Myelodysplastic Syndromes

Clinical Background

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

Refer to Myelodysplastic Syndrome topic at www.arupconsult.com for additional information about the 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)

See Also

Acute Myelogenous Leukemia - AML

Chronic Myelogenous Leukemia - CML

Leukemia Lymphoma Phenotyping

Myeloproliferative Diseases - MPD

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Diagnose myelodysplastic syndromes

Test name: Chromosome Analysis, Bone Marrow

ARUP #: 0097605

Methodology: Giemsa-Band Analysis

Use:

Identify recurrent chromosome abnormalities consistent with myelodysplastic syndromes

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive-Whole Blood)

ARUP #: 0096299

Methodology: Flow Cytometry

Use:

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

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive - Bone Marrow)

ARUP #: 0095244

Methodology: Flow Cytometry

Use:

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

Test name: Chromosome Analysis, FISH-Interphase

ARUP #: 0092615

Methodology: Fluorescence in situ Hybridization

Use:

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

Limitations:

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

Follow-up:

Repeat testing as clinically indicated to monitor disease progression

Test name: ARUP 005 Immunohistochemical Stain Offering

ARUP #:

Methodology:

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for CD15, CD117 and myeloperoxidase are available

Additional Tests Available

Test name: CBC with Platelet Count

ARUP #: 0040002

Methodology: Automated Cell Count

Comments:

Test name: Leukemia/Lymphoma Phenotyping (Comprehensive - Miscellaneous)

ARUP #: 0095243

Methodology: Flow Cytometry

Comments:

References

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.

Cited References

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

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.

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.

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

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

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.

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.

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

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.

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

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

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

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.

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

References from the ARUP Institute for Clinical and Experimental Pathology Research®

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.

Medical Reviewers

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