Non-malignant reactive disorders of leukocytes

Non-malignant reactive disorders

• These cells only function is to protect the body against invasion.

• Undergo physical changes (that is evaluated microscopically)

LEUKOCYTOSIS

• Increase in on or more of the cell types

• Leukocyte count >11 x 109 /L

LEUKOPENIA

• Decrease in neutrophils, lymphocytes or all cell types

• Leukocyte count <3 x 109 /L

PANCYTOPENIA

Reduction in the number of RBCs, WBC, and platelets

Physiologic neutrophilia

• Response to therapy

• Physical or emotional stimuli

• “stimuli”: the neutrophils shift or marginates cells to the circulating pool (pseudoneutrophilia)

• Mediated by catecholamine release à Involves norepinephrine and epinephrine which is induced by stress

• Transient (only last a few hours)

Lithium

• A common antidepressant

• Can cause direct stimulation of hematopoiesis

Inflammatory

• There is a pathologic neutrophilia when it responds to tissue injury.

• Main mechanism: release of substances by the dead or dying cells that act as a chemotactic agent or marrow-releasing agents or stimulators of marrow cell production

Reactive neutrophilia

• Acute & Chronic

• Both are frequently accompanied by increased numbers of immature forms called as neutrophilic left shift

Neutrophilic shift

• increased numbers of circulating nonsegmented/ immature neutrophils

• increased neutrophilic bands and myelocytes

Agranulocytosis

is applied when there is an extreme neutropenia. Count: <0.5 x 109/L.

Toxic changes

• Increased numbers of immature forms (neutrophilic bands and metamyelocytes)

• Left shift

LEUKOERYTHROBLASTIC REACTION/ LEUKOERYTHROBLASTIC ANEMIA/ LEUKOERYTHROBLASTOSIS

• Left shift & circulating nucleated RBCs

• Associated with myelophthisis (Space-occupying lesions in BM)

• Also happen in hemolytic anemia, uremia, megaloblastic anemia (mild and transitory)

TOXIC GRANULES

• Altered primary granules: azurophilic, peroxidase (+)

• Stimulation by organisms or antigens

• Granulations for toxic granules may represent the precipitation of ribosomal protein or the RNA caused by the metabolic toxicity within the cells

• Large, dark blue-black

• Tendency to cluster within the cell

DÖHLE BODIES

• Cytoplasmic inclusions

• Consist of ribosomal RNA o Arrangement: arrayed in parallel rows

• In segmented and band neutrophils

• Closely apposed to the cell membrane

• Pale blue round/ elongated bodies (1-5 µm)

• Can be transient: seen 1-3 days after injury

CYTOPLASMIC DEGRANULATION

• Normal function of activated or injured neutrophils

• Accompanied by cellular membrane destruction

CYTOPLASMIC PSEUDOPODS (Pseudopodia)

• Granule-free protrusions (ameboid in movement)

• Indicative of depressed neutrophil locomotion

CYTOPLASMIC SWELLING

• Also called Macropolycyte

• There is a swollen or edematous neutrophil

• Osmotic swelling of cytoplasm

• Increased adhesiveness to glass

• Neutrophilic anisocytosis

PYKNOTIC NUCLEI (Pyknosis)

• Shrunken and dense

• Seen in: Cells about to die or dehydrated cell, Septic conditions, Poor staining or preparation techniques

NECROTIC / DEAD CELL

• Rarely seen in fresh specimen

• Nuclei: dense and broken into 2 or more rounded portion

• No evidence of filamentous connections

HYPERSEGMENTED NEUTROPHIL (Hypersegmentation)

• Chronic infections

• Neutrophil is large or normal in size with hypersegmentation

• May reflect Vitamin B12 or folate deficiency

TOXIC NUCLEAR PROJECTIONS (Nuclear Projections)

• Hair-like projections seen in band forms (inner side)

• Patients with metastatic CA or after radiation

RINGED NUCLEI (Ring-shaped nuclei)

• Toxic states

• Malignant myeloproliferative disorders

• Early infection

TRUE

TRUE OR FALSE: Eosinophil attraction is T-lymphocyte directed and antibody-dependent

EOSINOPENIA

• Characteristic finding of acute bacterial infections

• ACTH administration

DEGRANULATION

• Most prominent alteration

• Reported if specimen is fresh

Hormones

Basophilia is caused by?

• Day

• Age

• Physical activity

Basophilia is not affected by these factors:

• Stress

• Acute infections

• Hyperthyroidism

• Increased levels of glucocorticoids

Basopenia is caused by:

Monocytosis

indicates recovery from agranulocytosis or bone marrow hyperplasia.

Variant lymphocytes

• This term is applied when lymphocytes are found in reactive disorders.

• Benign in nature

• Normal cells that are altered as a result of a normal response to a stimulus

TYPE I LYMPHOCYTES

• Plasmacytoid lymphocyte or Türk’s irritation cell

• Differentiated cells

• Immunocompetent cells of B-cell origin

TYPE II LYMPHOCYTES

Predominate in IM (IM Cell)

TYPE III LYMPHOCYTES

• Transformed/ Reticular Lymphocytes

• In an intermediate stage of transformation

INFECTIOUS MONONUCLEOSIS (IM)

• Other name “kissing” disease”

• Viral disease caused by Epstein Barr Virus (EBV)

• Teenagers/ young adults

• Self-limited & benign

• Reactive lymphocytes (Type II: IM Cell)

• (+) serologic test for Heterophil Ab

• Lymphatic involvement: posterior cervical lymph nodes

CYTOMEGALOVIRUS (CMV)

• Most common agent causing fetal infection

• Closely resembles IM

• Difference: no tonsillitis or enlarged lymph nodes in CMV

• Part of Β-group Herpes Virus

• Can be found in urine, oral & cervical secretions, semen, and leukocytes

• Transmission in adult is venereal or by blood transfusion

• Increased incidence in homosexual males

• Implicated as a possible agent of Kaposi’s sarcoma

ACUTE INFECTIOUS LYMPHOCYTOSIS

• Benign, self-limiting

• Children 1-10 years old

• Viral infection caused by enterovirus Coxsackie group A or nonviral

BORDETELLA PERTUSSIS INFECTION

• 70-90% of leukocytes are normal lymphocytes

• This is due to redistribution from tissue pools to circulating pools

Lymphocyte-promoting factor (LPF)

attaches to lymphocytes and blocks their movement from blood to lymph nodes thus increasing the number of circulating lymphocytes

LEUKEMOID REACTIONS

• Reactive leukocytoses resembling blood picture seen in leukemia

• it is differentiated from chronic myelogenous leukemia through LAP score by performing Leukocyte Alkaline Phosphatase (LAP) stain

• Total WBC: > 50 x 109/L or blast forms found in blood (myeloid or lymphoid)

TOXOPLASMOSIS

• Caused by Toxoplasma gondii (protozoa)

• Heterophil antibody (-)

• Fever and lymphadenopathy (generalized)

• General involvement of lymphatic tissue

• Splenomegaly & sore throat (less common)

• Relative increase in lymphocytes and presence of reactive lymphocytes

LYMPHOPENIA

• Decreased production

• Alterations in lymphocyte traffic

• Lymphocyte destruction