Myeloid Sarcoma

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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

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)[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

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)

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%

Characteristic Chromosomal Aberrations / Patterns

Complex karyotype is associated with poor outcome[3].

MS developing in aleukemic patients with favorable MDS, such as the 5q- syndrome, is rare[4].

Gains and losses, see below

Genomic Gain/Loss/LOH

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[5][6][7].

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

Epigenomics (Methylation)

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Genes and Main Pathways Involved

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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[3].

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%[8].

Familial Forms

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Other Information

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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

  1. 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. 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.
  3. 3.0 3.1 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.

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.