Sezary syndrome pathophysiology: Difference between revisions
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{{CMG}}; {{AE}}<nowiki> {{S.G.}]</nowiki> | {{CMG}}; {{AE}}<nowiki> {{S.G.}]</nowiki> | ||
==Overview== | ==Overview== | ||
The exact pathogenesis of | The exact pathogenesis of sezary syndrome is not fully understood but a majority of genes in Sezary syndrome are deregulated. | ||
==Pathogenesis== | |||
* The exact [[pathogenesis]] of Sezary syndrome is not fully understood.<ref name="SauliteHoetzenecker2016">{{cite journal|last1=Saulite|first1=Ieva|last2=Hoetzenecker|first2=Wolfram|last3=Weidinger|first3=Stephan|last4=Cozzio|first4=Antonio|last5=Guenova|first5=Emmanuella|last6=Wehkamp|first6=Ulrike|title=Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets|journal=BioMed Research International|volume=2016|year=2016|pages=1–15|issn=2314-6133|doi=10.1155/2016/9717530}}</ref> | * The exact [[pathogenesis]] of Sezary syndrome is not fully understood.<ref name="SauliteHoetzenecker2016">{{cite journal|last1=Saulite|first1=Ieva|last2=Hoetzenecker|first2=Wolfram|last3=Weidinger|first3=Stephan|last4=Cozzio|first4=Antonio|last5=Guenova|first5=Emmanuella|last6=Wehkamp|first6=Ulrike|title=Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets|journal=BioMed Research International|volume=2016|year=2016|pages=1–15|issn=2314-6133|doi=10.1155/2016/9717530}}</ref> | ||
* Sezary syndrome is an [[Erythroderma|erythrodermic]] [[cutaneous]] [[T-cell lymphoma]] with a [[leukemic]] involvement of [[malignant]] [[T cell|T cells]].<ref name="pmid12859741">{{cite journal |vauthors=Balfour EM, Glusac EJ, Heald P, Talley LL, Smoller BR |title=Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity |journal=J. Cutan. Pathol. |volume=30 |issue=7 |pages=437–42 |date=August 2003 |pmid=12859741 |doi= |url=}}</ref> | * Sezary syndrome is an [[Erythroderma|erythrodermic]] [[cutaneous]] [[T-cell lymphoma]] with a [[leukemic]] involvement of [[malignant]] [[T cell|T cells]].<ref name="pmid12859741">{{cite journal |vauthors=Balfour EM, Glusac EJ, Heald P, Talley LL, Smoller BR |title=Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity |journal=J. Cutan. Pathol. |volume=30 |issue=7 |pages=437–42 |date=August 2003 |pmid=12859741 |doi= |url=}}</ref> | ||
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==Genetics== | ==Genetics== | ||
*chromosomal instability has been noted. Losses on 1p, 10q, 13q, and 17p and gains of 4, 17q, and 18 have been identified <ref name="MaoOrchard2003">{{cite journal|last1=Mao|first1=Xin|last2=Orchard|first2=Guy|last3=Lillington|first3=Debra M.|last4=Russell-Jones|first4=Robin|last5=Young|first5=Bryan D.|last6=Whittaker|first6=Sean|title=Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma|journal=Genes, Chromosomes and Cancer|volume=37|issue=2|year=2003|pages=176–185|issn=10452257|doi=10.1002/gcc.10184}}</ref><ref name="pmid21323514">{{cite journal |vauthors=Iżykowska K, Przybylski GK |title=Genetic alterations in Sezary syndrome |journal=Leuk. Lymphoma |volume=52 |issue=5 |pages=745–53 |date=May 2011 |pmid=21323514 |doi=10.3109/10428194.2010.551159 |url=}}</ref> | *[[chromosomal]] instability has been noted. Losses on 1p, 10q, 13q, and 17p and gains of 4, 17q, and 18 have been identified <ref name="MaoOrchard2003">{{cite journal|last1=Mao|first1=Xin|last2=Orchard|first2=Guy|last3=Lillington|first3=Debra M.|last4=Russell-Jones|first4=Robin|last5=Young|first5=Bryan D.|last6=Whittaker|first6=Sean|title=Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma|journal=Genes, Chromosomes and Cancer|volume=37|issue=2|year=2003|pages=176–185|issn=10452257|doi=10.1002/gcc.10184}}</ref><ref name="pmid21323514">{{cite journal |vauthors=Iżykowska K, Przybylski GK |title=Genetic alterations in Sezary syndrome |journal=Leuk. Lymphoma |volume=52 |issue=5 |pages=745–53 |date=May 2011 |pmid=21323514 |doi=10.3109/10428194.2010.551159 |url=}}</ref> | ||
