Leukocyte Morphological Abnormalities and Non-Malignant Leukocyte Disorders

Hypersegmentation/Hypersegmented Neutrophils

Have more than five lobes and are usually larger than normal neutrophils.

Undritz Anomaly

Associated with hereditary neutrophil hypersegmentation.

Hyposegmented Neutrophils

Nuclei may appear round, ovoid (homozygous pelger-huet). Bilobed forms the characteristic spectacle-like ("pince-nez", dumbbell, peanut) morphology with the nuclei attached by a thin filament (heterozygous pelger-huet).

LE Cell

Usually a neutrophil that has ingested the antibody-coated nucleus of another neutrophil or has engulf the homogenous, globular nuclear mass of destroyed cell.

LE Cell

Presence of anti-nuclear antibodies, cell nuclei, phagocytes with ingested material.

LE Cell

Usually mistaken with a tart cell (monocyte with an ingested lymphocyte).

Barr Body

Represents the 2nd X chromosome in females. Seen in 2-3% of neutrophils.

Barr Body

Characteristic "drumstick" appearance of neutrophils.

Alder-Reilly Granules

Darkly staining metachromatic (purple-red) cytoplasmic granules in granulocytes (less often in monocytes and lymphocytes).

Alder-Reilly Granules

Abnormal large primary granules. Granules contain degraded mucopolysaccharides due to an enzyme defect. May resemble toxic granules (seen in infections and toxic states).

May-Hegglin Granules

Gray-blue spindle shaped inclusions in the cytoplasm.

May-Hegglin Granules

Large Dohle body-like inclusions in neutrophils, eosinophils, basophils, and monocytes.

May-Hegglin Granules

The basophilic Dohle-body like leukocyte inclusions are composed of precipitated myosin heavy chains (mRNA).

Dohle bodies

True _______ consist of lamellar rows of rough endoplasmic reticulum (rRNA).

Chediak-Higashi Granules

Giant red, blue, to grayish round inclusions in tthe cytoplasm.

Chediak-Higashi Granules

Giant lysosomal granules in granulocytes, monocytes, and lymphocytes.

Chediak-Higashi Granules

Cells in the body are affected and exhibit abnormally large lysosomes, which contain fused dysfunctional granules.

Pseudo-Chediak-Higashi Granules

Are cytoplasmic inclusions that resemble the fused lysosomal granules in Chediak Higashi syndrome.

Auer Rods

Pink or red shaped cytoplasmic granules; found in myeloid and monocytic series only.

Auer Rods

Fused primary granules (peroxidase stain positive)>

****** Cells

Bundle of auer rods. Seen in acute promyelocytic leukemia (APL) or M3; also associated with DIC.

Toxic Granulations

Appears as dark, blue-black granules in the cytoplasm of neutrophils, usually in segmented and band forms.

Toxic Granulations

Granulation may represent the precipitation of ribosomal protein (RNA) caused by metabolic toxicity within the cells.

Toxic Granulations

Are peroxidase positive and reflect an increase in acid mucosubstance within primary azurophilic granules that may enhance bactericidal activity.

Toxic Granulations

Primary granules are larger than secondary granules.

Toxic Granulation

It can mimic granulation found in alder-reilly anomaly; one helpful defining characteristic of toxic granulation is that in most cases, not all neutrophils are equally affected.

Dohle -Bodies/Dohle-Amato Bodies

Are light/pale blue round or elongated cytoplasmic inclusions between 1-5 um consisting of remnants of ribosomal ribonucleic acid (rRNA) arranged in parallel row; close to cellular membranes.

Dohle -Bodies/Dohle-Amato Bodies

Are typically found in band and segmented neutrophils and can appear together with toxic granulations; can be seen in eosinophils, basophils, monocytes, and lymphocytes.

Dohle -Bodies/Dohle-Amato Bodies

Localized failure of cytoplasmic maturation and PAS reaction positive. It is confused with May-Hegglin granules.

Cytoplasmic Vacuolations

Less encountered than toxic granules and Dohle bodies.

Cytoplasmic Vacuolations

Reflect phagocytosis, either of self (autophagocytosis) or of extracellular material.

Autophagocytic Vacuoles

Tend to be small (approximately 2 um) and distributed throughout the cytoplasm.

