Difference between revisions of "HAEM5:Histiocytic sarcoma"

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search
[checked revision][checked revision]
Line 1: Line 1:
 
{{DISPLAYTITLE:Histiocytic sarcoma}}
 
{{DISPLAYTITLE:Histiocytic sarcoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
Line 7: Line 7:
 
}}</blockquote>
 
}}</blockquote>
  
<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). 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>
+
<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>
  
 
==Primary Author(s)*==
 
==Primary Author(s)*==
Line 39: Line 39:
 
==Clinical Features==
 
==Clinical Features==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
  
EXAMPLE B-symptoms (weight loss, fever, night sweats)
+
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
  
EXAMPLE Fatigue
+
<span class="blue-text">EXAMPLE:</span> Fatigue
  
EXAMPLE Lymphadenopathy (uncommon)
+
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
+
|<span class="blue-text">EXAMPLE:</span> Cytopenias
  
EXAMPLE Lymphocytosis (low level)
+
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
|}
 
|}
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
+
<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}}
  
 
Patients with histiocytic sarcoma often present with systemic symptoms such as fatigue, weight loss and fever. Additional clinical manifestations are often related to site(s) of disease involvement. Some patients may come to clinical attention with a palpable mass or from organ compression by the malignant mass. Skin lesions may range from a minor rash to multiple tumors on the trunk and extremities. Gastrointestinal involvement may present with intestinal obstruction. Lytic lesions may arise from bone involvement. Hepatosplenomegaly is also described. Cytopenias are found in about a third of patients, with hemophagocytosis seen on bone marrow evaluation in a small fraction of patients. Additionally, histiocytic sarcoma may present in the setting of another hematologic neoplasm such as follicular lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, mantle cell lymphoma, hairy cell leukemia, chronic lymphocytic leukemia or MALT lymphoma. <ref name=":1" /><ref name=":3" /><ref>{{Cite journal|last=Zhang|first=Da|last2=McGuirk|first2=Joseph|last3=Ganguly|first3=Siddhartha|last4=Persons|first4=Diane L.|date=2009-05|title=Histiocytic/dendritic cell sarcoma arising from follicular lymphoma involving the bone: a case report and review of literature|url=https://pubmed.ncbi.nlm.nih.gov/19343479|journal=International Journal of Hematology|volume=89|issue=4|pages=529–532|doi=10.1007/s12185-009-0300-y|issn=1865-3774|pmid=19343479}}</ref><ref name=":5">{{Cite journal|last=Hure|first=Michelle C.|last2=Elco|first2=Christopher P.|last3=Ward|first3=David|last4=Hutchinson|first4=Lloyd|last5=Meng|first5=Xiuling|last6=Dorfman|first6=David M.|last7=Yu|first7=Hongbo|date=2012-02-10|title=Histiocytic sarcoma arising from clonally related mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22184374|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=30|issue=5|pages=e49–53|doi=10.1200/JCO.2011.38.8553|issn=1527-7755|pmid=22184374}}</ref><ref>{{Cite journal|last=Alvaro|first=T.|last2=Bosch|first2=R.|last3=Salvadó|first3=M. T.|last4=Piris|first4=M. A.|date=1996-11|title=True histiocytic lymphoma of the stomach associated with low-grade B-cell mucosa-associated lymphoid tissue (MALT)-type lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8898846|journal=The American Journal of Surgical Pathology|volume=20|issue=11|pages=1406–1411|doi=10.1097/00000478-199611000-00013|issn=0147-5185|pmid=8898846}}</ref><ref>{{Cite journal|last=Bouabdallah|first=R.|last2=Abéna|first2=P.|last3=Chetaille|first3=B.|last4=Aurran-Schleinitz|first4=T.|last5=Sainty|first5=D.|last6=Dubus|first6=P.|last7=Arnoulet|first7=C.|last8=Coso|first8=D.|last9=Xerri|first9=L.|date=2001-06|title=True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/11442501|journal=British Journal of Haematology|volume=113|issue=4|pages=1047–1050|doi=10.1046/j.1365-2141.2001.02841.x|issn=0007-1048|pmid=11442501}}</ref><ref>{{Cite journal|last=Castro|first=Eumenia C. C.|last2=Blazquez|first2=Cristina|last3=Boyd|first3=Jaime|last4=Correa|first4=Hernán|last5=de Chadarevian|first5=J.-P.|last6=Felgar|first6=Raymond E.|last7=Graf|first7=Nicole|last8=Levy|first8=Norman|last9=Lowe|first9=Eric J.|date=2010-05|title=Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/19642834|journal=Pediatric and Developmental Pathology: The Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society|volume=13|issue=3|pages=225–237|doi=10.2350/09-03-0622-OA.1|issn=1093-5266|pmid=19642834}}</ref><ref>{{Cite journal|last=Kumar|first=Riten|last2=Khan|first2=Shakila P.|last3=Joshi|first3=Divya-Devi|last4=Shaw|first4=Gene R.|last5=Ketterling|first5=Rhett P.|last6=Feldman|first6=Andrew L.|date=2011-02|title=Pediatric histiocytic sarcoma clonally related to precursor B-cell acute lymphoblastic leukemia with homozygous deletion of CDKN2A encoding p16INK4A|url=https://pubmed.ncbi.nlm.nih.gov/20973102|journal=Pediatric Blood & Cancer|volume=56|issue=2|pages=307–310|doi=10.1002/pbc.22810|issn=1545-5017|pmid=20973102}}</ref><ref>{{Cite journal|last=McClure|first=Rebecca|last2=Khoury|first2=Joseph|last3=Feldman|first3=Andrew|last4=Ketterling|first4=Rhett|date=2010-02|title=Clonal relationship between precursor B-cell acute lymphoblastic leukemia and histiocytic sarcoma: a case report and discussion in the context of similar cases|url=https://pubmed.ncbi.nlm.nih.gov/19744706|journal=Leukemia Research|volume=34|issue=2|pages=e71–73|doi=10.1016/j.leukres.2009.08.020|issn=1873-5835|pmid=19744706}}</ref><ref>{{Cite journal|last=Michonneau|first=David|last2=Kaltenbach|first2=Sophie|last3=Derrieux|first3=Coralie|last4=Trinquand|first4=Amelie|last5=Brouzes|first5=Chantal|last6=Gibault|first6=Laure|last7=North|first7=Marie-Odile|last8=Delarue|first8=Richard|last9=Varet|first9=Bruno|date=2014-12-10|title=BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24567436|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=32|issue=35|pages=e117–121|doi=10.1200/JCO.2013.49.0078|issn=1527-7755|pmid=24567436}}</ref><ref>{{Cite journal|last=Shao|first=Haipeng|last2=Xi|first2=Liqiang|last3=Raffeld|first3=Mark|last4=Feldman|first4=Andrew L.|last5=Ketterling|first5=Rhett P.|last6=Knudson|first6=Ryan|last7=Rodriguez-Canales|first7=Jaime|last8=Hanson|first8=Jeffrey|last9=Pittaluga|first9=Stefania|date=2011-11|title=Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases|url=https://pubmed.ncbi.nlm.nih.gov/21666687|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=24|issue=11|pages=1421–1432|doi=10.1038/modpathol.2011.102|issn=1530-0285|pmc=3175277|pmid=21666687}}</ref> Association of HS with a germ cell tumor or autoimmune lymphoproliferative syndrome has also been described.<ref name=":13">{{Cite journal|last=Nichols|first=C. R.|last2=Roth|first2=B. J.|last3=Heerema|first3=N.|last4=Griep|first4=J.|last5=Tricot|first5=G.|date=1990-05-17|title=Hematologic neoplasia associated with primary mediastinal germ-cell tumors|url=https://pubmed.ncbi.nlm.nih.gov/2158625|journal=The New England Journal of Medicine|volume=322|issue=20|pages=1425–1429|doi=10.1056/NEJM199005173222004|issn=0028-4793|pmid=2158625}}</ref>
 
