Sandbox: T cell: Difference between revisions

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==Overview==
==Overview==
Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.<ref name="pmid18042693">{{cite journal |vauthors=Matutes E |title=Adult T-cell leukaemia/lymphoma |journal=J. Clin. Pathol. |volume=60 |issue=12 |pages=1373–7 |year=2007 |pmid=18042693 |pmc=2095573 |doi=10.1136/jcp.2007.052456 |url=}}</ref><ref name=wiki>Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015</ref><ref name="wiki1">Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015</ref><ref name="patho">Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015</ref><ref name="patho2">Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015</ref> Development of adult T-cell leukemia is the result of multiple genetic mutations induced by an infection with human T‐cell lymphotropic virus (HTLV‐I). On gross pathology,  skin nodules, maculopapular eruption, and erythroderma are characteristic skin findings of adult T-cell leukemia. On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include pleomorphic, medium sized lymphocytes with a polylobated nucleus and agranular cytoplasm.
==Pathogenesis==
==Pathogenesis==
* Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune responses.
* Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.<ref name="pmid18042693">{{cite journal |vauthors=Matutes E |title=Adult T-cell leukaemia/lymphoma |journal=J. Clin. Pathol. |volume=60 |issue=12 |pages=1373–7 |year=2007 |pmid=18042693 |pmc=2095573 |doi=10.1136/jcp.2007.052456 |url=}}</ref><ref name=wiki>Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015</ref><ref name="wiki1">Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015</ref><ref name="patho">Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015</ref><ref name="patho2">Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015</ref>
* Adult T‐cell leukemia is mainly caused by an infection with human T‐cell lymphotropic virus (HTLV‐I).
* Adult T‐cell leukemia is mainly caused by an infection with human T‐cell lymphotropic virus (HTLV‐I).
* HTLV-1 is usually transmitted via breast feeding early in life.
* HTLV-1 is usually transmitted via breast feeding early in life.
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:* Multiple lytic bone lesions
:* Multiple lytic bone lesions
:* Hypercalcemia
:* Hypercalcemia
* Infiltration of malignant leukemic cells results in the expansion of the lymph nodes paracortical region, which may lead to the development of peripheral lymphadenopathy among adult T-cell leukemia patients.
* Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum concentrations of:
* Infiltration of the liver and spleen may lead to the development of organomegally among adult T-cell leukemia patients.
* Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukmeic cells along the dermis layer of the skin.
* Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum levels of:
:* IL-1
:* IL-1
:* TGFβ
:* TGFβ
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:* MIP-1α
:* MIP-1α
:* RANKL
:* RANKL
* Infiltration of malignant leukemic cells results in the expansion of the lymph nodes paracortical region, which may lead to the development of peripheral lymphadenopathy among adult T-cell leukemia patients.
* Infiltration of the liver and spleen may lead to the development of organomegally among adult T-cell leukemia patients.
* Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukmeic cells along the dermis layer of the skin.
* Cutaneous Pautrier's microabcesses formation (due to epidermotropism) may also be present among adult T-cell leukemia patients. These cutaneous lesions are indistinguishable from the ones found in Sézary syndrome and mycosis fungoides.
* Immune deficiency occurs in adult T-cell leukemia due to a defective cell-mediated immunity.


==Genetic==
* Development of adult T-cell leukemia is the result of multiple genetic mutations.<ref name="pmid18042693">{{cite journal |vauthors=Matutes E |title=Adult T-cell leukaemia/lymphoma |journal=J. Clin. Pathol. |volume=60 |issue=12 |pages=1373–7 |year=2007 |pmid=18042693 |pmc=2095573 |doi=10.1136/jcp.2007.052456 |url=}}</ref><ref name=wiki>Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015</ref><ref name="wiki1">Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015</ref><ref name="patho">Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015</ref><ref name="patho2">Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015</ref>


* Infiltration of the dermis skin infiltration, epidermotropism present and Pautrier's microabcesses
* Genes involved in the pathogenesis of adult T-cell leukemia include:
 
:* 14q11 gene mutation
* antibodies to HTLV‐I are demonstrable
:* TCR‐alpha chain gene mutation
* defects of cell-mediated immunity recurrent infections
:* TCR‐delta chain gene mutation
 
==Genetic==
* +3, +7, +21, monosomy X,deletion of chromosome Y and chromosomes 6 and 14q;
* 14q11 and  break points e TCR‐alpha and ‐delta chain genes TCRA and TCRD
* 14q32 of TCL1
* mutations of tumour‐suppressor genes CDKN2A (p16), CDKN2B (p15) and TP53 (p53)


==Gross==
==Gross Pathology==
* Nodules skin
* On gross pathology,  skin nodules, maculopapular eruption, and erythroderma are characteristic skin findings of adult T-cell leukemia.<ref name="patho2">Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015</ref><ref name="pmid18377598">{{cite journal| author=Pezeshkpoor F, Yazdanpanah MJ, Shirdel A| title=Specific cutaneous manifestations in adult T-cell leukemia/lymphoma. | journal=Int J Dermatol | year= 2008 | volume= 47 | issue= 4 | pages= 359-62 | pmid=18377598 | doi=10.1111/j.1365-4632.2008.03526.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18377598  }} </ref>


==Micro==
==Mircoscopic Pathology==
* pleomorphic, a medium size lymphocyte conndensed chromatin
* On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include:
* convoluted or polylobated nucleus
:* Pleomorphic, medium sized lymphocytes
* nucleoli are not visibl
:* Convoluted or polylobated nucleus with condensed chromatin (cloverleaf nuclei)
* cytoplasm agranular
:* Nucleoli are not visible
* “flower cell”
:* Agranular cytoplasm  
* Reed-Sternberg like cells may also be present
:* “Flower cells”
:* Reed-Sternberg like cells may also be present


