HAEM5:Hepatosplenic T-cell lymphoma: Difference between revisions

Michelle Don, MD, MS

==WHO Classification of Disease==

|-

|Haematolymphoid Tumours (5th ed.)

|T-cell and NK-cell lymphoid proliferations and lymphomas

|-

|Mature T-cell and NK-cell neoplasms

|-

|N/A

|Subtype(s)

|Hepatosplenic T-cell lymphoma

==Related Terminology==

|Acceptable

|N/A

|Not Recommended

|Erythrophagocytic Tγ lymphoma

==Gene Rearrangements==

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Clinical Relevance Details/Other Notes

|N/A

|N/A

|N/A

!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|7

|7q, chr7

|Unknown

|D, P

|Considered a primary aberration<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>, seen in 40-70% of cases<ref name=":1">{{Cite journal|displayauthors=1|last=Medeiros|first=Jeffrey|date=2024|title=Hepatosplenic T-cell lymphoma. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]|url=https://tumourclassification.iarc.who.int/chaptercontent/63/229|journal=WHO classification of tumours series, 5th ed.|volume=vol. 11|pages=|via=Lyon (France): International Agency for Research on Cancer}}</ref>

|Unknown

|D, P

|Considered a secondary aberration<ref name=":2" />, seen in 10-50% of cases<ref name=":1" />

|Unknown

|Unknown

|10

|10q, chr10

|Unknown

|P

|1

|1q, chr1

|Unknown

|P

|}

==Characteristic Chromosomal or Other Global Mutational Patterns==

7q aberrations and trisomy 8 are considered specific for HSTL, but not sensitive<ref name=":2" />

!Molecular Pathogenesis

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|Isochromosome 7q<ref name=":8">{{Cite journal|last=Wlodarska|first=Iwona|last2=Martin-Garcia|first2=Nadine|last3=Achten|first3=Ruth|last4=De Wolf-Peeters|first4=Chris|last5=Pauwels|first5=Patrick|last6=Tulliez|first6=Micheline|last7=de Mascarel|first7=Antoine|last8=Brière|first8=Josette|last9=Patey|first9=Martine|date=2002-03|title=Fluorescence in situ hybridization study of chromosome 7 aberrations in hepatosplenic T-cell lymphoma: isochromosome 7q as a common abnormality accumulating in forms with features of cytologic progression|url=https://pubmed.ncbi.nlm.nih.gov/11807981|journal=Genes, Chromosomes & Cancer|volume=33|issue=3|pages=243–251|doi=10.1002/gcc.10021|issn=1045-2257|pmid=11807981}}</ref> and chromosome 7 imbalances including ring chromosome 7.

|Cases with chromosome 7 abnormalities show:

*Gain of 7q22.11q31.1 (38.77 Mb; 86259620–124892276 bp)<ref name=":3" />

|Common

|D, P

|No

|See table under "Genomic Gain/Loss/LOH"

Co-occurrence of Isochromosome 7q and trisomy 8 can be seen in 8-53% of cases<ref name=":2" />

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  

Gain of chromosome 1q

|occur in a significant minority of HSTL cases<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!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|''STAT3''; missense mutation

|Recurrent

|T

|''STAT5b''; missense mutation

|Common

|D, T

|Highest functional potency: ''STAT5B'' N642H and V712E mutations<ref name=":2" />

 

 

One study showed increased CD56 expression with ''STAT5b''<ref name=":9">{{Cite journal|last=Nicolae|first=A.|last2=Xi|first2=L.|last3=Pittaluga|first3=S.|last4=Abdullaev|first4=Z.|last5=Pack|first5=S. D.|last6=Chen|first6=J.|last7=Waldmann|first7=T. A.|last8=Jaffe|first8=E. S.|last9=Raffeld|first9=M.|date=2014-11|title=Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/24947020|journal=Leukemia|volume=28|issue=11|pages=2244–2248|doi=10.1038/leu.2014.200|issn=1476-5551|pmc=7701980|pmid=24947020}}</ref>

Also seen in ~2% of T-large granular lymphocyte leukemia<ref name=":2" />

|''PIK3CD''

pathways important to cell survival<ref name=":4" />

|Recurrent

|T

|''SETD2''; biallelic LOF

 

 

71% of cases showing at least one LOF mutation<ref name=":4" />, and more than 44% of patients with ''SETD2'' mutations had more than 1 mutation detected<ref name=":2" />

|-

|Chromatin modifier*

|Common

|''ARID1B''

|Recurrent

|Unknown

|''TET3''

|Recurrent

|D, T

|''SMARCA2''

|Recurrent

|Unknown

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

*A single study has shown use of IFNα2c therapy-induced changes in CpG methylation<ref name=":7">{{Cite journal|last=Bhat|first=Jaydeep|last2=Bergmann|first2=Anke K.|last3=Waschina|first3=Silvio|last4=Nerl|first4=Christoph|last5=Kaleta|first5=Christoph|last6=Siebert|first6=Reiner|last7=Ammerpohl|first7=Ole|last8=Kabelitz|first8=Dieter|date=2021-05|title=DNA methylation profile of a hepatosplenic gamma/delta T-cell lymphoma patient associated with response to interferon-α therapy|url=https://pubmed.ncbi.nlm.nih.gov/32820235|journal=Cellular & Molecular Immunology|volume=18|issue=5|pages=1332–1335|doi=10.1038/s41423-020-0518-4|issn=2042-0226|pmc=8093208|pmid=32820235}}</ref>

**CpG methylation changes have the potential to serve as biomarkers of drug responses and/or disease progression<ref name=":7" />

!Gene; Genetic Alteration<ref name=":4" /><ref name=":5" />!!Pathway<ref name=":4" /><ref name=":5" />!!Pathophysiologic Outcome<ref name=":4" /><ref name=":5" />

|''SPRY2'', ''RHOB*'', ''MAP4K3'', and ''SPRY1'' overexpression

|''SYK**'' overexpression

<nowiki>*</nowiki>''RHOA'' mutations predominantly favor Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL)<ref name=":4" />  

''**SyK'' expression was seen one study, which is not typical for normal T-cells<ref name=":5" /> ''Syk'' is a protein tyrosine kinase usually involved in B-cell receptor signaling<ref name=":5" />

Clinical, morphologic, and immunophenotypic features are sufficient for diagnosis in most cases.  Cytogenetic testing could be used to support the diagnosis.

**Presence of ''RHOA'' mutation, can potentially exclude HSTL from the differential diagnosis<ref name=":5" />

Negative (subset) – CD5, CD4, CD8<ref name=":1" />

<references />

 

==Notes==

<nowiki>*</nowiki>''Citation of this Page'': Sargolzaeiaval F, Don M. “Hepatosplenic T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hepatosplenic_T-cell_lymphoma</nowiki>.

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

 

Prior Author(s): N/A