myelodysplasia

WKP

See also : myelodysplastic syndromes (MDS).

The features generally used to define a MDS are:
 blood cytopenias;
 ineffective hematopoiesis;
 dyserythropoiesis;
 dysgranulopoiesis;
 dysmegakaropoiesis;
 increased myeloblast.

Bone marrow aspirate and peripheral blood smear

Dysplasia can affect all three lineages seen in the bone marrow. The best way to diagnose dysplasia is by morphology and special stains (PAS) used on the bone marrow aspirate and peripheral blood smear.

Dysplasia in the myeloid series (myelodysplasia) is defined by:

 Granulocytic series

• Hypersegmented neutrophils (also seen in Vit B12/Folate deficiency)
• Hyposegmented neutrophils (Pseudo-Pelger Huet)
• Hypogranular neutrophils or pseudo Chediak Higashi large granules
• Auer rods - automatically RAEB II (if blast count @<@5% in the peripheral blood and @<@10% in the bone marrow aspirate) also note Auer rods may be seen in mature neutrophils in AML with translocation t(8;21)
• Dimorphic granules (basophilic and eosinophilic granules) within eosinophils

 Erythroid series

• Binucleated erythroid percursors and karyorrhexis
• Erythroid nuclear budding
• Erythroid nuclear strings or internuclear bridging (also seen in congenital dyserythropoietic anemias)
• Loss of E-cadherin in normoblasts is a sign of aberrancy
• PAS (globular in vacuoles or diffuse cytoplasmic staining) within erythroid precursors in the bone marrow aspirate (has no bearing on paraffin fixed bone marrow biopsy). Note: One can see PAS vacuolar positivity in L1 and L2 blasts (AFB classification; the L1 and L2 nomenclature is not used in the WHO classification)
• Ringed sideroblasts seen on Prussian blue iron stain (10 or more iron granules encircling 1/3 or more of the nucleus and >15% ringed sideroblasts when counted amongst red cell precursors)

 Megakaryocytic series (can be the most subjective)

• Hyposegmented nuclear features in platelet producing megakaryocytes (lack of lobation)
• Hypersegmented (osteoclastic appearing) megakaryocytes
• Ballooning of the platelets (seen with interference contrast microscopy)

Other stains can help in special cases (PAS and napthol ASD chloroacetate esterase positivity) in eosinophils is a marker of abnormality seen in chronic eosinophilic leukemia and is a sign of aberrancy.

Bone marrow biopsy

On the bone marrow biopsy, high grade dysplasia (RAEB-I and RAEB-II) may show atypical localization of immature precursors (ALIPs) which are islands of immature precursors cells (myeloblasts and promyelcytes) localized to the center of intertrabecular space rather than adjacent to the trabeculae or surrounding arterioles. This morphology can be difficult to recognize from treated leukemia and recovering immature normal marrow elements. Also topographic alteration of the nucleated erythroid cells can be seen in early myelodysplasia (RA and RARS), where normoblasts are seen next to bony trabeculae instead of forming normal interstitially placed erythroid islands.

Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores, vitamin deficiencies, and nutrient deficiencies are ruled out. Also congenital diseases such as congenital dyserythropoietic anemia (CDA I through IV) has been recognized, Pearson’s syndrome (sideroblastic anemia), Jordans anomaly - vacuolization in all cell lines may be seen in Chanarin-Dorfman syndrome, ALA (aminolevulinic acid) enzyme deficiency, and other more esoteric enzyme deficiencies are known to give a pseudomyelodysplastic picture in one of the cell lines, however, all three cell lines are never morphologically dysplastic in these entities with the exception of chloramphenicol, arsenic toxicity and other poisons.

All of these conditions are characterized by abnormalities in the production of one or more of the cellular components of blood (red cells, white cells other than lymphocytes and platelets or their progenitor cells, megakaryocytes).