Phagocytic Vacuoles

Tend to be large (up to 6 um) and often accompanied by toxic granulation. Induced by either bacteria or fungi are suggestive of sepsis.

Pyknotic Nuclei

__________ in neutrophils generally indicate imminent cell death.

Pyknotic Nucleus

In a _______, water has been lost and the chromatin becomes dense and dark; however, chromatin or filaments can still be seen between nuclear lobes (depending on whether the cell is a band or segmented form).

Necrotic Nuclei

Are found in dead neutrophils/necrobiotic neutrophils; they are rounded nuclear fragments with no filaments and no chromatin pattern.

Cytoplasmic Swelling

Is a result of osmotic swelling of the cytoplasm or by increased adhesion to the glass slide in stimulated neutrophils.

Ehrlichia and Anaplasma

Are small, obligate, intracellular bacteria transmitted by ticks to humans and other vertebrate hosts.

Ehrlichia and Anaplasma

These organisms grow as a cluster (morulae) in neutrophils and monocytes.

Morulae

It can be mistaken for Dohle bodies in neutrophils.

Human Granulocytic Erlichiosis (HGE)

Is transmitted by the black-legged tick (Ixodes scapularis) and the western black-legged tick (I. pacificus).

Histoplasma capsulatum

Is a fungus; this organism lives intracellularly in cells of the mononuclear phagocyte system, cells of the bone marrow, or cells from sputum or effusion specimens.

Histoplasma capsulatum

The fungus appears as a tiny oval body with a clear halo surrounding a small nucleus.

Basket/Smudge Cell

Associated with degenerated nucleus or ruptured cell in form or basket/smudge.

Basket/Smudge Cell

Thumbprint Appearance.

Basket/Smudge Cell

Fragile lymphocytes that appear during smear preparation.

Hairy Cell

Hair like cytoplasmic projections surrounding the nucleus (fried-egg appearance).

Hairy Cell

Isoenzyme 5 (tartrate resistant is produced in abundance in hairy cell leukemia).

Hairy Cell

TRAP (Tartrate-resistant acid phosphatase) stain positive.

Sezary Cell

Lymphocyte with a convoluted nucleus/brain-like nucleus.

Sezary Cell

Presence indicates leukemic phase of mycosis fungoides.

Reed-Sternberg/RS Cells

Abnormal lymphocyte with an "owl's eye appearance".

Reed-Sternberg/RS Cells

Pathognomonic sign for Hodgkin's lymphoma.

Rieder Cell

Lymphocyte with a clover leaf like nucleus.

Reactive Lymphocyte

AKA variant, atypical, transformed, effector, plasmacytoid, turk cells, downey, and immunoblasts.

Reactive Lymphocytes

Often present as a heterogenous population of various shapes and sizes.

Plasmacytoid Lymphocyte

Is a type of reactive lymphocyte that has some morphologic features of plasma cells.

Type I

Type of reactive lymphocyte; Turk's irration plasma cytoid; lymphocyte with a large block of chromatin.

Type II

Type of reactive lymphocyte; also known as IM cells; round mass of chromatin (ballerina skirt appearance).

Type III

Type of reactive lymphocyte; vacuolated (swiss cheese appearance).

Flame Cell

Abnormal plasma cell with red to pink cytoplasm.

Flame Cell

Associated with increased immunoglobulins (usually IgA).

Flame Cell

Its inclusion is Russel bodies (individual bodies of Immunoglobulin).

Grape Cell

Abnormal plasma cell with small colorless vacuoles.

Grape Cell

AKA Berry, Mott, Morula Cell.

Grape Cell

Its inclusion is Dutcher's bodies (intranuclear protein inclusions).

Grape Cell

Large protein globules giving appearance of grapes: "Honeycomb appearance".

Gaucher Cell

Abundant fibrillar blue-gray cytoplasm with a striated or wrinkled appearance (sometimes described as onion skin-like).

Gaucher Cell

Positive with trichrome, aldehyde fuchsin, periodic acid-Schiff (PAS) and acid phosphatase.

Foam Cell

Macrophages with cytoplasm packed with lipid-filled lysosomes that appear as small vacuoles (foam) after staining.

