Myelodysplastic Syndrome: Test and Diagnosis

1st-order laboratory parameters-obligatory laboratory tests.

• Small blood count
  • [Hemoglobin often < 12 g/dL
  • [Leukocyte count often < 4,000/μl
  • Platelet count often <100,000/μl]

  Note: Macrocytic anemia [MCV (mean corpuscular volume) ↑] is often present with lack of adequate increase in reticulocytes (young, immature red blood cells).

• Differential blood count – to determine the subgroups of leukocytes (white blood cells).
• Reticulocytes [often decreased]
• Ferritin
  • At levels above > 1,000 µg/l iron depletion therapy if necessary.
• Lactate dehydrogenase (LDH)
• Folic acid
• Vitamin B12
• Copper in serum – to exclude a copper deficiency (e.g., as a result of zinc oversupply).
• Erythropoietin
  • If necessary, therapy with an erythropoietin if the erythropoietin level < 500 U/l.
• Bone marrow aspiration with cytology, cytogenetics, histology, immunophenotyping (to estimate blast percentage and show signs of dysplasia) – to determine if the malproduction of blood cells is due to the hematopoietic system:
  • 1. collection of bone marrow by puncture of the iliac crest (bone marrow biopsy).
  • 2. histological examination
  • 3. if there are changes in the bone marrow, the subtype of myelodysplastic syndrome can now be determined.
• Mutation analysis
  • Bcr-abl, pdgfr-α/β, (for CMML (chronic myelomonocytic leukemia)/CML/aCML differentiation, if applicable).
  • SRSF2, ASXL1, and TET2 gene – indication of CMML.
  • Tet2, runx1, asxl1, sf3b1, srsf2, tp53, u2af1, dnmt3a, zrsr2, ezh2, nras, kras (securing diagnosis, prognosis estimation, if necessary).
• If necessary, HLA typing (due toallogeneic transplantation).

Significant for myelodysplastic syndrome (MDS) are blood count changes such as:

• Monocytopenia (decrease of monocytes in the blood) – Monocytes belong to the white blood cells. They are precursors of macrophages, which play an important role in the immune defense as “scavenger cells”.
• Bicytopenia – two cell series of hematopoiesis are affected by the disorder.
• Pancytopenia (tricytopenia) – reduction of all three cell series in the blood: leukocytes/white blood cells, platelets/platelets, erythrocytes/red blood cells).
• Dyshematopoiesis in peripheral blood (maturation disorders of progenitor cells).
  • Anisocytosis (unequal size distribution of normally equal-sized cells).
  • Basophilic stippling
  • Hypersegmented granulocytes
  • Hypogranulated granulocytes
  • Macrocytosis (enlargement of erythrocytes beyond the normal value).
  • Platelet anisometry
  • Poikilocytosis (occurrence of differently shaped, non-round erythrocytes).
  • Polychromasia
  • Pseudo-Pelger cells
  • Isolated blasts
  • Giant platelets
  • Etc.

Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification.

• Immunocytology, usually T cells – for suspected large granular lymphocyte lymphoma.
• Immunocytology, B-cell marker + CD103? – if hairy cell leukemia is suspected.
• Immunocytology, GPI anchor – in suspected paroxysmal nocturnal hemoglobinuria (PNH).
• Anti-platelet antibodies – in suspected idiopathic thrombocytopenic purpura (ITP, more recently called immune thrombocytopenia).