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Hematology and Clinical Microscopy Glossary - College of American ...

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eticulated, lacy <strong>and</strong> blast-like without clumping. A<br />

perinuclear halo corresponding to the Golgi apparatus<br />

is usually evident. The cytoplasm stains pale blue <strong>and</strong> is<br />

lighter blue than the cytoplasm <strong>of</strong> basophilic<br />

normoblasts. The N:C ratio is approximately 8:1.<br />

Basophilic Normoblast: Basophilic normoblasts are<br />

smaller (10 to 17 μm in diameter) than pronormoblasts,<br />

but similar in cellular <strong>and</strong> nuclear shape. They comprise<br />

6-8% <strong>of</strong> the nucleated erythroid cells in the bone<br />

marrow. The nucleus is round to slightly oval. The<br />

chromatin is open but, unlike pronormoblasts, the<br />

str<strong>and</strong>s are thickened or “beady.” The chromatin should<br />

not show prominent clumping; this is a feature <strong>of</strong><br />

polychromatophilic normoblasts. The nuclei <strong>of</strong> large<br />

or early basophilic normoblasts may reveal faint single<br />

nucleoli, but those <strong>of</strong> small or late basophilic<br />

normoblasts lack nucleoli. A perinuclear halo is<br />

<strong>of</strong>ten visible. The cytoplasm is more abundant than<br />

pronormoblasts <strong>and</strong> is intensely basophilic, imparting a<br />

royal blue color. The N:C ratio is approximately 6:1.<br />

Polychromatophilic Normoblast: Polychromatophilic<br />

normoblasts are round or ovoid cells, but are slightly<br />

smaller (10 to 15 μm in diameter) than earlier erythroid<br />

precursors. Together with orthochromic normoblasts,<br />

they normally represent 90% <strong>of</strong> nucleated erythroid cells<br />

in the bone marrow. The nucleus is round, lacks nucleoli,<br />

<strong>and</strong> may be centrally or eccentrically located. The<br />

chromatin is clumped, sometimes giving a cartwheel<br />

appearance. A perinuclear halo is visible. The cytoplasm<br />

is abundant <strong>and</strong> stains as admixtures <strong>of</strong> blue-gray (early<br />

polychromatophilic normoblasts) to pink-gray (late<br />

polychromatophilic normoblasts), depending on the<br />

relative proportions <strong>of</strong> RNA <strong>and</strong> hemoglobin present.<br />

The N:C ratio is approximately 4:1.<br />

Orthochromic Normoblast: Orthochromic normoblasts<br />

are round to ovoid cells that are 8 to 12 μm in diameter<br />

(smaller than polychromatophilic normoblasts). Together<br />

with polychromatophilic normoblasts, they normally<br />

represent 90% <strong>of</strong> nucleated erythroid cells in the bone<br />

marrow. The nucleus is very small, <strong>of</strong>ten pyknotic, <strong>and</strong><br />

sometimes appears as a homogeneous mass <strong>of</strong> dense<br />

chromatin. It is <strong>of</strong>ten eccentrically placed <strong>and</strong> at times<br />

may be fragmented or seen in the process <strong>of</strong> being<br />

extruded. The cytoplasm is relatively more abundant<br />

than in polychromatophilic normoblasts <strong>and</strong> usually<br />

stains pink-orange with little or no basophilia, similar to<br />

the cytoplasm <strong>of</strong> surrounding nonnucleated<br />

erythrocytes. The cytoplasmic color is uniform, unlike the<br />

variegated appearance typical <strong>of</strong> polychromatophilic<br />

normoblasts. The N:C ratio is approximately 1:2.<br />

Bone Marrow Cell Identification<br />

Erythrocyte Precursor, Abnormal/<br />

Dysplastic Nuclear Features (Includes<br />

Pronormoblast, Basophilic Normoblast,<br />

Polychromatophilic Normoblast, <strong>and</strong><br />

Orthochromic Normoblast)<br />

Dysplastic nucleated red blood cells are <strong>of</strong> similar size<br />

to their normal counterparts in the erythrocytic series,<br />

but characteristically exhibit strikingly abnormal nuclear<br />

features. Compared to the round nucleus <strong>of</strong> normal<br />

erythroid precursors, dysplastic erythrocytes <strong>of</strong>ten have<br />

a misshapen nucleus due to nuclear “budding”<br />

(lobation or rosette formation) or fragmentation.<br />

Multinucleation is also common, <strong>and</strong> internuclear<br />

bridging by thin str<strong>and</strong>s <strong>of</strong> chromatin may be<br />

present. Megaloblastic changes may also be present.<br />

The cytoplasm shows normal hemoglobinization <strong>and</strong> in<br />

some dysplastic red cells may be vacuolated, contain<br />

multiple Howell-Jolly bodies, or exhibit coarse basophilic<br />

stippling. Erythroid dysplasia may be seen in a variety<br />

<strong>of</strong> benign disorders (eg, vitamin B12, folate, or<br />

copper deficiency) or malignant conditions (eg,<br />

myelodysplastic syndromes).<br />

Erythrocyte Precursor with Megaloblastic<br />

Changes/Maturation<br />

Megaloblastic changes are the result <strong>of</strong> defective DNA<br />

synthesis <strong>and</strong> occur in a variety <strong>of</strong> disorders. Vitamin B12<br />

deficiency <strong>and</strong> folate deficiency are the classic<br />

examples <strong>of</strong> megaloblastic maturation, but stem cell<br />

abnormalities associated with myelodysplasia, toxins,<br />

drugs, or any number <strong>of</strong> other extrinsic factors may also<br />

alter DNA production. Megaloblastic nucleated red<br />

blood cells are larger than the corresponding normal<br />

cells <strong>of</strong> the erythrocytic series <strong>and</strong> are characterized by<br />

nuclear <strong>and</strong> cytoplasmic maturation dyssynchrony. This<br />

is manifest by delayed nuclear maturation relative to<br />

the degree <strong>of</strong> cytoplasmic maturation (ie, cells have an<br />

immature chromatin pattern compared to the degree<br />

<strong>of</strong> cytoplasmic hemoglobinization). Coexisting features<br />

<strong>of</strong> dyserythropoiesis, such as multinucleation, abnormal<br />

nuclear shapes, <strong>and</strong> cytoplasmic Howell-Jolly bodies,<br />

are <strong>of</strong>ten seen. Red cells with megaloblastic changes<br />

are classified into similar stages <strong>of</strong> development as<br />

their normal counterpart cells; the assumption is that<br />

cytoplasmic maturation is appropriate, <strong>and</strong> thus cell<br />

identification is based on cytoplasmic characteristics.<br />

Megaloblastic change is <strong>of</strong>ten difficult to appreciate in<br />

early erythroid precursors <strong>and</strong> is more easily recognized<br />

in polychromatophilic <strong>and</strong> orthochromic normoblasts.<br />

800-323-4040 | 847-832-7000 Option 1 | cap.org<br />

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