Pediatric Myelodysplastic Syndrome Workup

Updated: Jun 03, 2022
  • Author: Meena Kadapakkam, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Approach Considerations

Diagnostic studies for myelodysplastic syndrome center on a complete blood count (CBC) with differential, peripheral blood smears, bone marrow aspiration and biopsy. On the CBC count, patients often have anemia with high mean cellular volume and red blood cell distribution width. Neutropenia and thrombocytopenia may be found. Pediatric patients more commonly present with thrombocytopenia or neutropenia along with anemia.

In juvenile myelomonocytic leukemia (JMML), marked monocytosis may be present. Other diagnostic criteria for JMML include myeloid precursors in blood smears, clonal abnormality, granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors, and hemoglobin F levels above the reference range for age.

Pediatric myelodysplastic syndrome. A = binucleate Pediatric myelodysplastic syndrome. A = binucleate megaloblastoid erythroid precursor; B = megaloblastoid erythroid precursor; C = small megakaryocyte with monolobate nucleus.
Pediatric myelodysplastic syndrome. A = multinucle Pediatric myelodysplastic syndrome. A = multinucleate erythroid precursor; B = binucleate megaloblastoid erythroid precursor; C = dysplastic erythroid nuclei.
Pediatric myelodysplastic syndrome. A = vacuolated Pediatric myelodysplastic syndrome. A = vacuolated erythroblasts; B = hypogranular band.
Pediatric myelodysplastic syndrome. Internuclear b Pediatric myelodysplastic syndrome. Internuclear bridge between erythroid precursors (arrow).

Other studies include the following:

  • Bone marrow failure workup: Chromosome breakage studies for Fanconi anemia, telomere length for dyskeratosis congenita, PNH clone by flow cytometry, SBDS gene testing for Shwachman-Diamond syndrome, and a bone marrow failure panel genetic testing
  • Hemoglobin electrophoresis (elevated Hgb F)
  • Studies for cytomegalovirus (CMV),  Epstein-Barr virus (EBV), herpes simplex virus (HSV), and parvovirus to exclude marrow suppression due to a viral etiology
  • Folate and vitamin B-12 studies to evaluate for possible defects or deficiencies
  • Tissue typing of the patient and the family in anticipation of hematopoietic stem cell rescue
  • Testing for hypersensitivity to GM-CSF

Chromosomal analysis

Look for constitutional abnormalities if the patient has manifestations of Down syndrome (trisomy 21). Trisomy 21 with mosaicism occurs in 2-3% of cases in which 2 populations of cell types are present: a normal cell line with 46 chromosomes and a second cell line with trisomy 21. These children may appear phenotypically normal.

Children with complex chromosomal aberrations combined with a low platelet count and/or elevated hemoglobin F levels have a notably worsened outcome.

The presence of monosomy 7 should prompt an evaluation of family members.

Bone marrow studies

Performing a bone marrow aspiration and biopsy is essential in establishing diagnosis and classification. In MDS, bone marrow findings reveal evidence of morphologic myelodysplasia in at least two different myeloid cell lines or dysplasia that exceeds 10% in one single cell line, with evidence of a clonal cytogenetic abnormality in hematopoietic cells. Hypocellular marrow or dysplastic cells of various stages of differentiation with hypercellular findings may be evident.

Bone marrow should be sent for flow cytometry, karyotype, fluorescence in situ hybridization (FISH) for MDS panel (-7, 7q-, +8, -5, -5q, 20q-), and molecular testing for GATA2 for all samples and CBBPA, ETV6, RUNX1, SAMD9/SAMD9L, and CEBPA for patients with concern for familial MDS. [21]

Gene expression profile (GEP) analysis of bone marrow specimens has proved to be a powerful tool for the identification of gene signatures associated with distinct leukemia subtypes and has helped to stratify patients into different risk classes, as well as to identify deregulated genes involved in leukemia development. In 32 pediatric bone marrow specimens from MDS patients, GEP analysis was able to identify at diagnosis, patients with high risk to progress into AML. All MDS patients who evolved into AML showed AML-like signatures, while none of the MDS patients with a non AML-like signature showed evolution to AML. [22]


Histologic Findings

On peripheral smears, dysplastic shapes and cells with odd-appearing nuclear and cytoplasmic ratios (eg, anisocytosis, macrocytosis, microcytosis, poikilocytosis) are apparent. Although macrocytosis can indicate megaloblastic anemia (vitamin B-12 or folate deficiency), it is often observed in most bone marrow failure syndromes, including MDS. RBCs are often dimorphic (both hypochromic and normochromic). The number of reticulocytes is reduced in relation to the degree of anemia.

Depending on the class, variable granulocytic abnormalities are present. Pseudo–Pelger-Huët anomalies (eg, hyposegmented mature neutrophils, hypogranulation of cytoplasm) are characteristic of dysgranulopoiesis observed with MDS.

Pediatric myelodysplastic syndrome. Hypogranular P Pediatric myelodysplastic syndrome. Hypogranular Pelger-Huet neutrophils and dimorphic hypochromic and normochromic red blood cells.

As additional immature elements are observed in periphery, these elements often appear bizarre with abnormal nucleus-to-cytoplasm ratios and are often oddly shaped. In addition, the number of eosinophils and basophils may increase in patients with adult-type MDS. On smears, platelets markedly vary in size.

Myelodysplasia most commonly presents with a hypercellular marrow. In refractory anemia (RA), the ratio of erythroid to myeloid cells is abnormal, and the marrow appears similar to that of patients with megaloblastic anemia due to folate or vitamin B-12 deficiency. Erythroblasts are often large, with clumped chromatin and a large nucleolus.

In refractory anemia with excess blasts (RAEB), the myeloid component of marrow increases. Small myeloblasts and promyelocytes predominate in the marrow. These cells are often dysmorphic with abnormal nucleus-to-cytoplasm ratios.

Abnormal megakaryocytes may appear small (micromegakaryocytes) or large. They may have a variable number of nuclei in the same marrow sample.

Pediatric myelodysplastic syndrome. Micromegakaryo Pediatric myelodysplastic syndrome. Micromegakaryocytes with single or multiple, small, round nuclei.
Pediatric myelodysplastic syndrome. Bone marrow se Pediatric myelodysplastic syndrome. Bone marrow section, hematoxylin and eosin. Note the megakaryocytes (arrows) with a peripheral ring of nuclei (resembling Touton giant cells) and central eosinophilic inclusions displacing the nuclei.
Pediatric myelodysplastic syndrome. Bone marrow as Pediatric myelodysplastic syndrome. Bone marrow aspirate, Wright-Giemsa stain. Note the megakaryocyte with a central mass displacing the nuclei peripherally.


The minimal diagnostic criteria for MDS includes at least 2 of the following:

  • Sustained, unexplained cytopenia (neutropenia, thrombocytopenia, or anemia)
  • At least bilineage morphologic dysplasia
  • Acquired clonal cytogenetic abnormality in hematopoietic cells

In the prospective study of the European Working Group on MDS in Childhood, more than half of the patients with refractory cytopenia had a normal karyotype, followed in frequency by monosomy 7, trisomy 8, and other abnormalities. [23] Loss of the long arm of chromosome 5 (5q-), the most frequent chromosomal aberration in adults with RA, is rare in childhood.