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The myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant hematopoietic stem cell disorders characterized by dysplastic and ineffective blood cell production.

●The diagnosis of MDS should be considered in any patient with unexplained cytopenia(s) or monocytosis. Careful inspection of the peripheral blood smear and bone marrow aspirate is necessary to document the requisite dysplastic cytologic features identifiable in any or all of the hematopoietic lineages (table 3). Detection of certain chromosomal abnormalities distinguishes between MDS and acute myeloid leukemia (AML) in some cases, aids in the classification of MDS, and is a major factor in determining prognostic risk group and therapy. Some centers routinely incorporate DNA sequencing. (See 'Evaluation' above and 'Diagnosis' above.)

●The diagnosis of MDS requires both of the following:

•Otherwise unexplained quantitative changes in one or more of the blood and bone marrow elements (ie, red cells, granulocytes, platelets). The values used to define cytopenia are: hemoglobin <10 g/dL (100 g/L); absolute neutrophil count <1.8 x 109/L (<1800/microL); and platelets <100 x 109/L (<100,000/microL). However, failure to meet the threshold for cytopenia does not exclude the diagnosis of MDS if there is definite morphologic evidence of dysplasia.

•Morphologic evidence of significant dysplasia (ie, ≥10 percent of erythroid precursors, granulocytes, or megakaryocytes) upon visual inspection of the peripheral blood smear, bone marrow aspirate, and bone marrow biopsy in the absence of other causes of dysplasia (table 3). In the absence of morphologic evidence of dysplasia, a presumptive diagnosis of MDS can be made in patients with otherwise unexplained refractory cytopenia in the presence of certain genetic abnormalities. (See 'Genetic features' above.)

Importantly, blast forms must account for less than 20 percent of the total cells of the bone marrow aspirate and peripheral blood. In addition, the presence of myeloid sarcoma or certain genetic abnormalities, such as those with t(8;21), inv(16), or t(15;17), are considered diagnostic of AML, irrespective of the blast cell count. (See 'Acute myeloid leukemia' above.)

●MDS must be distinguished from other entities that may also present with cytopenias and/or dysplasia. Common conditions that present with features similar to MDS include HIV infection, deficiencies of vitamin B12, folate, or copper, and zinc excess. Other entities considered in a specific case depend largely upon the presenting features. (See 'Differential diagnosis' above.)

●MDS is classified using the World Health Organization (WHO) classification system based upon a combination of morphology, immunophenotype, genetics, and clinical feature (table 14). (See 'WHO classification' above.)

MDS occurs most commonly in older adults, with a median age at diagnosis in most series of ≥65 years and a male predominance [1]. It may occur de novo or arise years after exposure to potentially mutagenic therapy (eg, radiation exposure, chemotherapy).

Conservative estimates from cancer databases suggest that there are approximately 10,000 cases diagnosed annually in the United States [2].

Onset of the disease earlier than age 50 is unusual [3], with the exception of treatment-induced MDS [3].

MDS has been associated with environmental factors (eg, exposure to chemicals, particularly benzene [4], radiation, tobacco, or chemotherapy drugs), inherited genetic abnormalities (eg, trisomy 21, Fanconi anemia, Bloom syndrome, ataxia telangiectasia), and other benign hematologic diseases (eg, paroxysmal nocturnal hemoglobinuria, congenital neutropenia).

Familial MDS, while rare, has been associated with germ line mutations in RUNX1, ANKRD26, CEBPA, DDX41, ETV6, TERC, TERT, SRP72, and GATA2 (table 2). Familial MDS is discussed in more detail separately. (See "Familial acute leukemia and myelodysplastic syndromes".)

Although connective tissue disorders such as relapsing polychondritis, polymyalgia rheumatica, Raynaud phenomenon and Sjögren's syndrome, inflammatory bowel disease, pyoderma gangrenosum, Behçet's syndrome, and glomerulonephritis have been reported in association with MDS, a causal relationship has not been firmly established [66-71]. However, speculation that such clinically important immune dysregulation is a cause and/or consequence is enhanced by the observation that treatment of MDS with hypomethylating agents sometimes ameliorates the autoimmune condition and steroids occasionally improve the blood counts [72].

(See 'Autoimmune abnormalities' below.)

(See 'Epidemiology' above and 'Pathogenesis' above.)

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