Diagnostic Performance of Initial Bone Marrow Assessment in Cytopenia: Comparison with a Genetically Informed Multidisciplinary Tumour Board Diagnosis

Background: Unexplained cytopenia represents a common diagnostic challenge in clinical haematology, reflecting either benign conditions or early manifestations of myeloid neoplasms. Methods: In this retrospective cross-sectional study, we analysed 557 patients with cytopenia who underwent initial diagnostic evaluation. The diagnostic performance of the initial morphological assessment of the bone marrow and ancillary studies excluding genetic analyses was evaluated against a genetically supported reference diagnosis established by a multidisciplinary haematology tumour board. We examined the extent to which the initial morphological assessment could reliably detect or rule out myeloid neoplasia. The analysis was performed for the entire cohort and stratified by specific myeloid neoplasm entities. Results: In the overall cohort, the initial morphological assessment of the bone marrow showed high diagnostic performance (sensitivity, 0.864; specificity, 0.934). The misclassification analysis revealed more false negatives than false positives (31 vs. 21), with no significant asymmetry. In the entity-specific analysis, a sensitivity of 1.0 was observed for acute myeloid leukaemia, with a reduced specificity (0.400). Myelodysplastic neoplasms exhibited a higher rate of false-negative findings, whereas myelodysplastic/myeloproliferative overlap neoplasms were characterised by very high sensitivity (0.982) and limited specificity (0.632). A comparable diagnostic pattern was observed for myelofibrotic neoplasms. Conclusions: Initial morphological assessment demonstrates high overall diagnostic performance in cytopenia but shows important variation across individual entities. These findings highlight the need to consider entity-specific limitations and the role of genetic confirmation in the diagnostic work-up of specific entities.