Hepatosplenic T cell lymphoma pathophysiology: Difference between revisions

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Latest revision as of 02:02, 27 November 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [4]

Overview

Hepatosplenic T cell lymphoma arises from an immature cytotoxic T-cell clonally expressing the γδ T-cell receptor. Gamma delta (γδ) T cells constitute 1% to 5% of the circulating lymphocytes in human blood. These cells preferentially home in on some epithelial rich tissues and sinusoidal areas of the splenic red pulp where they represent up to 30% of the whole T-cell population. Hepatosplenic γδ T-cell lymphoma (HSTCL) is a rare aggressive subtype of extra nodal lymphoma. Genes involved in the pathogenesis of hepatosplenic T cell lymphoma include isochromosome 7q, TRG@, and T-cell receptor (TCR) Gamma/Delta genes. On gross pathology, diffuse enlargment of liver and spleen are characteristic findings of hepatosplenic T cell lymphoma. On microscopic histopathological analysis, monotonous appearance with a small amount of cytoplasm and inconspicuous nucleoli are characteristic findings of neoplastic cells of hepatosplenic T cell lymphoma.

Genetics

Genes involved in the pathogenesis of hepatosplenic T cell lymphoma are listed below.^[1]

2-5 copies of i(7)(q10)
Isochromosome 7q present
Numerical and structural aberrations of the second chromosome 7
Rearrangement TRG@, TRB@ genes
T-cell receptor (TCR) Gamma/Delta genes are clonally rearranged
Trisomy 8

Immunophenotype^[1]

The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature T-cell.

Status	Antigens
Positive	CD3, TCRδ1, TIA-1, granzyme M, multiple killer immunoglobulin-like receptors (KIR) isoforms
Negative	CD4, CD5, CD8, granzyme B, perforin, CD94

Association

Hepatosplenic T cell lymphoma is seen more often in

Immunosuppressed solid organ transplant recipients^[2]^[3]^[4]^[5]
Patients treated with the immunosuppressants azathioprine, infliximab, and adalimumab
Patients with inflammatory bowel disease

Gross Pathology

Spleen is enlarged with diffuse involvement of the red pulp and absence of any gross lesions
Diffuse hepatic enlargement is present

Microscopic Pathology

The characteristic features of neoplastic cells in hepatosplenic T cell lymphoma include:

Monotonous appearance
Small amount of cytoplasm
Inconspicuous nucleoli

Peripheral blood smear showing large atypical lymphoid cells with indented nuclei .[6]

Peripheral blood smear showing large atypical lymphoid cells with indented nuclei .^[6]
A: Bone marrow biopsy showing cellular marrow with diffuse intrasinusoidal and interstitial lymphoid cell infiltrates (Jenner Giemsa, ×100); B: Arrows indicating intrasinusoidal lymphoid cell infiltrate (Jenner Giemsa, ×400).^[6]

**Microscopic appearance of hepatosplenic T cell lymphoma**
Sites of involvement	Description
Spleen and liver	Are always involved Distinct sinusoidal pattern of infiltration which spares the splenic white pulp and hepatic portal triads
Bone marrow	Commonly involved Detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern Immunohistochemistry can aid in the detection
Peripheral blood	Cells of a similar morphology observed in solid organs are observed in peripheral blood

References

↑ ^1.0 ^1.1 Hepatosplenic T cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52ee/. Accessed on February 22, 2016
↑ [1]
↑ Ross CW, Schnitzer B, Sheldon S, Braun DK, Hanson CA. "Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen." Am J Clin Pathol. 1994 Sep;102(3):310-5. PMID: 8085554
↑ [2]
↑ Macon WR, Levy NB, Kurtin PJ, Salhany KE, Elkhalifa MY, Casey TT, Craig FE, Vnencak-Jones CL, Gulley ML, Park JP, Cousar JB. "Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas." Am J Surg Pathol. 2001 Mar;25(3):285-96. PMID: 11224598
↑ ^6.0 ^6.1 Hepatosplenic gamma delta T-cell lymphoma. Journal of medical case reports. http://www.jmedicalcasereports.com/content/7/1/269. Accessed on February 24, 2016

Template:WikiDoc Sources

[cancer.gov-1] 1.0 ^1.1 Hepatosplenic T cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52ee/. Accessed on February 22, 2016