**[[Deletion (genetics)|Deletions]] and [[translocations]] in different [[chromosomes]] or [[chromosomal]] segments | **[[Deletion (genetics)|Deletions]] and [[translocations]] in different [[chromosomes]] or [[chromosomal]] segments | ||
**[[Chromosomal]] [[amplification]] of JunB at 19p12 observed in mycosis fungoides and Sezary syndrome. | **[[Chromosomal]] [[amplification]] of JunB at 19p12 observed in mycosis fungoides and Sezary syndrome. | ||
The development of Sezary syndrome is the result of chromosomal instability by poor prognosising. | *The development of Sezary syndrome is the result of chromosomal instability by poor prognosising. | ||
==Gross Pathology== | ==Gross Pathology== | ||
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==Microscopic Pathology== | ==Microscopic Pathology== | ||
* '''Light microscopic findings''' : | * '''Light microscopic findings''':<ref name="pmid22496939">{{cite journal |vauthors=Arafah M, Zaidi SN, Kfoury HK, Al Rikabi A, Al Ghamdi K |title=The Histological Spectrum of Early Mycosis Fungoides: A Study of 58 Saudi Arab patients |journal=Oman Med J |volume=27 |issue=2 |pages=134–9 |date=March 2012 |pmid=22496939 |pmc=3321345 |doi=10.5001/omj.2012.28 |url=}}</ref><ref name="pmid2653459">{{cite journal |vauthors=Chu AC, Morris JF |title=Sézary cell morphology induced in peripheral blood lymphocytes: re-evaluation |journal=Blood |volume=73 |issue=6 |pages=1603–7 |date=May 1989 |pmid=2653459 |doi= |url=}}</ref><ref name="pmid11756953">{{cite journal |vauthors=Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, Willemze R |title=Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas |journal=J. Am. Acad. Dermatol. |volume=46 |issue=1 |pages=95–106 |date=January 2002 |pmid=11756953 |doi= |url=}}</ref> | ||
**On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], movement of the atypical [[Lymphocyte|lymphocytes]] into the [[Epidermis (skin)|epidermis]], atypical [[Cell (biology)|cells]] in intra [[Epidermis (skin)|epidermal]], and infiltrate of [[Inflammation|inflammatory]] [[T cell|T cells]] are characteristic findings of Sezary syndrome. | |||
* | **Sezary cells are aypical [[mononuclear cells]] with moderately to highly grooved [[nuclei]], termed seen in prepheral [[blood]] [[morphology]], Sezary [[Cell (biology)|cell]] is large than normal [[Lymphocyte|lymphocyt]] [[Cell (biology)|cell]]. | ||
* '''Clonality of the T cell receptor (TCR) gene rearrangement''' :<ref name="pmid16172316">{{cite journal |vauthors=Guitart J |title=Beyond clonal detection: defining the T-cell clone |journal=Arch Dermatol |volume=141 |issue=9 |pages=1159–60 |date=September 2005 |pmid=16172316 |doi=10.1001/archderm.141.9.1159 |url=}}</ref><ref name="pmid26446955">{{cite journal |vauthors=Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA |title=TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL |journal=Sci Transl Med |volume=7 |issue=308 |pages=308ra158 |date=October 2015 |pmid=26446955 |pmc=4765389 |doi=10.1126/scitranslmed.aaa9122 |url=}}</ref> | |||
**[[Clone (cell biology)|Clonality]] of the [[T cell receptor]] ([[T cell receptor|TCR]]) [[gene]] [[rearrangement]] by [[polymerase]] chain [[reaction]]. | |||
**High throughput [[T cell receptor|TCR]] sequen is more sensitive technique than [[T cell receptor]] ([[TCR]]). | |||
[[File:Sezary Cell smear 2009-12-21.jpg|300px|thumb|left|PBS showing Sezary cell [https://commons.wikimedia.org/wiki/File:Sezary_Cell_smear_2009-12-21.JPG#/media/File:Sezary_Cell_smear_2009-12-21.JPG]]] | [[File:Sezary Cell smear 2009-12-21.jpg|300px|thumb|left|PBS showing Sezary cell [https://commons.wikimedia.org/wiki/File:Sezary_Cell_smear_2009-12-21.JPG#/media/File:Sezary_Cell_smear_2009-12-21.JPG]]] | ||
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Latest revision as of 20:09, 13 February 2019
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Sezary syndrome Microchapters |
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Sezary syndrome pathophysiology On the Web |
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Risk calculators and risk factors for Sezary syndrome pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: {{S.G.}]
Overview
The exact pathogenesis of sezary syndrome is not fully understood but a majority of genes in Sezary syndrome are deregulated.
