Definition

• ≥5 iron staining granules (+)
• Encircling at least 1/3 of the nucleus

Diagnostic criteria for significant in MDS are ≥15% ring sideroblasts without evidence (or knowledge) of a SB3F1 mutation.  This threshold drops to ≥5% with a SB3F1 mutation)

Pathobiology

• Ring sideroblasts represent abnormal accumulation of iron in mitochondria.
• In neoplastic conditions, is strongly associated with SB3F1 heterozygous mutations (important for RNA splicing).
  • 80-90% of cases of MDS-RS SLD have SB3F1 mutation
  • 30-70% of cases of MDS-RS MLD have SB3F1 mutation
  • ~20% of MDS/MPN cases have SB3F1 mutation
  • ~25% of all cases of MDS have a SB3F1 mutation
  • The present of a SB3F1 mutation is not “specific” for a disease, but there is a 97.7% positive predictive value of finding ring sideroblasts in patients with a SB3F1 mutation.

Association with hematologic disease

• Multiple hematologic neoplasms may have ringed sideroblasts (following list is not all inclusive)
  • MDS-RS with SLD
  • MDS-RS with MLD
  • MDS with isolated del(5q)
  • Other MDS entities with higher grade features (e.g. MDS-EB, formally RAEB)
  • AML

Non-Neoplastic Etiology of Ring Sideroblasts

• Hereditary sideroblastic anemias
• Drug effect (INH, chloramphenicol, cycloserine)
• Nutritional deficiency (e.g. copper deficiency, which may be secondary to excessive zinc intake)
• Alcohol
• Toxin exposure (e.g. zinc, lead or benzene)

Type of Sideroblasts

• Type 1 – <5 cytoplasmic staining iron granules
• Type 2 – ≥5 cytoplasmic staining iron granules NOT in a perinuclear pattern
• Type 3 – ≥5 iron staining granules encircling at least 1/3 of the nucleus (ring sideroblast)

Photomircographs

References