HAEM5:Hepatosplenic T-cell lymphoma: Difference between revisions

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Hepatosplenic T-cell Lymphoma]].

*[[HAEM4:Mature T- and NK-cell Neoplasms]]

Aggressive subtype of peripheral T-cell lymphoma. HSTL is an extranodal T-cell lymphoma that is known to have a poor response to therapy and an overall poor prognosis. This lymphoma is characterized by sinusoidal infiltration of the liver spleen and often bone marrow by cytotoxic T-cells that most commonly express the γδ T-cell receptor. Less commonly, some patients may have a variant of this lymphoma that is associated with αβ expressing cytotoxic T-cells<ref name=":0">Medeiros LJ, O'Malley DP, Caraway NP, Vega F, Elenitoba-Johnson KS, Lim MS: AFIP Atlas of Tumor Pathology. Washington, DC: American Registry of Pathology, 2017.</ref><ref name=":1">Gaulard P, et al., (2017). Hepatosplenic T-cell lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p 381-382</ref><ref name=":2">Yabe M, Miranda RN, Medeiros LJ. Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. ''Hum Pathol''. 2018;74:5‐16. doi:10.1016/j.humpath.2018.01.005</ref>. Most cases occur de novo, with a subset of approximately 20-30% occurring in the setting of iatrogenic immunosuppression<ref name=":2" />. Thus, this entity is also included in the list of the World Health Organization's post-transplant lymphoproliferative disorders<ref name=":1" />.  

*1-2% of T-natural killer cell lymphomas<ref name=":1" />

*~80% are Classic γδ type<ref name=":1" />

*M:F ~ 3:1<ref name=":1" />

*Median age ~ 35 years old<ref name=":1" />

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

 

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Lymphadenopathy (uncommon)

|EXAMPLE Cytopenias

 

<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /></blockquote>

|Positive (typically)||CD3, γδ T-cell receptor, TIA1, Granzyme M<ref name=":1" />

|Negative||CD4, CD8<ref name=":1" />

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

 

 

 

 

 

 

 

*''SETD2, INO80, TET3'', and ''STAT5B -'' seen almost exclusively in hepatosplenic T-cell lymphoma, compared to other B and T-cell lymphoma, which can support a diagnosis of HSTL in difficult cases<ref name=":4" />

*''PI3KCD, JAK1/2,'' and ''STAT5B'' mutations suggest potential therapeutic targets<ref name=":2" />

 

 

 

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Therapeutic Significance (Yes, No or Unknown)

|-

|EXAMPLE

 

 

 

|EXAMPLE

 

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

|EXAMPLE

 

|EXAMPLE Gain

|EXAMPLE

 

|EXAMPLE

 

|EXAMPLE

 

 

 

|-

|8||Gain (trisomy)||Considered a secondary aberration<ref name=":2" />

|Seen in 19% of cases<ref name=":4" />

|Seen in 13% of cases<ref name=":4" />

|}

<br />

 

</blockquote>

Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>

!Prognostic Significance (Yes, No or Unknown)

|EXAMPLE

Co-deletion of 1p and 18q

|No

 

***Cases without diagnostic detection of i(7q) or trisomy 8, often have detection of these abnormalities at the time of relapse or disease progression<ref name=":2" />

*Loss of chromosome 10q and gain of chromosome 1q occur in a significant minority of HSTL cases<ref name=":4" />

 

</blockquote>

!'''Diagnostic Significance (Yes, No or Unknown)'''

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

|EXAMPLE: TP53; Variable LOF mutations

 

 

 

|EXAMPLE: 20% (COSMIC)

 

EXAMPLE: 30% (add Reference)

|EXAMPLE: IDH1 R123H

|EXAMPLE: EGFR amplification

|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

<br />

 

<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}

{| class="wikitable sortable"

!Gene!!Mutation!!Role/function!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence<ref name=":4" />

|-

|Signaling pathway||Oncogenic driver mutation||9%

|Signaling pathway

|Oncogenic driver mutation

|31%

|PIK3CD

|-

|SETD2

|SET2–RPB1 interacting domain (SRI) domain ( 31 ) at the COOH-terminus of the SETD2 protein product

*Most frequently silenced gene and most frequent mutated chromatin modifier in HSTL<ref name=":4" />

*More than 44% of patients had more than 1 mutation in SETD2.<ref name=":2" />

|21%

|15%

|10%

'''*'''Chromatin modifiers make up the most commonly mutated genes in HSTL<ref name=":4" />

 

 

*Only 1 reported case with both mutations present<ref name=":4">McKinney, M., Moffitt, A.B., Gaulard, P., Travert, M., De Leval, L., Nicolae, A., Raffeld, M., Jaffe, E.S., Pittaluga, S., Xi, L. and Heavican, T., 2017. The genetic basis of hepatosplenic T-cell lymphoma. ''Cancer discovery'', ''7''(4), pp.369-379.</ref>

 

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}

*Next generation sequencing to support mutations seen in HSTL including ''STAT3, STAT5B, PI3KCD,'' ''SETD2, INO80, TET3'', and ''STAT5B''<ref name=":4" />  

**Presence of RHOA mutation, can potentially exclude HSTL from the differential diagnosis<ref name=":4" />

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases H]]