Difference between revisions of "HAEM5:Myeloid sarcoma"

[checked revision]

Latest revision as of 12:41, 24 March 2025

Haematolymphoid Tumours (WHO Classification, 5th ed.)

This page is under construction

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

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

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). 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 in a table, click nearby within the table and select the > symbol that appears. 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)*

Yalda Naeini, MD, School of Medicine at University of California Los Angeles Fabiola Quintero-Rivera, MD, FACMG, School of Medicine at University of California Irvine

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	Myeloid proliferations and neoplasms
Family	Acute myeloid leukaemia
Type	N/A
Subtype(s)	Myeloid sarcoma

WHO Essential and Desirable Genetic Diagnostic Criteria

(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)


WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

(Instructions: The table will have the related terminology from the WHO autocompleted.)


Acceptable
Not Recommended

Gene Rearrangements

Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

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	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
EXAMPLE: ABL1	EXAMPLE: BCR::ABL1	EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.	EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: Common (CML)	EXAMPLE: D, P, T	EXAMPLE: Yes (WHO, NCCN)	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). BCR::ABL1 is generally favorable in CML (add reference).
EXAMPLE: CIC	EXAMPLE: CIC::DUX4	EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5.	EXAMPLE: t(4;19)(q25;q13)	EXAMPLE: Common (CIC-rearranged sarcoma)	EXAMPLE: D		EXAMPLE: DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
EXAMPLE: ALK	EXAMPLE: ELM4::ALK Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1	EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18.	EXAMPLE: N/A	EXAMPLE: Rare (Lung adenocarcinoma)	EXAMPLE: T		EXAMPLE: Both balanced and unbalanced forms are observed by FISH (add references).
EXAMPLE: ABL1	EXAMPLE: N/A	EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.	EXAMPLE: N/A	EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)	EXAMPLE: D, P, T

editv4:Chromosomal Rearrangements (Gene Fusions)

The content below was from the old template. Please incorporate above.

FISH and/or karyotypic aberrations are detected in about 55% of cases.

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
t(8;21)(q22;q22)	5'RUNX1 / 3'RUNXT1	der(8)	55%
KMT2A(MLL) rearrangement	5'KMT2A/ 3'variable	der(11)	55%
inv(16)(p13.1q22) or t(16;16)(p13.1;q22)	5'CBFB / 3'MYH11	der(16)	55%

End of V4 Section

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

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)

The clinical behavior and response to therapy seem not to be influenced by any of the following factors: age, sex, anatomical site(s) involved, de novo presentation, clinical history related to AML, MDS or MPN, histological features, immunophenotype or cytogenetic findings. Patients who undergo allogeneic or autologous bone marrow transplantation seem to have a higher probability of prolonged survival or cure. In one study the 5-year overall survival rate among 51 patients with myeloid sarcoma treated with allogenic bone marrow transplantation was 47%^[1].

End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

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
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7	EXAMPLE: Unknown	EXAMPLE: D, P	EXAMPLE: 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 references).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8	EXAMPLE: Unknown	EXAMPLE: D, P		EXAMPLE: Common recurrent secondary finding for t(8;21) (add references).
EXAMPLE: 17	EXAMPLE: Amp	EXAMPLE: 17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]	EXAMPLE: ERBB2	EXAMPLE: D, P, T		EXAMPLE: Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

editv4:Genomic Gain/Loss/LOH

The content below was from the old template. Please incorporate above.

Chromosome Number	Gain/Loss/Amp/LOH	Region
4	Gain	Chr4
8	Gain	Chr8
11	Gain	Chr11
5	Loss/deletion	Chr5q
7	Loss	Chr7
16	Loss /deletion	Chr16q
17	Loss /deletion	Chr17p
20	Loss /deletion	Chr20q

End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern	Molecular Pathogenesis	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
EXAMPLE: Co-deletion of 1p and 18q	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).	EXAMPLE: Common (Oligodendroglioma)	EXAMPLE: D, P
EXAMPLE: Microsatellite instability - hypermutated		EXAMPLE: Common (Endometrial carcinoma)	EXAMPLE: P, T

editv4:Characteristic Chromosomal Aberrations / Patterns

The content below was from the old template. Please incorporate above.

