NON-NEOPLASTIC WHITE BLOOD CELL DISORDERS Flashcards
Cellular Morphology
• Nuclear Characteristics
• Shape
• Presence/Absence of nucleoli
• Chromatin Pattern
Cellular Morphology
Cytoplasmic Characteristics
VIGSSQ
• Shape
• Granulation
• Quantity
• Staining color and intensity
• Vacuolation
• Inclusion Bodies
• 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
Morphology Changes
MORPHOLOGIC ABNORMALITIES OF LEUKOCYTE
TNDMLAP
- Toxic Granulation
- Neutrophil Hypersegmentation
- Dohle Bodies
- May-Hegglin Anomaly
- Lysososmal Storage Disease
- Alder-Reily Anomaly
- Pelger-Huet Anomaly
Prominent dark granulation, either fine or heavy = can be observed in band and segmented neutrophil or monocytes
TOXIC GRANULATION
• Represent the precipitation of ribosomal protein (RNA) = caused by metabolic toxicity within the cells
TOXIC GRANULATION
TOXIC GRANULATION
Azurophilic (primary) granules are…
peroxidase positive
• ASSOCIATED with infectious states, in conditions such as burns and malignant disorders or as the result of drug therapy
TOXIC GRANULATION
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.
Toxic granulation
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
DOHLE BODIES
● 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
Dohle bodies
Dohle bodies
Delay in preparation of smears make the inclusion more_____ than _____ or may not be visible at all
grey than blue
Dohle bodies
Nonspecific conditions: VBBIPS
- Bacterial infections
- Sepsis
- Pregnancy
- Vira infections
- Burns
- Intake of certain drugs
Autosomal dominant
• More that FIVE lobes or nuclear segmentation
Hyper segmentation
• Frequently associated with deficiencies of vitamin B12 or folic acid and exists along with abnormally enlarged,
oval shaped erythrocytes
Hyper segmentation
● HYPERsegmentation of Neutrophils (>5 lobes)
● if Acquired hypersegmentation: most often associated with Megaloblastic Anemia (Vit B9 or B12 deficiency)
Undritz Anomaly
• Benign, autosomal dominant disorder
Decreased nuclear segmentation
• Distinctive coarse chromatin clumping pattern
• NUCLEI: appear round, ovoid or peanut shaped
Pelger - Huet Anomaly (PHA)
• Mutation in the lamin B-receptor gene
• Neutrophils function formal
Pelger Huet Anomaly
HYPOlobulation / HYPOsegmentation (2 lobes) of neutrophils: failure of segmentation of granulocytic nuclei
○ Pince-nez (Spectacle-like)
○ Peanut
○ Dumbbell
○ cells have normal function
Pelger Huet Anomaly
Morphologic Abnormalities of Leukocyte
PHA vs Myelocyte/Metamyelocyte
Pelger Huet Anomaly
Cell size is smaller
N:C ratio is lower
Chromatin is darker, more coarse, more densely clumped
Colorless cytoplasm
PHA vs Myelocyte/Metamyelocyte
Myelocyte/Metamyelocyte
Relatively bigger
N:C ratio is higher
Cytoplasmic basophilia (+) neutrophilic left shift
One of the important characteristics we have to observe for in the Pelger-Huët Anomaly is the
“Pince-nez” morphology (Spectacle like)
Morphologic Abnormalities of Leukocyte
True PHA vs Pseudo PHA
PELGER-HUET ANOMALY vs
PSEUDO-PELGER-HUËT ANOMALY
Number of Affected Cells???
PELGER-HUET ANOMALY - 63%-93%
PSEUDO-PELGER-HUËT ANOMALY - <38%
All WBC Lineages are potentially affected
Examination of Family Member’s PBS may reveal same findings (Because it is Inherited - Autosomal Dominant)
PHA
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)
Pseudo PHA
Nuclear chromatin condenses —> segments disappear —> dark-staining spheres
● Apopotopic nucleus
● Dying neutrophils
Pyknotic nucleus
• LBR mutations impair nuclear membrane remodeling, causing neutrophils to remain in an immature, bilobed form.