Patients with histiocytic sarcoma often present with systemic symptoms such as fatigue, weight loss and fever. Additional clinical manifestations are often related to site(s) of disease involvement. Some patients may come to clinical attention with a palpable mass or from organ compression by the malignant mass. Skin lesions may range from a minor rash to multiple tumors on the trunk and extremities. Gastrointestinal involvement may present with intestinal obstruction. Lytic lesions may arise from bone involvement. Hepatosplenomegaly is also described. Cytopenias are found in about a third of patients, with hemophagocytosis seen on bone marrow evaluation in a small fraction of patients. Additionally, histiocytic sarcoma may present in the setting of another hematologic neoplasm such as follicular lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, mantle cell lymphoma, hairy cell leukemia, chronic lymphocytic leukemia or MALT lymphoma. <ref name=":1" /><ref name=":3" /><ref>{{Cite journal|last=Zhang|first=Da|last2=McGuirk|first2=Joseph|last3=Ganguly|first3=Siddhartha|last4=Persons|first4=Diane L.|date=2009-05|title=Histiocytic/dendritic cell sarcoma arising from follicular lymphoma involving the bone: a case report and review of literature|url=https://pubmed.ncbi.nlm.nih.gov/19343479|journal=International Journal of Hematology|volume=89|issue=4|pages=529–532|doi=10.1007/s12185-009-0300-y|issn=1865-3774|pmid=19343479}}</ref><ref name=":5">{{Cite journal|last=Hure|first=Michelle C.|last2=Elco|first2=Christopher P.|last3=Ward|first3=David|last4=Hutchinson|first4=Lloyd|last5=Meng|first5=Xiuling|last6=Dorfman|first6=David M.|last7=Yu|first7=Hongbo|date=2012-02-10|title=Histiocytic sarcoma arising from clonally related mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22184374|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=30|issue=5|pages=e49–53|doi=10.1200/JCO.2011.38.8553|issn=1527-7755|pmid=22184374}}</ref><ref>{{Cite journal|last=Alvaro|first=T.|last2=Bosch|first2=R.|last3=Salvadó|first3=M. T.|last4=Piris|first4=M. A.|date=1996-11|title=True histiocytic lymphoma of the stomach associated with low-grade B-cell mucosa-associated lymphoid tissue (MALT)-type lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8898846|journal=The American Journal of Surgical Pathology|volume=20|issue=11|pages=1406–1411|doi=10.1097/00000478-199611000-00013|issn=0147-5185|pmid=8898846}}</ref><ref>{{Cite journal|last=Bouabdallah|first=R.|last2=Abéna|first2=P.|last3=Chetaille|first3=B.|last4=Aurran-Schleinitz|first4=T.|last5=Sainty|first5=D.|last6=Dubus|first6=P.|last7=Arnoulet|first7=C.|last8=Coso|first8=D.|last9=Xerri|first9=L.|date=2001-06|title=True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/11442501|journal=British Journal of Haematology|volume=113|issue=4|pages=1047–1050|doi=10.1046/j.1365-2141.2001.02841.x|issn=0007-1048|pmid=11442501}}</ref><ref>{{Cite journal|last=Castro|first=Eumenia C. C.|last2=Blazquez|first2=Cristina|last3=Boyd|first3=Jaime|last4=Correa|first4=Hernán|last5=de Chadarevian|first5=J.-P.|last6=Felgar|first6=Raymond E.|last7=Graf|first7=Nicole|last8=Levy|first8=Norman|last9=Lowe|first9=Eric J.|date=2010-05|title=Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/19642834|journal=Pediatric and Developmental Pathology: The Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society|volume=13|issue=3|pages=225–237|doi=10.2350/09-03-0622-OA.1|issn=1093-5266|pmid=19642834}}</ref><ref>{{Cite journal|last=Kumar|first=Riten|last2=Khan|first2=Shakila P.|last3=Joshi|first3=Divya-Devi|last4=Shaw|first4=Gene R.|last5=Ketterling|first5=Rhett P.|last6=Feldman|first6=Andrew L.|date=2011-02|title=Pediatric histiocytic sarcoma clonally related to precursor B-cell acute lymphoblastic leukemia with homozygous deletion of CDKN2A encoding p16INK4A|url=https://pubmed.ncbi.nlm.nih.gov/20973102|journal=Pediatric Blood & Cancer|volume=56|issue=2|pages=307–310|doi=10.1002/pbc.22810|issn=1545-5017|pmid=20973102}}</ref><ref>{{Cite journal|last=McClure|first=Rebecca|last2=Khoury|first2=Joseph|last3=Feldman|first3=Andrew|last4=Ketterling|first4=Rhett|date=2010-02|title=Clonal relationship between precursor B-cell acute lymphoblastic leukemia and histiocytic sarcoma: a case report and discussion in the context of similar cases|url=https://pubmed.ncbi.nlm.nih.gov/19744706|journal=Leukemia Research|volume=34|issue=2|pages=e71–73|doi=10.1016/j.leukres.2009.08.020|issn=1873-5835|pmid=19744706}}</ref><ref>{{Cite journal|last=Michonneau|first=David|last2=Kaltenbach|first2=Sophie|last3=Derrieux|first3=Coralie|last4=Trinquand|first4=Amelie|last5=Brouzes|first5=Chantal|last6=Gibault|first6=Laure|last7=North|first7=Marie-Odile|last8=Delarue|first8=Richard|last9=Varet|first9=Bruno|date=2014-12-10|title=BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia|url=https://pubmed.ncbi.nlm.nih.gov/24567436|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=32|issue=35|pages=e117–121|doi=10.1200/JCO.2013.49.0078|issn=1527-7755|pmid=24567436}}</ref><ref>{{Cite journal|last=Shao|first=Haipeng|last2=Xi|first2=Liqiang|last3=Raffeld|first3=Mark|last4=Feldman|first4=Andrew L.|last5=Ketterling|first5=Rhett P.|last6=Knudson|first6=Ryan|last7=Rodriguez-Canales|first7=Jaime|last8=Hanson|first8=Jeffrey|last9=Pittaluga|first9=Stefania|date=2011-11|title=Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases|url=https://pubmed.ncbi.nlm.nih.gov/21666687|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=24|issue=11|pages=1421–1432|doi=10.1038/modpathol.2011.102|issn=1530-0285|pmc=3175277|pmid=21666687}}</ref> Association of HS with a germ cell tumor or autoimmune lymphoproliferative syndrome has also been described.<ref name=":13">{{Cite journal|last=Nichols|first=C. R.|last2=Roth|first2=B. J.|last3=Heerema|first3=N.|last4=Griep|first4=J.|last5=Tricot|first5=G.|date=1990-05-17|title=Hematologic neoplasia associated with primary mediastinal germ-cell tumors|url=https://pubmed.ncbi.nlm.nih.gov/2158625|journal=The New England Journal of Medicine|volume=322|issue=20|pages=1425–1429|doi=10.1056/NEJM199005173222004|issn=0028-4793|pmid=2158625}}</ref>
Line 99: Line 99:
 