Complex karyotype is associated with poor outcome^[2].

MS developing in aleukemic patients with favorable MDS, such as the 5q- syndrome, is rare^[3].

Gains and losses, see below

End of V4 Section

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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

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
EXAMPLE:EGFR	EXAMPLE: Exon 18-21 activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (lung cancer)	EXAMPLE: T	EXAMPLE: Yes (NCCN)	EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations	EXAMPLE: Variable LOF mutations	EXAMPLE: Tumor Supressor Gene	EXAMPLE: Common (breast cancer)	EXAMPLE: P		EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations	EXAMPLE: Activating mutations	EXAMPLE: Oncogene	EXAMPLE: Common (melanoma)	EXAMPLE: T

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

The content below was from the old template. Please incorporate above.

Some studies have reported genetic abnormalities in various AML-associated genes encoding tyrosine kinases (FLT3, KIT, and KRAS), tumor suppressors (WT1 and TP53), epigenetic modifiers (TET2 and ASXL1), spliceosome proteins (SF3B1 and SRSF2), and transcription factors (RUNX1). One study highlights that almost one-third of MS harbor a targetable mutation, in particular KIT D816V, IDH2 R140Q, and BRAF V600E. These mutations can also be found in non infiltrated bone marrows suggesting the existence of preleukemic clones in the bone marrow from MS patients^[4]^[5]^[6].

NPM1 16% more common in cases involving the skin

FLT3-ITD 15%

For specific mutation see under " links " section below.

Other Mutations

Type	Gene/Region/Other
Concomitant Mutations	EXAMPLE: IDH1 R123H
Secondary Mutations	EXAMPLE: Trisomy 7
Mutually Exclusive	EXAMPLE: EGFR Amplification

End of V4 Section

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

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

Genetic Diagnostic Testing Methods

Microscopy, flow cytometry, cytogenetics,molecular genetics. Chromosomal microarray analysis (CMA) could be performed on FFPE bone marrow clot to obtain important information about the leukemic karyotype^[2].

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

https://cancer.sanger.ac.uk/cosmic/gene/analysis?coords=AA%3AAA&sn=bone&ss=NS&hn=chordoma&sh=NS&wgs=off&id=581&ln=NPM1&start=1&end=295

https://cancer.sanger.ac.uk/cosmic/gene/analysis?all_data=&coords=AA%3AAA&dr=&end=994&gd=&hn=chordoma&id=10&ln=FLT3&seqlen=994&sh=NS&sn=bone&ss=NS&start=1#ts

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)

↑ Chevallier, Patrice; et al. (2011). "Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation". Haematologica. 96 (9): 1391–1394. doi:10.3324/haematol.2011.041418. ISSN 1592-8721. PMC 3166114. PMID 21685467.
↑ ^{Jump up to: 2.0} ^2.1 Mirza, M. Kamran; et al. (2014). "Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays". Leukemia Research. 38 (9): 1091–1096. doi:10.1016/j.leukres.2014.05.004. ISSN 1873-5835. PMC 4157130. PMID 25088808.
↑ Showalter, Josh A.; et al. (2017). "Myeloid Sarcoma in a Patient with Myelodysplastic Syndrome Associated with del(5q-): Case Report and Literature Review". Annals of Clinical and Laboratory Science. 47 (4): 466–473. ISSN 1550-8080. PMID 28801374.
↑ Falini, B.; et al. (2007). "Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas". Leukemia. 21 (7): 1566–1570. doi:10.1038/sj.leu.2404699. ISSN 0887-6924. PMID 17443224.
↑ Li, Z.; et al. (2015). "Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma". Leukemia. 29 (10): 2113–2116. doi:10.1038/leu.2015.81. ISSN 1476-5551. PMC 4575593. PMID 25787914.
↑ Pastoret, Cedric; et al. (2017). "Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing". Leukemia & Lymphoma. 58 (4): 1008–1012. doi:10.1080/10428194.2016.1225208. ISSN 1029-2403. PMID 27659839.