[2] [1]

[3] Ross CW, Schnitzer B, Sheldon S, Braun DK, Hanson CA. "Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen." Am J Clin Pathol. 1994 Sep;102(3):310-5. PMID: 8085554

[4] [2]

[5] Macon WR, Levy NB, Kurtin PJ, Salhany KE, Elkhalifa MY, Casey TT, Craig FE, Vnencak-Jones CL, Gulley ML, Park JP, Cousar JB. "Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas." Am J Surg Pathol. 2001 Mar;25(3):285-96. PMID: 11224598

[jmedicalcasereports-6] 6.0 ^6.1 Hepatosplenic gamma delta T-cell lymphoma. Journal of medical case reports. http://www.jmedicalcasereports.com/content/7/1/269. Accessed on February 24, 2016

[1]

[2]

[3]

[4]

[5]

[6]

@@ Line 1: / Line 1: @@
+__NOTOC__
 {{Hepatosplenic T cell lymphoma}}
-{{CMG}}
+{{CMG}}{{AE}} {{AS}}
 ==Overview==
+Hepatosplenic T cell lymphoma arises from an immature cytotoxic [[T-cell]] clonally expressing the γδ [[T-cell receptor]]. Gamma delta (γδ) T cells constitute 1% to 5% of the circulating lymphocytes in human blood. These cells preferentially home in on some epithelial rich tissues and sinusoidal areas of the splenic red pulp where they represent up to 30% of the whole T-cell population. Hepatosplenic γδ T-cell lymphoma (HSTCL) is a rare aggressive subtype of extra nodal lymphoma. Genes involved in the pathogenesis of hepatosplenic T cell lymphoma include isochromosome 7q, TRG@, and T-cell receptor (TCR) Gamma/Delta genes. On gross pathology, diffuse enlargment of [[liver]] and [[spleen]] are characteristic findings of hepatosplenic T cell lymphoma. On microscopic histopathological analysis, monotonous appearance with a small amount of [[cytoplasm]] and inconspicuous [[nucleoli]] are characteristic findings of neoplastic cells of hepatosplenic T cell lymphoma.
-==Sites of Involvement==
+==Genetics==
-The [[spleen]] and [[liver]] are always involved, with [[bone marrow]] involvement frequently present. Nodal involvement is exceedingly rare.[http://www.iarc.fr/WHO-BlueBooks/BBwebsite/bb3.html] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): ''World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues.'' IARC Press: Lyon 2001 </ref>
+* Genes involved in the pathogenesis of hepatosplenic T cell lymphoma are listed below.<ref name=cancer.gov> Hepatosplenic T cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52ee/.  Accessed on February 22, 2016</ref>
+:* 2-5 copies of i(7)(q10)
-==Morphology==
+:* Isochromosome 7q present
-The neoplastic cells in this disorder show a monotonous appearance, with a small amount of [[cytoplasm]] and inconspicuous [[nucleoli]].
+:* Numerical and structural aberrations of the second chromosome 7
+:* Rearrangement TRG@, TRB@ genes
-===Spleen and liver===
+:* T-cell receptor (TCR) Gamma/Delta genes are clonally rearranged
-This disease shows a distinct [[sinusoidal]] pattern of infiltration which spares the splenic [[white pulp]] and hepatic [[portal triads]].
+:* Trisomy 8
+===Immunophenotype<ref name=cancer.gov> Hepatosplenic T cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52ee/.  Accessed on February 22, 2016</ref>===
-===Bone marrow===
+The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature [[T-cell]].
-While the [[bone marrow]] is commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. [[Immunohistochemistry]] can aid in the detection of this [[lymphoma]].
-===Peripheral blood===
-Cells of a similar morphology observed in solid organs are observed in peripheral [[blood]].
-==Molecular Findings==
-===Immunophenotype===
-The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature [[T-cell]].<ref name="who1"/><ref name="coo1"/>
 {| border="1" cellpadding="5" cellspacing="0"
@@ Line 30: / Line 23: @@
 |-
 | rowspan="1"| Positive
-| colspan="1" align="center"| [[CD3]], [[TCRδ1]], [[TIA-1]]
+| colspan="1" align="center"| [[CD3]], [[TCRδ1]], [[TIA-1]], [[granzyme M]], multiple killer immunoglobulin-like receptors (KIR) isoforms
 |-
 | rowspan="1"| Negative
-| colspan="1" align="center"| [[CD4]], [[CD5]], [[CD8]]
