LEUCOCYTE DISORDERS

1
LEUCOCYTE DISORDERS NON-NEOPLASTIC DISORDERS OF
LEUCOCYTES
2

• NEUTROPHILS
• NEUTROPENIA (lt1.5 ? 109/L)
• Drug-induced, e.g. cancer chemotherapy,
  chloramphenicol.
• Immune neutropenia (antibodies to surface
  antigens) associated with autoimmune disorders
  (SLE or RA).
• Myelodysplastic syndromes (MDS).
• Infections HIV, increased utilization,
  increased adherence to damaged endothelium.
• Chronic idiopathic neutropenia possibly a
  mixture of congenital and acquired disorders.
• Congenital neutropenia, e.g. Kostmann's syndrome
  (very rare).
• Cyclic neutropenia (three week intervals), due
  to abnormal regulation of haemopoietic stem
  cells.
• Diagnosis BM helps to discriminate between
  peripheral destruction and decreased
  production.
• Management Remove underlying cause. Granulocyte
  transfusion has risk of alloimmunisation and
  CMV.

3
NEUTROPHILIA Often accompanied by other reactive
changes, e.g. atypical lymphocytes. Varied
aetiology, e.g. excercise, emotional (anger,
stress), inflammation, infection, chemicals or
drugs (glucocorticoids, epinephrine, G-CSF),
tumours, smoking. Left shift results from
increased granulopoiesis. Leukaemoid reactions
must be distinguished from CML. Morphological
changes include Döhle bodies (aggregates of
polyribosomes), toxic granulation (persistence of
primary granules) and cytoplasmic vacuolation.
4
FUNCTIONAL / MORPHOLOGIC DISORDERS OF NEUTROPHILS
Chediak-Higashi Syndrome Large cytoplasmic
granules in all leucocytes autosomal
recessive. Neutropenia, thrombocytopenia and
marked hepatosplenomegaly. Recurrent infections.
5
Chronic Granulomatous Disease (CGD) Impaired
generation of oxygen metabolites ingestion but
no killing of catalase-positive organisms.
Recurrent infections with catalase-positive
organisms, e.g. Staph. aureus Myeloperoxidase
Deficiency Diminished lysosomal effectiveness of
hydrogen peroxide. Other enzyme deficiencies
Lack of glutathione reductase, oxidase or
catalase.
6
May-Hegglin Anomaly Döhle bodies (RNA) in
granulocytes and monocytes thrombocytopenia with
giant platelets autosomal dominant inheritance.
Giant platelets
Döhle body
7
Alder-Reilly Anomaly Prominent red-purple
granules in neutrophils.
Pelger-Hüet Anomaly Bilobed or monolobed
granulocytes autosomal dominant inheritance.
Unsegmented eosinophil
8
Bone marrow transplantation and gene therapy are
currently being evaluated as possible remedies
for those neutrophil and monocyte disorders of
clinical concern. Diagnostic tests are not widely
available (difficult to control and
interpret). The more useful tests
include (a) Nitroblue tetrazolium (NBT) dye
reduction test. Reduction of NBT to insoluble
formazan is stimulated by normal phagocytosis of
bacteria by neutrophils. Markedly decreased in
CGD.  (b) Quantitative ingestion of labelled
particles (latex, bacteria, yeast) to test
phagocytic capacity.
9
EOSINOPHILS EOSINOPENIA occurs in association
with acute infections and with administration of
adrenocorticotropic hormone (ACTH),
prostaglandins, epinephrine and
glucocorticoids. An eosinophil-specific absolute
count must be performed as the eosinophil
percentage of the WBC is not accurate for low
counts.
EOSINOPHILIA (gt0.5 ? 109/L) is associated with
parasitic infestation, allergic states (asthma,
drug reactions) and neoplasms (e.g. CML).
10
BASOPHILS / MAST CELLS BASOPENIA is not readily
apparent or actively investigated. BASOPHILIA
(gt0.1 ? 109/L) is seen in reactive immunologic
conditions, e.g. IgE-mediated hypersensitivity or
in chronic inflammatory disorders, e.g.
RA. Basophilia is commonly found in CML (poor
prognosis). MASTOCYTOSIS (concentration of mast
cells) is seen locally in tissues associated with
hypersensitivity reactions and in lymph nodes or
