WHITE BLOOD CELL ABNORMALITIES
I. NUCLEAR ABNORMALITIES
ALDER-REILLY INCLUSIONS
 Stored mucopolysaccharides
 Granulocytes contain large, darkly staining metachromatic cytoplasmic granules
 Hunter's, Hurler's syndrome
1. PELGER-HUÈT(HYPOSEGMENTATION)

Genetically acquired, autosomal dominant disorder produces hyposegmentation of
many of the mature neutrophils
Nuclear shape may resemble a dumbbell or a pair of eyeglasses
Function of the cell is considered to be normal despite the morphological abnormality


ALDER-REILLY INCLUSIONS
 Purple-red particles of precipitated mucopolysaccharides
 Morphology may resemble heavy toxic granulation
PELGER-HUÈT ANOMALY




Autosomal dominant trait
Decreased nuclear segmentation in neutrophils; sometimes also affects other WBCs
In Alder-Reilly anomaly, the granules are found in lymphocytes and monocytes, ruling
out toxic granulation, which is exclusive for neutrophils
Neutrophilia, Döhle bodies, and left shift, which are usually associated with toxic
granulation, are not seen in Alder-Reilly anomaly
2.
AUER RODS

Pink or red rod-shaped cytoplasmic structures

Fused primary granules

Peroxidase positive

Found in myeloid and monocytic series only
3.
CHEDIAK-HIGASHI GRANULES
Gigantic, peroxidase-positive deposits representing abnormal lysosomal development
in neutrophils and other leukocytes, such as monocytes and lymphocytes
Neutrophils display impaired chemotaxis and delayed killing of ingested bacteria
PSEUDO-PELGER HUÈT ANOMALY


Acquired hyposegmentation
Myeloproliferative disorders
2. HYPERSEGMENTATION



Most frequently seen in segmented neutrophils with more than five lobes or nuclear
segments
This condition is frequently associated with deficiencies of vitamin B12 or folic acid
and exists along with abnormally enlarged, oval-shaped erythrocytes
Pseudohypersegmentation may be seen in old segmented neutrophils
II. CYTOPLASMIC ABNORMALITIES
1.





ALDER-REILLY INCLUSIONS
Large purple-black coarse cytoplasmic granules
Accumulation of degraded mucopolysaccharides
May be found in all leukocytes
Most commonly seen in patients with Hurler and Hunter types of
mucopolysaccharidosis; most of these disorders are transmitted as autosomal
recessive genes
Morphology may resemble heavy toxic granulation


CHEDIAK-HIGASHI INCLUSIONS
 Giant lysosomal granules in granulocytes, monocytes, and lymphocytes.
4.
MAY-HEGGLIN INCLUSIONS

Döhle body-like inclusions in neutrophils, eosinophils, and monocytes

Composed of precipitated myosin heavy chains
MAY-HEGGLIN ANOMALY


6.
Thrombocytopenia, giant platelets and large Döhle body-like inclusions in
neutrophils, eosinophils, basophils, and monocytes
Döhle body-like inclusions in May-Hegglin anomaly are composed of
precipitated myosin heavy chains
Döhle bodies are composed of lamellar rows of rough endoplasmic reticulum

5.
III. ABNORMALITY IN FUNCTION
DOHLE BODIES

Single or multiple, light blue- staining inclusions on Wright- stained blood smears

Predominantly seen in neutrophils, although they may be seen in monocytes or
lymphocytes

Döhle bodies represent aggregates of rough endoplasmic reticulum (RNA) and
may be associated with a variety of conditions such as viral infections, burns, or
certain drugs
1.
JOB SYNDROME - neutrophils have poor directionalmotility
2.
LAZY LEUKOCYTE SYNDROME - cells have poordirectional and random movement
3.
CHRONIC GRANULOMATOUS DISEASE

Neutrophils and monocytes are unable to kill catalase positive organisms due
to a defect in oxygen-dependent bacteriocidal mechanism
TOXIC GRANULES

Azurophilic (primary) granules that are peroxidase-positive; the granulation may
represent the precipitation of ribosomal protein (RNA) caused by metabolic
toxicity within the cells

Most frequently associated with infectious states; it may be seen in conditions
such as burns and malignant disorders or as the result of drug therapy
IV. CELLS EXHIBITING PHAGOCYTOSIS
TOXIC GRANULES
 May resemble Alder-Reilly inclusions


