Tests

1st tests to order

CBC with differential

Test
Result
Test

CBC will show one or more cytopenias (most commonly anemia) that are sustained (e.g., >4 months).[11][15]​​​​[16]

Approximately 90% of MDS patients have anemia.[59][60]

Approximately 40% of patients have neutropenia.[3][58]​​

Approximately 30% have thrombocytopenia.[3][61]

Result

one or more cytopenias

peripheral blood smear

Test
Result
Test

Peripheral blood smear will show cytopenias (most commonly anemia) and dysplasia.[16]

Anemia is usually normochromic or macrocytic.

May see hypogranular and hypolobulated granulocytes (pseudo-Pelger-Huet anomaly).[62][Figure caption and citation for the preceding image starts]: Blood film showing normal neutrophil (right) and dysplastic neutrophil with agranular cytoplasm and hypolobated nucleusImage used with permission from BMJ 1997;314:883 [Citation ends].com.bmj.content.model.Caption@56223a0

Result

cytopenias; normochromic or macrocytic red cells; dysplasia; hypogranular and hypolobulated granulocytes (pseudo-Pelger-Huet anomaly)

reticulocyte count

Test
Result
Test

Often low in MDS.[50]

Inadequate reticulocyte response for degree of anemia; if an adequate response is present, other diagnoses are more likely.

Result

inappropriately normal or low

red blood cell folate

Test
Result
Test

Used to rule out folate deficiency as cause of anemia.

Result

normal

serum vitamin B12

Test
Result
Test

Used to rule out vitamin B12 deficiency as cause of anemia.

Result

normal

iron studies

Test
Result
Test

Serum iron, total iron-binding capacity, ferritin used to rule out iron deficiency.

Result

normal

bone marrow aspiration with iron stain

Test
Result
Test

A diagnosis of MDS can be made in a patient with persistent cytopenia in the presence of one of the following three criteria: significant bone marrow dysplasia (≥10% in one or more of three major bone marrow lineages); blasts in the peripheral blood and/or bone marrow (<20%); or a clonal cytogenetic abnormality or somatic mutation.​[1][2][11]​ Biologic features are more important than a strict blast cutoff value.[15] Patients with blasts ≥20% should be assessed for acute myeloid leukemia. (See Acute myeloid leukemia)

Prussian blue iron staining of bone marrow aspirate can show ringed sideroblasts - abnormal erythroid precursor cells that have granules around the nucleus.

May need to repeat to assess: transformation into AML; persistence of morphologic abnormalities (as other conditions such as vitamin B12 deficiency and infections can cause transient dysplastic abnormalities).

[Figure caption and citation for the preceding image starts]: Large mononuclear megakaryocyte in bone marrow of patient with MDS-del(5q)Image used with permission from BMJ 1997;314:883 [Citation ends].com.bmj.content.model.Caption@647cb6c9

Result

dysplasia (≥10% in one or more of three major bone marrow lineages); ringed sideroblasts; bone marrow blasts (<20%)

bone marrow core biopsy

Test
Result
Test

Can assess overall bone marrow cellularity and architecture and help differentiate MDS from myeloproliferative disorder (reticulin deposits, fibrosis). Hypocellular marrow may be seen in some patients with MDS, but this is rare.

May need to repeat to assess: transformation into AML; persistence of morphologic abnormalities (as other conditions such as vitamin B12 deficiency and infections can cause transient dysplastic abnormalities).

Result

usually hypercellular marrow; rarely hypocellular marrow

genetic testing

Test
Result
Test

Genetic testing for MDS-associated cytogenetic abnormalities (e.g., -5, del(5q), -7, del(7q), del(11q), del(12p), -17, del(17p), del(20q)) and somatic mutations (e.g., DNMT3A, TET2, ASXL1, TP53, SF3B1) informs the diagnosis and prognostic risk stratification.[11][15]

The presence of certain cytogenetic abnormalities or somatic mutations (e.g., -7/del(7q), del(5q), or SF3B1) may establish a diagnosis without dysplasia.[1][2]​​​​ 

Genetic testing may be carried out on peripheral blood if bone marrow testing is not possible.

Patients with significant dysplasia who do not have a clonal cytogenetic abnormality or somatic mutation should undergo further evaluation to exclude a nonmalignant cause of dysplasia.

Result

MDS-associated cytogenetic abnormalities (e.g., -5, del(5q), -7, del(7q), del(11q), del(12p), -17, del(17p), del(20q)); MDS-associated somatic mutations (e.g., DNMT3A, TET2, ASXL1, TP53, SF3B1)

Investigations to avoid

fluorescence in situ hybridization (FISH)

Recommendations
Rationale
Recommendations

Do not perform MDS-related FISH panels on bone marrow samples obtained for cytopenias if an adequate conventional karyotype is obtained.[11][15][53]

Rationale

MDS-related FISH panels are expensive tests which are only indicated if standard cytogenetics (with ≥20 metaphases) cannot be obtained.[11][15][53]

Tests to consider

viral serology

Test
Result
Test

Testing for viral infection (e.g., HIV; hepatitis B, C, and E; cytomegalovirus; parvovirus) can be carried out if there are risk factors for prior exposure.[11][15]​​​[16]​​

HIV infection can cause dysplastic bone marrow changes that are similar to those seen in MDS.[51]

Result

may be positive for viral infection

serum erythropoietin

Test
Result
Test

Serum erythropoietin levels can be measured to guide treatment with erythropoiesis-stimulating agents.[15][16][54] 

Elevated in MDS except in concurrent renal failure, in which case it is low.

Result

elevated

lactate dehydrogenase

Test
Result
Test

Lactate dehydrogenase has prognostic value and can be measured to inform risk stratification and management.[15][16]

Elevated lactate dehydrogenase is associated with poorer outcomes.[55][56]

Result

varies

HLA typing

Test
Result
Test

Useful for candidates for hematopoietic stem cell transplantation, or those requiring extensive platelet transfusions.[54]

Result

varies

flow cytometry

Test
Result
Test

Can be performed on bone marrow samples to support a diagnosis of MDS (by identifying dysplastic features and blasts).[52]

May be used (alongside STAT3 mutation testing) for the evaluation of a concurrent paroxysmal nocturnal hemoglobinuria clone, and possible large granular lymphocytic leukemia.[3][15]

Result

dysplasia (≥10% in one or more of three major bone marrow lineages); bone marrow blasts (<20%)

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