Pathogenesis
- The exact pathogenesis of Sezary syndrome is not fully understood.[1]
- Sezary syndrome is an erythrodermic cutaneous T-cell lymphoma with a leukemic involvement of malignant T cells.[2]
- Cutaneous T cell lymphoma arises from T-cell lymphocytes, which are normally involved in the cell mediated immune response.[3]
- Sezary syndrome's patients have suppressed immunity, as the malignant cells produce type-2, T-cell (Th2) cytokines which suppress Th1 immunity by decreasing the production of IL-12. The role of IL-12 is to stimulate the production of interferon gamma and tumor necrosis factor-alpha (TNF-a), thus protecting against tumors.[1]
- The tumor cells originate from memory T cells or skin homing CD4+ T cells expressing cutaneous lymphocyte antigen (CLA) and chemokine receptors CCR4 and CCR7.[4]
- A few patients of Sezary syndrome are associated with human T-lymphotropic virus types 1 and 2 (HTLV1 and HTLV2) In Japan, Caribbean islands, and the Middle East.[5][6]
- In Sezary syndrome's patients blood flow cytometry shown measurement of the CD4+CD26- population of lymphocytes is a valuable tool for monitoring and CD26 seen in >90% of patients and CD7 loss in 50% of patients. [7][8]
- In majority of Sezary syndrome's patients peripheral blood T cell seen CD3+, CD4+, CD7-, CD26-, CD8-.[9]
- In some Sezary syndrome patients CD8+ phenotype seen with retroviral infections (HTLV-1/2 or HIV).[10][11][12]
- Sezary syndrome cells are T-cells that have pathological quantities of mucopolysaccharides.
- When Sezary cells move from the blood into the skin, the skin problem is seen and Sezary cells are finded in rash.
- In sezary syndrome maybe one or more chromosomal abnormalities, such as the loss or gain of genetic.[13][14]
Genetics
- chromosomal instability has been noted. Losses on 1p, 10q, 13q, and 17p and gains of 4, 17q, and 18 have been identified [15][16]
- Deletions and translocations in different chromosomes or chromosomal segments
- Chromosomal amplification of JunB at 19p12 observed in mycosis fungoides and Sezary syndrome.
- The development of Sezary syndrome is the result of chromosomal instability by poor prognosising.
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- Light microscopic findings:[17][18][19]
- On microscopic histopathological analysis, movement of the atypical lymphocytes into the epidermis, atypical cells in intra epidermal, and infiltrate of inflammatory T cells are characteristic findings of Sezary syndrome.
- Sezary cells are aypical mononuclear cells with moderately to highly grooved nuclei, termed seen in prepheral blood morphology, Sezary cell is large than normal lymphocyt cell.
- Clonality of the T cell receptor (TCR) gene rearrangement :[20][21]
- Clonality of the T cell receptor (TCR) gene rearrangement by polymerase chain reaction.
- High throughput TCR sequen is more sensitive technique than T cell receptor (TCR).
![[1]](https://commons.wikimedia.org/wiki/File:Sezary_Cell_smear_2009-12-21.JPG#/media/File:Sezary_Cell_smear_2009-12-21.JPG){kind=link}
References
- ↑ 1.0 1.1 Saulite, Ieva; Hoetzenecker, Wolfram; Weidinger, Stephan; Cozzio, Antonio; Guenova, Emmanuella; Wehkamp, Ulrike (2016). "Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets". BioMed Research International. 2016: 1–15. doi:10.1155/2016/9717530. ISSN 2314-6133.
- ↑ Balfour EM, Glusac EJ, Heald P, Talley LL, Smoller BR (August 2003). "Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity". J. Cutan. Pathol. 30 (7): 437–42. PMID 12859741.
- ↑ Wilcox RA (January 2016). "Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (1): 151–65. doi:10.1002/ajh.24233. PMC 4715621. PMID 26607183.
- ↑ Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS (October 1997). "Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells". Nature. 389 (6654): 978–81. doi:10.1038/40166. PMID 9353122.
- ↑ Graham RL, Burch M, Krause JR (July 2014). "Adult T-cell leukemia/lymphoma". Proc (Bayl Univ Med Cent). 27 (3): 235–8. PMC 4059578. PMID 24982574.
