Bailey.Glen at 18:47, 3 November 2023

2023-11-03T18:47:00Z

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			{{DISPLAYTITLE:Myeloid Sarcoma}}


			<blockquote class='blockedit'>{{Box-round\|title=PREVIOUS EDITION\|This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition [[HAEM5:Table_of_Contents\|Table of Contents]].
			}}</blockquote>
	==Primary Author(s)*==		==Primary Author(s)*==

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	==Notes==		==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 CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
			[[Category:HAEM4]] [[Category:DISEASE]]

	[[Category:~~Recently Added Pages~~]]

Bailey.Glen: Created page with "==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 Ca..."

2023-11-03T18:07:18Z

Created page with "==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 Ca..."

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==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

__TOC__

==Cancer Category/Type==

Acute myeloid leukemia and related precursor neoplasms

==Cancer Sub-Classification / Subtype==

Myeloid sarcoma

==Definition / Description of Disease==

Tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow.

==Synonyms / Terminology==

Extramedullary myeloid tumor,
Granulocytic sarcoma,
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==

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>.

==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==

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.

About 16% of tumors stain for NPM1 at the nuclear and cytoplasmic level; this indicates the presence of ''NPM1'' mutation.

Promyelocytic cases lack CD34 and TdT but express MPO and CD15.

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" />.

==Chromosomal Rearrangements (Gene Fusions)==

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

{| class="wikitable sortable"
|-
!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%
|-
|}

==Characteristic Chromosomal Aberrations / Patterns==
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>.

MS developing in aleukemic patients with favorable MDS, such as the 5q- syndrome, is rare<ref>{{Cite journal|last=Showalter|first=Josh A.|last2=Tandon|first2=Nidhi|last3=Zhao|first3=Bihong|last4=Tang|first4=Guilin|last5=Nguyen|first5=Nghia D.|last6=Medeiros|first6=L. Jeffrey|date=2017|title=Myeloid Sarcoma in a Patient with Myelodysplastic Syndrome Associated with del(5q-): Case Report and Literature Review|url=https://www.ncbi.nlm.nih.gov/pubmed/28801374|journal=Annals of Clinical and Laboratory Science|volume=47|issue=4|pages=466–473|issn=1550-8080|pmid=28801374}}</ref>.

Gains and losses, see below

==Genomic Gain/Loss/LOH==

{| class="wikitable sortable"
|-
!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
|}

==Gene Mutations (SNV/INDEL)==

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>.

''NPM1'' 16% more common in cases involving the skin

''FLT3''-ITD 15%

For specific mutation see under " links " section below.

===Other Mutations===
{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
|}

==Epigenomics (Methylation)==

Put your text here

==Genes and Main Pathways Involved==

Put your text here

==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<ref name=":1" />.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

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>.

==Familial Forms==

Put your text here

==Other 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==
<references />

==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.

[[Category:Recently Added Pages]]

HAEM4:Myeloid Sarcoma - Revision history

Bailey.Glen at 18:47, 3 November 2023

Bailey.Glen: Created page with "==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 Ca..."