Refractory Cytopenia with Multilineage Dysplasia (RCMD)
Definition
- Myelodysplastic syndrome characterized by bi- or trilineage dysplasia
Diagnostic Criteria
- Exclusions
- Non-clonal causes for dysplasia must be excluded (see Differential Diagnosis)
- 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)
- Lack of Auer rods (if present, diagnose asRAEB-2 or AML)
- Cytopenias in 1 or more lineages
- Dysplasia in >10% of more than one cell lineage
(see below for criteria for dysplasia)
- Refractory anemia - Hemoglobin <10
mg/dL
- Ring sideroblasts <15% of erythroid lineage cells (if ≥15% see Refractory Anemia with Ring Sideroblasts)
- Refractory neutropenia - Absolute neutrophil count <1.8 x 103/μL
- Refractory thrombocytopenia - Platelet count <100 x 103/μL
- If dysplasia present in only 1 lineage, see Refractory Cytopenia with Unilineage Dysplasia
- Refractory anemia - Hemoglobin <10
mg/dL
- Peripheral blood blasts <1%, based on 200 leukocyte differential
- Bone marrow blasts <5%, based on 500 nucleated cell differential
- Cytogenetics should be performed on every patient to verify the presence of a clonal abnormality
- Present in about half of refractory anemia cases
- Incidence in other refractory cytopenias is currently unknown
- If no clone present, patient must be observed for 6 months before diagnosis of MDS is given
- Present in about half of refractory anemia cases
- Marrow fibrosis and/or hypocellularity may cause problems with diagnosis
- If present, add to the diagnosis as a modifier
- (i.e. RCUD with fibrosis or hypocellular RCUD)
- 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
