Transcript Work up of Lymphocytosis and Lymphadenopathy

Work up of Lymphocytosis
and Lymphadenopathy
Dr Tara Seshadri
Haematologist
GCH
Overview
Work up of Lymphocytosis
Work up of Lymphadenopathy
Common Lymphomas
Overview of Chemotherapy for Lymphoma
Work up of Lymphocytosis
Introduction
Clonal
– Acute
– Chronic
Reactive
Normal Lymphocytes
T cells: (CD3pos)– 60-80%
– CD4 75%; CD 8 25%
B cells (CD19/20 pos)10-20%
NK cells (CD3 neg, CD56 pos)
5-10%
Clonal Lymphoid Disorders
B cell disorders 85%
T cell disorders 13%
NK cell disorders
<2%
Reactive Lymphocytosis
Viral Infections
– EBV
– CMV
– Other
Bacterial
Parasitic
Post Trauma
– Cardiac event
– Seizure
Post splenectomy
Hyperthyroidism
Unknown.
Determining Clonality
History
– Reactive cause present?
Examination –
– presence of LAD or H-S megaly
Chronicity
Other blood parameters
Level of lymphocyte count.
Blood film
Flow Cytometry
Flow cytometry: AKA immunophenotype / cell surface
markers
Allows for identification of cells based on surface and
intracellular markers.
Principle: Ab conjugated with a light emitting
fluorochrome.
Added to sample and if Ag present –get binding.
Pass the cell sample though a light source and light is
scattered depending on wavelength of the fluorochrome
Flurochrome bound to
anti CD 20
T
B
B
B
20
T
Monoclonal Population
B cells: surface Ig expressed.
– Only 2 light chains kappa and lambda (2-4:1)
Monoclonal defined if above ratio is altered.
T cells: TCR receptor is 98% AB versus GD –
therefore can’t use receptor status for
monoclonality
– Use aberrant markers by flow
TCR gene rearrangement studies.
Worrisome FBE findings in
lymphocytosis
Other lineage cytopenias
Immature cells on FBE
Presence of concurrent haemolysis
Rapidly rising lymphocytosis.
Atypical lymphoid morphology.
Mild Lymphocytosis,
Normal FBE Otherwise
No reactive
Cause
Monitor FBE
over next
6 months
Repeat FBE
When Pt well
FBE normalises
Persistent
lymphocytosis
Flow cytometry
Non clonal or
cannot determine
Monitor FBE
Presence of
reactive cause
Lymphocytosis
rises
or counts change
Clonal
Population
Refer to Haem
Chronic Lymphocytic
Leukaemia
CLL
Indolent B cell NHL
Clinical presentation
– Often picked up on routine
FBE
– Can present with LAD
– AIHA
– Cytopenias / splenomegaly
Diagnosis:
– CD19 / CD20 / CD23 / CD5
positive light chain
restricted population
– BM and CT in young /
symptomatic patients
MBL / CLL
MBL
Asymptomatic
CLL
“Pre CLL”
Phenotype is same as CLL
Like MGUS is to MM
1-2% progress to symptomatic CLL pa
Defined as B lymphocytes < 5 x109/L in pb
Symptomatic
CLL
Richters
Transformation
Treatment Principles
Watch and Wait
Chemotherapy for Symptomatic Disease
Common Rx
Fludarabine / Rituximab +/- Cyclophosphamide
– Profoundly immunosuppressive
Prone to shingles / PCP up to 6-12 months after completion
of chemo.
Need irradiated blood up to 2 years post Rx.
– Myelosuppressive
– AIHA
Chlorambucil
– Myelosuppressive
– Used in elderly / frail patients
Prognosis - CLL
Variable
– Clinical Tempo
– Cytogenetics
– Stage
Ranges from many years (dying with the
disease) to 3-5 years
Work Up
Lymphadenopathy
Consider Benign Causes
Reactive LAD
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Follicular hyperplasia
Viral infection
EBV
CMV
Toxoplasmosis
HIV
ACE level
Most pathological LN are > 1cm
Stick a Needle in it.
FNA
Used as first line to Ix LAD in patients with low
clinical risk of lymphoma
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Known other cancer
Fluctuant lump
Tender lump
No LAD elsewhere
Small (< 1-1.5cm) LN
Patient is otherwise well.
