NON-NEOPLASTIC WHITE BLOOD CELL DISORDERS

Question 1

Cellular Morphology

• Nuclear Characteristics

Answer 1

• Shape
• Presence/Absence of nucleoli
• Chromatin Pattern

Question 2

Cellular Morphology

Cytoplasmic Characteristics

VIGSSQ

Answer 2

• Shape
• Granulation
• Quantity
• Staining color and intensity
• Vacuolation
• Inclusion Bodies

Question 3

• Often the body’s response to various diseases and toxic challenges
• The type of cell affected depends on its function
• Automated hematology analyzer do not detect certain abnormalities

Answer 3

Morphology Changes

Question 4

MORPHOLOGIC ABNORMALITIES OF LEUKOCYTE

TNDMLAP

Answer 4

1. Toxic Granulation
2. Neutrophil Hypersegmentation
3. Dohle Bodies
4. May-Hegglin Anomaly
5. Lysososmal Storage Disease
6. Alder-Reily Anomaly
7. Pelger-Huet Anomaly

Question 5

Prominent dark granulation, either fine or heavy = can be observed in band and segmented neutrophil or monocytes

Answer 5

TOXIC GRANULATION

Question 6

• Represent the precipitation of ribosomal protein (RNA) = caused by metabolic toxicity within the cells

Answer 6

TOXIC GRANULATION

Question 7

TOXIC GRANULATION

Azurophilic (primary) granules are…

Answer 7

peroxidase positive

Question 8

• ASSOCIATED with infectious states, in conditions such as burns and malignant disorders or as the result of drug therapy

Answer 8

TOXIC GRANULATION

Question 9

occurs due to increased production and retention of primary (azurophilic) granules in neutrophils in response to infections, inflammation, or stress conditions such as burns or trauma.

These granules are normally present in immature neutrophils but are usually lost as they mature. However, in conditions requiring an accelerated immune response, neutrophils mature rapidly, retaining their granules.

Answer 9

Toxic granulation

Question 10

These are the intracytoplasmic pale blue, round inclusion, seen near the periphery of the cytoplasm of neutrophils but may also be seen in monocytes or lymphocytes

○ Delay in preparation of smears make the inclusion more grey than blue or may not be visible at all

Answer 10

DOHLE BODIES

Question 11

● aggregates of RER (remnants of rRNA)

● may be seen in conjunction with toxic granulation

● may also be seen normally but in small amounts

● associated with burns, infectious disease, scarlet fever, aplastic anemia, but nonspecific because it can also be seen in pregnancy

Answer 11

Dohle bodies

Question 12

Dohle bodies

Delay in preparation of smears make the inclusion more_____ than _____ or may not be visible at all

Answer 12

grey than blue

Question 13

Dohle bodies

Nonspecific conditions: VBBIPS

Answer 13

1. Bacterial infections
2. Sepsis
3. Pregnancy
4. Vira infections
5. Burns
6. Intake of certain drugs

Question 14

Autosomal dominant
• More that FIVE lobes or nuclear segmentation

Answer 14

Hyper segmentation

Question 15

• Frequently associated with deficiencies of vitamin B12 or folic acid and exists along with abnormally enlarged,
oval shaped erythrocytes

Answer 15

Hyper segmentation

Question 16

● HYPERsegmentation of Neutrophils (>5 lobes)

● if Acquired hypersegmentation: most often associated with Megaloblastic Anemia (Vit B9 or B12 deficiency)

Answer 16

Undritz Anomaly

Question 17

• Benign, autosomal dominant disorder

Decreased nuclear segmentation

• Distinctive coarse chromatin clumping pattern

• NUCLEI: appear round, ovoid or peanut shaped

Answer 17

Pelger - Huet Anomaly (PHA)

Question 18

• Mutation in the lamin B-receptor gene
• Neutrophils function formal

Answer 18

Pelger Huet Anomaly

Question 19

HYPOlobulation / HYPOsegmentation (2 lobes) of neutrophils: failure of segmentation of granulocytic nuclei
○ Pince-nez (Spectacle-like)
○ Peanut
○ Dumbbell
○ cells have normal function

