Difference between revisions of "HAEM5:Myeloid sarcoma"
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| − | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11- | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Myeloid Sarcoma]]. |
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==Primary Author(s)*== | ==Primary Author(s)*== | ||
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| − | ==Cancer Category/Type== | + | ==Cancer Category / Type== |
Acute myeloid leukemia and related precursor neoplasms | Acute myeloid leukemia and related precursor neoplasms | ||
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| − | ==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.'') </span> | ||
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| − | ==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 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> | ||
Revision as of 15:45, 30 November 2023
Haematolymphoid Tumours (5th ed.)
 | This page is under construction |
editHAEM5 Conversion NotesThis page was converted to the new template on 2023-11-30. The original page can be found at HAEM4:Myeloid Sarcoma.
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
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
Put your text here and fill in the table (Instruction: Can include references in the 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) |
editv4:Clinical FeaturesThe 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)[1][2].
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 (Instruction: Can include references in the table)
| Finding | Marker |
|---|---|
| Positive (universal) | EXAMPLE CD1 |
| Positive (subset) | EXAMPLE CD2 |
| Negative (universal) | EXAMPLE CD3 |
| Negative (subset) | EXAMPLE CD4 |
editv4:ImmunophenotypeThe content below was from the old template. Please incorporate above.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[2].
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). |
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%
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%[3].
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.)
| 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). |
editv4:Genomic Gain/Loss/LOHThe 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
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)
| 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). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.Complex karyotype is associated with poor outcome[4].
MS developing in aleukemic patients with favorable MDS, such as the 5q- syndrome, is rare[5].
Gains and losses, see below
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 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.)
| 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.
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[6][7][8].
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
Epigenomic Alterations
Put your text here
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in 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[4].
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
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.)
- ↑ Pileri, S. A.; et al. (2007). "Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients". Leukemia. 21 (2): 340–350. doi:10.1038/sj.leu.2404491. ISSN 0887-6924. PMID 17170724.
- ↑ 2.0 2.1 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.
- ↑ 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.
- ↑ 4.0 4.1 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 CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome. *Citation of this Page: “Myeloid sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/30/2023, https://ccga.io/index.php/HAEM5:Myeloid_sarcoma.