Diagnostic Approaches in Myeloid Sarcoma
Abstract
:1. Introduction
2. Historical Perspective
3. Epidemiology
4. Etiopathogenesis of EM AML
5. Clinical Presentation
6. Diagnosis of MS
7. Cytomorphology
8. Histopathology
9. Flow Cytometry
10. Genetics
11. Imaging Tests
12. Differential Diagnosis
13. Treatment of MS
14. Prognostic Implications
15. Conclusions
Author Contributions
Funding
Use of Artificial Intelligence
Conflicts of Interest
References
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Etiopathogenesis of Myeloid Sarcoma | ||
---|---|---|
General factors predisposing to AML | Occupational exposures | Workers exposed to rubber, paint, embalming fluids, pesticides, ethylene oxide, petroleum, poultry, munitions, automobiles, nuclear power, plastics, and electrical wiring, as well as gasoline station attendants, beauticians, barbers, and cosmetologists. |
Environmental factors | Ionising radiation | |
Lifestyle-related factors | Smoking, obesity | |
Heritable genetic factors | CEBPA, DDX41, RUNX1, ANKRD26, ETV6, GATA2, ELANE, HAX1, G6PC3, MPL, RBM8A, SBDS, SRP72, trisomy 21, monosomy 7 | |
Clonal haematopoiesis | DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1, SF3B1, EZH2 | |
Therapy-related AML | Cytotoxic therapy: alkylating agents, topoisomerase II inhibitors, nucleoside analogues, anti-tubulins Radiation therapy | |
Factors predisposing to MS | Genetics | t(8;21), inv(16); KMT2Ar, CBFB, monosomy7, del(5q), del(9q), loss of X, loss of Y, trisomy 4, trisomy 8 |
Molecular abnormalities | (1) RAS pathway: NRAS, KRAS, PTPN11, CBL, NF1, BRAF (2) Activated signalling: FLT3, BCR::ABL1, JAK2, KIT, SH2B3, CBL, CSF3R (3) DNA methylation: DNMT3A, KMT2A, TET2, IDH1, IDH2 (4) Cohesin complex: STAG2, RAD21, SMC3 (5) RNA splicing: SRSF2, SF3B1, U2AF1 (6) Transcription factors: GATA2, RUNX1, CEBPA, ETV6, BCOR, BCORL1, STAT3 (7) Chromatin modification: ASXL1, EZH2, SETD2 (8) Tumour suppressors: TP53, WT1, NF1, PHF6 (9) Others: NPM1, SETBP1 Most patients harbour multiple mutations (>1), with the most frequently observed being: NPM1, NRAS, DNMT3A | |
Cells morphology | Monocytic component | |
Aberrant antigen expression | Aberrant expression of myeloid cell, B-cell: CD19, T-cell: CD4, CD7, NK-cell: CD56 antigens | |
Pathogenic pathways | BONE MARROW AND EXTRAMEDULLARY NICHE Regulatory abnormalities: (1) Loss of RAF kinase inhibitor protein and activation of RAS-MAPK/ERK pathway (2) Deregulation in the EMT pathway, altered ECM–receptor interactions and local adhesion pathways, formation of a CsC-supportive niche Contributors to EMT and invasiveness: (1) ECM proteins, the upregulation of six collagen isoforms: FN1, TNC, THBS2, and LAMA/LAMB1, the promotion of EMT and drug resistance (2) The role of transcription factor TWIST1 in EMT and apoptosis: the interactions with adhesion molecules, the disruption of the epithelial–mesenchymal balance, the enhancement of leukemic cell invasion, the promotion of EMT, and the increase in overall invasiveness STEM CELL MIGRATION (1) Altered expression and dysregulation of membrane adhesion molecules, chemokine receptors/ligands, and integrins (2) Impaired adhesion of LSCs to BM niches, the mobilisation and migration of LSCs into PB, spleen, and EM sites (3) Overexpression of CXCR4, CCR5, CX3CR1, CXCR7, CCR2 (4) Interactions between CLA and E-selectin on skin endothelial cells; ICAM-1 with LFA-1; CCL3 with CCR5 on blasts (5) Expression of PD-L1 (6) Activation of the RAS-MAPK/ERK pathway (7) Pathogenic NEF2 mutations (8) Presence of macrophage-like leukaemia subset with complement C1Q positivity | |
