HAEM5:Histiocytic sarcoma: 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:Histiocytic Sarcoma]].

<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

 

==Cancer Category / Type==

 

 

==Cancer Sub-Classification / Subtype==

 

 

 

Histiocytic sarcoma (HS) is a very rare and aggressive non-Langerhans histiocyte neoplasm. It is included among histiocytic and dendritic cell neoplasms in the World Health Organization classification<ref name=":0">Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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.</ref> and among malignant histiocytoses (M group) in the revised classification of the Histiocyte Society.<ref>{{Cite journal|last=Emile|first=Jean-François|last2=Abla|first2=Oussama|last3=Fraitag|first3=Sylvie|last4=Horne|first4=Annacarin|last5=Haroche|first5=Julien|last6=Donadieu|first6=Jean|last7=Requena-Caballero|first7=Luis|last8=Jordan|first8=Michael B.|last9=Abdel-Wahab|first9=Omar|date=2016-06-02|title=Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages|url=https://pubmed.ncbi.nlm.nih.gov/26966089|journal=Blood|volume=127|issue=22|pages=2672–2681|doi=10.1182/blood-2016-01-690636|issn=1528-0020|pmc=5161007|pmid=26966089}}</ref> While, the etiology of HS remains unknown, it appears that it is generally derived from the myeloid (monocyte-macrophage) lineage. Some cases may nevertheless arise from evolutionary mechanisms such as transdifferentiation of another primary hemopathy, often of B-cell lineage, as evidenced by shared identical molecular alterations between the two malignancies.<ref name=":1">{{Cite journal|last=Feldman|first=Andrew L.|last2=Arber|first2=Daniel A.|last3=Pittaluga|first3=Stefania|last4=Martinez|first4=Antonio|last5=Burke|first5=Jerome S.|last6=Raffeld|first6=Mark|last7=Camos|first7=Mireia|last8=Warnke|first8=Roger|last9=Jaffe|first9=Elaine S.|date=2008-06-15|title=Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone|url=https://pubmed.ncbi.nlm.nih.gov/18272816|journal=Blood|volume=111|issue=12|pages=5433–5439|doi=10.1182/blood-2007-11-124792|issn=1528-0020|pmc=2424145|pmid=18272816}}</ref> Additionally, in other cases, separate development of two malignancies from a common progenitor may lead to HS occurring in the setting of another clonally-related hemopathy.<ref name=":2">{{Cite journal|last=Bleeke|first=Matthias|last2=Johann|first2=Pascal|last3=Gröbner|first3=Susanne|last4=Alten|first4=Julia|last5=Cario|first5=Gunnar|last6=Schäfer|first6=Hansjörg|last7=Klapper|first7=Wolfram|last8=Khoury|first8=Joseph|last9=Pfister|first9=Stefan|date=2020-02|title=Genome-wide analysis of acute leukemia and clonally related histiocytic sarcoma in a series of three pediatric patients|url=https://pubmed.ncbi.nlm.nih.gov/31737984|journal=Pediatric Blood & Cancer|volume=67|issue=2|pages=e28074|doi=10.1002/pbc.28074|issn=1545-5017|pmid=31737984}}</ref><ref name=":3">{{Cite journal|last=Brunner|first=P.|last2=Rufle|first2=A.|last3=Dirnhofer|first3=S.|last4=Lohri|first4=A.|last5=Willi|first5=N.|last6=Cathomas|first6=G.|last7=Tzankov|first7=A.|last8=Juskevicius|first8=D.|date=2014-09|title=Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor|url=https://pubmed.ncbi.nlm.nih.gov/24850291|journal=Leukemia|volume=28|issue=9|pages=1937–1940|doi=10.1038/leu.2014.167|issn=1476-5551|pmid=24850291}}</ref>

 

|'''Signs and Symptoms'''

|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)

 

 

 

<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)

|'''Laboratory Findings'''

|<span class="blue-text">EXAMPLE:</span> Cytopenias

 

!Finding!!Marker

|Positive (universal)||One of CD68, CD163, lysozyme

|Positive (subset)||CD45, HLA-DR, α1-antitrypsin, CD4

|-

|Negative (universal)||HMB45, EMA, keratin

|Negative (subset)||CD1a, langerin, CD21, CD35, CD13, MPO, CD15, S100

|}

Put your text here and fill in the table

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

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

|Yes

|No

|Yes

|<span class="blue-text">EXAMPLE:</span>

 