- ↑ Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, Wood G, Demierre MF, Pittelkow M, Wilson LD, Pinter-Brown L, Advani R, Parker S, Kim EJ, Junkins-Hopkins JM, Foss F, Cacchio P, Duvic M (February 2011). "Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC)". J. Am. Acad. Dermatol. 64 (2): 352–404. doi:10.1016/j.jaad.2010.08.037. PMID 21145619.
- ↑ Introcaso CE, Hess SD, Kamoun M, Ubriani R, Gelfand JM, Rook AH (September 2005). "Association of change in clinical status and change in the percentage of the CD4+CD26- lymphocyte population in patients with Sézary syndrome". J. Am. Acad. Dermatol. 53 (3): 428–34. doi:10.1016/j.jaad.2005.06.001. PMID 16112348.
- ↑ Gorczyca, Wojciech; Weisberger, James; Liu, Z.; Tsang, Patricia; Hossein, Monowar; Wu, C. Daniel; Dong, Henry; Wong, John Y.L.; Tugulea, Sorina; Dee, Simpson; Melamed, Myron R.; Darzynkiewicz, Zbigniew (2002). "An approach to diagnosis of T-cell lymphoproliferative disorders by flow cytometry". Cytometry. 50 (3): 177–190. doi:10.1002/cyto.10003. ISSN 0196-4763.
- ↑ Pulitzer M (September 2017). "Cutaneous T-cell Lymphoma". Clin. Lab. Med. 37 (3): 527–546. doi:10.1016/j.cll.2017.06.006. PMC 5710803. PMID 28802499.
- ↑ Kim EJ, Hess S, Richardson SK, Newton S, Showe LC, Benoit BM, Ubriani R, Vittorio CC, Junkins-Hopkins JM, Wysocka M, Rook AH (April 2005). "Immunopathogenesis and therapy of cutaneous T cell lymphoma". J. Clin. Invest. 115 (4): 798–812. doi:10.1172/JCI24826. PMC 1070436. PMID 15841167.
- ↑ Kashanchi, Fatah; Coelho-dos-Reis, Jordana Grazziela Alves; Passos, Livia; Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Trindade, Bruno Caetano; dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis (2013). "Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders". PLoS Neglected Tropical Diseases. 7 (7): e2328. doi:10.1371/journal.pntd.0002328. ISSN 1935-2735.
- ↑ Myskowski, Patricia L. (1991). "Cutaneous T-Cell Lymphoma and Human Immunodeficiency Virus". Archives of Dermatology. 127 (7): 1045. doi:10.1001/archderm.1991.01680060119017. ISSN 0003-987X.
- ↑ Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM, Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R, Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ (June 2016). "Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome". Blood. 127 (26): 3387–97. doi:10.1182/blood-2016-02-699843. PMID 27121473.
- ↑ Wilcox RA (January 2016). "Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (1): 151–65. doi:10.1002/ajh.24233. PMC 4715621. PMID 26607183.
- ↑ Mao, Xin; Orchard, Guy; Lillington, Debra M.; Russell-Jones, Robin; Young, Bryan D.; Whittaker, Sean (2003). "Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma". Genes, Chromosomes and Cancer. 37 (2): 176–185. doi:10.1002/gcc.10184. ISSN 1045-2257.
- ↑ Iżykowska K, Przybylski GK (May 2011). "Genetic alterations in Sezary syndrome". Leuk. Lymphoma. 52 (5): 745–53. doi:10.3109/10428194.2010.551159. PMID 21323514.
- ↑ Arafah M, Zaidi SN, Kfoury HK, Al Rikabi A, Al Ghamdi K (March 2012). "The Histological Spectrum of Early Mycosis Fungoides: A Study of 58 Saudi Arab patients". Oman Med J. 27 (2): 134–9. doi:10.5001/omj.2012.28. PMC 3321345. PMID 22496939.
- ↑ Chu AC, Morris JF (May 1989). "Sézary cell morphology induced in peripheral blood lymphocytes: re-evaluation". Blood. 73 (6): 1603–7. PMID 2653459.
- ↑ Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, Willemze R (January 2002). "Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas". J. Am. Acad. Dermatol. 46 (1): 95–106. PMID 11756953.
- ↑ Guitart J (September 2005). "Beyond clonal detection: defining the T-cell clone". Arch Dermatol. 141 (9): 1159–60. doi:10.1001/archderm.141.9.1159. PMID 16172316.
- ↑ Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA (October 2015). "TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL". Sci Transl Med. 7 (308): 308ra158. doi:10.1126/scitranslmed.aaa9122. PMC 4765389. PMID 26446955.