Myelodysplastic Syndromes (MDS) are disorders affecting the bone marrow, the body’s blood cell factory. These conditions cause the bone marrow to produce defective or too few blood cells, leading to low blood counts (cytopenias). MDS is classified as a type of blood cancer, and an accurate diagnosis is essential for appropriate treatment. Misdiagnosis is a concern because the signs and symptoms can easily be mistaken for more common, non-cancerous conditions.
Why MDS Diagnosis is Inherently Complex
The diagnosis of Myelodysplastic Syndromes is difficult, especially in the early stages. MDS develops when hematopoietic stem cells in the bone marrow become damaged, leading to abnormal blood cell production. Patients often present with non-specific symptoms like persistent fatigue, weakness, and shortness of breath, which are consequences of low red blood cell counts (anemia).
Initial routine blood tests, such as a complete blood count (CBC), reveal cytopenias (a reduction in one or more types of blood cells). This finding is not unique to MDS and is characteristic of many other conditions. Definitive diagnosis relies on examining the bone marrow, where early MDS cells can show a “morphological overlap” with cells affected by benign processes. Under a microscope, the abnormal features (dysplasia) can look similar to changes caused by non-cancerous inflammation or deficiency states.
Conditions Commonly Mistaken for MDS
The low blood counts and abnormal cell appearances seen in MDS can be mimicked by various conditions, leading to misdiagnosis. Severe nutritional deficiencies, particularly a lack of Vitamin B12 or folate, can cause changes in blood cell morphology that resemble MDS-related dysplasia. Treating the deficiency with supplements can resolve the blood count issues, making it important to test for these vitamins first.
Aplastic Anemia is another bone marrow disorder frequently mistaken for MDS, as both conditions result in pancytopenia (a low count of all three blood cell lines). Unlike MDS, Aplastic Anemia is characterized by a significantly underactive bone marrow without the prominent dysplasia or genetic abnormalities typical of MDS. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired blood disorder that shares symptoms like anemia and can exhibit similar bone marrow findings. Chronic infections or systemic inflammation can also induce reactive changes in the bone marrow, causing morphological abnormalities that may be misinterpreted as MDS.
The Essential Role of Specialized Testing for Accuracy
To distinguish MDS from its many mimics, a definitive diagnosis requires a high-quality bone marrow biopsy and aspiration, followed by specialized molecular analyses. A hematopathologist must examine the bone marrow aspirate to quantify the degree of dysplasia and the percentage of immature blast cells. The presence of dysplasia in at least 10% of cells in a blood cell line is often a minimum requirement for an MDS diagnosis.
Specialized testing looks for the disease’s underlying genetic signature. Cytogenetics examines the chromosomes for structural abnormalities, such as the deletion of a part of chromosome 5 (del(5q)) or the loss of chromosome 7, which are commonly associated with MDS. Molecular sequencing identifies specific acquired mutations in genes like SF3B1, TET2, and TP53, which are frequently mutated in MDS patients. Identifying these clonal mutations is often necessary to confirm the diagnosis, especially when morphological changes are ambiguous. Diagnoses are formally classified using systems like the World Health Organization criteria.
Seeking Confirmation and Second Opinions
Given the complexity and potential for misdiagnosis, patients should consider seeking a second opinion, especially from a hematologist specializing in MDS. Studies show that a significant percentage of initial MDS diagnoses are reclassified after review by an expert pathologist at a specialized cancer center. This reclassification can prevent unnecessary, intensive treatment for a benign condition or avoid undertreatment of a true blood cancer. Consulting a specialist ensures that specialized testing, including genetic sequencing, is performed correctly and interpreted within the latest clinical guidelines.