Figure - available from: Annals of Hematology
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The bone marrow was hypercellular for age (a, × 20 magnification) and showed scattered hypolobated megakaryocytes and myeloid left shifted (b, × 40 magnification). A CD34 stain highlighted up to 10–12% blasts (c, × 40 magnification). Erythroid dysplasia including megaloblastoid changes, binucleation, and nuclear irregularities were noted on the aspirate (d, 100× magnification)
Source publication
In patients suspected to have myelodysplastic syndrome (MDS), especially in those patients without cytogenetic abnormalities or blast excess, accurate morphologic review by an expert hematopathologist and meticulous exclusion of other secondary causes of myelodysplasia are vital to establish the diagnosis. Errors in diagnosis can lead to dangerous...
Citations
... Chronic smoking is also associated with leukocytosis and right-shifted myelopoiesis (neutrophilia). Both smoking and chronic alcoholism are known to cause dysgranulopoiesis and are putative risk factors for the development of MDS.38 ...
Dysgranulopoiesis is a condition in which granulocytic production is defective and is most often described in neoplastic conditions. However, it can also be frequently seen in non‐neoplastic conditions. Early suspicion and detection of these non‐neoplastic causes may prevent further invasive and expensive interventions. In this review, we take a look at the various causes of dysgranulopoiesis with an emphasis on non‐neoplastic etiologies, followed by a detailed outline of the laboratory approach for determining its many causes.
... Accurate peripheral blood and marrow blast percentage measurement is critical to diagnosis, which can differentiate CMML from AMML and the different categories of CMML from each other (e.g., CMML-0 vs. CMML-1 vs. CMML-2); this can be accomplished by manual cell count or flow cytometric analysis. In addition to persistent monocytosis without with a clear cause, the presence of circulating immature monocytic or other myeloid forms, peripheral leukocyte or erythroid dysplasia in the absence of a secondary cause [36], or concurrent cytopenias/thrombocytosis all provide evidence of an underlying myeloid malignancy and the ultimate consideration as a peripheral blood AMC ≥ 1000 cells/μL and ≥ 10% monocytes for ≥ 3 months but proceed with evaluation if criteria not met, but concurrent constitutional symptoms/signs, splenomegaly, cytopenias, peripheral blood blasts present. †Consider monocyte partitioning to increase specificity for the diagnosis Curr Hematol Malig Rep for a bone marrow evaluation. ...
Purpose of Review
In this review, we provide a comprehensive and contemporary understanding of malignant monocytosis and provide a framework by which the appropriate diagnosis with malignant monocytosis can be rendered.
Recent Findings
Increasing data support the use of molecular data to refine the diagnostic approach to persistent monocytosis. The absence of a TET2, SRSF2, or ASXL1 mutation has ≥ 90% negative predictive value for a diagnosis of CMML. These data may also reliably differentiate chronic myelomonocytic leukemia, the malignancy that is most associated with mature monocytosis, from several other diseases that can be associated with typically a lesser degree of monocytosis. These include acute myelomonocytic leukemia, acute myeloid leukemia with monocytic differentiation, myelodysplastic syndromes, and myeloproliferative neoplasms driven by BCR-ABL1, PDGFRA, PDGFRB, or FGFR1 rearrangements or PCM1-JAK2 fusions among other rarer aberrations. The combination of monocyte partitioning with molecular data in patients with persistent monocytosis may increase the predictive power for the ultimate development of CMM but has not been prospectively validated.
Summary
Many conditions, both benign and malignant, can be associated with an increase in mature circulating monocytes. After reasonably excluding a secondary or reactive monocytosis, there should be a concern for and investigation of malignant monocytosis, which includes hematopathologic review of blood and marrow tissues, flow cytometric analysis, and cytogenetic and molecular studies to arrive at an appropriate diagnosis.
... The initial evaluation of anemia in MDS should seek to identify alternative etiologies for the anemia such as iron deficiency, nutrient deficiencies, hypothyroidism, renal disease, or gastrointestinal bleeding. 27 Copper deficiency should be considered, especially in patients with a history of gastrointestinal surgery or zinc supplementation, as this can lead to hematologic abnormalities that are very similar to MDS and which may resolve completely with supplementation alone. 28,29 It is also important to assess for symptoms, as asymptomatic low-risk patients without any significant cytopenias can undergo active surveillance alone with deferred treatment. ...
For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to alleviate the symptoms associated with the resultant cytopenias and to minimize the transfusion burden. While supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or will eventually develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Several additional therapeutics are now available in select patients with LR-MDS and symptomatic anemia including luspatercept, lenalidomide, and immunosuppressive therapy. Furthermore, several novel agents are currently in development to address this area of clinical need such as imetelstat and roxadustat. In this article, we review the currently available therapeutic options for symptomatic anemia in LR-MDS as well as review the therapeutic agents in development.
... be recognized that there are a wide variety of causes of secondary morphologic dysplasia, including infections, medications, nutritional deficiencies, toxins, bone marrow lymphomas and plasma cell neoplasms, and autoimmune diseases, and this list continues to grow ❚Table 2❚. 12 Possible secondary causes of cytopenia and dysplasia should be excluded prior to making a definitive diagnosis of MDS, through careful clinical examination of the clinical history and laboratory parameters. ...
Objectives:
Myelodysplastic syndromes (MDS) are a group of myeloid neoplasms that are often difficult to diagnose due to their pathologic and clinical heterogeneity. The key features of MDS are peripheral blood cytopenias, ineffective hematopoiesis manifesting as morphologic dysplasia, and clonal genetic abnormalities. The most difficult diagnostic dilemmas often arise in low-grade MDS cases (lacking excess blasts), which can be difficult to distinguish from other causes of cytopenia. This distinction requires the integration of information from the peripheral blood (both CBC parameters and morphology), bone marrow morphology, genetic studies, and interrogation of the clinical record to exclude secondary causes.
Methods:
We discuss the approach to the diagnosis of low-grade MDS (cases lacking increased blasts), including a diagnostic algorithm and two illustrative cases.
Results:
The appropriate use of ancillary studies is important to support or dispute the likelihood of low-grade MDS in conjunction with the findings of morphologic dysplasia. Interpreting the results of cytogenetics and next-generation sequencing can be challenging and must incorporate the emerging knowledge of clonal hematopoiesis of indeterminate potential.
Conclusions:
The role of pathologists in integrating data from multiple sources in the diagnosis of low-grade MDS is evolving and becoming increasingly complex; in this challenging diagnostic setting, it is important to feel comfortable with uncertainty and maintain a conservative approach.
The clinicopathology of MDS and MPN are not mutually exclusive and for this reason the category of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) exists. Several sub-entities have been included under the MDS/MPN umbrella, including MDS/MPN-unclassifiable (MDS/MPN-U) for those cases whose morphologic and clinical phenotype do not meet criteria to be classified as any other MDS/MPN sub-entity. Though potentially regarded as a wastebasket diagnosis, since its integration into myeloid disease classification, MDS/MPN-U has been refined with increasing understanding of the mutational and genomic events that drive particular clinicopathologic phenotypes, even within MDS/MPN-U. The prototypical example is the identification of SF3B1 mutations and its durable association with MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), an entity previously buried within, but now a separate category outside of MDS/MPN-U. Continued and enhanced study of those entities under MDS/MPN-U, a perhaps provisional category itself, is likely to progressively identify commonality between many “unclassifiables” to establish a new classifiable diagnosis.
