Myelodysplastic Syndrome Diagnosis and Management

Diagnostic Criteria

• The presence of increased poikilocytosis, anisocytosis, and burr cells on peripheral blood smear strongly suggests a myelodysplastic syndrome (MDS) and requires bone marrow examination with cytogenetic analysis for definitive diagnosis and risk stratification, as recommended by the American Society of Hematology 1, 2
• Bone marrow aspirate and biopsy are essential to evaluate cellularity, dysplasia in one or more hematopoietic cell lines, blast percentage, ring sideroblasts, and fibrosis, according to the American Society of Hematology 2
• Cytogenetic analysis is crucial for detection of acquired clonal chromosomal abnormalities and has the highest prognostic value in MDS, as stated by the International Society for Experimental Hematology and ESMO 1, 2

Differential Diagnosis

• Anisocytosis and poikilocytosis can be seen in various hematologic disorders, including iron deficiency, which typically has low serum ferritin (<30 μg/L without inflammation), as noted by the European Crohn’s and Colitis Organisation 3
• Chronic hemolysis with increased reticulocyte count, LDH, and bilirubin can present with anisocytosis and poikilocytosis, and is characterized by echinocytes (3-30%), particularly after splenectomy, as described by the American Society of Hematology 4
• Other conditions such as lymphoma, sarcoidosis, hemochromatosis, and amyloidosis can cause infiltration of hematopoietic tissues, leading to the presence of teardrop cells, as recommended by the American College of Physicians and the American Academy of Ophthalmology 5

Management

• High-risk MDS can be treated with hypomethylating agents (azacitidine or decitabine) and consideration for allogeneic stem cell transplantation in eligible patients, as recommended by the European Society for Medical Oncology 1
• Treatment of underlying causes, such as iron deficiency or vitamin deficiencies, is essential, and supportive care with transfusions, splenectomy in severe cases, and monitoring for complications like iron overload and gallstones may be necessary for pyruvate kinase deficiency, as noted by the American Society of Hematology 4
• Basophilic stippling is a morphological finding in red blood cells associated with various pathological conditions, including myelodysplastic syndromes and hemolytic anemias, and represents a characteristic feature of erythroid dysplasia, as noted by the American Society of Hematology and ESMO 2, 6
• When basophilic stippling or teardrop cells are identified on a peripheral blood smear, further evaluation should include a complete blood count, thorough peripheral blood smear examination, and bone marrow examination in cases suspicious for myelodysplastic syndromes or other hematological disorders, as recommended by the National Comprehensive Cancer Network and ESMO guidelines 2, 5, 1
• Molecular testing should be performed to evaluate for mutations associated with myeloid disorders, such as DNMT3A, ASXL1, TET2, JAK2, and TP53, to help distinguish between different myeloid disorders, according to ESMO guidelines 1
• Risk stratification using IPSS-R score should be performed, and treatment should be based on risk category and patient factors, as recommended by ESMO for patients with myelofibrosis or MDS 1
• Consideration should be given to JAK inhibitors for myelofibrosis, and hypomethylating agents for higher-risk MDS, as recommended by ESMO 1