!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|<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)
EXAMPLE 30% (add reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
Line 110: Line 110:
 
 
  
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
+
<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}}
  
 
Very few reports have described the genetic landscape of histiocytic sarcoma, with current literature being restricted to case reports and case series, thus limiting the ability to derive a comprehensive portrait of genetic alterations in HS.
 
Very few reports have described the genetic landscape of histiocytic sarcoma, with current literature being restricted to case reports and case series, thus limiting the ability to derive a comprehensive portrait of genetic alterations in HS.
Line 127: Line 127:
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Please incorporate this section into the relevant tables found in:
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Individual Region Genomic Gain/Loss/LOH
 
* Individual Region Genomic Gain/Loss/LOH
Line 144: Line 144:
 
==Individual Region Genomic Gain / Loss / LOH==
 
==Individual Region Genomic Gain / Loss / LOH==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 154: Line 154:
 
!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
7
 
7
|EXAMPLE Loss
+
|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7
 
chr7
Line 167: Line 167:
 
|Yes
 
|Yes
 
|No
 
|No
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
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).
 
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
+
|<span class="blue-text">EXAMPLE:</span>
  
 
8
 
8
|EXAMPLE Gain
+
|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8
 
chr8
Line 184: Line 184:
 
|No
 
|No
 
|No
 
|No
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
 
|}
 
|}
  
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
+
<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}}
  
 
None recurrent.
 