Low morbidity
FNA - Drawbacks
Often not representative
Cannot be used to
subtype lymphoma
Can be sent for flow – not
always enough sample.
Harder to do
immunocytology
– Dx is by morphology alone
Always follow the patient post FNA
Core biopsy
14 or 16 gauge needle
Size is 1mm x 3-4mm
Histological examination is
difficult due to small sample.
Can do IHC and other special
stains
Can be sent of flow
Often crushed / necrotic tissue
and hence non diagnostic.
Excision biopsy
Gold standard
Plenty of tissue for pathologists
– IHC
– FISH
Can be sent for flow
Can see entire LN architecture
Morbidity of surgery for patient
Wait for OT time.
Core versus Excision
Excision if node is palpable or peripheral.
Choose the largest node
If there is a choice of LN – avoid inguinal.
CT guided core biopsy internal LN
– Mediastinal
– Retroperitoneal
Laparotomy / Mediastinoscopy if core bx is non
diagnostic.
Common Lymphomas
Diffuse Large B cell Lymphoma
Aggressive B cell NHL
Curable ~70%
Rx: R-CHOP +/- XRT
Can affect any part of the body
Follicular Lymphoma
Indolent B cell NHL
Advanced stages
generally incurable
Treat early stage
disease with XRT
– 50% cured
Treat symptomatic
advanced stage
disease
– R-CHOP or R-CVP +
maintenance R
– Long remissions (5 +
years often achieved
Mantle Cell Lymphoma
Poor prognosis B cell NHL
Usually advanced disease at diagnosis
M >> F
Incurable
Rx: R-CHOP based chemo + transplant
– Improves survival 7-8 years is median.
Hodgkin Disease
15-30yo and 60-80yo
is peak incidence
Generally presents
with nodal disease in
young patients
Old pts – atypical
presentation.
90% cured
Rx: ABVD +/- XRT
Chemotherapy
Nomenclature of Chemo
Day 1 = first day of treatment
Cycle Frequency = 2-4 weeks.
Common Chemotherapy Regimens
CHOP +/- Rituximab
– D1: 2-3 week cycles
FC +/- Rituximab
– D1-3: 4 week cycles
ABVD
– D1 and 15 of 4 week cycles.
Vaccinations and Chemo
Routine vaccinations: Best not to give whilst on
chemo
– Flu shot is fine – suggest wait till day before chemo is
due.
Post chemo – no issues but may have
suboptimal response
– Ideally wait 3-4 months.
Live vaccines (MMR, oral live polio, varicella)
should be avoided for up to 2 years post chemo.
Concomitant Meds
To Avoid
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Aspirin
NSAIDS
Regular Paracetamol
Herbal / alternative
meds.
Generally OK
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Benzos
Frusemide
PPI / Ranitidine
OCP
Anti-depressants
Anti HT / Chol / DM
Multivitamins
Opiods
Antibiotics
Anticoagulation and Chemo
Indication for anticoagulation
– Acute Thrombosis
– Prevention of thrombosis
– AF / cardiomyopathy
Agent
– LMWH versus Warfarin
Chemotherapy Regimen complexity
Risk of Thrombocytopenia
Monitoring
Renal impairment
Common SE of Chemo
Steroid related SE
– DM
– Irritability
– Come down effect
Constipation
diarrhoea
Peripheral neuropathy
Fatigue – cumulative
Sun sensitivity
Depression
Anorexia / N / V
Alopecia
Skin and Nail
changes
Mucositis / oral thrush
Infection and Chemo
Whilst on Chemo
– Neutrophil nadir 7 -13 days post chemo
– UTI / Chest / Line / Gut
– Bug often not identified
Post Chemo
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Immune system is still down
Shingles
PCP
Prone to colds / flus
Late Effects of Chemotherapy
Cardiac Failure 1-10+ years post
Gonadal dysfunction
– Low testosterone
– Early menopause
Sterility
– 10-90% depends on age of patient.
- Chemotherapy regimen
Bone loss
Second Cancers.
– Cumulative effect of chemo and specific agents
– Influence of XRT
Conclusion
Lymphocytosis:
Other blood parameters
Blood film
Lymphadenopathy:
Beware false negative biopsies
Lymphoma:
Many different types
Stage IV disease can still be curable
Chemotherapy:
Neutropenia: day 7-13