10.1038/leu.2014.351.
- ↑ Harris, N. L.; Jaffe, E. S.; Stein, H; Banks, P. M.; Chan, J. K.; Cleary, M. L.; Delsol, G; De Wolf-Peeters, C; Falini, B; Gatter, K. C. (1994). "A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group". Blood. 84 (5): 1361–92. PMID 8068936.