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 Associate Editor 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):

*Citation of this Page: “Myeloid sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/24/2025, https://ccga.io/index.php/HAEM5:Myeloid_sarcoma.

[1] Chevallier, Patrice; et al. (2011). "Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation". Haematologica. 96 (9): 1391–1394. doi:10.3324/haematol.2011.041418. ISSN 1592-8721. PMC 3166114. PMID 21685467.

[:1-2] {Jump up to: 2.0} ^2.1 Mirza, M. Kamran; et al. (2014). "Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays". Leukemia Research. 38 (9): 1091–1096. doi:10.1016/j.leukres.2014.05.004. ISSN 1873-5835. PMC 4157130. PMID 25088808.

[3] Showalter, Josh A.; et al. (2017). "Myeloid Sarcoma in a Patient with Myelodysplastic Syndrome Associated with del(5q-): Case Report and Literature Review". Annals of Clinical and Laboratory Science. 47 (4): 466–473. ISSN 1550-8080. PMID 28801374.

[4] Falini, B.; et al. (2007). "Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas". Leukemia. 21 (7): 1566–1570. doi:10.1038/sj.leu.2404699. ISSN 0887-6924. PMID 17443224.

[5] Li, Z.; et al. (2015). "Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma". Leukemia. 29 (10): 2113–2116. doi:10.1038/leu.2015.81. ISSN 1476-5551. PMC 4575593. PMID 25787914.

[6] Pastoret, Cedric; et al. (2017). "Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing". Leukemia & Lymphoma. 58 (4): 1008–1012. doi:10.1080/10428194.2016.1225208. ISSN 1029-2403. PMID 27659839.

[1]

[2]

[3]

[4]

[5]

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Difference between revisions of "HAEM5:Myeloid sarcoma"

Latest revision as of 12:41, 24 March 2025

Contents

Primary Author(s)*

WHO Classification of Disease

WHO Essential and Desirable Genetic Diagnostic Criteria

Related Terminology

Gene Rearrangements

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal or Other Global Mutational Patterns

Gene Mutations (SNV/INDEL)

