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ASH Image Bank (2001); doi:10.1182/ashimagebank-2001-100188
Copyright © 2001 by the American Society of Hematology.
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Full Case Study

Myeloid Neoplasms. Myelodysplastic Syndrome: Refractory Ctyopenia with Multilineage Dysplasia

James W Vardiman, M.D.

University of Chicago


Figure 1
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  		Figure 1. Refractory cytopenia with multilineage dysplasia (RCMD). Peripheral blood smear (Wright-Giemsa stain). This composite photograph shows representative fields of the blood smear. Occasional macro-ovalocytes are seen. Some neutrophils have peculiar nuclear segmentation. There is thrombocytopenia. Blasts were not identified in the blood smear.

 

Figure 2
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  		Figure 2. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow biopsy (H & E stain). The bone marrow biopsy specimen shows normally cellular bone marrow.

 

Figure 3
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  		Figure 3. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow biopsy (H & E stain). The biopsy demonstrates erythroid hyperplasia. Immature erythroid precursors (arrows) have round to oval vesicular nuclei, a prominent, comma-shaped nucleolus that often is close to the nuclear membrane, and a rim of amphophilic cytoplasm. Erythroid precursors that are more mature (double arrows) have homogenous, darkly-stained nuclei.

 

Figure 4
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  		Figure 4. Refractory cytopenia with multilineage

 

Figure 5
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  		Figure 5. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow biopsy (H&E stain). This photomicrograph illustrates an abnormally small megakaryocyte with hypolobated nucleus. Note the dense, pink-staining cytoplasm.

 

Figure 6
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  		Figure 6. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow aspirate smear (Wright-Giemsa stain). This composite illustrates typical fields from the bone marrow aspirate. In the photograph on the left side, the arrows point to dyspoietic erythroid precursors, with abnormally shaped nuclei. In the photograph on the right, an abnormal neutrophil with a hypolobated nucleus is seen at the arrow, and an abnormal megakaryocyte is also present (double arrow). More than 30% of the erythroid precursors and over one-half of the megakaryocytes in the specimen were dysplastic. Relatively few (~10%) of the neutrophils show abnormalities. Note that there is no increase in the number of blasts, which totaled 3% in a 500-cell differential performed on the aspirate smear.

 

Figure 7
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  		Figure 7. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow aspirate smear (Wright-Giemsa stain). In the left panel of this figure, abnormal megakaryocytes that are small with hypolobated nuclei are seen. In the right panel, some dysplastic erythroid precursors are noted. A single blast with a few fine azuorphil granules is seen (arrow).

 

Figure 8
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  		Figure 8. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow aspirate smear (Iron stain). No ringed sideroblasts were noted on the iron stain.

 

Figure 9
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  		Figure 9. Refractory cytopenia with multilineage dysplasia (RCMD). Bone marrow aspirate smear (Wright-Giemsa stain). This composite of an aspirate smear is from a different patient, but also illustrates multilineage dysplasia. Hypogranular neutrophils (arrows) and an abnormal, small megakaryocyte (double arrows) are readily appreciated.

 

Figure 10
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  		Figure 10. Refractory cytopenia with multilineage dysplasia (RCMD). Cytogenetic preparation. The karyotype performed from bone marrow cells was: 46, XY [80%] 46, XY, del (5q)(q11q33), del (7q)(q11q36) [20%].

 

   Clinical Summary
TOP
 Clinical Summary
Diagnosis
 Discussion
 Differential Diagnosis
 
This 65 year old man presented with gradual onset of fatigue and shortness of breath. A CBC showed WBC=2.0 x 109/L, with 40% neutrophils, Hb=7.2g/dl, and platelets=49 x 109/L. The patient gave no history of drug or alcohol abuse, and was on no medications. Studies for B12, serum folate and serum ferritin were normal. A bone marrow biopsy and aspiration were performed, and a specimen was submitted for cytogenetic analysis. He has had no improvement in his blood counts after a 6 month period of observation.