7.
1.
LE CELL

Neutrophil with large purple homogenous round inclusion with nucleus wrapped
around

Three factors needed to produce cell:
1. Antinuclear antibodies
2. Cell nuclei
3. Phagocytes with ingested material
2.
TART CELL

Confused with LE cell

Monocyte which has ingested another cell or the nucleus of another cell
(lymphocyte nucleus or phagocytized material with definite nuclear pattern)
Neutrophilia, Döhle bodies, and left shift, which are usually associated with toxic
granulation, are not seen in Alder-Reilly anomaly
In Alder-Reilly anomaly, the granules are found in lymphocytes and monocytes,
ruling out toxic granulation, which is exclusive for neutrophils
TOXIC VACUOLES

Large empty white areas within cytoplasm

Represent end stage phagocytosis

Septicemia, severe infections and toxic states
4.
HAIRY CELL

Lymphocytes with hair like cytoplasmic projections surrounding nucleus

Thought to be of B cell origin

Stains positive with tartrate resistant acid phosphatase (TRAP)
5.
SEZARY CELL

Round lymph cell with nucleus that is grooved or convoluted

Represents leukemic phase of mycosis fungoides

T Cell characteristics
V. LYMPHOCYTE ABNORMALITIES
1.


SMUDGE CELLS

Represent the bare nuclei of lymphocytes and neutrophils

Increased fragility of cells contributes to the increased percentage of smudge cells

Increased proportions in lymphocytosis, particularly CLL
BASKET CELL
Nuclear remnant of granulocytic cells
Netlike chromatin pattern


SMUDGE CELL
Nuclear remnant of lymphocytes
Thumbprint appearance
VI. PLASMA CELL ABNORMALITIES
2.
3.
RIDER CELL

Cells are similar to normal lymphocytes except that the nucleus is notched,
lobulated, and cloverleaf-like

Occur in CLL or can be artificially produced through blood smear preparation

FLAME CELL

Red to pink cytoplasm

Associated with increase in Ig

Multiple myeloma
2.
RUSSELL BODIES

Large, red staining globules in the cytoplasm
3.
GRAPE/BERRY/MORULA/MOTT CELL

Numerous globular bodies present in the cytoplasm

Multiple myeloma, reactive states
4.
DUTCHER BODIES

Inclusions present in the nucleus
DOWNEY CELL
 “Atypical / Variant / Reactive / Stimulated Lymphocyte”
TYPE I
Plasmacytoid lymphocyte
Turk's irritation cell

1.
Heavy strands or dense
blocks of chromatin
May also have a foamy
appearance and may
contain azurophilic
granules
TYPE II
Infectious mononucleosis
(IM) cell

Resembling fried egg or
a flared skirt
VII. MONOCYTE-MACROPHAGE DISORDERS
TYPE III
Transformed lymphocytes
Reticular lymphocytes

Vacuolated with
abundant basophilia
LIPID STORAGE DISEASES


Inherited disorders in which lipid catabolism is defective
Two of these disorders are characterized by macrophages with distinctive
morphology
DISEASE
Gaucher disease
Niemann-Pick disease
Fabry disease
Tay-Sachs disease
Sandhoff disease
DEFICIENT ENZYME
ß-Glucocerebrosidase
Sphingomyelinase
α-Galactosidase
Hexosaminidase
SUBSTANCE STORED
Glucocerebroside
Sphingomyelin
Ceramide trihexoside
GM2 ganglioside
1.
2.
3.
GAUCHER'S DISEASE

Most common of the lysosomal lipid storage diseases

Disorder represents a deficiency of B- glucocerebrosidase(beta-glucosidase)

As the result of this enzyme deficiency, cerebroside accumulates in (macrophages)
histiocytes

Gaucher cell is large, with one to three eccentric nuclei and a characteristically
wrinkled cytoplasm

Strongly periodic acid Schiff (PAS) positive
NIEMANN-PICK DISEASE

Disorder represents a deficiency of the enzyme that normally cleaves phosphoryl
choline from its parent sphingolipid, sphingomyelin

Sphingomyelin accumulates in the tissue macrophages

Pick cell, is similar in appearance to the

Gaucher cell; however, the cytoplasm of the cell is foamy in appearance
SEA - BLUE HISTIOCYTOSIS

Cells contain an accumulation of lipid and found in association with increased
tissue stores of phospholipids and glycolipids