Other Mutations

Epigenomic Alterations

Genes and Main Pathways Involved

Genetic Diagnostic Testing Methods

Familial Forms

Additional Information

Links

References

Notes

Navigation menu

Search

@@ Line 1: / Line 1: @@
 {{DISPLAYTITLE:Myeloid sarcoma}}
-[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
 {{Under Construction}}
-<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:Myeloid Sarcoma]].
+<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid Sarcoma]].
 }}</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 focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], 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 in a table, click nearby within the table and select the > symbol that appears. 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)*==
@@ Line 13: / Line 13: @@
 Yalda Naeini, MD, School of Medicine at University of California Los Angeles
 Fabiola Quintero-Rivera, MD, FACMG, School of Medicine at University of California Irvine
+==WHO Classification of Disease==
-__TOC__
+{| class="wikitable"
+!Structure
+!Disease
+|-
+|Book
+|Haematolymphoid Tumours (5th ed.)
+|-
+|Category
+|Myeloid proliferations and neoplasms
+|-
+|Family
+|Acute myeloid leukaemia
+|-
+|Type
+|N/A
+|-
+|Subtype(s)
+|Myeloid sarcoma
+|}
-==Cancer Category / Type==
+==WHO Essential and Desirable Genetic Diagnostic Criteria==
+<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
-Acute myeloid leukemia and related precursor neoplasms
+{| class="wikitable"
+|+
-==Cancer Sub-Classification / Subtype==
+|WHO Essential Criteria (Genetics)*
+|
-Myeloid sarcoma
+|-
+|WHO Desirable Criteria (Genetics)*
-==Definition / Description of Disease==
+|
+|-
-Tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow.
+|Other Classification
+|
-==Synonyms / Terminology==
+|}
+<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
-Extramedullary myeloid tumor,
+==Related Terminology==
-Granulocytic sarcoma,
+<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
-Chloroma
-==Epidemiology / Prevalence==
-Rare neoplasm with predilection for males and older individuals with male:female ratio of 1.2:1. The median age is 56 years.
-==Clinical Features==
-Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 {| class="wikitable"
-|'''Signs and Symptoms'''
+|+
-|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+|Acceptable
+|
-EXAMPLE B-symptoms (weight loss, fever, night sweats)
-EXAMPLE Fatigue
-EXAMPLE Lymphadenopathy (uncommon)
 |-
-|'''Laboratory Findings'''
+|Not Recommended
-|EXAMPLE Cytopenias
+|
-EXAMPLE Lymphocytosis (low level)
 |}
+==Gene Rearrangements==
-<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
-Myeloid sarcoma may occur ''de novo'' in about one quarter of cases. Its detection should be considered as the equivalent of a diagnosis of AML. It may precede or coincide with AML or represent acute blastic transformation of MDS, MPN or MDS/MPN. Myeloid sarcoma may also be the initial manifestation of relapse in a patient with previously diagnosed AML, regardless of peripheral blood or bone marrow findings. In addition, isolated myeloid sarcoma occurs in 8-20% of patients who have undergone allogenic stem cell transplantation (reason still unclear), or in patients with simultaneously or previously treated non-Hodgkin lymphoma or a previous history of non-hematopoietic tumor (therapy-related)<ref>{{Cite journal|last=Pileri|first=S. A.|last2=Ascani|first2=S.|last3=Cox|first3=M. C.|last4=Campidelli|first4=C.|last5=Bacci|first5=F.|last6=Piccioli|first6=M.|last7=Piccaluga|first7=P. P.|last8=Agostinelli|first8=C.|last9=Asioli|first9=S.|date=2007|title=Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients|url=https://www.ncbi.nlm.nih.gov/pubmed/17170724|journal=Leukemia|volume=21|issue=2|pages=340–350|doi=10.1038/sj.leu.2404491|issn=0887-6924|pmid=17170724}}</ref><ref name=":0">Pileri SA, et al., (2017). Myeloid sarcoma, 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 D, Hasserjian R, Le Beau M, Orazi A, Siebert R, Editors. IARC Press: Lyon, France, p167-168.</ref>.
-</blockquote>
-==Sites of Involvement==
-Almost every site of the body can be involved, the skin, lymph node, gastro-intestinal tract, bone, soft tissue and testis being more frequently affected. In less than 10% of cases, myeloid sarcoma presents at multiple anatomical sites.
-==Morphologic Features==
-A myeloid sarcoma most commonly consists of myeloblasts with or without features of promyelocytic or neutrophilic maturation that partially or totally efface the tissue architecture. In a significant proportion of cases, it displays myelomonocytic or pure monoblastic morphology. Tumors with trilineage haematopoiesis or predominantly erythroid precursors or megakaryoblasts are rare and may occur in conjunction with transformation of MPN. Architecturally, at extranodal sites neoplastic cells may mimic metastatic carcinoma with cohesive sheets.