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

No universal or recurrent chromosomal rearrangement are identified in histiocytic sarcoma. In cases where HS arises in association with follicular lymphoma, both neoplasms may exhibit the translocation t(14;18)(q32;q21) with identical breakpoints. In fact, such cases may reflect a phenomenon of transdifferentiation from a lymphoid to a histiocytic phenotype. This was suggested by Feldman et al. in a compelling study reporting on 8 cases of clonally related follicular lymphoma and HS (with presence of t(14;18) in both tumors and identical ''IGH'' and ''BCL2'' gene rearrangements). The authors posited that transdifferentiation may be mediated by changes in transcription factors (as evidenced by repression of PAX5, a B-cell lineage commitment factor, with upregulation of the myeloid transcription factors C/EBPα and β). <ref name=":1" /> Interestingly, the translocation t(14;18) has also rarely been documented in sporadic HS. <ref>{{Cite journal|last=Hayase|first=Eiko|last2=Kurosawa|first2=Mitsutoshi|last3=Yonezumi|first3=Masakatsu|last4=Suzuki|first4=Sachiko|last5=Suzuki|first5=Hiroaki|date=2010-11|title=Aggressive sporadic histiocytic sarcoma with immunoglobulin heavy chain gene rearrangement and t(14;18)|url=https://pubmed.ncbi.nlm.nih.gov/20976632|journal=International Journal of Hematology|volume=92|issue=4|pages=659–663|doi=10.1007/s12185-010-0704-8|issn=1865-3774|pmid=20976632}}</ref><ref name=":12">{{Cite journal|last=Chen|first=Wei|last2=Lau|first2=Sean K.|last3=Fong|first3=Dean|last4=Wang|first4=Jun|last5=Wang|first5=Endi|last6=Arber|first6=Daniel A.|last7=Weiss|first7=Lawrence M.|last8=Huang|first8=Qin|date=2009-06|title=High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/dendritic cell sarcomas|url=https://pubmed.ncbi.nlm.nih.gov/19145200|journal=The American Journal of Surgical Pathology|volume=33|issue=6|pages=863–873|doi=10.1097/PAS.0b013e31819287b8|issn=1532-0979|pmid=19145200}}</ref> Similarly, a ''CCND1-IgH'' fusion has been described by Hure et al in patients diagnosed with HS and mantle cell lymphoma.<ref name=":5" /> In addition, other gene fusions have been reported sporadically in individual cases. For example, Egan et al have identified a novel fusion between exon 12 of ''TTYH3'' and exon 8 of ''BRAF'' on chromosome 7 using RNA-Seq. This ''TTYH3-BRAF'' fusion, subsequently confirmed with RT-PCR, was associated with increased levels of BRAF transcripts.<ref name=":6">{{Cite journal|last=Egan|first=Caoimhe|last2=Nicolae|first2=Alina|last3=Lack|first3=Justin|last4=Chung|first4=Hye-Jung|last5=Skarshaug|first5=Shannon|last6=Pham|first6=Thu Anh|last7=Navarro|first7=Winnifred|last8=Abdullaev|first8=Zied|last9=Aguilera|first9=Nadine S.|date=2020-04|title=Genomic profiling of primary histiocytic sarcoma reveals two molecular subgroups|url=https://pubmed.ncbi.nlm.nih.gov/31439678|journal=Haematologica|volume=105|issue=4|pages=951–960|doi=10.3324/haematol.2019.230375|issn=1592-8721|pmc=7109753|pmid=31439678}}</ref>

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}

==Individual Region Genomic Gain / Loss / LOH==

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

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

 

chr7:1- 159,335,973 [hg38]

 

|Yes

|No

 

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).

 

chr8:1-145,138,636 [hg38]

 

|No

|No

 

Common recurrent secondary finding for t(8;21) (add reference).

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

In a series of 28 cases of HS assessed with targeted next-generation sequencing, ''CDKN2A'' was frequently inactivated by focal deletion at 9p21.3.<ref name=":7">{{Cite journal|last=Shanmugam|first=Vignesh|last2=Griffin|first2=Gabriel K.|last3=Jacobsen|first3=Eric D.|last4=Fletcher|first4=Christopher D. M.|last5=Sholl|first5=Lynette M.|last6=Hornick|first6=Jason L.|date=2019-06|title=Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma|url=https://pubmed.ncbi.nlm.nih.gov/30626916|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=32|issue=6|pages=830–843|doi=10.1038/s41379-018-0200-x|issn=1530-0285|pmid=30626916}}</ref> Loss of ''CDKN2A'' has also been documented in some patients by FISH analysis.<ref name=":6" /> Copy-number loss or Loss-of-heterozygosity (LOH) involving chromosome 17 (including the ''NF1'' gene) and amplification of ''PTPN11'' can also be seen.<ref name=":6" /> In a case series describing three pediatric patients with clonally related HS with predating acute leukemia, methylation array profiling revealed the presence of ''CDKN2A'' deletions at chromosome 9p in two patients.<ref name=":2" />

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|Yes

|No

|No

 

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

No characteristic chromosomal aberrations have been described in HS. Rarely, histiocytic sarcoma may arise in patients with mediastinal germ cell tumor. In this setting, the germ cell tumor and HS may display isochromosome 12p.<ref name=":13" />

==Gene Mutations (SNV / INDEL)==

!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''

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

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations

<span class="blue-text">EXAMPLE:</span>

 

EGFR; Exon 20 mutations

 

<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations

|<span class="blue-text">EXAMPLE:</span> TSG

|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

 

<span class="blue-text">EXAMPLE:</span> 30% (add Reference)

|<span class="blue-text">EXAMPLE:</span> IDH1 R123H

|<span class="blue-text">EXAMPLE:</span> EGFR amplification

|}

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

 

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>

|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations

|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />

<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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

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