Benign Leukocytoses

Kristine Krafts, M.D. Pathology for Dental Students

N ORMAL N EUTROPHIL P HYSIOLOGY

Myeloid cell growth and differentiation
B lymphoblast (L1 or (L3) L2) T lymphoblast (L1 or L2) B lymphoblast (L1 or (L3) L2) T lymphoblast (L1 or L2) B lymphocyte T lymphocyte

B lymphocyte T lymphocyte

Proerythroblast

Red cell

Stem cell

Megakaryoblast

Megakaryocyte Promegakaryocyte

Platelets
Basophil Red cell

Proerythroblast

Stem cell

Megakaryoblast

Megakaryocyte Promegakaryocyte

Platelets
Basophil Eosinophil

Myeloblast Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte Band

Neutrophil Eosinophil Neutrophil

Promyelocyte

Myelocyte

Metamyelocyte Band

Monocyte Monoblast Monoblast Promonocyte Monocyte Promonocyte

Neutrophil pools
Marrow (95%) dividing = 25% storage = 75% Blood (5%) marginal = 50% circulating = 50%

Neutrophil count
Normal range = 2.0 - 8.0 x 109/L Physiologic variations: Hormone-related ( in pregnancy and menstruation, after menopause) Diurnal variation (evening > morning) Miscellaneous stuff (stress, smoking, and alcohol use all count)
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Mechanisms of the neutrophil response

Demargination Mobilization Production Transit time in blood Colony-stimulating factor (CSF) Catecholamines Steroids Endotoxins Bone destruction

Stimulators of the neutrophil response

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N EUTROPHILIC L EUKOCYTOSES
Proliferation of mature neutrophils
Infection. Look for toxic changes: Toxic granulation Dhle bodies Cytoplasmic vacuolization Inflammation Malignant disease Metabolic disease Redistribution

Proliferation of immature neutrophils

1. Left shift Definition: Increased early neutrophil precursors in blood. Causes: Infections. Remember: look for toxic changes! Inflammation/necrosis. Brisk hemolysis or hemorrhage. Space-occupying lesions in marrow, such as granulomas or cancer. 2. Leukemoid reaction (Bad term! Dont use!) Definition: Very high neutrophil count with or without marked left shift (looks like leukemia but it's not). Causes: Chronic infections. Remember: look for toxic changes! Malignancies. Severe stresses: metabolic, inflammatory, infectious. 3. Leukoerythroblastotic reaction (LEBR) Definition: Very early neutrophil precursors and erythroid precursors in blood Causes: Malignant (2/3 of cases): carcinoma, lymphoma, leukemia. Benign (1/3 of cases): anemia, sepsis.

Dhle bodies infection

leukoerythroblastotic reaction patient with metastatic carcinoma

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N ORMAL L YMPHOCYTE P HYSIOLOGY

Lymphocyte growth and differentiation
Most lymphoid stem cells in adults are in bone marrow. Growth factors (including IL-2) induce differentiation into T, B, and NK cell precursors which then travel to different organs (e.g., lymph nodes, spleen, thymus, mucosa- associated lymphoid tissue) for further processing.

Lymphocyte count
Normal range varies with age. Highest in infants (at 2 weeks: 2.0 - 17.0 x 109/L) Intermediate in children (at age 4: 2.0 - 8.0 x 109/L) Lowest in adults (by age 18: 1.0 - 4.0 x 109/L) Normal immunophenotype of blood lymphocytes: T cells: 60 - 80% B cells: 10 - 20% 00000000NK cells: 5 - 10%

L YMPHOID L EUKOCYTOSES
Proliferation of Mature Lymphocytes
Infectious lymphocytosis (lymphocyte count = 35 100 x 109/L) Whooping cough (Bordetella pertussis) (lymphocyte count = 10 55 x 109/L) Transient stress lymphocytosis (lymphocyte count = 6 8 x 109/L)

Proliferation of Reactive Lymphocytes

Types of reactive lymphocytes Downey I lymphocytes (small cells with lobed nuclei and scant, compact cytoplasm) Downey II lymphocytes (large cells with copious cytoplasm containing radial striations) Downey III lymphocytes (large cells with reticular chromatin) Plasmacytoid lymphocytes Plasma cells and their precursors (immunoblasts and proplasmacytes) Causes of reactive lymphocytosis Infectious mononucleosis (IM) lymphocyte count = 10 30 x 109/L Downey lymphocytes Pediatric viral infections (rubella, rubeola, mumps, chickenpox) lymphocyte count = 4 10 x 109/L Downey I lymphocytes proplasmacytes and plasma cells Viral hepatitis lymphocyte count = 4 10 x 109/L) proplasmacytes and plasma cells Immune disorders (autoimmune diseases, drug reactions, immunization)

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immunoblasts

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D IFFERENTIATING B ENIGN FROM M ALIGNANT L EUKOCYTOSES

Neutrophilic Leukocytoses
Left shift Fewer immature cells than in CML. Toxic changes present, if infectious cause. No basophilia. LAP normal or increased. Chronic myeloid leukemia (CML) WBC (50,000 - 100,000) Marked left shift with "bulges" at the myelocyte and segmented neutrophil stages. Basophilia. LAP (leukocyte alkaline phosphatase) decreased or absent.

Lymphoid Leukocytoses
Reactive lymphocytosis Increased number of atypical lymphocytes. Most commonly occurs in young patients (<40). Mature lymphocytosis Increased number of mature lymphocytes. Most commonly occurs in very young patients (<14). Chronic lymphocytic leukemia (CLL) Monomorphous population of mature-appearing lymphocytes. Generally occurs in older patients (>40).

O THER L EUKOCYTOSES
Monocytosis
Normal = 0.3 - 0.5 x 109/L Monocytosis may be associated with malignancies, autoimmune disease, and infection. Normal = 0.01 - 0.1 x 109/L Basophilia: always rule out CML! Normal = 0.05 - 0.3 x 109/L Frequent causes of eosinophilia: Drug allergies Bronchial asthma Skin diseases Occasional causes: Intestinal parasitism Chronic ulcerative colitis Chronic active hepatitis Sarcoidosis

Basophilia

Eosinophilia

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