-==Immunophenotype==
-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">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 {| class="wikitable sortable"
 |-
-!Finding!!Marker
+!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
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
 |-
-|Positive (universal)||EXAMPLE CD1
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|<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). BCR::ABL1 is generally favorable in CML (add reference).
 |-
-|Positive (subset)||EXAMPLE CD2
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
-|-
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
-|Negative (universal)||EXAMPLE CD3
+|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
+|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
+|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
+|<span class="blue-text">EXAMPLE:</span> D
+|
+|<span class="blue-text">EXAMPLE:</span>
+''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
 |-
-|Negative (subset)||EXAMPLE CD4
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
-|}
+|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
-<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
+Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
-On immunohistochemistry in paraffin sections, tumors with more mature myeloid profile express CD33, CD34, CD68 (KP1) and CKIT. Staining for terminal deoxynucleotidyl transferase (TdT), MPO and CD45 are inconsistent.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
-About 16% of tumors stain for NPM1 at the nuclear and cytoplasmic level; this indicates the presence of ''NPM1'' mutation.
+|<span class="blue-text">EXAMPLE:</span> T
+|
-Promyelocytic cases lack CD34 and TdT but express MPO and CD15.
+|<span class="blue-text">EXAMPLE:</span>
-Myelomonocytic tumors are homogeneneously positive for CD68 or CD163, but lack MPO and CD34.
-Exceptionally, aberrant antigenic expressions are observed (cytokeratins, B- or T-cell markers).
-Cases that meet criteria for mixed phenotype acute leukemia are not classified as myeloid sarcoma<ref name=":0" />.
-</blockquote>
-==Chromosomal Rearrangements (Gene Fusions)==
-Put your text here and fill in the table
-{| class="wikitable sortable"
+Both balanced and unbalanced forms are observed by FISH (add references).
 |-
-!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''
-!Diagnostic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> N/A
-!Prognostic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
-!Therapeutic Significance (Yes, No or Unknown)
+|<span class="blue-text">EXAMPLE:</span> N/A
-!Notes
+|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
 |-
-|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).
+|
 |}
-<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=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
 FISH and/or karyotypic aberrations are detected in about 55% of cases.
@@ Line 143: / Line 139: @@
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-<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=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|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)}}
+* Gene Mutations (SNV/INDEL)}}</blockquote>
 The clinical behavior and response to therapy seem ''not'' to be influenced by any of the following factors: age, sex, anatomical site(s) involved, ''de novo'' presentation, clinical history related to AML, MDS or MPN, histological features, immunophenotype or cytogenetic findings. Patients who undergo allogeneic or autologous bone marrow transplantation seem to have a higher probability of prolonged survival or cure. In one study the 5-year overall survival rate among 51 patients with myeloid sarcoma treated with allogenic bone marrow transplantation was 47%<ref>{{Cite journal|last=Chevallier|first=Patrice|last2=Labopin|first2=Myriam|last3=Cornelissen|first3=Jan|last4=Socié|first4=Gérard|last5=Rocha|first5=Vanderson|last6=Mohty|first6=Mohamad|last7=ALWP of EBMT|date=2011|title=Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation|url=https://www.ncbi.nlm.nih.gov/pubmed/21685467|journal=Haematologica|volume=96|issue=9|pages=1391–1394|doi=10.3324/haematol.2011.041418|issn=1592-8721|pmc=3166114|pmid=21685467}}</ref>.
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==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 rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
 {| class="wikitable sortable"
 |-
-!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
-!Diagnostic Significance (Yes, No or Unknown)