None recurrent.
Line 198: Line 198:
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
  
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>
+
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. Do not delete table.'')</span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 208: Line 208:
 
!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
Line 214: Line 214:
 
|No
 
|No
 
|No
 
|No
|EXAMPLE:
+
|<span class="blue-text">EXAMPLE:</span>
  
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
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=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
+
<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" />
 
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" />
Line 226: Line 226:
 
==Gene Mutations (SNV / INDEL)==
 
==Gene Mutations (SNV / INDEL)==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 236: Line 236:
 
!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE: TP53; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
  
EXAMPLE:
+
<span class="blue-text">EXAMPLE:</span>
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
EXAMPLE: BRAF; Activating mutations
+
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|EXAMPLE: TSG
+
|<span class="blue-text">EXAMPLE:</span> TSG
|EXAMPLE: 20% (COSMIC)
+
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
  
EXAMPLE: 30% (add Reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|EXAMPLE: IDH1 R123H
+
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|EXAMPLE: EGFR amplification
+
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
Line 258: Line 258:
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
+
<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}}
  
 
''BRAF'' mutations (V600E and non-V600E) have been identified in a subset of patients with histiocytic sarcoma. Additionally, a study in which targeted next-generation sequencing was performed on 28 cases, reported recurrent mutations in the MAP kinase pathway (including ''KRAS, NRAS, MAP2K1, BRAF, PTPN11, NF1, CBL''), and the PI3K signaling pathway (including ''PTEN, MTOR, PIK2R1, PIK3CA''). Also, some cases, mostly those with a prior diagnosis of B-cell lymphoma, harbored a mutational signature of “aberrant somatic hypermutation” with mutations in genes such as ''BCL6, BCL2, CIITA, MYC, SOCS1, PAX5''. In this study, ''CDNK2A'' was the most commonly altered gene (13/28, 46%). The authors identified a mean coding mutational burden of 3.56/Mb in their cohort, a number that is relatively low as compared with other malignancies.<ref name=":7" /> In another series reporting on 21 cases of primary HS investigated with whole-exome sequencing and RNA sequencing, Egan et al identified a high frequency of alterations within the RAS/RAF/MAPK pathway (such as ''NF1, PTPN11, MAP2K1, NRAS, KRAS'').<ref name=":6" />
 
''BRAF'' mutations (V600E and non-V600E) have been identified in a subset of patients with histiocytic sarcoma. Additionally, a study in which targeted next-generation sequencing was performed on 28 cases, reported recurrent mutations in the MAP kinase pathway (including ''KRAS, NRAS, MAP2K1, BRAF, PTPN11, NF1, CBL''), and the PI3K signaling pathway (including ''PTEN, MTOR, PIK2R1, PIK3CA''). Also, some cases, mostly those with a prior diagnosis of B-cell lymphoma, harbored a mutational signature of “aberrant somatic hypermutation” with mutations in genes such as ''BCL6, BCL2, CIITA, MYC, SOCS1, PAX5''. In this study, ''CDNK2A'' was the most commonly altered gene (13/28, 46%). The authors identified a mean coding mutational burden of 3.56/Mb in their cohort, a number that is relatively low as compared with other malignancies.<ref name=":7" /> In another series reporting on 21 cases of primary HS investigated with whole-exome sequencing and RNA sequencing, Egan et al identified a high frequency of alterations within the RAS/RAF/MAPK pathway (such as ''NF1, PTPN11, MAP2K1, NRAS, KRAS'').<ref name=":6" />
Line 370: Line 370:
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
+
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>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
+
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|-
 
|-
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
+
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
+
|<span class="blue-text">EXAMPLE:</span>  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.}}
+
<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}}
  
 
A recent molecular profiling study by Shanmugam et al highlighted that alterations in the MAP kinase, PI3K- and cyclin-CDK4/6-INK4 signaling pathways appear involved in the pathogenesis of histiocytic sarcoma.<ref name=":7" /> Egan et al also identified a high frequency of alterations within the RAS/RAF/MAPK pathway.<ref name=":6" /> Histiocytic sarcoma may also be associated with perturbations of chromatin regulation.<ref>{{Cite journal|last=Hung|first=Yin P.|last2=Qian|first2=Xiaohua|date=2020-05|title=Histiocytic Sarcoma|url=https://pubmed.ncbi.nlm.nih.gov/31070934|journal=Archives of Pathology & Laboratory Medicine|volume=144|issue=5|pages=650–654|doi=10.5858/arpa.2018-0349-RS|issn=1543-2165|pmid=31070934}}</ref>
 
A recent molecular profiling study by Shanmugam et al highlighted that alterations in the MAP kinase, PI3K- and cyclin-CDK4/6-INK4 signaling pathways appear involved in the pathogenesis of histiocytic sarcoma.<ref name=":7" /> Egan et al also identified a high frequency of alterations within the RAS/RAF/MAPK pathway.<ref name=":6" /> Histiocytic sarcoma may also be associated with perturbations of chromatin regulation.<ref>{{Cite journal|last=Hung|first=Yin P.|last2=Qian|first2=Xiaohua|date=2020-05|title=Histiocytic Sarcoma|url=https://pubmed.ncbi.nlm.nih.gov/31070934|journal=Archives of Pathology & Laboratory Medicine|volume=144|issue=5|pages=650–654|doi=10.5858/arpa.2018-0349-RS|issn=1543-2165|pmid=31070934}}</ref>
Line 411: Line 411:
 
==Links==
 
==Links==
  
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
+
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
  
 
==References==
 
==References==

Revision as of 11:37, 1 September 2024

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Histiocytic Sarcoma.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Marie-France Gagnon, MD, Mayo Clinic, Xinjie Xu, PhD FACMG, Mayo Clinic

Cancer Category / Type

Histiocytic and dendritic cell neoplasms

Cancer Sub-Classification / Subtype

Not applicable

Definition / Description of Disease

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[1] and among malignant histiocytoses (M group) in the revised classification of the Histiocyte Society.[2] 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.[3] 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.[4][5]

Synonyms / Terminology

True histiocytic lymphoma (obsolete)

Epidemiology / Prevalence

Owing to the rarity of histiocytic sarcoma, only a limited number of cases of this malignancy have been described in the literature. While HS may affect patients of all ages, it occurs mainly in adulthood. A study based on the Surveillance, Epidemiology, and End Results (SEER) database reporting on 159 cases, documented an overall incidence of 0.17 per 100,000 individuals. Median age at diagnosis was 63 years.[6] Also, a higher incidence of HS has been reported, although inconsistently, in males.

