Fibrotic marrow limiting morphologic classification in MDS/MPN with SF3B1 mutation and thrombocytosis: diagnostic implications under the ICC 2022 framework

Myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) is a genetically defined overlap entity integrating morphologic and molecular features. Assessment of ring sideroblasts may be unreliable in fibrotic marrows, creating diagnostic uncertainty under morphology-dependent systems. A 76-year-old man presented in 2021 with anemia, thrombocytosis, and splenomegaly. Bone marrow biopsy showed a hypercellular marrow with atypical megakaryocytic proliferation and MF-2 fibrosis; aspirate was a dry tap, precluding evaluation of ring sideroblasts. Next-generation sequencing identified JAK2 p.V617F (variant allele frequency 6.9%), SF3B1 p.D781G (16.5%), NRAS p.G12D (5.2%) and ASXL1 p.E635Rfs*15 (33%). Although findings strongly suggested MDS/MPN with ring sideroblasts and thrombocytosis, WHO 2017 criteria could not be met. After ruxolitinib therapy, he later developed leukocytosis and 2% circulating blasts. Repeat marrow demonstrated ≥ 15% ring sideroblasts. Retrospectively, the initial biopsy fulfills ICC 2022 criteria for MDS/MPN-SF3B1-T, highlighting the diagnostic value of genetics-integrated classification in fibrotic marrows.