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
-!Prognostic Significance (Yes, No or Unknown)
+!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
-!Therapeutic Significance (Yes, No or Unknown)
+!'''Clinical Relevance Details/Other Notes'''
-!Notes
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-|EXAMPLE Loss
+|<span class="blue-text">EXAMPLE:</span> Loss
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-chr7:1- 159,335,973 [hg38]
-|EXAMPLE
 chr7
-|Yes
+|<span class="blue-text">EXAMPLE:</span>
-|Yes
+Unknown
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span> No
+|<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 references).
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-|EXAMPLE Gain
+|<span class="blue-text">EXAMPLE:</span> Gain
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
-chr8:1-145,138,636 [hg38]
-|EXAMPLE
 chr8
-|No
+|<span class="blue-text">EXAMPLE:</span>
-|No
+Unknown
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|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 references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
+|<span class="blue-text">EXAMPLE:</span>
+''ERBB2''
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|<span class="blue-text">EXAMPLE:</span>
+Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
+|-
+|
+|
+|
+|
+|
+|
+|
 |}
-<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=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
 {| class="wikitable sortable"
@@ Line 228: / Line 239: @@
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==Characteristic Chromosomal Patterns==
+==Characteristic Chromosomal or Other Global Mutational 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 and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 {| class="wikitable sortable"
 |-
 !Chromosomal Pattern
-!Diagnostic Significance (Yes, No or Unknown)
+!Molecular Pathogenesis
-!Prognostic Significance (Yes, No or Unknown)
+!'''Prevalence -'''
-!Therapeutic Significance (Yes, No or Unknown)
+'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
-!Notes
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
+!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
+!'''Clinical Relevance Details/Other Notes'''
 |-
-|EXAMPLE
+|<span class="blue-text">EXAMPLE:</span>
 Co-deletion of 1p and 18q
-|Yes
+|<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).
-|No
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
-|No
+|<span class="blue-text">EXAMPLE:</span> D, P
-|EXAMPLE:
+|
+|
-See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+Microsatellite instability - hypermutated
+|
+|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
+|<span class="blue-text">EXAMPLE:</span> P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
 |}
-<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=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
 Complex karyotype is associated with poor outcome<ref name=":1">{{Cite journal|last=Mirza|first=M. Kamran|last2=Sukhanova|first2=Madina|last3=Stölzel|first3=Friedrich|last4=Onel|first4=Kenan|last5=Larson|first5=Richard A.|last6=Stock|first6=Wendy|last7=Ehninger|first7=Gerhard|last8=Kuithan|first8=Friederike|last9=Zöphel|first9=Klaus|date=2014|title=Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays|url=https://www.ncbi.nlm.nih.gov/pubmed/25088808|journal=Leukemia Research|volume=38|issue=9|pages=1091–1096|doi=10.1016/j.leukres.2014.05.004|issn=1873-5835|pmc=4157130|pmid=25088808}}</ref>.
@@ Line 259: / Line 288: @@
 Gains and losses, see below
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
-==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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
 {| class="wikitable sortable"
 |-
-!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
+!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
-!'''Diagnostic Significance (Yes, No or Unknown)'''
+'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
-!Prognostic Significance (Yes, No or Unknown)
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
-!Therapeutic Significance (Yes, No or Unknown)
+!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
-!Notes
+!'''Clinical Relevance Details/Other Notes'''
 |-
-|EXAMPLE: TP53; Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span>''EGFR''
-EXAMPLE:
+<br />
+|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
-EGFR; Exon 20 mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
-EXAMPLE: BRAF; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> T
-|EXAMPLE: TSG
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
-|EXAMPLE: 20% (COSMIC)
+|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
+|-
-EXAMPLE: 30% (add Reference)
