Part 1: Myelodysplastic Syndromes – Laboratory workup to confirm diagnosis Objective This article presents the guidelines on the examinations that are needed to confirm the diagnosis of myelodysplastic syndromes. PICO system Using the PICO system, the P corresponds to patients with suspected myelodysplastic syndrome, I to the indication of examinations, and O to the outcomes (diagnosis). Thus, 38 studies were found and selected to answer the clinical question (. What examinations are needed to confirm the diagnosis of myelodysplastic syndromes? Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell (HSC) clonal diseases resulting from a sequence of acquired genetic alterations with the formation of an anomalous and genetically unstable clone or clones, with potential to evolve to acute myeloid leukemia. So far, there is no single reliable biological or genetic marker for diagnosis. Dysplastic alterations of peripheral blood (PB) and bone marrow (BM) are still fundamental for the diagnosis and classification of this group of diseases.

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The detection of increased blasts facilitates diagnosis of the most advanced phases of the disease; however, in the early phases with minor morphological abnormalities, diagnosis is mainly based on the exclusion of other nonclonal cytopenias and diseases. These clonal disorders may occur at any age, but they are more common in adults, with exponential increases after the 5th decade with a mean age at diagnosis of 70 years. Most patients acquire de novo clonal anomalies, with some acquiring somatic mutations after exposure to genotoxic agents, such as chemotherapy or radiotherapy for other neoplasms. Moreover, aging-associated inflammation (inflammaging) contributes to genetic instability and MDS predisposition. The complete blood count with reticulocyte count and cytomorphological analysis are the vital first steps in the diagnosis of MDS.

Isolated or combined, persistent for at least six months and unexplained cytopenias are common. Anemia, the most common cytopenia, is usually macrocytic, associated with a significant reduction in the reticulocyte count. All other causes of cytopenias/dysplasias should be excluded, as well as other clonal diseases and congenital abnormalities. Subsequently, a morphological analysis of BM cytological smears and an investigation of ring sideroblasts by Perls staining are performed.

BM biopsy is complementary as it allows a better evaluation of the morphology and distribution of megakaryocytes, topography of other lineages, search for lymphoid aggregates and assessment of the degree of fibrosis by a standardized staining procedure. This is followed by classical and molecular cytogenetic analysis and immunophenotyping(D). Bone marrow histology Cellularity, established as the percentage of parenchyma and adipocytes, should be checked by histology allowing the classification of BM as hypocellular, normocellular, or hypercellular. Interpretation should consider the normal range for age. Abnormal distribution of cellularity may occur. Ectopia is the abnormal location of cells: megakaryocytes and erythroblasts in a paratrabecular location, clusters of myeloblasts and/or promyelocytes containing >5 cells in the intertrabecular region of marrow (ALIPs - Abnormal Localization of Immature Precursors). An evaluation of the reticulin network is important, as it has shown prognostic significance.