Sea-Blue Histiocytes

Are macrophages with lipofuscin, glycophospholipid, and sphingomyelin contained in cytoplasmic granules, that appear blue with Wright's stain.

Pelger-Huet Anomaly (PHA)

Autosomal dominant disorder characterized by decreased nuclear segmentation and distinctive coarse chromatin clumping pattern.

Pelger-Huet Anomaly (PHA)

Mutations in the lamin B-receptor gene.

Lamin B Receptor

Is an inner nuclear membrane protein that combines B-type lamins and heterochromatin and plays a major role in leukocyte nuclear shape changes that occur during normal maturation.

Heterozygous PHA

Type of PHA; normal individuals, pince-nez appearance of the nucleus.

Homozygous PHA

Type of PHA; cognitive impairment, heart defects, and skeletal abnormalities may occur; single nuclei.

Alder-Reilly Anomaly

Is a rare inherited disorder characterized by granulocytes (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules.

Alder-Reilly Anomaly

It was initially reported in patients with gargoylism; however, it can be seen in otherwise healthy individuals.

Alder-Reilly Anomaly

Granulations are also seen in mucopolysaccharides (MPSs).

May-Hegglin Anomaly

A rare, autosomal dominant disorder characterized by variable thrombocytopenia, giant platelets, and large Dohle body-like inclusions in neutrophils, eosinophils, basophils, and monocytes.

May-Hegglin Anomaly

Caused by a mutation in the MYH9 gene with disordered production of myosin heavy chain type IIA, which affects megakaryocyte maturation and platelet fragmentation.

Chediak-Higashi Syndrome

A rare autosomal recessive disease of immune dysregulation. Mutation in the CHS1 LYST gene.

Chediak-Higashi Syndrome

Many types of cells in the body are affected and exhibit abnormally large lysosomes, which contain fused dysfunctional granules.

Chediak-Higashi Syndrome

Clinical manifestations begin in infancy with partial albinism and severe recurrent life-threatening bacterial infections.

Chediak-Higashi Syndrome

Patients often have bleeding issues as a result of abnormal dense granules in platelets; death occurs before the age of 10 years.

Job's Syndrome

Normal random movement; abnormal chemotactic/directional motility.

Job's Syndrome

Patients suffer from persistent boils and recurrent "cold" staphylococcal abscesses. Associated with increased IgE.

Lazy-Leukocyte Syndrome

Abnormal random and chemotactic movement. Cells failed to respond to inflammatory stimuli but have normal phagocytic and bactericidal activity.

Leukocyte Adhesion Disorders (LADs)

Are rare autosomal recessive inherited conditions resulting in the inability of neutrophils and monocytes to move from circulation to the site of inflammation (called extravasation).

Leukocyte Adhesion Disorders (LADs)

Consequences of these disorders are recurrent severe bacterial and fungal infections.

Leukocyte Adhesion Disorders (LADs)

Hematopoietic stem cell transplant is the only curative treatment.

LAD I

Mutation in the ITGB2 gene; gene that encodes CD18 subunit of b2 integrins, resulting in either a decreased or truncated form of the b2 integrin, which is necessary for adhesion to endothelial cells, recognition of bacteria, and outside-in signaling.

LAD I

Shortly after birth, patients suffer from recurrent infections, often affecting skin and mucosal infections.

LAD II

Mutation in the SLC35C1 gene ; leukocytes have normal b2 integrins. Defective fucose transporter and selectin synthesis.

LAD II

Patients have recurring infections, neutrophilia, growth retardation, a coarse face, and other physical deformities.

LAD III

Caused by mutations in Kindlin-3; Kindlin-3 protein along with talin are required for activation of b integrin and leukocyte rolling.

LAD III

Leukocytes and platelets have normal expression of integrins; however, there is failure in response to external signals that normally results in leukocyte activation.

LAD III

______ patients experience a mild LAD I-like immunodeficiency with recurrent infections. Additionally, there is decreased platelet glycoprotein IIb/IIIa, resulting in bleeding similar to that seen in Glanzmann's Thrombasthenia.

Warts

Hypogammaglobulinemia

Infections

Myelokathexis Syndrome

Transcribe WHIM.

WHIM Syndrome

Defect in intrinsic and innate immunity. Mutations in the CXCR4 gene.