Myelodysplastic Syndromes
Definition
- A group of clonal stem cell diseases characterized by dysplastic and ineffective hematopoiesis
Diagnostic Criteria
- Generally result in cytopenias
- Marrow is usually cellular
- Displays dysplastic features (see below)
- Occasionally hypocellular, leading to special diagnostic problems
- Occasionally increased fibrosis, leading to special diagnostic problems
- Increased risk of blast transformation
- Have been considered preleukemia by some
- Occurs mainly in older patients
- Select specific disorders below for details
Myelodysplastic Syndromes
| Circulating Blasts | Marrow Blasts | Ring Sideroblasts | Dysplastic Lineages | Cytopenias | |
|---|---|---|---|---|---|
| RCUD | <1% | <5% | <15% | Any 1 lineage | 1 or 2 |
| RARS | 0 | <5% | ≥15% | Only erythroid | 1 or 2 |
| RCMD | <1% | <5% | Variable | 2 or more lineages | 1, 2 or 3 |
| <5% | 5-9% | Variable | 1 or more | 1, 2 or 3 | |
| 5-19% | 10-19% or Auer rods | Variable | 1 or more | 1, 2 or 3 | |
| del(5q) | <1% | <5% | Variable | Frequently hypolobated small megakaryocytes | Usually 1 (anemia) |
- RCUD = refractory cytopenia (anemia, neutropenia or thrombocytopenia) with unilineage dysplasia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; del(5q) = 5q- syndrome
- All MDS must not have absolute monocytosis
- If present, consider chronic myelomonocytic leukemia
- If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
- In children, consider provisional WHO entity "refractory cytopenia of childhood" for low blast count MDS
- Myelodysplastic syndrome unclassifiable (MDS-U)
- Must not meet criteria of any specific WHO category
- Persistent cytopenia(s) with any of the following:
- Unilineage marrow dysplasia with pancytopenia OR
- <1% blasts in blood, <5% blasts in marrow and cytogenetic abnormalities but no lineage with ≥10% dysplastic forms OR
- Findings of RCUD or RCMD but with 1% blasts in peripheral blood
- (2-4% blasts would be classified as RAEB-1)
- Nonclonal causes must be excluded
Myelodysplasia is defined by morphologic features of abnormal cellular maturation in at least one bone marrow lineage
- Not all features are applicable to all disorders
- Dyserythropoeisis
- Peripheral blood erythrocyte abnormalities
- Normocytic, normochromic anemia
- Macrocytosis
- Dimorphic red blood cells (RBC)
- Mixture of normal RBC and hypochromic microcytic RBC
- Often seen in Sideroblastic Anemia (RARS)
- Mixture of normal RBC and hypochromic microcytic RBC
- Basophilic stippling
- Poikilocytosis
- Varying shapes, frequently macro-ovalocytes
- Bone marrow erythroid lineage abnormalties
- Erythroid hyperplasia or hypoplasia
- Megaloblastoid / megaloblastic changes
- Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
- Nucleus lags behind cytoplasm
- Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
- Megaloblastoid / megaloblastic changes
- Ring sideroblasts
- ≥5 iron granules encircling ≥1/3 of the nucleus
- Usually either many or none
- Cytoplasmic vacuoles
- Also seen in copper deficiency
- Nuclear changes
- Multinuclearity
- Nuclear budding, hyperlobulation and satellite nuclei
- Internuclear bridging
- Erythroid hyperplasia or hypoplasia
- Peripheral blood erythrocyte abnormalities
- Dysgranulopoiesis
- Peripheral blood and/or bone marrow findings (easier seen in peripheral blood)
- Hypogranularity
- Pale cytoplasm almost indistinguishable from background on slide
- Nuclear hypolobation or irregular hypersegmentation (>5 lobes)
- Pseudo Pelger-Huet anomaly
- Two equal size nuclear lobes connected by a thin strand of chromatin
- Pseudo Pelger-Huet anomaly
- Infrequent findings
- Abnormal cytoplasmic granules (pseudo Chediak-Higashi granules)
- Giant grey to red granules
- Dohle bodies
- Small blue cytoplasmic inclusions
- Often found at periphery of cell
- Auer rods
- Rod-like structures formed by fusion of primary granules
- May be found in blasts or maturing granulocytes
- Abnormal cytoplasmic granules (pseudo Chediak-Higashi granules)
- Hypogranularity
- Peripheral blood and/or bone marrow findings (easier seen in peripheral blood)
- Dysmegakaryopoiesis
- Peripheral blood platelet abnormalities
- Giant
- Larger than a red blood cell
- Bizarre
- Irregular shapes and protrusions
- Hypogranularity
- Compare to normal platelets with purple granules
- Giant
- Bone marrow megakaryocyte abnormalities
- Micromegakaryocytes
- Smaller than a promyelocyte
- Nuclear hypolobation
- Prominent in 5q- syndrome
- A single lobe is typically seen in a small megakaryocyte
- Multinucleation
- Distinct nuclei without a connecting strand of chromatin
- Cytoplasmic hypogranularity
- Micromegakaryocytes
- Peripheral blood platelet abnormalities
Dita Gratzinger MD PhD
Tracy I George MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting: 10/23/11