HS may occur in isolation as well as synchronously or metachronously to another hematologic malignancy such as follicular lymphoma. Cases occurring in the setting of an existing hematologic malignancy are often referred to as secondary HS (as opposed to primary HS).

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Signs and Symptoms EXAMPLE: Asymptomatic (incidental finding on complete blood counts)

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

EXAMPLE: Fatigue

EXAMPLE: Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE: Cytopenias

EXAMPLE: Lymphocytosis (low level)


editHAEM5 Conversion Notes
Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

Patients with histiocytic sarcoma often present with systemic symptoms such as fatigue, weight loss and fever. Additional clinical manifestations are often related to site(s) of disease involvement. Some patients may come to clinical attention with a palpable mass or from organ compression by the malignant mass. Skin lesions may range from a minor rash to multiple tumors on the trunk and extremities. Gastrointestinal involvement may present with intestinal obstruction. Lytic lesions may arise from bone involvement. Hepatosplenomegaly is also described. Cytopenias are found in about a third of patients, with hemophagocytosis seen on bone marrow evaluation in a small fraction of patients. Additionally, histiocytic sarcoma may present in the setting of another hematologic neoplasm such as follicular lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, mantle cell lymphoma, hairy cell leukemia, chronic lymphocytic leukemia or MALT lymphoma. [3][5][7][8][9][10][11][12][13][14][15] Association of HS with a germ cell tumor or autoimmune lymphoproliferative syndrome has also been described.[16]

Sites of Involvement

Histiocytic sarcoma may present as unifocal or multifocal disease. While, isolated lymph node involvement is seen in a subset of patients, extranodal involvement is more common. Among extranodal sites, the skin, soft tissues, gastrointestinal tract and nervous system are most frequently involved.[6]

Morphologic Features

According to the WHO, microscopic evaluation of histiocytic sarcoma reveals a diffuse discohesive proliferation of malignant cells with features suggestive of mature tissue histiocytes. A sinusoidal distribution may also be seen. HS is characterized by large, atypical pleomorphic neoplastic cells. These display abundant, eosinophilic cytoplasm in which fine vacuoles may be found. While focal spindling may be noted, malignant cells are usually round to ovoid. Nuclei, often large in size, may appear round or oval or display more irregular folded forms. Multinucleated cells are often described. Chromatin pattern may appear vesicular with a variable degree of atypia. Neoplastic cells may be admixed with reactive cells. Sometimes, these may form a prominent inflammatory infiltrate shrouding the malignant cells. Importantly, tumors with features consistent with histiocytic sarcoma arising in association with acute monocytic leukemia should not be classified as HS.[1]

Immunophenotype

Histiocytic sarcoma is characterized by the expression of at least one histiocytic marker such as CD68, CD163 (KP1 and PGM1) and lysozyme. Langerhans cell (CD1a, langerin), follicular dendritic cell (CD21, CD35) and myeloid cell (CD13, MPO) markers are typically negative. B-cell and T-cell markers are also usually absent. There is no expression of HMB45, EMA and keratin. Conversely, CD45, HLA-DR and α1-antitrypsin are commonly positive. Weak staining with CD15 may seldom be found. CD4 is often expressed at the cytoplasmic level. S100 is usually negative, yet a focal and weak pattern of expression may be seen.

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

Chromosomal Rearrangements (Gene Fusions)

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) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

Yes No Yes EXAMPLE:

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).


editHAEM5 Conversion Notes
Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

Very few reports have described the genetic landscape of histiocytic sarcoma, with current literature being restricted to case reports and case series, thus limiting the ability to derive a comprehensive portrait of genetic alterations in HS.


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). [3] Interestingly, the translocation t(14;18) has also rarely been documented in sporadic HS. [17][18] Similarly, a CCND1-IgH fusion has been described by Hure et al in patients diagnosed with HS and mantle cell lymphoma.[8] 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.[19]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
t(14;18) (q32;q21) IGH/BCL2 der(14) Unknown


editHAEM5 Conversion Notes
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)

Histiocytic sarcoma is a very rare neoplasm and very little is known about the genetic landscape of this malignancy. Reports on the clinical significance of genomic alterations are scarce and limited to case reports and case series, limiting the ability to draw conclusions regarding their prognostic and therapeutic significance.

Diagnosis: The diagnosis of HS is largely based on morphologic and immunophenotypic findings rather than on genetic features.

Prognosis: More data is warranted to decipher the prognostic relevance of genetic alterations found in HS.

Therapeutic: While case reports have documented the use of BRAF inhibitors in the setting of BRAF V600E mutations and of MEK inhibitors for MAP2K1 pathway mutations, these agents should not be used as first-line therapy outside of a clinical trial.

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)

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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

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

EXAMPLE:

chr7

Yes Yes No 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:

8

EXAMPLE: Gain EXAMPLE:

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

EXAMPLE:

chr8

No No No EXAMPLE:

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

editHAEM5 Conversion Notes
Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

None recurrent.

In a series of 28 cases of HS assessed with targeted next-generation sequencing, CDKN2A was frequently inactivated by focal deletion at 9p21.3.[20] Loss of CDKN2A has also been documented in some patients by FISH analysis.[19] Copy-number loss or Loss-of-heterozygosity (LOH) involving chromosome 17 (including the NF1 gene) and amplification of PTPN11 can also be seen.[19] 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.[4]

Characteristic Chromosomal Patterns

Put your text here (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. Do not delete table.)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

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

editHAEM5 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.[16]

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.)