• Despite the abnormal morphology, neutrophils retain normal function
PHA
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.
Pyknosis
Pyknotic nucleus
X or Sex Chromatin
● Deactivated or inactive X chromosome → also known as
Barr bodies
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
barr body
AUER RODS FORM CLUSTER
• Suggestive of Acute Promyelocytic Leukemia
• Usually forms in the cytoplasm of promyelocytes or blast
Faggot Cells
Faggot cells
: Pink or red stained needle like crystals in the cytoplasm of myeloid cells
AUER RODS
Faggot cells
Agglomeration of primary granules
Positive for: MEA
Diagnostic of…
Myeloperoxidase
esterase
acid phosphatase
myeloid neoplasm
Autosomal dominant disorder
• Variable thrombocytopenia, giant platelet, and large Dohle body-like inclusion in neutrophils, eosinophils, basophils and monocytes
May-Hegglin Anomaly
May Hegglin
• MUTATION:_____ gene on chromosome_____
Affects megakaryocyte maturation and platelet fragmentation when shedding from megakaryocytes
MYH9; 22q12-13
• 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)
May Hegglin anomaly
• Group of more than 50 inherited enzyme deficiencies resulting from mutations in genes that code for the production of lysosomal enzymes.
Lysosomal Storage Disease
• Flawed degradation of phagocytized material and buildup of undigested substrates within lysosomes
• All cells containing lysosomes can be affected
Lysosomal storage disease
• This includes:
• Shpingolipidoses, oiligosachraridoses,
mucolipidoses, mucopolysaccharidoses (MPS), lipoprotein, storage disoders, and lysosomal transport defects.
Lysosomal storage disease
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
Mucopolysaccharisoses
Lysosomal Storage Disease
• SPHYNGOLIPIDOSES (2)
• GAUCHER DISEASE
• NIEMANN-PICK DISEASE (FOAM CELLS)
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.
• GAUCHER DISEASE
- abundant fibrillar blue-gray cytoplasm with a striated or wrinkled appearance (sometimes described as onion skin-like)
GAUCHER CELLS
SPHYNGOLIPIDOSES
• B-glucosidase(glucocerebrosidase) is available to confirm diagnosis
• TREATMENT: enzyme replacement therapy with recombinant glucocerebrosidase
• GAUCHER DISEASE
• GAUCHER DISEASE
stains positive with: TAPA
- Trichome
- Aldehyde Fuchsin
- Periodic Acid Schiff
- Acid Phosphatase
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
• NEIMANN-PICK DISEASE
- macrophage with lipid-filled lysosomes that appear as small vacuoles; nucleus is eccentric
FOAM CELL
• NEIMANN-PICK DISEASE
• NEIMANN-PICK DISEASE
Stains positive with: SO
- Sudan Black B
- Oil Red 0
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
• SEA BLUE HISTIOCYTES
Autosomal recessive
• Characterized by granulocyte (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules
•______ = granulation
• Also found in mucopolysaccharidoses
Alder - Reilly Anomaly
REILLY BODIES
Autosomal recessive
• Characterized by granulocyte (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules
•______ = granulation
• Also found in mucopolysaccharidoses
Alder - Reilly Anomaly
REILLY BODIES
Toxic granulation
Represent the precipitation of…
Ribosomal protein
Dohle bodies represent aggregates of
Rough endoplasmic reticulum
Hyper segmentation is frequently associated with…
Deficiencies of vitamin b12 and folic acid
Pelger-Huet Anomaly
Mutation in the…
Lamin B-receptor gene
True or false
In PHA neutrophils function normally
True
Has large dohle body-like inclusion
May-Hegglin Anomaly
Mucopolysaccharide disorder that has skeletal deformities and mental retardation
Hunter syndrome
Mycopolysaccharide disorder that has corneal clouding, umbilical hernia, dysostosis multiplex, hepato splenomegaly, upper respiratory infection, cognitive impairment, death before 10y
Hurler syndrome
Gaucher disease
Defect in the enzyme
B-glucocerobrosidase
1q21-q22
Neimann-Pick Diesease
Mutations in
SMPD1 gene
Deficiency in acid sphingomyelinase (ASM)
