Work up of Lymphocytosis and Lymphadenopathy Dr Tara Seshadri HaematologistGCH.

Presentation on theme: "Work up of Lymphocytosis and Lymphadenopathy Dr Tara Seshadri HaematologistGCH."— Presentation transcript:

1 Work up of Lymphocytosis and Lymphadenopathy Dr Tara Seshadri HaematologistGCH

2 Overview Work up of Lymphocytosis Work up of Lymphadenopathy Common Lymphomas Overview of Chemotherapy for Lymphoma

3 Work up of Lymphocytosis

4 Introduction Clonal –Acute –Chronic Reactive

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6 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%

7 Clonal Lymphoid Disorders B cell disorders 85% T cell disorders 13% NK cell disorders <2%

8 Reactive Lymphocytosis Viral Infections –EBV –CMV –Other BacterialParasitic Post Trauma –Cardiac event –Seizure Post splenectomy HyperthyroidismUnknown.

9 Determining Clonality History –Reactive cause present? Examination – –presence of LAD or H-S megaly Chronicity Other blood parameters Level of lymphocyte count. Blood film

10 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

11 B B T T B 20 antiCD20 3 3 3 3 Flurochrome bound to anti CD 20

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15 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.

16 Worrisome FBE findings in lymphocytosis Other lineage cytopenias Immature cells on FBE Presence of concurrent haemolysis Rapidly rising lymphocytosis. Atypical lymphoid morphology.

17 Mild Lymphocytosis, Normal FBE Otherwise Presence of reactive cause No reactive Cause Monitor FBE over next 6 months Repeat FBE When Pt well FBE normalises Persistent lymphocytosis Flow cytometry Refer to Haem Non clonal or cannot determine Clonal Population Monitor FBE Lymphocytosis rises or counts change

18 Chronic Lymphocytic Leukaemia

19 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

20 MBL / CLL MBL Asymptomatic CLL Symptomatic CLL Richters Transformation “Pre CLL” Phenotype is same as CLL Like MGUS is to MM 1-2% progress to symptomatic CLL pa Defined as B lymphocytes < 5 x10 9 /L in pb

21 Treatment Principles Watch and Wait Chemotherapy for Symptomatic Disease

22 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

23 Prognosis - CLL Variable –Clinical Tempo –Cytogenetics –Stage Ranges from many years (dying with the disease) to 3-5 years

24 Work Up Lymphadenopathy

25 Consider Benign Causes Reactive LAD –Follicular hyperplasia –Viral infection –EBV –CMV –Toxoplasmosis –HIV ACE level Most pathological LN are > 1cm

26 Stick a Needle in it.

27 FNA Used as first line to Ix LAD in patients with low clinical risk of lymphoma –Known other cancer –Fluctuant lump –Tender lump –No LAD elsewhere –Small (< 1-1.5cm) LN –Patient is otherwise well. Low morbidity

28 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

29 Always follow the patient post FNA

30 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.

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32 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.

33 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.

34 Common Lymphomas

35 Diffuse Large B cell Lymphoma Aggressive B cell NHL Curable ~70% Rx: R-CHOP +/- XRT Can affect any part of the body

36 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

37 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.

38 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

39 Chemotherapy

40 Nomenclature of Chemo Day 1 = first day of treatment Cycle Frequency = 2-4 weeks.

41 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.

42 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.

43 Concomitant Meds To Avoid –Aspirin –NSAIDS –Regular Paracetamol –Herbal / alternative meds. Generally OK –Benzos –Frusemide –PPI / Ranitidine –OCP –Anti-depressants –Anti HT / Chol / DM –Multivitamins –Opiods –Antibiotics

44 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

45 Common SE of Chemo Steroid related SE –DM –Irritability –Come down effect Constipationdiarrhoea Peripheral neuropathy Fatigue – cumulative Sun sensitivity Depression Anorexia / N / V Alopecia Skin and Nail changes Mucositis / oral thrush

46 Infection and Chemo Whilst on Chemo –Neutrophil nadir 7 -13 days post chemo –UTI / Chest / Line / Gut –Bug often not identified Post Chemo –Immune system is still down –Shingles –PCP –Prone to colds / flus

47 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

48 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