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
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.


editHAEM5 Conversion Notes
Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

BRAF mutations (V600E and non-V600E) have been identified in a subset of patients with histiocytic sarcoma. Additionally, a study in which targeted next-generation sequencing was performed on 28 cases, reported recurrent mutations in the MAP kinase pathway (including KRAS, NRAS, MAP2K1, BRAF, PTPN11, NF1, CBL), and the PI3K signaling pathway (including PTEN, MTOR, PIK2R1, PIK3CA). Also, some cases, mostly those with a prior diagnosis of B-cell lymphoma, harbored a mutational signature of “aberrant somatic hypermutation” with mutations in genes such as BCL6, BCL2, CIITA, MYC, SOCS1, PAX5. In this study, CDNK2A was the most commonly altered gene (13/28, 46%). The authors identified a mean coding mutational burden of 3.56/Mb in their cohort, a number that is relatively low as compared with other malignancies.[20] In another series reporting on 21 cases of primary HS investigated with whole-exome sequencing and RNA sequencing, Egan et al identified a high frequency of alterations within the RAS/RAF/MAPK pathway (such as NF1, PTPN11, MAP2K1, NRAS, KRAS).[19]

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
BRAF p.V600E[19][21][22] and non-V600E p.F595[23], p.G464V[24], p.G466R[24] p.N581S[24], p.G469R[20], p.G469A, p.D594N, p.G469V[19]) Oncogene GOF 12%[19]
KRAF p.Q61H[24], p.G13D[20], p.A146T, p.G12D[19], p.G12C[19], p.Q61H[19], p.A146V[19],

p.A66fs[4]

Oncogene GOF
NRAS p.G61K[25], p.Q61R[19], p.G12C[20], p.G12D[26] Oncogene GOF
MAP2K1 p.C121S[20], p.I103N[19][20], p.L177M[20], p.F53S[20], p.F53L[19][20][27][28], p.C121S [19][29], p.K57E[19],  p.Y125C[19], p.R181K[19] Oncogene GOF
ARID1A p.L2011fs[19], p.G2087R[19] Chromatin remodeling LOF
HRAS p.G61R(23)[23] Oncogene GOF
PTPN11 p.G503[24], p.Y63S[30], p.Q506R[30], p.E72K[31], p.G60V[20], p.E69K[20], p.F71V[19], p.E76G[19], p.A72V[19] Oncogene GOF
NF1 p.W229*[20], p.C1032Lfs*7[20], p.Q1822*[19], p.V1182D[19], p.Q1086*[19], p.R304*[19], p.Q1775*[19], p.L298*[19], p.K600fs[19] Tumor suppressor LOF
CBL p.Y371C(29)[29], T402_L405del[20] Oncogene GOF
PTEN p.L125E[24], p.R130Q[24], p.Q171*[19][20], p.D24H[19][20], c.79+1G>C(19)[19], p.L140*(19)[19] Tumor suppressor LOF
PIK3CA p.H1047L[20][24] Oncogene GOF
MTOR p.S2215F[20], p.I2501F Oncogene GOF
SGK1 p.R285K[19], p.I238T[19], p.H237Y[19], p.K213R[19], p.P147S[19], p.E162G[19], p.K136R[19], p.Q125H[19], c.437+1G>A[19], c.362-1G>A[19] Other (stress response, apoptosis…)
SETD2 c.7432-2A>C[19], p.V1820E[19], p.P132fs[19], c.4715_1G>T[19], c.7432-1G>A[19] Epigenetic regulator/tumor suppressor LOF
CREBBP p.Y1433C[19] Tumor suppressor LOF
KMT2D pE2225fs(19)[19], p.K1752fs(19)[19], p.G5428S[29], p.Q2796*[29], p.R904*[29], p.R5351Q[29], p.A2119Rfs[29], p.L3432D[29] Epigenetic modification, tumor suppressor LOH

Other Mutations

Please refer to the above “Gene Mutations (SNV/INDEL)” section.

Epigenomic Alterations

KMT2D, a gene involved in epigenetic regulation, has been reported as recurrently mutated in histiocytic sarcoma.[29] Egan et al also reported mutations in epigenetic modifier genes such as SETD2, ARID1A and KMT2D.[19]

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)

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
editHAEM5 Conversion Notes
Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

A recent molecular profiling study by Shanmugam et al highlighted that alterations in the MAP kinase, PI3K- and cyclin-CDK4/6-INK4 signaling pathways appear involved in the pathogenesis of histiocytic sarcoma.[20] Egan et al also identified a high frequency of alterations within the RAS/RAF/MAPK pathway.[19] Histiocytic sarcoma may also be associated with perturbations of chromatin regulation.[32]

Genetic Diagnostic Testing Methods

Histiocytic sarcoma diagnosis relies on histopathologic evaluation. In addition to histologic appearance, immunohistochemistry is central in diagnosing this malignancy and in excluding other morphologic mimics. Excisional or incisional biopsy is generally preferable to fine needle aspirate or core needle biopsy.

Of note, in the 2001 World Health Organization (WHO) classification, HS was originally defined based on the absence of clonal immunoglobulin heavy chain (IGH) or T-cell receptor (TCR) gene rearrangements. However, in 2008, the WHO revised the classification to include IGH and TCR rearrangements in light of a growing literature describing such rearrangements in HS cases. [18][33] While, clonal immunoglobulin receptor gene rearrangements may be seen in the setting of secondary HS from a phenomenon of cross-lineage transdifferentiation of neoplastic B cells into malignant histiocytes,[34] they have also been described in primary HS. In this respect, in a study reporting on 23 patients with sporadic HS, Chen et al identified that IGH (+/- IGK) rearrangements were present in 39% of cases.[18]

Staging at diagnosis is further completed by imaging studies such as PET scan or computed tomography scans.

