Major Conditions Lymphocytosis With features of lymphocyte Active immune responses, especially in children.

transformation, ie, medium and large Immunizations; bacterial infections (pertussis); viral infections lymphocytes and plasmacytoid cells (infectious mononucleosis, mumps, measles, viral hepatitis, 1 rubella, influenza); toxoplasmosis Primary neoplasms some variants of chronic lymphocytic leukemia (CLL), lymphoma Majority resemble resting small lymphocytes

Immunology Mixed T and B cell (polyclonal)

T or B cell (monoclonal) 2

Chronic infections (tuberculosis, syphilis, brucellosis); Mixed T and B cell (polyclonal) autoimmune diseases (myasthenia gravis); metabolic diseases (thyrotoxicosis, Addison's disease) Primary neoplasms CLL, some small cell lymphomas T or B cell (monoclonal) 2 Nonmarking or T cell or B cell (monoclonal) 2 Abnormal cells are T or B cells (monoclonal) 2 often admixed with residual normal cells

Lymphocytes resemble fetal lymphoblasts Admixture of abnormal lymphoid cells (rare)

Primary neoplasms acute lymphoblastic leukemia, lymphoblastic lymphoma Primary neoplasms involvement of blood by lymphoma or myeloma

Lymphopenia Deficiency of T cells or B cells (or subsets thereof) or of both T and B cells Toxic drugs and chemicals; steroid therapy, Cushing's disease; early phase of marrow involvement by leukemia; immunodeficiency states

Peripheral Blood morhoplogy Normal numbers of neutrophils With shift to the left (less mature

Conditions Leukoerythroblastic anemia Primary neoplasms: early preleukemic myeloid leukemia

comments Physical replacement of BM by fibrosis/ neoplasms Leukemic marrow or any myeloproliferative disorders Vitamin 12 or folate levels decreased in blood; may also produce neutropenia

With shift to the right (more mature)

Megaloblastic anemias: folate antagonists

With abnormal giant granulocytes or inclusions

Mucopolysaccharidosis (AlderReilly; rare) ChdiakHigashi syndrome (rare) Toxic granules - severe infection (common)

Neutrophil leukocytosis Mainly mature segmented forms; mild left shift

high proportion of less mature cells (bands/ metamyelocytes); marked left shift high proportion of blasts; extreme left shift Neutropenia May occur alone or may accompany lymphopenia, thrombocytopenia, anemia

Metabolic diseases (uremia, gout); drugs (phenacetin, digitalis); postnecrosis (myocardial infarction, burns); postsurgery; acute infections (pyogenic cocci, Escherichia coli, Proteus, Pseudomonas, less often typhus, cholera, diphtheria) Leukemoid reaction (very severe acute infections, especially in child) Primary neoplasms: CML; less often, polycythemia rubra vera or myelosclerosis Primary neoplasms; AML and variants

Toxic granulation Giant toxic granules (Dhle bodies)

High leukocyte alkaline phosphatase (LAP) level. Low LAP level in CML Auer rods in blast cells

Variable

Infections: many viral (hepatitis, measles); some rickettsial rare bacterial (typhoid fever, brucellosis); malaria; any very severe infection (septicemia, miliary TB) Acute leukemia Drugs Marrow aplasia Vitamin B12, folate deficiency Autoimmune diseases; Felty's syndrome Familial cyclic neutropenia

Early phase Sulfonamides, analgesics, Including druginduced Antileukocyte antibodies Cyclic stem cell failure (?)

Etiologic Mechanisms and Causes of Neutropenia. 1. Decreased marrow proliferation a. Infantile neutropenia (Kostmann): a rare autosomal recessive disease manifesting with severe neutropenia at birth.

b. Cyclic neutropenia: usually familial, autosomal dominant with onset in childhood. Profound neutropenia lasts 34 days and occurs in cycles of about 3 weeks. c. Drugs that suppress granulopoiesis: anticancer drugs certain antihistamines, antithyroid drugs, tranquilizers gold salts, diuretics, penicillins, chloramphenicol, and antituberculous drugs. d. Radiation e. Megaloblastic anemia (decreased DNA synthesis). f. Aplastic anemias, certain refractory anemias. g. Marrow replacement by leukemia, lymphoma, fibrosis: leukoerythroblastic anemia. 2. Reduced peripheral granulocyte survival a. Viral and rickettsial infection b. Severe bacterial sepsis c. Drugs that cause immune destruction of granulocytes: phenylbutazone, cephalothin, aminopyrine d. Systemic lupus erythematosus and Felty's syndrome (immune destruction) e. Hypersplenism 3. Increased egress from circulation (pseudoneutropenia) a. Viral and rickettsial infections b. Histamine 4. Decreased mobilization from marrow a. Lazy leukocyte syndrome Abnormality Toxic granulation Dhle bodies Auer rods PelgerHut anomaly MayHegglin anomaly hronic granulomatous disease of childhood Appearance Cytoplasmic granules become coarse and more darkly staining 1 to 2m blue granules in cytoplasm Disease Infections and inflammatory disease As toxic granulation, plus myeloid leukemias (also seen in cyclophosphamide therapy) 1 to 4m red rods in blast cells Acute myeloblastic leukemia Bilobed or nonsegmented Hereditary; also myeloid neutrophils leukemias Basophil inclusions that resemble MayHegglin syndrome (giant Dhle bodies platelets and thrombocytopenia) Xlinked recessive Failure to produce peroxide by neutrophils, monocytes, leading to recurrent infections with catalaseproducing organisms ( Staphylococcus aureu s, Candida spp, gramnegative enteric bacilli, Aspergillus spp) Autosomal Asymptomatic Myeloperoxidase deficiency in neutrophils, recessive monocytes; usually no clinical effect Chromosomal Abnormality Philadelphia chromosome t(9;22) t(9;22) + 8, 2 isochromosome of 17 or 4 t(8;21), t(9;22) +8, 7, 5, 7q, 5q 7q, 5q t(9;11), t(11;23) t(15;17) Childhood

Myeloperoxidase deficiency

Type of Leukemia Chronic myelocytic leukemia (CML) CML in blast crisis Acute myeloblastic leukemia (AML) Erythroleukemia Acute monocytic leukemia Acute promyelocytic (M3) leukemia

Polycythemia rubra vera Acute lymphoblastic leukemia (ALL) Chronic lymphocytic leukemia (CLL)

20q 6q, t(4;11), t(9;22), t(8;14) +12

Type

Peroxidase Sudan Black

Chloroacetate Esterase

Nonspecific Esterase

Periodic AcidSchiff +

Morphologic Features Single nucleolus

Lymphoblastic (ALL) 1 Myeloblastic (AML) Monocytic Myelomonocytic Unclassified

Multiple nucleoli, Auer rods

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raditional Nomenclature

Lineage

T Cell Antigens (CD2, CD3, CD5, CD7, CD8) 2

B Cell Antigen (CD19) +

CALLA 3 (CD10)

Tdt Gene 4 Rearrangement Ig TCR

Null cell

Earliest recognizable B cell Early B cell Late fetal B cell T cell

Common 5 B cell 6 T cell

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