Benign Disorders of White Blood

Cells
Dr Afshan Sumera
Session outcomes
 You should have learnt at end of this session to:
 Explain the categories of the various qualitative alterations of
leukocytes.
 Describe procedures performed for the detection and
diagnosis of qualitative alterations of leukocytes.
 Discuss the disease states/ conditions seen in qualitative
alterations of leukocytes.
 Differentiate the peripheral blood findings seen in qualitative
alterations of leukocytes.
 Classify various quantitative alterations of leukocytes.
 Define relative and absolute values
 List the major causes of quantitative alterations of leukocytes
 The white cells (Leukocytes)

Function in protecting the body

against infection is closely
connected with
1. Immunoglobulins
2. Complement system
Normal counts
Leukocytes
Formation of the neutrophil and monocyte
phagocytes

Eosinophils and basophils are also formed in the marrow in a process similar to that for neutrophils.
Granulopoiesis

Myeloblast Metamyelo
cyte

Proliferative
Promyelo
cyte or mitotic Band
Post-mitotic
pool pool

Myelocyte Segment
ed
Absolute cell counts
 Absolute count = absolute cell value =
total leukocyte count x percentage of cell type

 Total leukocytes: 4.00-11.0 x 109/L

 Neutrophils: 2.5–7.5 x 109/L
 Lymphocytes: 1.5–3.5 x 109/L
 Monocytes: 0.2–0.8 x 109/L
 Eosinophils: 0.04-0.4 x 109/L
 Basophils: 0.01-0.1 x 109/L
Question

Identify this cell

A. Lymphocyte
B. Blast
C. Myelocyte
D. Monocyte
E. Promyelocyte
Question
Which of the two cells shown here is most likely to
be phagocytic ?

A. monocyte
B. neutrophil
C. lymphocyte
D. basophil
E. myelocyte
Disorders of neutrophil and monocyte
function
 Normalfunction of neutrophils and
monocytes may be divided into three
phases

1. Chemotaxis (cell mobilization & migration)

2. Phagocytosis
3. Killing & digestion
Phagocytosis & bacterial destruction
 Defects of phagocytic cell function
 Chemotaxis
 Congenital abnormalities
 Lazy leukocyte syndrome
 Drugs
 Corticosteroid therapy
 Abnormalities of WBC
 Acute or chronic myeloid leukemia
 Myelodysplasia
 Myeloproliferative syndromes
Defects of phagocytic cell function
 Phagocytosis (lack of opsonisation)

 Congenital or acquired causes of

hypogammaglobulinaemia

 Lack of complements components

Defects of phagocytic cell function
 Killing
 Chronic granulomatous disease
 Myeloperoxidase deficiency
 Chediak- Higashi syndrome

 Acute or chronic myeloid leukaemia and myelodysplastic

syndromes may also be associated with defective killing of
ingested microorganisms.
 Benign disorders- Hereditary
 Pelger-Huet anomaly
 Uncommon
 Autosomal dominant inheritance
 Bilobed neutrophils in peripheral blood

 May-Hegglin anomaly
 Rare
 Neutrophils contain basophilic RNA inclusions
 Mild thrombocytopenia & giant platelets
 Autosomal dominant inheritance

 Chediak-Higashi syndrome
 Autosomal recessive inheritance
 Giant granules
 Neutropenia, thrombocytopenia
 hepatosplenomegaly
Neutrophils-
Morphological abnormalities

 Hypersegmented neutrophils (megaloblastic

anaemia)

 Dohle bodies & toxic granulation (infection)

 Drumstick appearance (females with two x

chromosomes)

 Pelger cells (myeloid leukemia, myelodysplasia)

Abnormal white blood cells

basophilic inclusions
toxic changes Dohle body hypersegmented

pince nez configuration giant granules violet granules in the cytoplasm of a

neutrophil
 Causes of leucocytosis & monocytosis
 Neutrophil leucocytosis (>7.5 x 109/L) may associated
with
 Fever
 ‘Shift to left’ in peripheral blood differential white cell count
 Increase in band forms
 Occasional presence of metamyelocytes & myelocytes
 Presence of cytoplasmic toxic granulation & Dohle bodies
 Elevated neutrophil alkaline phosphatase (NAP) score

toxic granulation Dohle body

 Causes of neutrophil leucocytosis
Bacterial infections
• Pyogenic bacterial (localized or generalized)