Familial Forms

Not applicable

Additional Information

None

Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (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. 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.)

  1. 1.0 1.1 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.
  2. Emile, Jean-François; et al. (2016-06-02). "Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages". Blood. 127 (22): 2672–2681. doi:10.1182/blood-2016-01-690636. ISSN 1528-0020. PMC 5161007. PMID 26966089.
  3. 3.0 3.1 3.2 Feldman, Andrew L.; et al. (2008-06-15). "Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone". Blood. 111 (12): 5433–5439. doi:10.1182/blood-2007-11-124792. ISSN 1528-0020. PMC 2424145. PMID 18272816.
  4. 4.0 4.1 4.2 Bleeke, Matthias; et al. (2020-02). "Genome-wide analysis of acute leukemia and clonally related histiocytic sarcoma in a series of three pediatric patients". Pediatric Blood & Cancer. 67 (2): e28074. doi:10.1002/pbc.28074. ISSN 1545-5017. PMID 31737984. Check date values in: |date= (help)
  5. 5.0 5.1 Brunner, P.; et al. (2014-09). "Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor". Leukemia. 28 (9): 1937–1940. doi:10.1038/leu.2014.167. ISSN 1476-5551. PMID 24850291. Check date values in: |date= (help)
  6. 6.0 6.1 Kommalapati, Anuhya; et al. (2018-01-11). "Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes". Blood. 131 (2): 265–268. doi:10.1182/blood-2017-10-812495. ISSN 1528-0020. PMC 5757688. PMID 29183888.
  7. Zhang, Da; et al. (2009-05). "Histiocytic/dendritic cell sarcoma arising from follicular lymphoma involving the bone: a case report and review of literature". International Journal of Hematology. 89 (4): 529–532. doi:10.1007/s12185-009-0300-y. ISSN 1865-3774. PMID 19343479. Check date values in: |date= (help)
  8. 8.0 8.1 Hure, Michelle C.; et al. (2012-02-10). "Histiocytic sarcoma arising from clonally related mantle cell lymphoma". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 30 (5): e49–53. doi:10.1200/JCO.2011.38.8553. ISSN 1527-7755. PMID 22184374.
  9. Alvaro, T.; et al. (1996-11). "True histiocytic lymphoma of the stomach associated with low-grade B-cell mucosa-associated lymphoid tissue (MALT)-type lymphoma". The American Journal of Surgical Pathology. 20 (11): 1406–1411. doi:10.1097/00000478-199611000-00013. ISSN 0147-5185. PMID 8898846. Check date values in: |date= (help)
  10. Bouabdallah, R.; et al. (2001-06). "True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms". British Journal of Haematology. 113 (4): 1047–1050. doi:10.1046/j.1365-2141.2001.02841.x. ISSN 0007-1048. PMID 11442501. Check date values in: |date= (help)
  11. Castro, Eumenia C. C.; et al. (2010-05). "Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature". Pediatric and Developmental Pathology: The Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 13 (3): 225–237. doi:10.2350/09-03-0622-OA.1. ISSN 1093-5266. PMID 19642834. Check date values in: |date= (help)
  12. Kumar, Riten; et al. (2011-02). "Pediatric histiocytic sarcoma clonally related to precursor B-cell acute lymphoblastic leukemia with homozygous deletion of CDKN2A encoding p16INK4A". Pediatric Blood & Cancer. 56 (2): 307–310. doi:10.1002/pbc.22810. ISSN 1545-5017. PMID 20973102. Check date values in: |date= (help)
  13. McClure, Rebecca; et al. (2010-02). "Clonal relationship between precursor B-cell acute lymphoblastic leukemia and histiocytic sarcoma: a case report and discussion in the context of similar cases". Leukemia Research. 34 (2): e71–73. doi:10.1016/j.leukres.2009.08.020. ISSN 1873-5835. PMID 19744706. Check date values in: |date= (help)
  14. Michonneau, David; et al. (2014-12-10). "BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 32 (35): e117–121. doi:10.1200/JCO.2013.49.0078. ISSN 1527-7755. PMID 24567436.
  15. Shao, Haipeng; et al. (2011-11). "Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 24 (11): 1421–1432. doi:10.1038/modpathol.2011.102. ISSN 1530-0285. PMC 3175277. PMID 21666687. Check date values in: |date= (help)
  16. 16.0 16.1 Nichols, C. R.; et al. (1990-05-17). "Hematologic neoplasia associated with primary mediastinal germ-cell tumors". The New England Journal of Medicine. 322 (20): 1425–1429. doi:10.1056/NEJM199005173222004. ISSN 0028-4793. PMID 2158625.
  17. Hayase, Eiko; et al. (2010-11). "Aggressive sporadic histiocytic sarcoma with immunoglobulin heavy chain gene rearrangement and t(14;18)". International Journal of Hematology. 92 (4): 659–663. doi:10.1007/s12185-010-0704-8. ISSN 1865-3774. PMID 20976632. Check date values in: |date= (help)
  18. 18.0 18.1 18.2 Chen, Wei; et al. (2009-06). "High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/dendritic cell sarcomas". The American Journal of Surgical Pathology. 33 (6): 863–873. doi:10.1097/PAS.0b013e31819287b8. ISSN 1532-0979. PMID 19145200. Check date values in: |date= (help)
