Adult T-cell leukemia pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Adult T‐cell leukemia arises from post‐thymic [[lymphocyte]]s, which are normally involved in the process of [[immune system|cell-mediated immune response]]. Development of adult T-cell leukemia is the result of multiple [[genetic mutation]]s induced by an [[infection]] with human T‐cell lymphotropic virus ([[HTLV]]). On gross pathology, | Adult T‐cell leukemia arises from post‐thymic [[lymphocyte]]s, which are normally involved in the process of [[immune system|cell-mediated immune response]]. Development of adult T-cell leukemia is the result of multiple [[genetic mutation]]s induced by an [[infection]] with human T‐cell lymphotropic virus ([[HTLV]]). On gross pathology, skin [[nodule]]s, [[maculopapular]] eruption, and [[erythema]] 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 polylobulated [[nucleus]] and agranular [[cytoplasm]]. | ||
==Pathogenesis== | ==Pathogenesis== | ||
* Adult T‐cell leukemia arises from post‐thymic [[lymphocytes]], which are normally involved in the process of [[immune system|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 arises from post‐thymic [[lymphocytes]], which are normally involved in the process of [[immune system|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]]). | * Adult T‐cell leukemia is mainly caused by an [[infection]] with human T‐cell lymphotropic virus ([[HTLV]]). | ||
* [[HTLV]] is usually transmitted via [[breast feeding]] early in life. | * [[HTLV]] is usually transmitted via [[breast feeding]] early in life. Other minor routes of transmission for [[Human T-lymphotropic virus|HTLV]] may include [[sexual contact]], exposure to [[contamination|contaminated]] [[blood]], or vertical maternal transmission. | ||
* There appears to be a long latent period between [[Human T-lymphotropic virus|HTLV]]-1 infection and the development of adult T‐cell leukemia. | |||
* There appears to be a long latent period between HTLV-1 infection and the development of adult T‐cell leukemia. | * The oncogenesis of [[Human T-lymphotropic virus|HTLV]] infection, which results in the development of adult T-cell leukemia, is due to: | ||
* The oncogenesis of HTLV infection, which results in the development of adult T-cell leukemia, is due to: | :* [[Human T-lymphotropic virus|HTLV]] basic [[leucine zipper]] factor | ||
:* HTLV basic [[leucine zipper]] factor | :* [[Human T-lymphotropic virus|HTLV]] p40 tax viral [[protein]] | ||
:* HTLV p40 tax viral [[protein]] | :* Activation of [[JAK]]/[[STAT]] signaling pathway by [[Human T-lymphotropic virus|HTLV]] | ||
:* Activation of [[JAK]]/[[STAT]] signaling pathway by HTLV | :* Enhancement of [[CREB]] [[transcription factor]] by [[Human T-lymphotropic virus|HTLV]] | ||
:* Enhancement of [[CREB]] [[transcription factor]] by HTLV | |||
* Adult T‐cell leukemia can manifests as either a [[leukemic]] form (75% of the cases) or a pure [[lymphoma|lymphomatous]] form (25% of the cases). | * Adult T‐cell leukemia can manifests as either a [[leukemic]] form (75% of the cases) or a pure [[lymphoma|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 node]]s, [[liver]], [[spleen]], [[skin]], and [[CNS]]. | * Adult T‐cell leukemia is a widely disseminated disease which may involve the peripheral [[Blood cell|blood cells]], [[bone marrow]], [[lymph node]]s, [[liver]], [[spleen]], [[skin]], and [[CNS]]. | ||
* | * Hematopathological features of adult T-cell leukemia are variable, which may include: | ||
:* [[Anemia]] | :* [[Anemia]] | ||
:* [[Thrombocytopenia]] | :* [[Thrombocytopenia]] | ||
:* [[Neutrophilia]] | :* [[Neutrophilia]] | ||
:* [[Eosinophilia]] | :* [[Eosinophilia]] | ||
* Patchy bone marrow infiltration among adult T-cell leukemia patients may result in: | * Patchy [[Bone marrow suppression|bone marrow infiltration]] among adult T-cell leukemia patients may result in: | ||
:* Tumor-induced osteolysis due to increased [[osteoclast|osteoclastic activity]] | :* Tumor-induced [[osteolysis]] due to increased [[osteoclast|osteoclastic activity]] | ||
:* Multiple [[lytic]] bone lesions | :* Multiple [[lytic]] bone lesions | ||
:* [[Hypercalcemia]] | :* [[Hypercalcemia]] | ||
* Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum concentrations of: | * [[Hypercalcemia]] among adult T-cell leukemia patients has been associated with elevated serum concentrations of: | ||
:* [[IL-1]] | :* [[IL-1]] | ||
:* [[TGFβ]] | :* [[TGFβ]] | ||
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:* [[RANKL]] | :* [[RANKL]] | ||
