Nonmalignant WBC Disorders

3rd, 4th editions: Chapters 21, 22

Leukocytes (all WBCs)
• Quantitative/qualitative changes normal response
– Disease processes
– Toxic challenges
• Normal ranges lab established (age, sex, ethnicity)
– Leukocytosis : WBC > 11.0 x103/µL
– Leukopenia : WBC < 4.5 x103/µL
• Microscopic evaluation
Neutrophils [40-80%]
• Quantitative disorders
– Majority WBC fluctuations attributed to neutrophil counts
• Benign (nonmalignant) – normal physiologic response
• Malignant – neoplastic transformation of HSC
– Neutrophilia [reactive] (ANC) > 7 x103/µL (> 8.8 x103/µL)
– Neutropenia [granulocytopenia] < 1.8 x103/µL
• Qualitative disorders
– Nuclear and cytoplasmic abnormalities
Neutrophilia
• Immediate (segs)
– Transient pseudoneutrophilia
– Demargination from exercise, anxiety, medications, etc
• Acute (segs, bands, metas)
– BM egress (left shift) from *bacterial infection*, toxin
• Chronic (segs, bands, metas, myelos)
–  BM production from persistent acute stimulus
Neutrophilia
• WBC < 50 x103/µL with left shift
– NE toxic granulation, Döhle bodies, vacuolization
– ↑ Leukocyte alkaline phosphatase (LAP)
• Associated conditions
– *Bacterial infections* (ANC = 10-25 x103/µL)
– Tissue destruction/injury, inflammation
– Leukemoid reaction in severe infections, tissue necrosis
– Leukoerythroblastic reaction (HDN, MPN)
Neutrophilia
Neutropenia
• Agranulocytosis (ANC < 0.5 x103/µL)
– Decreased immunity, susceptible to infections
– ↓ basophils and eosinophils
• Associated conditions
– ↑ immune destruction (↑ cell loss)
– ↓ BM production (M:E?)
– ↑ neutrophil margination/tissue egress (pseudo)
– Erroneous (in vitro artifacts – aged sample)
Nuclear Abnormalities Disorder?

• Hypersegmentation
• Pyknotic/dying nucleus
Nuclear Abnormalities
• Pelger-Hüet (function normal)
– ↓ segmentation of the granulocyte nucleus
• coarse chromatin clumping in nucleus
– Homozygote = round/oval nucleus
– Heterozygote = bilobed
 Cytoplasmic Abnormalities
• Severe infections, burns, cancer, toxic drugs
– Döhle bodies
• Aggregates of RER = gray-blue
inclusions in cytoplasm of neutrophils or
eosinophils
– Toxic granulation
• Large, deeply staining blue-black primary
granules in segs, bands and metas
– Cytoplasmic vacuoles
Cytoplasmic Abnormalities
• Intracellular organisms
– Bacteria, yeast (Candida), Erlichia (morulae)
 Inherited Functional Abnormalities
• Alder-Reilly (Hunter's/Hurler's syndrome)
– Aggregate of incomplete mucopolysaccharides degradation
– Large, purplish granules in cytoplasm of all WBCs
– Metachromatic stain with toluidine blue
– Cells function normal
 Inherited Functional Abnormalities
• Chédiak-Higashi
– Fusion of primary + secondary granules in NEs and LYs
• Decreased bactericidal effect
• Giant green-gray bodies
 Inherited Functional Abnormalities
• May-Hegglin
– Cytoplasmic inclusions of RNA from RER
– Blue, large, and round Dohle-like bodies in all granulocytes
– Cells function normal
– Giant platelets
Lymphocytes [25-35%]
• Lymphocyte normal counts differ with age
– Higher in children [>65%]
• Rare cause of leukocytosis
• Lymphocytosis > 4.8 x103/µL (> 3.9 x103/µL)
– Normal, self limited reactive response to
infection/inflammatory process
• Involves B and T cells
• Lymphocytopenia < 1.0 x103/µL (adults)
Lymphocytosis
• Lymphocytes become activated/reactive/atypical
• Absolute lymphocytosis (> 4.8 x103/µL)
– Infectious mononucleosis
– Infectious lymphocytosis
– Bordetella pertussis
• (Whooping cough)
– CMV
– Lymphocytic leukemia
Lymphocytosis
• Infectious Mononucleosis
– Self-limiting infection with Epstein-Barr
virus (EBV)
• Benign, peak age 14–24 years
• Viral infection of B lymphocytes
– Limited by T lymphocytes
– PB > 20% reactive lymphocytes, ↓ PLT
– Serologic test heterophile Ab +
• Nonspecific for EBV
 Lymphocytosis
• Toxoplasmosis
– Toxoplasma gondii (intracellular
protozoan)
• Cytomegalovirus (CMV)
– Herpes-group virus
• Laboratory findings:
– Negative heterophile Ab
– Require specific serologic tests for diagnosis
– ↑ reactive lymphocyte forms
Lymphocytosis
• Reactive Lymphocytosis
– Adenovirus, coxsackie virus, Bordetella pertussis
• Small, normal, not reactive lymphocytes
• Plasmacytosis
– Occasionally seen in intense viral, bacterial
infections
– Morphologic variation is flame cell (red-purple
cytoplasm)
• Contain more Ig than normal plasma cells
Lymphocytopenia
• Results from ↓ production or ↑ destruction
– Adults < 1.0 x103/µL
– Children < 3.0 x103/µL
• Acquired Immune Deficiency Syndrome (AIDS)
– HIV-1 retrovirus (not all infected have AIDS)
• Infects TH lymphocytes (via CD4 receptor)
– DNA incorporation
• Selective depletion [lysis] of this lymphocyte subset
– Inverted CD4/CD8 ratio (normal 2:1)
Lymphocytopenia
• Congenital Immune Deficiency Disorders
– Wiskott-Aldrich syndrome
• Progressive ↓ CD4+, CD8+ T lymphocytes
• ↓ or absent Abs to blood group Ags
– DiGeorge syndrome
• Absence or hypoplasia of the thymus
• ↓ peripheral blood T lymphocytes
Other Leukocytes
• Monocytosis > 0.8 x103/µL
– Myeloid neoplasms (CML, CMML, some ALs)
• Hypereosinophilia (HE) > 0.4 x103/µL
– Helminthic parasites
• Basophilia > 0.2 x103/µL
– Immediate hypersensitivity reactions
– Chronic myeloproliferative diseases (PV, IMF, ET, CML)
 Qualitative Disorders
• Gaucher disease
– Deficiency of β-glucosidase (glucocerebrosidase)
• Lipid accumulates in macrophages
• Cytoplasm wrinkled or striated
• Large (20–100µm)
• Small eccentric nuclei
 Qualitative Disorders
• Neimann-Pick disease
– Deficiency in sphingomyelinase
• Enzyme needed to break down lipids
– Foamy macrophages
– Large (20–100 µm)
– Eccentric nucleus
– Globular cytoplasmic inclusions