Inflammation & tissue necrosis

•Myositis, vasculitis, cardiac infarct, trauma

Metabolic disorders
• Uraemia, eclampsia, acidosis, gout

Neoplasms
• Carcinoma, lymphoma, melanoma

Acute haemorrhage or haemolysis

Drugs
• corticosteroids

CML, Myeloproliferative disease, polycythemia vera, myefibrosis,

essential thrombocythaemia

Treatment with myeloid growth factors

The leukaemoid reaction
 Reactive & excessive leukocytes
 Presence of immature cells (myeloblasts,
promyelocytes & myelocytes) in peripheral blood
 Associated disorders
 Severe or chronic infections
 Severe haemolysis
 Metastatic cancer
 Toxic granulation, dohle bodies & High NAP score
help to differentiate from chronic myeloid leukemia
Eosinophilic leucocytosis (eosinophilia)

 Above 0.4 x 109/L

 Hypereosinophilic syndrome
 No underlying cause of eosinophilia
 >1.5 x 109/L for six months
 Tissue damage
Eosinophilia
 Causes of eosinophilia
Allergic diseases
• Bronchial asthma, hay fever, urticaria, food sensitivity

Parasitic diseases
• Amoebiasis, hookworm, ascariasis, tapeworm infestation, filariasis

Recovery from acute infection

Skin diseases
• Psoriasis, pemphigus

Drug sensitivity

Polyarteritis nodosa, vasculitis, serum sickness

Graft-versus-host disease
Basophil leucocytosis (Basophilia)
 Above 0.1 x 109/L (uncommon)
 Myeloproliferative disorders
 Chronic myeloid leukaemia

 Polycythaemia vera

 Reactive increase
 Myxoedema

 Chicken pox

 Ulcerative colitis
 Monocytosis
 Above 0.8 x 109/L (usually infrequent)

Chronic bacterial infections Connective tissue diseases

• SLE,
•Tb, brucellosis, • Rheumatoid arthritis Protozoan infections
•bacterial endocarditis,
•typhoid

Hodgkin’s lymphoma, AML & Chronic myelomonocytic

Chronic neutropenia
other malignancies leukaemia
Neutropenia
 Lower limit of the normal neutrophil count is
2.5 x 109/L except in black people and in the
Middle East where 1.5 x 109/L is normal
 below 0.5 x 109/L results in
 Recurrent infections
 Neutropenia
 Selective or part of general pancytopenia
 Causes of neutropenia

Congenital Acquired Benign Cyclical Immune Infections

Kostmann’s Racial or Auto-

Viral
syndrome
Drug familial immune
induced
Fulminant
Anti-
inflammatory
SLE Bacterial
(typhoid)
drugs,
Antibacterial
drugs, Felty’s
Anticonvulsants, syndrome
Antithyroids
Hypoglycaemics
Psychotropics Hyper-
sensitivity &
anaphylaxis
 Neutropenia
 Congenital neutropenia
 Kostmann’s syndrome
 Autosomal recessive disease
 Life threatening infections (first year of life)
 Mutation of gene coding for neutrophil elastase
 Drug induced
 Induce neutropenia by direct toxicity or immune-mediated damage
 Cyclical
 Rare syndrome with 3-4 week periodicity
 Autoimmune
 Antibody against neutrophil specific antigens
 Idiopathic benign neutropenia
 Africans, in Middle East
 Neutropenia- Clinical features
 Infections of mouth & throat
 Ulcerations
 Septicaemia
 Staphlococcus epidermidis
 Gram negative organisms