  19. 19.00 19.01 19.02 19.03 19.04 19.05 19.06 19.07 19.08 19.09 19.10 19.11 19.12 19.13 19.14 19.15 19.16 19.17 19.18 19.19 19.20 19.21 19.22 19.23 19.24 19.25 19.26 19.27 19.28 19.29 19.30 19.31 19.32 19.33 19.34 19.35 19.36 19.37 19.38 19.39 19.40 19.41 19.42 19.43 19.44 19.45 19.46 19.47 19.48 19.49 19.50 19.51 19.52 19.53 Egan, Caoimhe; et al. (2020-04). "Genomic profiling of primary histiocytic sarcoma reveals two molecular subgroups". Haematologica. 105 (4): 951–960. doi:10.3324/haematol.2019.230375. ISSN 1592-8721. PMC 7109753 Check |pmc= value (help). PMID 31439678. Check date values in: |date= (help)
  20. 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 20.10 20.11 20.12 20.13 20.14 20.15 20.16 20.17 20.18 20.19 Shanmugam, Vignesh; et al. (2019-06). "Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 32 (6): 830–843. doi:10.1038/s41379-018-0200-x. ISSN 1530-0285. PMID 30626916. Check date values in: |date= (help)
  21. Go, Heounjeong; et al. (2014-08). "Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms". Histopathology. 65 (2): 261–272. doi:10.1111/his.12416. ISSN 1365-2559. PMID 24720374. Check date values in: |date= (help)
  22. Shimono, Joji; et al. (2017-11-17). "Prognostic factors for histiocytic and dendritic cell neoplasms". Oncotarget. 8 (58): 98723–98732. doi:10.18632/oncotarget.21920. ISSN 1949-2553. PMC 5716762. PMID 29228722.
  23. 23.0 23.1 Kordes, M.; et al. (2016-04). "Cooperation of BRAF(F595L) and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling". Leukemia. 30 (4): 937–946. doi:10.1038/leu.2015.319. ISSN 1476-5551. PMID 26582644. Check date values in: |date= (help)
  24. 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 Liu, Qingqing; et al. (2016-08). "Somatic mutations in histiocytic sarcoma identified by next generation sequencing". Virchows Archiv: An International Journal of Pathology. 469 (2): 233–241. doi:10.1007/s00428-016-1965-2. ISSN 1432-2307. PMID 27259537. Check date values in: |date= (help)
  25. Burger, Jan A.; et al. (2016-05-20). "Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition". Nature Communications. 7: 11589. doi:10.1038/ncomms11589. ISSN 2041-1723. PMC 4876453. PMID 27199251.
  26. Thakral, Beenu; et al. (2016-11-17). "Histiocytic sarcoma: secondary neoplasm or "transdifferentiation" in the setting of B-acute lymphoblastic leukemia". Blood. 128 (20): 2475. doi:10.1182/blood-2016-08-735795. ISSN 1528-0020. PMID 27856472.
  27. Gounder, Mrinal M.; et al. (2018-05-17). "Trametinib in Histiocytic Sarcoma with an Activating MAP2K1 (MEK1) Mutation". The New England Journal of Medicine. 378 (20): 1945–1947. doi:10.1056/NEJMc1511490. ISSN 1533-4406. PMC 6062005. PMID 29768143.
  28. Kumamoto, Tadashi; et al. (2019-02). "A case of recurrent histiocytic sarcoma with MAP2K1 pathogenic variant treated with the MEK inhibitor trametinib". International Journal of Hematology. 109 (2): 228–232. doi:10.1007/s12185-018-2553-9. ISSN 1865-3774. PMID 30361829. Check date values in: |date= (help)
  29. 29.0 29.1 29.2 29.3 29.4 29.5 29.6 29.7 29.8 Hung, Yin P.; et al. (2017-08). "Histiocytic sarcoma: New insights into FNA cytomorphology and molecular characteristics". Cancer Cytopathology. 125 (8): 604–614. doi:10.1002/cncy.21851. ISSN 1934-6638. PMID 28805986. Check date values in: |date= (help)
  30. 30.0 30.1 Batra, Sandeep; et al. (2016). "Histiocytic Sarcoma Associated with Coombs Negative Acute Hemolytic Anemia: A Rare Presentation". Case Reports in Oncological Medicine. 2016: 3179147. doi:10.1155/2016/3179147. ISSN 2090-6706. PMC 4939191. PMID 27429816.
  31. Voruz, Sophie; et al. (2018-01). "Response to MEK inhibition with trametinib and tyrosine kinase inhibition with imatinib in multifocal histiocytic sarcoma". Haematologica. 103 (1): e39–e41. doi:10.3324/haematol.2017.179150. ISSN 1592-8721. PMC 5777214. PMID 29097496. Check date values in: |date= (help)
  32. Hung, Yin P.; et al. (2020-05). "Histiocytic Sarcoma". Archives of Pathology & Laboratory Medicine. 144 (5): 650–654. doi:10.5858/arpa.2018-0349-RS. ISSN 1543-2165. PMID 31070934. Check date values in: |date= (help)
  33. Alonso-Dominguez, J. M.; et al. (2012). "Cytogenetics findings in a histiocytic sarcoma case". Case Reports in Hematology. 2012: 428279. doi:10.1155/2012/428279. ISSN 2090-6579. PMC 3420615. PMID 22937328.
  34. Takahashi, Emiko; et al. (2013). "Histiocytic sarcoma : an updated literature review based on the 2008 WHO classification". Journal of clinical and experimental hematopathology: JCEH. 53 (1): 1–8. doi:10.3960/jslrt.53.1. ISSN 1880-9952. PMID 23801128.

Notes

*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. *Citation of this Page: “Histiocytic sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/1/2024, https://ccga.io/index.php/HAEM5:Histiocytic_sarcoma.