Epigenetic/microRNA profiles | Some cases shared features between MS and BPDCN |
Surgical (Excisional) Tissue Biopsy | Fine Needle Biopsy | Core Biopsy | Body Fluids (e.g., Cerebrospinal Fluid, Pleural Effusion) | |
---|---|---|---|---|
Tissue architecture | Undisturbed, broad heterogeneity | Disrupted | Locally undisturbed, reduced heterogeneity | Not applicable |
Morphology | Low-power architecture and high-power cytomorphology | Detailed cellular morphology | Low-power architecture limited by biopsy size | Detailed cellular morphology |
Procedure invasiveness | Surgical excision procedure The most invasive procedure | The least invasive procedure The lowest risk of complications Image guidance may be necessary | A minimally invasive procedure The possibility of performing percutaneously or endoscopically. Image guidance may be necessary. | Usually less invasive than direct tissue biopsy |
Limitations | Accessibility may be challenging depending on the anatomical location (e.g., brain, retroperitoneum, mediastinum). | Inappropriate for cases with rare malignant cells or structural characteristics that limit aspiration (e.g., fibrosis, necrosis). | Inappropriate for cases requiring analysis of extensive heterogeneity or scarce malignant cells. | Often relatively low in cellularity, mainly when obtained from small-volume or relatively sterile sites. Limited effectiveness of specific techniques, e.g., cell block preparation. |
Most appropriate for diagnostics | Cell block preparation. Scarce malignant cells and/or diagnostic features depending on low-power architectural distortion. | Homogeneous populations of readily identifiable (immunophenotypically aberrant) cells | Aberrant cell populations homogeneous or mixed, or displaying distinct architectural patterns. Biopsy of deep or relatively inaccessible lesions that are not readily amenable to surgical resection. | Assessment of cells in cerebrospinal fluid, pleural, pericardial, peritoneal effusions, bronchoalveolar lavage, and vitreous fluid. |
Morphologic examination methods | Cells collected into a tissue block and embedded in paraffin and immunophenotyping via IHC. | Cells smeared on glass slides and stained or collected into a tissue block and embedded in paraffin and immunophenotyping via IHC | Cells smeared on glass slides and stained or collected into a tissue block and embedded in paraffin and immunophenotyping via IHC | The workup used techniques similar to those used in FNA samples: stained smears for cytomorphology and collected tissue fragments for embedding into a cell block. |
Type of obtained cells | Fixed cells | Viable and intact, disaggregated cells | A reasonable number of viable cells suitable for morphology assessment. | Viable cells |
Diagnostics methods | Immunophenotyping by IHC, FISH, NGS | Immunophenotyping by flow cytometry, conventional karyotyping, FISH and a wide range of molecular genetic studies Cultures | Immunophenotyping by IHC and flow cytometry, conventional karyotyping, FISH and a wide range of molecular genetic studies Cultures | Immunophenotyping by flow cytometry, conventional karyotyping, FISH and a wide range of molecular genetic studies Cultures |
Characteristics | The highest potential diagnostic yield. | The intermediate potential diagnostic yield. | The intermediate potential diagnostic yield. It could be combined with FNA, similar to the combination of bone marrow aspirate and core biopsy. | The intermediate potential diagnostic yield. Depending on the site, e.g., cerebrospinal fluid, pleural or peritoneal effusions, or bronchoalveolar lavage. |
