Megaloblastic Anemia

Epidemiology and Etiology:

•  Causes:
• vitamin B12 deficiency
• most common cause is pernicious anemia (autoimmune)
• folate deficiency
• inadequate intake is the most common cause
• alcoholism
• drugs
• anti-metabolite therapy (chemotherapeutic agents)
• others
• toxins
• rare constitutional genetic disorders

Common sites:

Gross features:

Histologic features:

•  Peripheral blood:
• Macrocytosis
• Characteristic macrocyte with oval cytoplasmic contour
• RBC fragments and schistocytes may also be evident due to damage in peripheral circulation
• RDW typically very high
• Howell-Jolly bodies maybe
• Cabot rings if anemia is profound
• Note: MCV may be normal if combined deficiency anemia
• Giant bands
• Hypersegmented neutrophils
• Bone marrow:
• Markedly hypercellular typically, with an increase in all lineages
• Erythroid hyperplasia frequently predominates causing reverse M:E ratio
• N:C dissociation is evident in all lineages but most predominant in erythroid
• Mild dyspoietic changes, particularly in erythroid lineage
• Nuclear lobation
• Minimal multinucleation
• Increased sideroblastic iron
• DDx with MDS can be challenging
• Storage iron increased typically
• megaloblastic myelopoiesis in bone marrow (caused by any inhibition of DNA synthesis):
• left-shifted
• giant metamyelocytes
• 15-25um (much larger than normal metamyelocyte)
• n:c ratio 1.5:1
• nucleus indented, kidney shaped
• chromatin loosely clumped, less condensed than normal metamyelocyte
• no nucleolus
• pale pink cytoplasm with many lilac granules
• giant bands
• 15-20um
• N:C ratio 1:3
1. “sausage-like” nucleus (giant horseshoe-like)
2. bizarre S and C shapes
• Loosely clumped chromatin, less condensed than normal band
• No nucleoli
• Pale pink cytoplasm with many lilac granules
• hypersegmented neutrophils
• enlarged
• 6 or more nuclear lobes
• red cell changes:
• megaloblastic, oval macrocytes
• megaloblastic nucleated red cells:
• seen in every stage of development
• larger size of cell
• cytoplasmic maturation is ahead of nuclear maturation
1. hemoglobinization of the cytoplasm while maintaining an immature nuclear chromatin pattern
• fine, sieve-like, stippled chromatin
• co-existing dyserythropoietic changes often:
1. multinucleate cells
2. abnormal nuclear configurations
3. Howell-Jolly bodies

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

Other features:

• Pancytopenia in advanced cases
• Serum vitamin B12
• Fasting may be more useful
• Serum folate
• RBC folate levels
• Considered more accurate refletion of overall folate stores

References:

• CAP Color Atlas of Hematology, 1998