Refractory Anemia with Excess Blasts (RAEB)
Definition
- Myelodysplastic syndrome characterized by elevated blasts, but below leukemic levels
Diagnostic Criteria
- Exclusions
- Non-clonal causes for dysplasia must be excluded (see Differential Diagnosis)
- Increased blasts make these less likely
- If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
- <1 x 103/μL monocytes (if present consider Chronic Myelomonocytic Leukemia)
- Lack of neutrophilia (if present consider BCR-ABL1+CML or atypical CML)
- Non-clonal causes for dysplasia must be excluded (see Differential Diagnosis)
- Elevated blasts, but not to leukemic levels in either:
- Peripheral blood blasts 2-19%, based on 200 leukocyte differential, OR
- Bone marrow blasts 5-19%, based on 500 nucleated cell differential
- Divided into two prognostic groups:
- RAEB 1
- 2-4% peripheral blood blasts AND/OR
- 5-9% bone marrow blasts
- RAEB 2
- 5-19% peripheral blood blasts AND/OR
- 10-19% bone marrow blasts AND/OR
- Auer rods
- Presence should raise suspicion for AML (see Differential Diagnosis)
- RAEB 1
- Hypercellular marrow with dysplasia in >10% of one or more cell lineage
- Abnormal localization of immature precursors (ALIP) frequently present
- Aggregates (3-5%) or clusters (>5%) of immature cells located in center portion of marrow
- Away from normal perivascular or endosteal locations
- Aggregates (3-5%) or clusters (>5%) of immature cells located in center portion of marrow
- Cytogenetics should be performed on every patient to verify the presence of a clonal abnormality
- Present in about half
- Marrow fibrosis and/or hypocellularity may cause problems with diagnosis
- If present, add to the diagnosis as a modifier
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