Megaloblasten

Megaloblasts are enlarged erythroblasts found in the bone marrow during megaloblastic anemia. They arise when DNA synthesis is impaired, most commonly due to deficiencies of vitamin B12 (cobalamin) or folate, but also from certain drugs or other disruptions of nucleotide production. The defective DNA synthesis causes nuclear maturation to lag behind cytoplasmic development, yielding cells with increased size and asynchronous maturation.

Morphology in the marrow includes erythroblasts that are larger than normal and show a relatively immature nucleus with open chromatin and often prominent nucleoli. The cytoplasm is more basophilic due to continued ribosomal RNA synthesis, and cytoplasmic maturation can proceed without concurrent nuclear maturation. Vacuolations may be seen in some early megaloblasts. In peripheral blood, macrocytosis and oval macrocytes are common, and a significant fraction of neutrophils may be hypersegmented.

Clinical significance and diagnosis: The presence of megaloblasts supports a diagnosis of megaloblastic anemia and reflects ineffective erythropoiesis. Diagnostic workup includes a complete blood count, peripheral smear review, and measurement of serum vitamin B12 and folate levels. Additional tests may include methylmalonic acid and homocysteine to help distinguish B12 deficiency from folate deficiency.

Treatment and prognosis: Correcting the underlying deficiency usually leads to normalization of hematopoiesis within weeks. B12 deficiency requires appropriate cobalamin replacement (often parenteral), while folate deficiency is treated with folate supplementation. Caution is advised when treating with folate in suspected B12 deficiency, as it can mask neurological symptoms.