Cells are large, with eccentric nucleus containing one nucleolus

Cytoplasm contains varying numbers of granules, which are blue to blue-green in
color when stained with Wright stain
4.
5.
6.
Which of the following represents the principal defect in chronic granulomatous
disease (CGD)?
A. Chemotactic migration
B. Phagocytosis
C. Lysosomal formation and function
D. Oxidative respiratory burst
7.
The neutrophils in chronic granulomatous disease are incapable of producing:
A. Hydrogen peroxide
B. Hypochlorite
C. Superoxide
D. All of the above
8.
The atypical lymphocyte seen in the
peripheral smear of patients with
infectious mononucleosis is probably
derived from which of the following?
A. T lymphocytes
B. B lymphocytes
C. Monocytes
D. Mast cells
REVIEW QUESTION
1.
Which of the following inherited leukocyte disorders is caused by a mutation in the
lamin B receptor?
A. Pelger-Huët anomaly
B. Chédiak-Higashi disease
C. Alder-Reilly anomaly
D. May-Hegglin anomaly


The disorder is a result of a mutation in the lamin B-receptor gene.
The lamin B plays a major role in leukocyte nuclear shape changes that occur during normal
maturation.
2.
In which anomaly is a failure of granulocytes to divide beyond the band or two-lobed
stage observed?
A. Pelger-Huet
B. May-Hegglin
C. Alder-Reilly
D. Chediak-Higashi
Which of the following inherited leukocyte disorders might be seen in Hurler
syndrome?
A. Pelger-Huët anomaly
B. Chédiak-Higashi disease
C. Alder-Reilly anomaly
D. May-Hegglin anomaly
3.
Which of the following inherited leukocyte disorders is one of a group of disorders with
mutations in nonmuscle myosin heavy-chain lIA?
A. Pelger-Huët anomaly
B. Chédiak-Higashi disease
C. Alder-Reilly anomaly
D. May-Hegglin anomaly Inclusions in May-Hegglin anomaly are composed of
precipitated myosin heavy chains.
What leukocyte cytoplasmic inclusion is composed of ribosomal RNA?
A. Primary granules
B. Toxic granules
C. Döhle bodies
D. Howell-Jolly bodies
9.
The atypical lymphocyte seen in the
peripheral smear of patients with
infectious mononucleosis is reacting to
which of the following?
A. T lymphocytes
B. B lymphocytes
C. Monocytes
D. Mast cells
10. Which of the following lysosomal storage diseases is characterized by macrophages
with striated cytoplasm and storage of glucocerebroside?
A. Sanfilippo syndrome
B. Gaucher disease
C. Fabry disease
D. Niemann-Pick disease
PLATELET MORPHOLOGIC ANOMALIES
1.
2.
3.
4.
5.
6.
Mononuclear megakaryocyte
Small/micromegakaryocyte
Large/macromegakaryocyte
Vacuolated megakaryocyte
Giant platelets

May-Hegglin anomaly

Alport syndrome

Bernard-Soulier syndrome
Small platelets

Wiskott-Aldrich syndrome
ABNORMAL PLATELET MORPHOLOGY
1.
2.
3.
May-Hegglin anomaly, which is characterized by the presence of large platelets and the
presence of Döhle-like bodies in the granulocytic leukocytes.
Alport syndrome, a disorder that exhibits giant platelets and thrombocytopenia.
Bernard-Soulier syndrome, which demonstrates the largest platelets seen and is also
referred to as giant platelet syndrome.
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
4.
In this disorder, it has been demonstrated that the giant platelets are probably an
artifact of the slide preparation.
Actual measurement of the platelets reveals that their mean platelet volume
(MPV) is normal
Wiskott-Aldrich syndrome, which demonstrates the smallest platelets seen.
RETICULATED (STRESS) PLATELETS


Appear in compensation for thrombocytopenia
Markedly larger than ordinary mature circulating platelets; their diameter in
peripheral blood films exceeds 6 um, and their MPV reaches 12 to 14 Fl
Elevated reticulated platelets indicates "stress" platelets from increased bone marrow
production and is consistent with a diagnosis of
IMMUNE THROMBOCYTOPENIC PURPURA
LEUKEMIA




Abnormal, uncontrolled proliferation and accumulation of one or more of the
hematopoietic cells
Major symptoms of leukemia are fever, weight loss, and increased sweating.
Bone pain from a large leukemic cell mass in the bone marrow is typical in the
acute leukemias
Enlargement of the liver, spleen and lymph nodes may occur more predominantly
in the chronic leukemias