Flow Cytometry | Immunohistochemistry | |
---|---|---|
Markers number analysed | Many (typically 8–12 in the majority of clinical laboratories) | One (occasionally two) |
Spectrum of measurable intensity | Broad | Limited |
Category of information collected | Quantitative | Qualitative |
Processing duration | Fast (under 1 h) | More time-consuming (several hours) |
Sample | Undamaged, disaggregated cells | Cryopreserved tissue or formalin-fixed, paraffin-embedded tissue samples |
Correlation with cell morphology | Indirect | Direct |
Most appropriate for | Samples of non-cohesive live cells require analysis of multiple markers per cell—no critical correlation with morphology. | Paraffin-embedded samples or populations not suited to disaggregation. Limited markers per cell analysed—uncommon populations of cells with morphological abnormalities. |
Characteristics | Counting cells and immunophenotyping with cell differentiation | The effacement of tissue architecture. Pleomorphic infiltrate of early-stage myelopoietic cells with maturation arrest at the blast phase. Variable sizes of cells. |
Antigens expressed | Myeloblasts: CD34, CD117, CD13, CD15, CD33, HLA-DR, CD45, MPO Mature and immature monocytic cells: CD64, CD14, CD4, CD36, CD13, CD15, CD11b, CD11c, CD56 Megakaryoblastic or erythroid differentiation: CD41, CD61 or CD71, CD105, and CD235a | Frequently: MPO, CD33, CD13, CD68, and CD45 An immature granulocytic profile: CD34 and KIT (CD117) Monoblasts and immature monocytic cells: CD11b, CD11c, CD15, CD64, CD117 and lysozyme Less frequently: CD14 or CD34 More mature monocytic cell: CD14, CD68, CD163 Megakaryoblastic and erythroid differentiation: CD61 and glycophorin A. Exceptionally aberrantly expressed: markers of B-cells: CD19, T-cells: CD4, CD7 and NK-cells: CD56 Weak or only in a subset of cells: CD123, CD99, and TdT Rarely: aberrant cytokeratin expression as AE1/AE3 and CK8/18 Non-specific but highly sensitive for MS: lysozyme, CD68, CD43 |
ELN 2022 Risk Category by Genetics at AML Diagnosis | Mutated Genes and Genetic Alterations | Rates (%) in MS Patients |
---|---|---|
Favourable | RUNX1::RUNX1T1 | 2–23 |
CBFB::MYH11 | 9–17 | |
NPM1 | 15–54 | |
Intermediate | FLT3-ITD | 6–15 |
MLL rearrangement | 7–11 | |
Adverse | TP53 | 8–22 |
RUNX1 | 7–11 | |
Monosomy 7 | 8–11 | |
Del(5q) | 5–8 | |
Cytogenetic and/or molecular abnormalities not classified by ELN as favourable or adverse | NRAS | 11–31 |
KRAS | 11–15 | |
IDH1 | 15 | |
IDH2 | 11–31 | |
DNMT3A | 8–28 | |
TET2 | 17–22 | |
FLT3-TKD | 17 | |
PTPN11 | 11–15 | |
KIT | 14–15 | |
CBL | 11 | |
Trisomy 8 | 11–15 |
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Patkowska, E.; Krzywdzinska, A.; Solarska, I.; Wojtas, M.; Prochorec-Sobieszek, M. Diagnostic Approaches in Myeloid Sarcoma. Curr. Issues Mol. Biol. 2025, 47, 111. https://doi.org/10.3390/cimb47020111
Patkowska E, Krzywdzinska A, Solarska I, Wojtas M, Prochorec-Sobieszek M. Diagnostic Approaches in Myeloid Sarcoma. Current Issues in Molecular Biology. 2025; 47(2):111. https://doi.org/10.3390/cimb47020111
Chicago/Turabian StylePatkowska, Elzbieta, Agnieszka Krzywdzinska, Iwona Solarska, Magdalena Wojtas, and Monika Prochorec-Sobieszek. 2025. "Diagnostic Approaches in Myeloid Sarcoma" Current Issues in Molecular Biology 47, no. 2: 111. https://doi.org/10.3390/cimb47020111
APA StylePatkowska, E., Krzywdzinska, A., Solarska, I., Wojtas, M., & Prochorec-Sobieszek, M. (2025). Diagnostic Approaches in Myeloid Sarcoma. Current Issues in Molecular Biology, 47(2), 111. https://doi.org/10.3390/cimb47020111