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The Internist Approach to Lymphocytosis
Clin Assoc Prof P KuperanFRCP, FRCPA, FRCPath
Head & Senior ConsultantDept of Haematology
Tan Tock Seng Hospital
Lymphocytes in the Blood
B cells
10 – 20%
NK cells
5 – 10%
T cells
60 – 80%
HelperT cells
60 – 70%
SuppressorT cells
30 – 40%
Lymphocytes in the Blood
98%
2%
Blood Lymphoid TissueBoneMarrow
Approach to Lymphocytosis
? Is there a lymphocytosis
RelativeLymphocytosis
AbsoluteLymphocytosis
Total WBC/ l 8000 4000 10,000
% neutrophils 60% 20% 30%
% lymphocytes 30% 80% 70%
Absolute neutrophils l 4800 800 3000
Absolute lymphocytes l 2400 3200 7000
Case IICase INormalWBC
NeutropeniaBut No
Lymphocytosis
No NeutropeniaBut
Lymphocytosis
Approach to Lymphocytosis
Absolute Lymphocytosis Present
Transient<24 hours
Acute Stress• Cardiac emergencies• Trauma• Status epilepticus• Stroke
Transient Lymphocytosisor
Sustained Lymphocytosis
Approach to Lymphocytosis
Sustained Lymphocytosis
Benign Malignant
Approach to Lymphocytosis
Benign Lymphocytosis
Infectious MononucleosisSyndrome
• Drug allergy• Serum sickness
InfectionOthersHypersensitivity
Syndrome
Primary EBV infection • Phenytoin• Allopurinol• Carbamezapine• Dapsone
Primary CMV infectionToxoplasma
Viral Hepatitis
Approach to Lymphocytosis
60 years old male
WBC 9000/l
Neutrophils 2000/l
Lymphocytes 6000/l
Cause for Lymphocytosis
Benign
Post splenectomy
Approach to Lymphocytosis
History
Phsyical examination
LFT
LDH
WBCHBPlateletsDifferential
FBC
Examination of the Peripheral Blood Film
Typical Infectious Mononucleosis
20 years old male
Fever, sore throat, malaise
Posterior cervical lymphadenopathy
Mild splenomegaly
WBC 18 x 109/L ALT 150 (15 – 41)HB 13.0 gm/dL AST 140 (17 – 63)Platelets 140 x 109/L Bilirubin 38 (7 – 31)Neutrophils 30% LDH 1500 (250 – 580)Lymphocytes 60%
PBF – Reactive lymphocytes present (>10%)
Typical Infectious Mononucleosis
Leave him alone
Monitor for any complications
Monitor FBC/ LFT
May take 1 – 2 months to normalise
Approach to Lymphocytosis
Malignant Lymphocytosis
Aggressive Indolent
Urgent Referral Non-urgent Referral
Typical Chronic Lymphocytic Leukaemia
60 years old man
Admitted for routine surgery
WBC 60 x 109/L
HB 13 gm/dL
Platelets 230 x 109/L
Neutrophils 10%
Lymphocytes 80%
PBF – Typical Mature B cells
Typical CLL
Not symptomatic
Non-urgent referral to haematologist
Approach to Lymphocytosis
? InfectiousMononucleosis
Syndrome
? Malignant
• Age• Constitutional symptoms• Extent & size of lymphadenopathy/ hepatosplenomegaly• FBC• LFT / LDH• Peripheral blood film
Approach to Lymphocytosis
15 – 30 years old
> 30 years old
Generalised lymphadenopathy
Posterior cervical lymphadenopathy
Mild splenomegaly
> Mild splenomegaly
Significant constitutionalsymptoms
Fever / malaise
Approach to Lymphocytosis
No anaemia
Significant Anaemia
Lymphocytes > 20,000
Lymphocytes < 20,000
Leucoerythroblastic picture
No early cells
Moderate to severe thrombocytopenia
Mild thrombocytopenia
LDH
(mild)
ALT/ AST
(mild to moderate
LDH > 3000
ALT/ AST markedly increased
Approach to Lymphocytosis
Only Mild Lymphocytosis
Benign Aggressive Lymphoma
Not Typical Infectious Mononucleosis
EBV - IgM VCA / IgG VCA
CMV - IgM CMV
HIV - Anti HIV
Hepatitis
HBsAg
Anti HCV
Anti HAV
Malignant Lymphocytosis
Aggressive Indolent
• Acute Lymphoid Leukaemia• Aggressive Lymphoma
• Chronic Lymphocytic Leukaemia
• Other Chronic Lymphoproliferative Disorder
Malignant Lymphocytosis
Aggressive Indolent
Significant constitutional syndrome
Significant organomegaly
Anaemia/ thrombocytopenia/ neutropenia
LDH – markedly increased
No significant constitutional symptoms
WBC 9 x 109/L
80 x 109/L
Approach to Lymphocytosis
Examination of the peripheral blood film by experienced staff
Lymphocytosis
ClinicallyInfectiousMononucleosis
Syndrome
ClinicallyMalignant Lymphocytosis
Lymphocyte Subsets
Most of the lymphocytes are T-cell suppressor cells
(CD8+)
B cell malignant (common)CD19+)
Lymphocytes in the Blood
B cells
10 – 20%
NK cells
5 – 10%
T cells
60 – 80%
HelperT cells
60 – 70%
SuppressorT cells
30 – 40%
Lymphocytosis
Total WBC Absolute Lymphocytes
CD3 CD4 CD8 CD19
4000 – 10,000 1000 – 3500 600 – 2500 280 – 1430 165 – 1045 65 – 620
Norm
alCase I
19410,00099312,23013,40018,700 19410,00099312,23013,40018,700
52,8008001400220055,00060,000 52,8008001400220055,00060,000
Case II
Approach to Lymphocytosis
Examination of the peripheral blood film
Immunophenotyping of lymphocytes
If Malignant Lymphocytosis is more likely
Morphology MolecularGenetics
FlowCytometry
Cytogenetics
Bone Marrow
Approach to Lymphocytosis
When to refer to haematologists?
Not sure whether IMS?
? Malignant Lymphocytosis
Urgent Non-urgent
Approach to Lymphocytosis
Is there absolute lymphocytosis?
Detailed history/ examination to exclude hypersensitivity syndrome/ post-spenectomy
? Infectious mononucleosis syndrome
EBV/ CMV/ HIV/ Hepatitis/ Toxoplasma
FBC/ LFT/ LDH/ PBF
Monitor clinical features
Monitor FBC/ LFT/ LDH
Summary
Approach to Lymphocytosis
Summary
? Malignant Lymphocytosis
Haematologist is always there to help you!!
Aggressive Indolent
Thank You
For Your
Kind Attention