 Diagnosis by Bone marrow

examination
Histiocytic disorders
 Dendritic cells
 Specialized antigen-presenting cells
 Skin, lymph nodes, spleen & thymus
 Comprise myeloid & monocyte-derived cells
 Langerhans’ cells
 Antigen presentation to T & B lymphocytes
Langerhans' cell histiocytes
 Langerhans' cell histiocytosis (LCH)
 Previuosly known as histiocytosis X, LettererSiwe
disease, Hand-Schiiller-Christian disease and
eosinophilic granuloma
 Single organ or multisystem
 lesions include Langerhans' cells
 presence of tennis racquet shaped Birbeck granules
 Haemophagocytic Lymphohistiocytosis
(haemophagocytic syndrome)
 Rare
 Recessive inherited or acquired (viruses EBV or herpes
virus, bacterial or fungal infection)
 In immunocompromised patients
 Fever, pancytopenia, splenomegaly & liver dysfunction
 Histiocytes in bone marrow ingest RBC, WBC & platelets
 Lymphocytes & their benign disorders
 Lymphocyte, immunologically competent cells
 Lymphoid organs
 Primary (development of lymphocytes)
 Bone marrow & thymus
 Secondary (specific immune response generation)
 Lymph nodes, spleen & lymphoid tissues (GIT & respiratory system)
 B & T cells
 B cell mature in bone marrow peripheral blood activation &
then maturation memory cells or plasma cells
 T cell maturation in thymus
 Negative selection (deletion of self-reactive)
 Positive selection (selection of HLA specific T cells )
 CD4 (Th) & CD8 (cytotoxic)
 Natural killer cells
 CD8 cells lack T-cell receptor (TCR)

 Cytoplasmic granules

 Low level of expression of HLA class I

 small lymphocyte activated lymphocyte

large granular lymphocyte plasma cell

Lymphocytosis
 Often occurs in infants & young children in response to
infections

 Glandular fever
 Fever, sore throat, lymphadenopathy & atypical lymphocytes in blood

 Infection with EBV, CMV, HIV or toxoplasma

Causes of lymphocytosis
Infections

• Acute (infectious mononucleosis, rubella, pertussis, mumps,

hepatitis, CMV, HIV, Herpes)
• Chronic (TB, toxoplasmosis, brucellosis, syphilis

Chronic lymphoid leukaemias

Acute lymphoblastic leukaemia

Non- Hodgkin lymphoma (some)

Thyrotoxicosis
Infectious mononucleosis
 Infection with EBV

 Mostly subclinical infection

 Lymphocytosis
 Clonal expansion of T cells reacting against B lymphocytes infected with EBV

 High titre of heterophile (react with cells of another species) antibody (sheep,
horse or ox red cells)
 Infectious mononucleosis- Clinical features
 Age 15-40 years (usually teenagers & young adults)
 Prodromal period
 Lethargy, malaise, headaches, stiff neck & dry cough
 Established disease
 Bilateral cervical lymphadenopathy (75%)
 Generalized lymphadenopathy (50%)
 Sore throat with inflamed oral & pharyngeal surfaces (50%)
 Fever mild or severe
 Morbilliform rash, eye signs (photophobia,
conjuctivitis & periorbital oedema)
 Splenomegaly (50%), Hepatomegaly (15%)
 Peripheral neuropathy, severe anaemia or purpura
Infectious mononucleosis- Diagnosis
 Pleomorphic atypical lymphocytosis
 rise in white cell count (e.g. 10-20 x 109/L) with absolute
lymphocytosis
 Heterophile antibodies
 High titres during 2nd -3rd week & persist for 6 weeks)
 Paul-Bunnell test
 Monospot test (formalinized horse red cells)
 EBV antibody
 First 2-3 weeks
 Specific antibody to EBV nuclear develops later & persist for life
 Haematological abnormalities
 Autoimmune hemolytic anaemia (cold type)
 thrombocytopenia
 Autoimmune thrombocytopenic purpura
Infectious mononucleosis- Reactive lymphocytes
Lymphopenia
 Etiology
 Bone marrow failure
 Corticosteroid & immunosuppressive therapy
 Hodgkin’s disease
 Irradiation
 Immunodeficiency syndromes
 HIV infection
 Immunodeficiency

Primary Secondary

X-linked agammaglobulinaemia,
Acquired
hypogammaglobulinaemia
B cell B cell Myeloma, Nephrotic
syndrome, protein losing
enteropathy

AIDS, Hodgkin’s
Thymic aplasia
(DiGeorge's syndrome) T cell T cell lymphoma, non-
Hodgkin’s lymphoma,
drugs

SCID, Bloom’s syndrome,

Ataxia telangiectasia,
Mixed B Mixed B CLL, post-bone marrow
transplantation & post-
Wiskott-Aldrich syndrome
& T cell & T cell chemotherapy/ radiotherapy
Thanks