bone marrow affected by low-grade
lymphoproliferative disorders.
11
MONOCYTES / MACROPHAGES   MONOCYTOPENIA is most
frequently part of a general leocopenia seen in
autoimmune disorders (e.g. SLE), hairy cell
leukaemia (HCL) or chemotherapy.   MONOCYTOSIS
(gt1.0 ? 109/L) is seen in MDS, leukaemias,
lymphoma, myeloma and TB.  
12
LANGERHAN'S CELL HISTIOCYTOSIS (LCH)
Langerhan's cells are dendritic cells derived
from bone marrow precursor cells. They can
proliferate and invade organs and tissues
producing a collection of disorders previously
known as Histiocytosis X. Ultrastructural
examination shows Birbeck granules.
13
HAEMOPHAGOCYTIC SYNDROMES These disorders usually
result from viral infection. Patients present
with significant anaemia, thrombocytopenia and
leucopenia. Bone marrow, lymph nodes, liver or
spleen contain tissue macrophages full of
phagocytosed blood cells.
14
LYMPHOCYTES LYMPHOCYTOPENIA (lt1.0 ?
109/L) Decreased production, e.g. congenital
immunodeficiency, aplastic anaemia or
chemotherapy. Increased destruction, e.g. HIV or
autoimmune disorder. Maldistribution, e.g.
abnormal thorasic duct drainage.   LYMPHOCYTOSIS
(gt4 ? 109/L) must distinguish non-neoplastic
from neoplastic, e.g. CLL, ALL.
15
MONONUCLEOSIS SYNDROMES The most common cause of
benign lymphocytosis. Epstein-Barr virus (EBV)
and CMV are the most notable. Hepatitis virus,
adenovirus, Toxoplasma gondii and HIV can all
produce heterophile antibody-negative
mononucleosis. Atypical Lymphocytes (T-cells)
increased basophilic cytoplasm, less mature
nuclear chromatin and a tendency to show moulding
around adjacent red cells. The E-B virus attaches
to receptors on B-cells that induce a T-cell
proliferation. The T-cells are cytotoxic for
infected B-cells which then release antigen.
16
Heterophile Antibodies reactive against sheep,
horse and bovine red cells but not guinea pig red
cells. These IgM antibodies are generated in
response to antigen released from infected
B-cells. They give a positive Monospot test with
EBV but not other causes of mononucleosis. Mononuc
leosis syndromes are self-limiting and specific
treatment usually is unnecessary.
17
INFECTION-INDUCED LYMPHOCYTOSIS lymphocytes are
normal in appearance, mature and
small. Bordetella pertussis infections are
associated with significant lymphocytosis. Acute
infectious lymphocytosis is a contagious disorder
of unknown aetiology.
18
IMMUNODEFICIENCY DISORDERS Impaired B-cell
function bacterial infections Impaired T-cell
function viral, fungal, opportunistic
infections Severe combined immunodeficiency
disorder (SCID) haemopoietic stem cell defect
(autosomal recessive). Adenosine deaminase (ADA)
deficiency absence of T-cells due to toxic
effect of adenosine metabolites in the
thymus. IgA deficiency most common primary
immunodeficiency. Allo anti-IgA can cause
anaphylactic reactions to transfused
blood. Wiskott-Aldrich syndrome eczema,
thrombocytopenia, decreased T-cells. X-linked
agammaglobulinaemia (Bruton's disease) normal T
cell function but absence of mature
B-cells. Duncan's disease inadequate T-cell
response permits excessive B-cell
proliferation. di George syndrome T-cells
decreased due to thymic hypoplasia. Acquired
immune deficiency syndrome (AIDS) CD4 cells
affected, e.g. T-cells, monocytes, astrocytes.
19
REACTIVE LYMPHADENOPATHIES lymph nodes enlarge
due to inflammation, infection or
cancer. Follicular hyperplasia reflects B-cell
reactivity. Diffuse paracortical hyperplasia
reflects T-cell reactivity. Mixed patterns with
both follicular and diffuse components are
common. Granulomatous patterns feature aggregates
of histiocytes and lymphocytes in response to
foreign material or as a consequence of
cell-mediated immunity, e.g. TB, toxoplasmosis
and fungal infections.