Myelodysplastic Syndromes (MDS) represent a group of disorders where the bone marrow fails to produce enough healthy, mature blood cells. The diagnosis of this condition is complex, requiring a multi-step process that moves from initial suspicion based on simple blood work to definitive confirmation using specialized analysis of bone marrow tissue. MDS is characterized by ineffective hematopoiesis, meaning the stem cells in the marrow are abnormal and produce dysfunctional blood cells, which leads to low counts of one or more cell types in the circulation. Establishing the exact disease profile is necessary for proper management and risk assessment, as MDS is considered a type of cancer.
Recognizing the Initial Warning Signs
The first indication of a potential problem often emerges from routine medical testing. Many individuals with MDS initially experience non-specific symptoms related to the shortage of mature blood cells. Fatigue, weakness, and shortness of breath are common due to anemia (low red blood cell count). A decrease in white blood cells, known as neutropenia, can lead to frequent infections. Low platelet counts, or thrombocytopenia, manifest as easy bruising, bleeding gums, or tiny red spots on the skin called petechiae. These generalized symptoms typically prompt a healthcare provider to order a Complete Blood Count (CBC) test, which is the first objective step in the diagnostic pathway.
The CBC provides a detailed snapshot of the cells circulating in the blood and ultimately raises the suspicion of MDS. It typically reveals cytopenias, which are abnormally low levels of one, two, or all three major blood cell lines. For instance, a common finding is macrocytic anemia, where the red blood cells are larger than normal. The finding of unexplained, persistent cytopenias, especially when other causes like vitamin deficiencies are ruled out, necessitates a deeper investigation into the bone marrow.
The Essential Bone Marrow Assessment
The definitive diagnosis of Myelodysplastic Syndrome requires a direct examination of the bone marrow, accomplished through a bone marrow aspiration and a biopsy. These two procedures are typically performed together, often from the back of the hipbone (posterior iliac crest), and are the central step in confirming the disease. The aspiration uses a thin, hollow needle to draw out a small amount of the liquid marrow, while the biopsy removes a small, solid piece of the bone containing the marrow tissue.
The samples are sent to a specialized laboratory for analysis by a pathologist. The liquid aspirate is primarily used to evaluate cellular morphology, assessing the shape and appearance of the developing blood cells under a microscope. The pathologist looks for signs of dysplasia—abnormal development—in the red cells, white cells, and megakaryocytes (platelet precursors), which is a characteristic feature of MDS.
The solid biopsy core provides complementary information, allowing the pathologist to assess the overall cellularity of the marrow (the ratio of blood-forming cells to fat cells). Both the aspirate and the biopsy are used to determine the percentage of blasts, which are immature, early-stage blood cells. A finding of less than 20% blasts in the bone marrow is required for an MDS diagnosis; a count of 20% or more typically signifies progression to acute myeloid leukemia (AML).
Advanced Lab Testing for Disease Classification
After the bone marrow sample is secured, specialized laboratory techniques are employed to analyze the cells’ genetic material for precise disease classification and risk assessment.
Cytogenetics
Cytogenetics involves examining the chromosomes within the dividing bone marrow cells, often performed through conventional karyotyping or Fluorescence In Situ Hybridization (FISH). This analysis searches for structural changes such as deletions, translocations, or additions of entire chromosomes. About half of all MDS patients show a chromosomal abnormality, with common findings including the loss of a part of the long arm of chromosome 5 (del(5q)), the loss of chromosome 7, or an extra copy of chromosome 8 (trisomy 8). These specific chromosomal changes are diagnostic indicators and factor into the patient’s prognosis.
Molecular Testing
Molecular or Genetic testing is an essential layer of analysis, which uses technology like Next-Generation Sequencing (NGS) to detect specific gene mutations. These tests identify somatic mutations in genes such as TET2, ASXL1, and SF3B1, which drive the development and progression of MDS. Molecular testing is highly sensitive and can detect abnormalities even when the chromosomes appear normal, providing deeper insight into the underlying biology of the disease. The results from both cytogenetics and molecular analysis define the specific molecular fingerprint of the individual’s MDS.
Determining MDS Subtype and Risk Level
The final stage integrates all data from the CBC, bone marrow morphology, cytogenetics, and molecular testing to classify the disease and predict its likely course. The World Health Organization (WHO) classification system categorizes MDS into distinct subtypes based on the degree of dysplasia, the percentage of blasts, and the presence of specific genetic abnormalities. This classification defines the biological nature of the disease and guides initial treatment decisions.
To assess the patient’s prognosis, the Revised International Prognostic Scoring System (IPSS-R) is widely used. This system assigns a score by weighting five factors: the percentage of blasts, the type of cytogenetic abnormality, and the degree of cytopenia in all three peripheral blood cell lines. The IPSS-R stratifies patients into five risk groups, providing an estimate of survival and the likelihood of transformation into acute myeloid leukemia (AML). A newer tool, the International Prognostic Scoring System-Molecular (IPSS-M), further refines this assessment by incorporating the status of multiple somatic gene mutations.