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Disease Categories > Oncologic Disease > Lymphoma-Leukemia

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Myelodysplastic Syndromes

Myelodysplastic syndromes are clonal stem cell diseases characterized by ineffective hematopoiesis, cytopenia, multilineage dysplasia and susceptibility to leukemia.

Epidemiology

Incidence
- 3.5 to 10/100,000 in the general population
- 12 to 50/100,000 in the elderly population
- 0.5 to 4/1,000,000 in children
Age – median age of onset is 60-70 years

Classification

Click here for a chart of WHO classification of the Myelodysplastic Syndromes

Risk Factors

Increased age
Occupational exposures
- Benzene-containing products
- Pesticides
- Organic solvents
- Heavy metals (lead, arsenic)
Drug exposures
- Alkylating agents
- Azathioprine
- Mycophenolate
Previous radiation treatment
Genetic
- Fanconi anemia
- Familial myelodysplasia

Pathophysiology

Clonal expansion of the multipotential hematopoietic cell
Primary mechanism is defective maturation of immature marrow cells with premature death

Clinical Presentation

May be asymptomatic
Most common symptoms
- Anemia – pallor, weakness, exertional dyspnea
- Hepatomegaly/splenomegaly (5-10%)
- Arthralgias
Complications
- Progression to AML (~30%)
- Death from complications of cytopenia (neutropenia in particular)

Diagnosis

Indications for testing
- Abnormal CBC with peripheral smear – may see macrocytic anemia, other cyotpenias, dysplastic cells in peripheral smear
Laboratory testing
- Bone marrow biopsy – diagnosis is almost exclusively made using marrow appearance
Cytogenetic testing for recurrent chromosome abnormalities consistent with MDS including 5q, 7q, 12p, 13q, and 20q deletions; trisomies 8, 9, 11, 19, and 21, and structural abnormalities of chromosomes 3, 6, 9, 11, 16, and 17 (this list is not exhaustive, but represents the various abnormalities associated with MDS)

Differential Diagnosis

Acute leukemia
Chronic leukemia
Myeloproliferative disorder

Indications for Ordering

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations	Follow Up
CBC with Platelet Count & Automated Differential 0040003 Method: Automated Cell Count with Flow Cell Differential	Diagnose myelodysplastic syndromes
Chromosome Analysis, Bone Marrow 0097605 Method: Giemsa-Band Analysis	Identify recurrent chromosome abnormalities consistent with myelodysplastic syndromes
Leukemia/Lymphoma Phenotyping (Comprehensive-Whole Blood) 0096299 Method: Flow Cytometry	Identify blasts and aberrant antigen expression patterns associated with myeloproliferative disorders in tissue or fluid specimens Available myeloid antigens: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase
Leukemia/Lymphoma Phenotyping (Comprehensive - Bone Marrow) 0095244 Method: Flow Cytometry	Identify blasts and aberrant antigen expression patterns associated with myeloproliferative disorders in bone marrow specimen Available myeloid antigens: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase
Chromosome Analysis, FISH-Interphase 0092615 Method: Fluorescence in situ Hybridization	Monitor disease and identify specific abnormalities suspected clinically Specific FISH probes must be requested and for this indication include 5q deletion, monosomy 7/ 7q deletion, +8, and 20q deletion	Limit of detection is probe dependent and approximately 1-5% in interphase nuclei Some of these abnormalities can also be detected in acute myelogenous leukemia and myeloproliferative disorders and therefore are not sufficient for diagnosis but rather consistent with the suspected diagnosis	Repeat testing as clinically indicated to monitor disease progression
ARUP 005 Immunohistochemical Stain Offering	For fixed tissue samples, consultative services as well as immunohistochemical staining for CD15, CD117 and myeloperoxidase are available

Additional Tests Available

Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Comments
CBC with Platelet Count 0040002 Method: Automated Cell Count
Leukemia/Lymphoma Phenotyping (Comprehensive - Miscellaneous) 0095243 Method:

Guidelines

Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstocker M, Ruter B, Sperr WR, Stauder R, Wells DA. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: Consensus statements and report from a working conference. Leuk Res. 2007;31(6):727-736. (Link to PubMed)

Cited References

Bain B. The WHO classification of the myelodysplastic syndromes. Exp Oncol. 2004;26(3):166-169. (Link to PubMed)

General References

Corey SJ, Minden MD, Barber DL, Kantarjian H, Wang JC, Schimmer AD. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007;7(2):118-129. (Link to PubMed)

Elghetany MT. Myelodysplastic syndromes in children: a critical review of issues in the diagnosis and classification of 887 cases from 13 published series. Arch Pathol Lab Med. 2007;131(7):1110-1116. (Link to PubMed)

Fortenbaugh C. MDS: navigating the complex course. ONS News. 2006;21(8 Suppl):17-18. (Link to PubMed)

Kurtin SE. Myelodysplastic syndromes: diagnosis, treatment planning, and clinical management. Oncology (Williston Park). 2007;21(11 Suppl Nurse Ed):41-48. (Link to PubMed)

Kussick SJ, Fromm JR, Rossini A, Li Y, Chang A, Norwood TH, Wood BL. Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia. Am J Clin Pathol. 2005;124(2):170-181. (Link to PubMed)

Naeem RC. Cytogenetics of Hematologic Neoplasms. In: Gersen SL, Keagle MB, eds. The Principles of Clinical Cytogenetics. Totowa, NJ: Humana Press Inc, 2005. pp. 365-420.

Nakao S, Deeg HJ, Ishikawa T, Marsh J, List A, Tomonaga M. Myelodysplastic syndrome. Int J Hematol. 2005;82(5):412-416. (Link to PubMed)

Orazi A. Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases. Pathobiology. 2007;74(2):97-114. (Link to PubMed)

Pfeilstocker M, Karlic H, Nosslinger T, Sperr W, Stauder R, Krieger O, Valent P. Myelodysplastic syndromes, aging, and age: correlations, common mechanisms, and clinical implications. Leuk Lymphoma. 2007;48(10):1900-1909. (Link to PubMed)

Sekeres MA. The myelodysplastic syndromes. Expert Opin Biol Ther. 2007;7(3):369-377. (Link to PubMed)

Shadduck RK, Latsko JM, Rossetti JM, Haq B, Abdulhaq H. Recent advances in myelodysplastic syndromes. Exp Hematol. 2007;35(4 Suppl 1):137-143. (Link to PubMed)

Steensma DP, Bennett JM. The myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2006;81(1):104-130. (Link to PubMed)

Stetler-Stevenson M, Arthur DC, Jabbour N, Xie XY, Molldrem J, Barrett AJ, Venzon D, Rick ME. Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. Blood. 2001;98(4):979-987. (Link to PubMed)

Wood BL. Myeloid malignancies: myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia. Clin Lab Med. 2007;27(3):551-75, vii. (Link to PubMed)

References from the ARUP Institute for Clinical and Experimental Pathology®

Dunphy CH, O'Malley DP, Perkins SL, Chang CC. Analysis of immunohistochemical markers in bone marrow sections to evaluate for myelodysplastic syndromes and acute myeloid leukemias. Appl Immunohistochem Mol Morphol. 2007;15(2):154-159. (Link to PubMed)

Reviewed by

Bahler, David W., M.D., Ph.D. Medical Director, Hematologic Flow Cytometry, and Acting Medical Director, Molecular Hematopathology at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah

Comprehensive Review: May 2008
Last Update: July 2008