Sex
Male

Age
65

Ethnicity
n/a


   Diagnosis
TOP
 Clinical Summary
 Diagnosis
Discussion
 Differential Diagnosis
 
Myelodysplastic Syndrome (MDS), Refractory Cytopenia with Multilineage Dysplasia


   Discussion
TOP
 Clinical Summary
 Diagnosis
 Discussion
Differential Diagnosis
 
Definition of RCMD (WHO): Refractory cytopenia with multilineage dysplasia (RCMD) is a myelodysplastic syndrome (MDS) with bi- or pancytopenia, and dysplastic changes in 10% or more of the cells in two or more myeloid cell lines (granulocytes, erythroid, and/or megakaryocytes). There are < 1% blasts in the blood and less than 5% blasts in the bone marrow. Auer rods are not present and monocytes in the blood are < 1 x 10^9/L. If ringed sideroblasts are more than 15% of the erythroid precursors, the designation of Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) should be made.

Synonyms: Myelodysplastic syndrome, unclassifiable (FAB). Some cases may have been previously included in the FAB subgroups of refractory anemia or refractory anemia with ringed sideroblasts.

Epidemiology: Occurs mainly in older individuals. It accounts for approximately 20-30% of all cases of MDS.

Etiology: The etiology of primary (de novo) RCMD is unknown. A history of exposure to toxins, such as benzene, pesticides, and other chemicals has been correlated with an increased incidence of MDS in some populations examined. Cigarette smoking increases the risk by about two-fold. A significant number of patients who have therapy-related MDS may initially present with the features of RCMD.

Clinical features: Most patients present with symptoms related to one or more of the cytopenias.

Morphology: The diagnosis of RCMD can be made when blasts account for fewer than 1% of the white cells in the blood, and monocytes are < 1 x 10^9/L. In the bone marrow, blasts number fewer than 5% of the marrow cells, and Auer rods are not found. Dysplastic changes are present in >10% of the cells in two or more myeloid cell lines. The dysplasia is often marked in one or more of the lineages. Neutrophils in the blood and/or bone marrow may hypogranulation of their cytoplasm or nuclear abnormalities, including nuclear hyposegmentation (pseudo Pelger-Huet change), bizarrely segmented nuclei, and hypercondensation of nuclear chromatin. Erythroid precursors in the bone marrow can show cytoplasmic vacuoles, nuclear irregularity with multilobation, multinucleation, and megaloblastoid nuclei. If ringed sideroblasts are not seen or account for fewer than 15% of the erythroid precursors, the designation of RCMD is made. If 15% or more of the erythroid precursors are ringed sideroblasts, the diagnosis is RCMD-RS. Megakaryocytic abnormalities may include hypolobulation of nuclei, widely separated nuclear lobes, and/or micromegakaryocytes.

Genetics: Clonal chromosomal abnormalities are found in nearly one-half of the patients, and may include +8, del(7/7q), del(20q), del(5/5q), as well as complex abnormalities.

Clinical Outcome: The median survival times reported for patients with RCMD has varied from approximately 20 to 35 months. Patients may progress to higher grades of MDS, or to overt acute myeloid leukemia, but many will die of complications of their bone marrow failure.


   Differential Diagnosis
TOP
 Clinical Summary
 Diagnosis
 Discussion
 Differential Diagnosis
 
The differential diagnosis includes secondary, non-clonal causes of multilineage dysplasia that may occur in a number of disorders, including HIV-related disease, heavy metal (particularly arsenic) poisoning, and after therapy with some cytotoxic drugs and cytokines. However, the major differential diagnoses of RCMD is with other myelodysplastic syndromes, particularly RA, RARS, and RAEB-1. The distinguishing features between these entities are listed in Table 2 above. In addition, the Myelodysplastic/Myeloproliferative disease, Chronic myelomonocytic leukemia (CMML)


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Related ASH-SAP Chapter:space logo
Chapter 9: Myelodysplastic syndrome and overlap syndromes

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PubMed
Right arrow Articles by Vardiman, J. W
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Right arrow Myelodysplastic Syndromes
Right arrow Related ASH-SAP Chapter
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Copyright © 2001 by the American Society of Hematology.