Answer 19

Pelger Huet Anomaly

Question 20

Morphologic Abnormalities of Leukocyte
PHA vs Myelocyte/Metamyelocyte

Pelger Huet Anomaly

Answer 20

Cell size is smaller
N:C ratio is lower
Chromatin is darker, more coarse, more densely clumped
Colorless cytoplasm

Question 21

PHA vs Myelocyte/Metamyelocyte

Myelocyte/Metamyelocyte

Answer 21

Relatively bigger
N:C ratio is higher
Cytoplasmic basophilia (+) neutrophilic left shift

Question 22

One of the important characteristics we have to observe for in the Pelger-Huët Anomaly is the

Answer 22

“Pince-nez” morphology (Spectacle like)

Question 23

Morphologic Abnormalities of Leukocyte
True PHA vs Pseudo PHA

PELGER-HUET ANOMALY vs
PSEUDO-PELGER-HUËT ANOMALY

Number of Affected Cells???

Answer 23

PELGER-HUET ANOMALY - 63%-93%

PSEUDO-PELGER-HUËT ANOMALY - <38%

Question 24

All WBC Lineages are potentially affected

Examination of Family Member’s PBS may reveal same findings (Because it is Inherited - Autosomal Dominant)

Answer 24

PHA

Question 25

Hypogranularity of the Cytoplasm of Neutrophils (Mistaken as Blast Cells) Only in Neutrophils except for some cases of Myelodysplastic Syndrome (will affect Eosinophils and Monocytes)

Answer 25

Pseudo PHA

Question 26

Nuclear chromatin condenses —> segments disappear —> dark-staining spheres ● Apopotopic nucleus ● Dying neutrophils

Answer 26

Pyknotic nucleus

Question 27

• LBR mutations impair nuclear membrane remodeling, causing neutrophils to remain in an immature, bilobed form. • Despite the abnormal morphology, neutrophils retain normal function

Answer 27

PHA

Question 28

refers to the irreversible condensation of nuclear chromatin, leading to nuclear shrinkage and increased chromatin density. It is a sign of cell death—either by apoptosis or necrosis.

Answer 28

Pyknosis

Question 29

Pyknotic nucleus X or Sex Chromatin ● Deactivated or inactive X chromosome → also known as

Answer 29

Barr bodies

Question 30

Pyknotic nucleus Since the female contains two x chromosomes - the other chromosome is inactivated - sometimes it forms like a_____ In males, barr bodies are not that visible since they only have one X chromosome - it is always active Some disorders, where there is an excess X chromosome in males - barr bodies will be present, because the other X will be deactivate

Answer 30

barr body

Question 31

AUER RODS FORM CLUSTER • Suggestive of Acute Promyelocytic Leukemia • Usually forms in the cytoplasm of promyelocytes or blast

Answer 31

Faggot Cells

Question 32

Faggot cells : Pink or red stained needle like crystals in the cytoplasm of myeloid cells

Answer 32

AUER RODS

Question 33

Faggot cells Agglomeration of primary granules Positive for: MEA Diagnostic of…

Answer 33

Myeloperoxidase esterase acid phosphatase myeloid neoplasm

Question 34

Autosomal dominant disorder • Variable ***thrombocytopenia, giant platelet,*** and large Dohle body-like inclusion in neutrophils, eosinophils, basophils and monocytes

Answer 34

May-Hegglin Anomaly

Question 35

May Hegglin • MUTATION:_____ gene on chromosome_____ Affects ***megakaryocyte maturation and platelet fragmentation*** when shedding from megakaryocytes

Answer 35

MYH9; 22q12-13

Question 36

• Most individuals with ______are asymptomatic, but a few have mild bleeding tendencies related to the degree of thrombocytopenia • ***Large, hypo granular platelets.*** ***Thrombocytopenia*** (approx 40- 80 x 10^9/L) • Prolonged BT usually larger and rounder in shape (vs. Dohte bodies)

Answer 36

May Hegglin anomaly

Question 37

• Group of more than 50 inherited enzyme ***deficiencies resulting from mutations in genes that code for the production of lysosomal enzymes.***

Answer 37

Lysosomal Storage Disease

Question 38

• Flawed degradation of phagocytized material and buildup of undigested substrates within lysosomes • All cells containing lysosomes can be affected

Answer 38

Lysosomal storage disease

Question 39

• This includes: • Shpingolipidoses, oiligosachraridoses, mucolipidoses, mucopolysaccharidoses (MPS), lipoprotein, storage disoders, and lysosomal transport defects.