+| colspan="1" align="center"| [[CD4]], [[CD5]], [[CD8]], [[granzyme B]], [[perforin]], [[CD94]]
 |-
 |}
-===Genetic Findings===
+==Association==
-Clonal rearrangement of the γ gene of the [[T-cell receptor]] is the hallmark of this disease. A few cases have shown rearrangement of the [[T-cell receptor]] β gene.<ref name="who1"/> [[Isochromosome]] 7q has been observed in all cases described so far, sometimes in conjunction with other [[chromosomal]] abnormalities such as [[trisomy]] 8.<ref name="alo1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9264394&query_hl=16&itool=pubmed_ExternalLink]
+* Hepatosplenic T cell lymphoma is seen more often in
-Alonsozana EL, Stamberg J, Kumar D, Jaffe ES, Medeiros LJ, Frantz C, Schiffer CA, O'Connell BA, Kerman S, Stass SA, Abruzzo LV. "Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma." '''Leukemia'''. 1997 Aug;11(8):1367-72. PMID: 9264394</ref>
+:* Immunosuppressed solid organ transplant recipients<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8085554&query_hl=10&itool=pubmed_ExternalLink]</ref><ref>Ross CW, Schnitzer B, Sheldon S, Braun DK, Hanson CA. "Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen." '''Am J Clin Pathol'''. 1994 Sep;102(3):310-5. PMID: 8085554</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11224598&query_hl=12&itool=pubmed_ExternalLink]</ref><ref>Macon WR, Levy NB, Kurtin PJ, Salhany KE, Elkhalifa MY, Casey TT, Craig FE, Vnencak-Jones CL, Gulley ML, Park JP, Cousar JB. "Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas." '''Am J Surg Pathol'''. 2001 Mar;25(3):285-96. PMID: 11224598</ref>
+:* Patients treated with the immunosuppressants [[azathioprine]], [[infliximab]], and [[adalimumab]]
+:* Patients with [[inflammatory bowel disease]]
+==Gross Pathology==
+* Spleen is enlarged with diffuse involvement of the red pulp and absence of any gross lesions
+* Diffuse hepatic enlargement is present
+==Microscopic Pathology==
+The characteristic features of neoplastic cells in hepatosplenic T cell lymphoma include:
+* Monotonous appearance
+* Small amount of [[cytoplasm]]
+* Inconspicuous [[nucleoli]]
+<gallery widths=200px>
+Image:Hepatosplenic T cell lymphoma peripheral blood smear|Peripheral blood smear showing large atypical lymphoid cells with indented nuclei .<ref name=jmedicalcasereports>Hepatosplenic gamma delta T-cell lymphoma. Journal of medical case reports. http://www.jmedicalcasereports.com/content/7/1/269. Accessed on February 24, 2016 </ref>
+Image:Hepatosplenic T cell lymphoma bone marrow biopsy.jpg|A: Bone marrow biopsy showing cellular marrow with diffuse intrasinusoidal and interstitial lymphoid cell infiltrates (Jenner Giemsa, ×100); B: Arrows indicating intrasinusoidal lymphoid cell infiltrate (Jenner Giemsa, ×400).<ref name=jmedicalcasereports>Hepatosplenic gamma delta T-cell lymphoma. Journal of medical case reports. http://www.jmedicalcasereports.com/content/7/1/269. Accessed on February 24, 2016 </ref>
+</gallery>
+{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
+|+ ''' Microscopic appearance of hepatosplenic T cell lymphoma
+! style="background: #4479BA; color:#FFF;" | Sites of involvement
+! style="background: #4479BA; color:#FFF;" | Description
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" | Spleen and liver
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Are always involved
+* Distinct [[sinusoidal]] pattern of infiltration which spares the splenic [[white pulp]] and hepatic [[portal triads]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" | Bone marrow
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Commonly involved
+* Detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern
+* [[Immunohistochemistry]] can aid in the detection
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" | Peripheral blood
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Cells of a similar morphology observed in solid organs are observed in peripheral [[blood]]
+|}
 ==References==
@@ Line 46: / Line 79: @@
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