* Infiltration of malignant leukemic cells results in the expansion of the [[lymph node]]s paracortical region, which may lead to the development of peripheral [[lymphadenopathy]] among adult T-cell leukemia patients. | * Infiltration of malignant leukemic cells results in the expansion of the [[lymph node]]s 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 | * Infiltration of the [[liver]] and [[spleen]] may lead to the development of [[organomegaly]] among adult T-cell leukemia patients. | ||
* [[Cutaneous]] manifestations of adult T-cell leukemia is due to the infiltration of | * [[Cutaneous]] manifestations of adult T-cell leukemia is due to the infiltration of [[Leukemic|leukemic cells]] along the [[dermis]] layer of the [[skin]]. | ||
* Cutaneous | * Cutaneous Pautrier's microabscesses 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. | * [[Immune deficiency]] occurs in adult T-cell leukemia due to a defective [[cell-mediated immunity]]. | ||
==Genetic== | ==Genetic== | ||
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* On gross pathology, [[skin]] nodules, [[maculopapular]] eruption, and [[erythema]] are characteristic 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> | * On gross pathology, [[skin]] nodules, [[maculopapular]] eruption, and [[erythema]] are characteristic 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> | ||
== | ==Microscopic Pathology== | ||
* On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include: | * On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include: | ||
:* Pleomorphic, medium sized [[lymphocyte]]s | :* Pleomorphic, medium sized [[lymphocyte]]s | ||
:* Convoluted or | :* Convoluted or polylobulated [[nucleus]] with condensed [[chromatin]] (cloverleaf nuclei) | ||
:* [[Nucleoli]] are not visible | :* [[Nucleoli]] are not visible | ||
:* Agranular [[cytoplasm]] | :* Agranular [[cytoplasm]] | ||
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:* [[Reed-Sternberg cells|Reed-Sternberg]]-like cells may also be present | :* [[Reed-Sternberg cells|Reed-Sternberg]]-like cells may also be present | ||
* On immunohistochemical analysis, characteristic findings of adult T-cell leukemia include: | * On [[Immunohistochemistry|immunohistochemical]] analysis, characteristic findings of adult T-cell leukemia include: | ||
:* [[CD2]] +ve | :* [[CD2]] +ve | ||
:* [[CD4]] +ve | :* [[CD4]] +ve | ||
Revision as of 21:10, 1 November 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response. Development of adult T-cell leukemia is the result of multiple genetic mutations induced by an infection with human T‐cell lymphotropic virus (HTLV). On gross pathology, skin nodules, maculopapular eruption, and erythema 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 polylobulated 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).
- HTLV is usually transmitted via breast feeding early in life. Other minor routes of transmission for HTLV 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 infection, which results in the development of adult T-cell leukemia, is due to:
- HTLV basic leucine zipper factor
- HTLV p40 tax viral protein
- Activation of JAK/STAT signaling pathway by HTLV
- Enhancement of CREB transcription factor by HTLV
- 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.
- Hematopathological features of adult T-cell leukemia are variable, which may include:
- 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:
- 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 organomegaly among adult T-cell leukemia patients.
- Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukemic cells along the dermis layer of the skin.
- Cutaneous Pautrier's microabscesses 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
- Genes involved in the pathogenesis of adult T-cell leukemia include:
Gross Pathology
- On gross pathology, skin nodules, maculopapular eruption, and erythema are characteristic findings of adult T-cell leukemia.[5][6]
Microscopic Pathology
- On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include:
- Pleomorphic, medium sized lymphocytes
- Convoluted or polylobulated 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:
References
- ↑ 1.0 1.1 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.
- ↑ 2.0 2.1 Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015
- ↑ 3.0 3.1 Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015
- ↑ 4.0 4.1 Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015
- ↑ 5.0 5.1 5.2 Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015
- ↑ 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.