Answer 39

Lysosomal storage disease

Question 40

Lysosomal Storage Disease • • Caused by ***deficient activity of an enzyme necessary for the degradation of dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate*** • FUNCTION is not affected • Results in serious physical and cognitive problems and shortened survival

Answer 40

Mucopolysaccharisoses

Question 41

Lysosomal Storage Disease • SPHYNGOLIPIDOSES (2)

Answer 41

• GAUCHER DISEASE • NIEMANN-PICK DISEASE (FOAM CELLS)

Question 42

SPHYNGOLIPIDOSES • Defect of deficiency in the catabolic enzyme b-glucocerebrosidase (gene located at 1q21-22 • ACCUMULATION of unmetabolized substrate sphingolipid glucocerebroside in macrophage throughout the body, including osteoclast and microglia.

Answer 42

• GAUCHER DISEASE

Question 43

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

Answer 43

GAUCHER CELLS

Question 44

SPHYNGOLIPIDOSES • B-glucosidase(glucocerebrosidase) is available to confirm diagnosis • TREATMENT: enzyme replacement therapy with recombinant glucocerebrosidase

Answer 44

• GAUCHER DISEASE

Question 45

• GAUCHER DISEASE stains positive with: TAPA

Answer 45

1. Trichome 2. Aldehyde Fuchsin 3. Periodic Acid Schiff 4. Acid Phosphatase

Question 46

SPHYNGOLIPIDOSES • Accumulation of FAT in cellular lysosomes of vital organs • Recessive mutations in the SMPD1 gene = a deficiency of acid sphingomyelinase (ASM) and a subsequent buildup of the sphingomyelin in the liver, spleen, and lungs

Answer 46

• NEIMANN-PICK DISEASE

Question 47

- macrophage with lipid-filled lysosomes that appear as small vacuoles; nucleus is eccentric

Answer 47

FOAM CELL • NEIMANN-PICK DISEASE

Question 48

• NEIMANN-PICK DISEASE Stains positive with: SO

Answer 48

1. Sudan Black B 2. Oil Red 0

Question 49

SPHYNGOLIPIDOSES • NEIMANN-PICK DISEASE • Adult form of Niemann pick disease and chronic granulocytic leukemia • Histiocytes filled with LIPID RICH GRANULES •BLUE GREEN with Polychrome stain such as Giemsa or Wright Stain

Answer 49

• SEA BLUE HISTIOCYTES

Question 50

Autosomal recessive • Characterized by granulocyte (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules •______ = granulation • Also found in mucopolysaccharidoses

Answer 50

Alder - Reilly Anomaly REILLY BODIES

Question 51

Autosomal recessive • Characterized by granulocyte (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules •______ = granulation • Also found in mucopolysaccharidoses

Answer 51

Alder - Reilly Anomaly REILLY BODIES

Question 52

Toxic granulation Represent the precipitation of…

Answer 52

Ribosomal protein

Question 53

Dohle bodies represent aggregates of

Answer 53

Rough endoplasmic reticulum

Question 54

Hyper segmentation is frequently associated with…

Answer 54

Deficiencies of vitamin b12 and folic acid

Question 55

Pelger-Huet Anomaly Mutation in the…

Answer 55

Lamin B-receptor gene

Question 56

True or false In PHA neutrophils function normally

Answer 56

True

Question 57

Has large dohle body-like inclusion

Answer 57

May-Hegglin Anomaly

Question 58

Mucopolysaccharide disorder that has skeletal deformities and mental retardation

Answer 58

Hunter syndrome

Question 59

Mycopolysaccharide disorder that has corneal clouding, umbilical hernia, dysostosis multiplex, hepato splenomegaly, upper respiratory infection, cognitive impairment, death before 10y

Answer 59

Hurler syndrome

Question 60

Gaucher disease Defect in the enzyme

Answer 60

B-glucocerobrosidase 1q21-q22

Question 61

Neimann-Pick Diesease Mutations in

Answer 61

SMPD1 gene Deficiency in acid sphingomyelinase (ASM)