Bone marrow neoplastic

• Microscopic criteria
  • Characterized by cytopenias (1 - 2 MDS RS SLD, 1 - 3 MDS RS MLD)
  • Ring sideroblasts and morphological dysplasia (1 lineage [erythroid] or 2 - 3 lineages), often with concomitant SF3B1 mutations
  • In the absence of SF3B1 mutations, ≥ 15% ring sideroblasts are needed, whereas > 5% ring sideroblasts are required for diagnosis in the presence of SF3B1 mutations
  • Ring sideroblasts are erythroid precursors with ≥ 5 iron granules encircling one - third or more of the nucleus (Haematologica 2008;93:1712)
  • Lacks Auer rods, < 5% bone marrow blasts, < 2% peripheral blood blasts
• Bone marrow histology
  • Cellularity
    • Hypercellular or normocellular marrow
  • Erythropoiesis
    • Erythroid hyperplasia (with mild to moderate dysplasia, including irregular nuclear contours, nuclear budding, megaloblastic change)
  • Myelopoiesis
    • Myeloblasts < 5% (or call MDS with excess blasts)
  • Megakaryopoiesis
    • Normal numbers and morphology (in SLD)
  • In addition to the presence of ring sideroblasts, erythroid hyperplasia and dysplasia, > 10% dysplastic cells in other lineages (myeloid or megakaryocyte) noted in multilineage dysplasia subtype
  • Increased storage iron
• References: Mediterr J Hematol Infect Dis 2015;7:e2015035, Blood 2016;127:2391

Contributed by Cecilia C.S. Yeung, M.D.

AFIP images

AFIP images

Bone marrow aspirate with iron stain is shown in the image above. Which molecular alteration is most commonly observed in patients who have myelodysplastic syndrome (MDS) with this histologic feature?

1. Isolated del 5q
2. JAK 617F mutation
3. Monosomy 7
4. SF3B1 mutation

D. SF3B1 mutation. SF3B1 mutations are associated with ringed sideroblasts in almost 90% of cases. Answer A is incorrect because isolated del 5q may or may not be associated with ring sideroblasts and these MDS cases are classified as MDS with 5q deletion irrespective of ring sideroblasts. Answer B is incorrect because JAK 617F mutation is frequently associated with myeloproliferative neoplasms like polycythemia vera and essential thrombocytosis; however, some cases of myelodysplastic / myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis can have JAK2 V617F comutation and these cases show the presence of ring sideroblasts. Answer C is incorrect because MDS with monosomy 7 is not usually associated with ring sideroblasts.

Comment Here

Reference: MDS with mutated SF3B1

Which of the following statements is true regarding myelodysplastic syndrome (MDS) with ring sideroblasts?

1. MDS with mutated SF3B1 has poor disease outcomes as compared to other subtypes of MDS
2. Presence of excess blasts has a worse prognosis, even in the presence of SF3B1 mutation
3. Presence of ring sideroblasts is an essential diagnostic requirement for MDS with mutated SF3B1
4. Ring sideroblasts as well as SF3B1 mutation are not detected in other MDS types or other myeloid neoplasms

B. Presence of excess blasts has a worse prognosis, even in the presence of SF3B1 mutation. The favorable outcome associated with SF3B1 mutation is lost as soon as an excess of blasts is observed. Answer C is incorrect because the presence of ring sideroblasts is not a diagnostic requirement if SF3B1 mutation is present at allele fraction > 35%. Ring sideroblasts are seen in more than 90% of these cases; however, if SF3B1 is not available, > 15% ring sideroblasts are required for diagnosis of MDS with low blasts and ring sideroblasts. Answer A is incorrect because MDS with low blasts and SF3B1 mutation has a better prognosis than other MDS types with low blasts. Answer D is incorrect because ring sideroblasts as well as SF3B1 mutation can be detected in other MDS types or other myeloid neoplasms, including acute myeloid leukemia and MDS with increased blasts. Cases that fulfill the criteria for MDS with low blasts and 5q deletion should be classified as such, even if ring sideroblasts or SF3B1 mutation are identified. In patients who present with thrombocytosis, detection of SF3B1 mutation concurrently with JAK2 p.V617F, CALR or MPL mutations qualifies for a diagnosis of myelodysplastic / myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis.

Comment Here

Reference: MDS with mutated SF3B1