What Diagnostic Tests Are Needed for Myelodysplastic Syndromes?

Diagnosing myelodysplastic syndromes (MDS) requires a comprehensive approach that combines several laboratory and clinical assessments. Early and accurate detection is crucial for effective treatment planning and long-term management. Physicians rely on a combination of blood tests, bone marrow evaluations, and genetic analyses to confirm MDS and differentiate it from other blood disorders with similar symptoms.

Complete Blood Count and Reticulocyte Analysis

A complete blood count (CBC) is typically the first step in evaluating potential MDS. This test measures levels of red blood cells, white blood cells, and platelets. Patients with MDS often show persistent cytopenias—low counts in one or more blood cell lines. Additionally, reticulocyte counts are assessed to evaluate the bone marrow's ability to produce new red blood cells. In MDS, reticulocyte levels are usually low, indicating inadequate compensatory production despite anemia.

Bone Marrow Examination: The Core of MDS Diagnosis

The definitive diagnosis of MDS hinges on a thorough bone marrow evaluation. This includes two key components:

Bone Marrow Aspiration and Morphological Assessment

During this procedure, a sample of liquid bone marrow is extracted, typically from the hip bone. A hematopathologist examines the cells under a microscope to identify dysplasia—abnormal shapes, sizes, or maturation patterns—in red blood cells, white blood cells, and megakaryocytes. Dysplasia in at least 10% of cells in one or more lineages supports an MDS diagnosis.

Bone Marrow Biopsy and Histopathology

A biopsy provides a tissue sample to assess the overall architecture of the bone marrow. It helps determine cellularity (whether the marrow is hypercellular or hypocellular) and detect abnormal cell clustering, such as micromegakaryocytes or increased blasts—immature blood cells. The presence of excess blasts (5–19%) is a critical diagnostic and prognostic factor.

Cytogenetic and Molecular Testing

Genetic analysis plays a vital role in confirming MDS and guiding prognosis. Two primary methods are used:

Karyotype Analysis: This test examines chromosomes in bone marrow cells for deletions, translocations, or duplications. Common abnormalities in MDS include deletions in chromosomes 5, 7, or 20q, and trisomy 8. These findings help classify the subtype of MDS and predict disease progression.

Fluorescence In Situ Hybridization (FISH): FISH targets specific genetic mutations associated with MDS, offering higher sensitivity than standard karyotyping, especially when abnormal cells are scarce. It can detect changes not visible under routine microscopy, improving diagnostic accuracy.

Serum Biochemical and Nutritional Assessments

To rule out conditions that mimic MDS, doctors test serum levels of vitamin B12 and folate. While deficiencies in these nutrients cause megaloblastic anemia—a disorder with abnormal red blood cell development—patients with true MDS typically have normal or even elevated levels. Distinguishing between these conditions is essential to avoid misdiagnosis and inappropriate treatment.

Erythropoietin (EPO) Level Testing

Serum erythropoietin levels are measured to evaluate the body's hormonal response to anemia. In some MDS patients, EPO levels are inappropriately low relative to the degree of anemia, which may influence treatment decisions, including the use of erythropoiesis-stimulating agents. This test helps tailor therapy based on individual patient profiles.

Iron Studies and Ferritin Evaluation

Assessing iron stores through serum ferritin, transferrin saturation, and iron-binding capacity is important, especially in patients requiring frequent blood transfusions. Chronic transfusion therapy can lead to iron overload, which damages organs like the heart and liver. Monitoring ferritin levels helps guide chelation therapy to prevent complications.

In summary, diagnosing myelodysplastic syndromes involves a multifaceted strategy combining hematology, pathology, and genetics. Accurate testing not only confirms MDS but also informs risk stratification and personalized treatment plans, ultimately improving patient outcomes.