* On immunohistochemical analysis, characteristic findings of adult T-cell leukemia include:
:* CD2 +ve
:* CD4 +ve
:* CD5 +ve
:* CD8 +ve
:* CD7 -ve
:* CD3 and T‐cell receptor (TCR)‐β may be down‐regulated


* CD4 positive CD8 positive
==References==
* CD2 and CD5 positive
{{Reflist}}
* CD7 negativ
* CD3 and T‐cell receptor (TCR)‐β may be down‐regulated
* CD2, CD3, CD4, CD5, CD25, TCR α/β, CD45ROCD56 expressionCCR4, FOXP3, HLA-DR, L-selectin (CD62), MUM-1

Latest revision as of 13:14, 28 December 2015

Overview

Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.[1][2][3][4][5] Development of adult T-cell leukemia is the result of multiple genetic mutations induced by an infection with human T‐cell lymphotropic virus (HTLV‐I). On gross pathology, skin nodules, maculopapular eruption, and erythroderma are characteristic skin findings of adult T-cell leukemia. On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include pleomorphic, medium sized lymphocytes with a polylobated nucleus and agranular cytoplasm.

Pathogenesis

  • Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.[1][2][3][4][5]
  • Adult T‐cell leukemia is mainly caused by an infection with human T‐cell lymphotropic virus (HTLV‐I).
  • HTLV-1 is usually transmitted via breast feeding early in life.
  • Other minor routes of transmission for HTLV-1 may include sexual contact, exposure to contaminated blood, or vertical maternal transmission.
  • There appears to be a long latent period between HTLV-1 infection and the development of adult T‐cell leukemia.
  • The oncogenesis of HTLV‐I infection, which results in the development of adult T-cell leukemia, is due to:
  • HTLV-I basic leucine zipper factor
  • HTLV-I p40 tax viral protein
  • Activation of JAK/STAT signaling pathway by HTLV-I
  • Enhancement of CREB transcription factor by HTLV-I
  • Adult T‐cell leukemia can manifests as either a leukemic form (75% of the cases) or a pure lymphomatous form (25% of the cases).
  • Adult T‐cell leukemia is a widely disseminated disease which may involve the peripheral blood cells, bone marrow, lymph nodes, liver, spleen, skin, and CNS.
  • Haematopathological features of adult T-cell leukemia are variable, patients may present with:
  • Anemia
  • Thrombocytopenia
  • Neutrophilia
  • Eosinophilia
  • Patchy bone marrow infiltration among adult T-cell leukemia patients may result in:
  • Tumor-induced osteolysis due to increased osteoclastic activity
  • Multiple lytic bone lesions
  • Hypercalcemia
  • Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum concentrations of:
  • IL-1
  • TGFβ
  • PTHrP
  • MIP-1α
  • RANKL
  • Infiltration of malignant leukemic cells results in the expansion of the lymph nodes paracortical region, which may lead to the development of peripheral lymphadenopathy among adult T-cell leukemia patients.
  • Infiltration of the liver and spleen may lead to the development of organomegally among adult T-cell leukemia patients.
  • Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukmeic cells along the dermis layer of the skin.
  • Cutaneous Pautrier's microabcesses formation (due to epidermotropism) may also be present among adult T-cell leukemia patients. These cutaneous lesions are indistinguishable from the ones found in Sézary syndrome and mycosis fungoides.
  • Immune deficiency occurs in adult T-cell leukemia due to a defective cell-mediated immunity.

Genetic

  • Development of adult T-cell leukemia is the result of multiple genetic mutations.[1][2][3][4][5]
  • Genes involved in the pathogenesis of adult T-cell leukemia include:
  • 14q11 gene mutation
  • TCR‐alpha chain gene mutation
  • TCR‐delta chain gene mutation

Gross Pathology

  • On gross pathology, skin nodules, maculopapular eruption, and erythroderma are characteristic skin findings of adult T-cell leukemia.[5][6]

Mircoscopic Pathology

  • On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include:
  • Pleomorphic, medium sized lymphocytes
  • Convoluted or polylobated nucleus with condensed chromatin (cloverleaf nuclei)
  • Nucleoli are not visible
  • Agranular cytoplasm
  • “Flower cells”
  • Reed-Sternberg like cells may also be present
  • On immunohistochemical analysis, characteristic findings of adult T-cell leukemia include:
  • CD2 +ve
  • CD4 +ve
  • CD5 +ve
  • CD8 +ve
  • CD7 -ve
  • CD3 and T‐cell receptor (TCR)‐β may be down‐regulated

References

  1. ↑ 1.0 1.1 1.2 Matutes E (2007). "Adult T-cell leukaemia/lymphoma". J. Clin. Pathol. 60 (12): 1373–7. doi:10.1136/jcp.2007.052456. PMC 2095573. PMID 18042693.
  2. ↑ 2.0 2.1 2.2 Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015
  3. ↑ 3.0 3.1 3.2 Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015
  4. ↑ 4.0 4.1 4.2 Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015
  5. ↑ 5.0 5.1 5.2 5.3 Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015
  6. ↑ Pezeshkpoor F, Yazdanpanah MJ, Shirdel A (2008). "Specific cutaneous manifestations in adult T-cell leukemia/lymphoma". Int J Dermatol. 47 (4): 359–62. doi:10.1111/j.1365-4632.2008.03526.x. PMID 18377598.
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