Hematology · Myeloid Neoplasms
The facts most likely to be tested
Myelodysplastic syndrome is a clonal stem cell disorder characterized by ineffective hematopoiesis and peripheral cytopenias despite a hypercellular bone marrow.
Peripheral blood smears typically reveal macro-ovalocytes and dysplastic neutrophils with hyposegmentation known as pseudo-Pelger-Huët anomaly.
Bone marrow biopsy is the diagnostic gold standard, demonstrating dysplasia in at least one myeloid lineage and ringed sideroblasts in specific subtypes.
Patients frequently present with refractory anemia that is unresponsive to iron, folate, and B12 supplementation.
The risk of transformation to acute myeloid leukemia (AML) is determined by the blast percentage in the bone marrow, with >20% blasts defining the transition to AML.
5q deletion is a specific cytogenetic abnormality associated with a better prognosis and a favorable response to lenalidomide.
Allogeneic hematopoietic stem cell transplantation remains the only curative treatment option, typically reserved for younger or higher-risk patients.
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A 72-year-old male presents for a routine physical exam and is found to have a hemoglobin of 9.8 g/dL. He reports mild fatigue but denies bleeding, bruising, or weight loss. Laboratory studies show an MCV of 108 fL, a leukocyte count of 3,200/µL, and a platelet count of 110,000/µL. Peripheral smear reveals macro-ovalocytes and neutrophils with hyposegmented nuclei. Bone marrow biopsy demonstrates hypercellularity with dysplastic changes in the erythroid and myeloid lineages.
What is the most likely diagnosis?
Myelodysplastic syndrome
The patient presents with classic cytopenias, macrocytosis, and dysplastic neutrophils (pseudo-Pelger-Huët anomaly) in the setting of a hypercellular marrow, which is diagnostic for myelodysplastic syndrome.
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Etiology / Epidemiology
Primarily affects elderly patients (>65); secondary cases follow chemotherapy or radiation.
Clinical Manifestations
Presents with cytopenias; pseudo-Pelger-Huet anomaly is the pathognomonic finding.
Diagnosis
Bone marrow biopsy showing dysplasia in ≥10% of myeloid cell lines.
Treatment
Azacitidine or Lenalidomide (for 5q- syndrome); supportive care for low-risk.
Prognosis
High risk of transformation to Acute Myeloid Leukemia (AML); median survival varies by IPSS score.
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Epidemiology & Etiology
MDS is a clonal hematopoietic stem cell disorder occurring predominantly in the elderly. Secondary MDS is a known complication of prior alkylating agents or topoisomerase II inhibitors. Exposure to benzene or ionizing radiation are significant environmental risk factors.
Pertinent Anatomy
The disease originates in the bone marrow niche, leading to ineffective hematopoiesis. The marrow is typically hypercellular despite peripheral cytopenias due to intramedullary apoptosis.
Pathophysiology
Clonal expansion of mutated stem cells results in ineffective hematopoiesis and maturation arrest. This leads to peripheral cytopenias despite a hypercellular marrow. Genetic instability often progresses to AML transformation.
Clinical Manifestations
Patients present with symptoms of anemia, infection, or bleeding. Peripheral blood smears reveal pseudo-Pelger-Huet anomaly (hyposegmented neutrophils). Unexplained macrocytic anemia in an older adult is a classic red flag.
Diagnosis
Bone marrow biopsy with aspirate is the gold standard to confirm dysplasia in ≥10% of cells. Cytogenetic analysis is mandatory to identify del(5q) or complex karyotypes. Serum erythropoietin levels should be checked to guide therapy.
Treatment
Low-risk patients receive supportive care (transfusions, growth factors). Lenalidomide is the treatment of choice for 5q- syndrome. Azacitidine is the first-line agent for higher-risk disease. Allogeneic stem cell transplant is the only curative option for eligible candidates.
Prognosis
Prognosis is determined by the IPSS-R score, which incorporates cytogenetics and cytopenia severity. The primary cause of mortality is transformation to AML or complications of pancytopenia (infection/hemorrhage).
Differential Diagnosis
Aplastic Anemia: hypocellular marrow vs. hypercellular in MDS
Vitamin B12/Folate Deficiency: corrected by supplementation
Copper Deficiency: mimics MDS morphology
Acute Myeloid Leukemia: >20% blasts in marrow
Paroxysmal Nocturnal Hemoglobinuria: flow cytometry shows CD55/CD59 deficiency