How I Diagnose Low-grade Myelodysplastic Syndromes

Alexa J. Siddon, MD; Robert P. Hasserjian, MD


Am J Clin Pathol. 2020;154(1):5-14. 

In This Article

Case Presentations

Case 1

A 68-year-old man who recently moved to the area was referred to a local hematologist with isolated anemia (hemoglobin [Hb], 8.1 g/dL [reference range (RR), 12.0–18.0]; mean corpuscular volume [MCV], 95.1 fL [RR, 78.0–94.0]). He had had anemia for years, which was observed without treatment, but recently it worsened, and he had been receiving treatment with epoetin alfa. Because the anemia continued to be significant, a diagnosis of myelodysplastic syndrome (MDS) was being considered. A bone marrow biopsy and aspirate were performed, which showed a hypercellular, erythroid predominant marrow with dyserythropoiesis Image 1, including megaloblastoid changes, nuclear budding, and irregular nuclear contours but no ring sideroblasts on an iron stain. The myeloid and megakaryocyte lineages were morphologically unremarkable. There was no increase in blasts morphologically or by flow cytometry. Conventional cytogenetics showed a normal male karyotype in 20 metaphases. A next-generation sequencing (NGS) panel revealed a single pathogenic DNMT3A variant found at 4% variant allelic frequency.

Image 1.

Case 1 aspirate smear (Wright-Giemsa, ×100) showing an erythroid-predominant marrow with scattered dysplastic erythroid precursors (arrows).

Case 2

An 84-year-old man was referred to a hematologist for symptomatic isolated anemia (Hb, 7.3 g/dL [RR, 13.5–17.5]; MCV, 76.9 fL [RR, 80.0–100.0]). Iron studies were normal. The patient reported that he had a history of anemia but new onset of fatigue. A bone marrow biopsy and aspirate were performed, which showed a hypercellular marrow for age with erythroid predominance, left shift, and significant dyserythropoiesis manifesting as nuclear irregularities Image 2. No dysplasia was seen in granulocytes or megakaryocytes, but an iron stain on the bone marrow aspirate showed ring sideroblasts comprising 25% of erythroid elements. Subsequent to the bone marrow biopsy, results of hemoglobin electrophoresis came back showing elevated hemoglobin A2 of 5.4% (RR, 2.0%-3.3%) and hemoglobin F of 2.7% (RR, 0%-0.9%), consistent with β-thalassemia. Conventional cytogenetics showed an abnormal 46, XY, del(20)(q11.2q13.3) karyotype in 18 of 20 metaphases. An NGS panel revealed a single pathogenic SF3B1 variant found at 8% variant allelic frequency.

Image 2.

Case 2 bone marrow images. A, The bone marrow biopsy (H&E, ×20) is hypercellular for the patient's age, with erythroid predominance and normal-appearing megakaryocytes. B, The aspirate smear shows many dysplastic erythroid precursors with nuclear irregularities (arrows) (Wright-Giemsa, ×100). C, On the iron-stained aspirate smear, ring sideroblasts are present (×100).