Digital image analysis of erythroblastic islands in myelodysplastic syndromes.

Abstract

Myelodysplastic syndromes (MDS) encompass a diverse group of myeloid neoplasms for which the diagnosis of low-grade subtypes remains challenging. Erythroblastic islands (EBIs) are highly organized units of erythroid proliferation, differentiation, and enucleation. EBI disruption is frequently observed and is believed to be one of the early changes in MDS. In this study, we digitally analyzed bone marrow biopsies dual stained with alpha-hemoglobin stabilizing protein (AHSP) and CD163 to quantitatively study features of EBIs in MDS, among MDS subtypes, as well as those in normal marrows and marrows with other causes of anemia. EBIs in MDS specimens were smaller in size and higher in density compared to both normal and non-MDS anemia specimens. Increased CD163 expression within the EBIs is observed in both MDS and other causes of anemia. A combination of increased EBI density and CD163 expression is seen in association with MDS with high-risk cytogenetics and multiple adverse mutations. As a proof-of-concept study, we show that EBI features can be relatively easily quantified with AHSP/CD163 dual immunohistochemistry and open-source imaging analysis software, highlighting those that are unique to MDS, and which may be prognostically relevant. Further studies of the measurable EBI features may provide valuable and novel tools to aid MDS diagnosis and prognostication in the era of digital pathology.