The Internist Approach to Lymphocytosis Approach to Lymphocytosis No anaemia Significant Anaemia...

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

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Aggressive Indolent

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For Your

Kind Attention