Introduction to Hematology by gks27426

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									Benign Leukocytoses
     Kristine Krafts, M.D.
 Pathology for Dental Students
N ORMAL N EUTROPHIL P HYSIOLOGY
Myeloid cell growth and differentiation

                                                                                                               B lymphocyte
                        B lymphoblast (L1 or L2)      (L3)
                                                                                                               T lymphocyte
                        T lymphoblast (L1 or L2)

                                                                                                                 Red cell
                              Proerythroblast
                                                                                                             º
                                                                                                                Platelets
                              Megakaryoblast                           Promegakaryocyte     Megakaryocyte   º º
     Stem cell
                                                                                                                 Basophil
                                                                                                                 Eosinophil
                              Myelo-
                              blast                                                                             Neutrophil
                                                Promyelocyte      Myelocyte        Metamyelocyte    Band


                                                                                                                 Monocyte
                           Monoblast            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)
Mechanisms of the neutrophil response
•   Demargination
•   Mobilization
•    Production
•    Transit time in blood
Stimulators of the neutrophil response
•   Colony-stimulating factor (CSF)
•   Catecholamines
•   Steroids
•   Endotoxins
•   Bone destruction




                                                    benign leukocytoses | 2 of 5
N EUTROPHILIC L EUKOCYTOSES
Proliferation of mature neutrophils
•   Infection. Look for toxic changes:
    • Toxic granulation
    • Döhle 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! Don’t 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.




     Döhle bodies
     infection                                                     leukoerythroblastotic reaction
                                                                   patient with metastatic carcinoma




                                            benign leukocytoses | 3 of 5
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%
    • NK 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)
   • immunoblasts




                                              benign leukocytoses | 4 of 5
megaloblasts




               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.
               Basophilia
               •   Normal = 0.01 - 0.1 x 109/L
               •   Basophilia: always rule out CML!
               Eosinophilia
               •   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




                                                           benign leukocytoses | 5 of 5

								
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