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 Diagnosis

  1. Upon discussion with the hematologist, you learn that the patient has a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) and has frequent epistaxis as a cause of his anemia. The findings of erythroid predominance and dysplasia in the marrow are therefore interpreted as secondary changes due to the frequent and significant bleeding episodes. The single DNMT3A variant is likely an incidental CHIP mutation in the absence of evidence of primary myelodysplasia or other clonal abnormalities.

  2. The presence of a known inherited cause for anemia (β-thalassemia) and microcytosis tended to discourage a diagnosis of MDS in this patient. Patients with β-thalassemia often show erythroid hyperplasia and may exhibit dyserythropoiesis and even ring sideroblasts on bone marrow examination.[38] Subsequent review of the patient's chart documented that he had been anemic for at least 5 years. However, longitudinal examination of CBC parameters showed that the patient had recently developed worsening of his anemia coincident with a rising MCV Figure 2; thus, although the patient's anemia was microcytic, it was actually macrocytic relative to his baseline MCV. Finally, although the del(20q) cytogenetic abnormality can be seen in non-MDS conditions, the SF3B1 mutation favors a neoplastic etiology for the ring sideroblasts. The comprehensive morphologic, clinical, and genetic data, in the clinical context of worsening unexplained anemia in a patient with lifelong β-thalassemia minor, lead to a final pathologic diagnosis of MDS with ring sideroblasts and single-lineage dysplasia.

Figure 2.

Graph of mean corpuscular volume (MCV) (A) and hemoglobin (B) levels over time in the patient from case 2. The patient has chronic microcytic anemia (due to β-thalassemia minor), which more recently has worsened and become less microcytic, due to the development of myelodysplastic syndrome. *A transient drop in hemoglobin and rise in MCV was due to surgery at this time point.