+|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
-|EXAMPLE: IDH1 R123H
+<br />
-|EXAMPLE: EGFR amplification
+|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
+|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
+|<span class="blue-text">EXAMPLE:</span> P
+|
+|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|
+|-
+|
+|
+|
+|
 |
 |
 |
-|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+|}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.
-<br />
-|}
-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=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
 Some studies have reported genetic abnormalities in various AML-associated genes encoding tyrosine kinases (''FLT3'', ''KIT'', and ''KRAS''), tumor suppressors (''WT1'' and ''TP53''), epigenetic modifiers (''TET2'' and ''ASXL1''), spliceosome proteins (''SF3B1'' and ''SRSF2''), and transcription factors (''RUNX1''). One study highlights that almost one-third of MS harbor a targetable mutation, in particular ''KIT'' D816V, ''IDH2'' R140Q, and ''BRAF'' V600E. These mutations can also be found in non infiltrated bone marrows suggesting the existence of preleukemic clones in the bone marrow from MS patients<ref>{{Cite journal|last=Falini|first=B.|last2=Lenze|first2=D.|last3=Hasserjian|first3=R.|last4=Coupland|first4=S.|last5=Jaehne|first5=D.|last6=Soupir|first6=C.|last7=Liso|first7=A.|last8=Martelli|first8=M. P.|last9=Bolli|first9=N.|date=2007|title=Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas|url=https://www.ncbi.nlm.nih.gov/pubmed/17443224|journal=Leukemia|volume=21|issue=7|pages=1566–1570|doi=10.1038/sj.leu.2404699|issn=0887-6924|pmid=17443224}}</ref><ref>{{Cite journal|last=Li|first=Z.|last2=Stölzel|first2=F.|last3=Onel|first3=K.|last4=Sukhanova|first4=M.|last5=Mirza|first5=M. K.|last6=Yap|first6=K. L.|last7=Borinets|first7=O.|last8=Larson|first8=R. A.|last9=Stock|first9=W.|date=2015|title=Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma|url=https://www.ncbi.nlm.nih.gov/pubmed/25787914|journal=Leukemia|volume=29|issue=10|pages=2113–2116|doi=10.1038/leu.2015.81|issn=1476-5551|pmc=4575593|pmid=25787914}}</ref><ref>{{Cite journal|last=Pastoret|first=Cedric|last2=Houot|first2=Roch|last3=Llamas-Gutierrez|first3=Francisco|last4=Boulland|first4=Marie-Laure|last5=Marchand|first5=Tony|last6=Tas|first6=Patrick|last7=Ly-Sunnaram|first7=Beatrice|last8=Gandemer|first8=Virginie|last9=Lamy|first9=Thierry|date=2017|title=Detection of clonal heterogeneity and targetable mutations in myeloid sarcoma by high-throughput sequencing|url=https://www.ncbi.nlm.nih.gov/pubmed/27659839|journal=Leukemia & Lymphoma|volume=58|issue=4|pages=1008–1012|doi=10.1080/10428194.2016.1225208|issn=1029-2403|pmid=27659839}}</ref>.
@@ Line 309: / Line 355: @@
 !Type!!Gene/Region/Other
 |-
-|Concomitant Mutations||EXAMPLE IDH1 R123H
+|Concomitant Mutations||<span class="blue-text">EXAMPLE:</span> IDH1 R123H
 |-
-|Secondary Mutations||EXAMPLE Trisomy 7
+|Secondary Mutations||<span class="blue-text">EXAMPLE:</span> Trisomy 7
 |-
-|Mutually Exclusive||EXAMPLE EGFR Amplification
+|Mutually Exclusive||<span class="blue-text">EXAMPLE:</span> EGFR Amplification
 |}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
 </blockquote>
 ==Epigenomic Alterations==
 Put your text here
+==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: Please include references throughout the table. Do not delete the table.)''</span>
 {| class="wikitable sortable"
 |-
 !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
+|-
+|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 |-
-|EXAMPLE: CDKN2A; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
-|EXAMPLE: Cell cycle regulation
+|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
-|EXAMPLE: Unregulated cell division
+|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 |-
-|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+|
-|EXAMPLE:  Histone modification, chromatin remodeling
+|
-|EXAMPLE:  Abnormal gene expression program
+|
 |}
 ==Genetic Diagnostic Testing Methods==
@@ Line 345: / Line 399: @@
 ==Familial Forms==
 Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 ==Additional Information==
@@ Line 358: / Line 412: @@
 ==References==
-(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 />
+(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
-'''
+<br />
 ==Notes==
-<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.
+<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):
 <nowiki>*</nowiki>''Citation of this Page'': “Myeloid sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid_sarcoma</nowiki>.
-[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
+[[Category:HAEM5]]
+[[Category:DISEASE]]
+[[Category:Diseases M]]