Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

ALL YOU NEED TO KNOW ABOUT HAEMATOLOGICAL MALIGNANCIES Harish Bava Here’s whatwedo: ■ Weekly tutorialsopento all! ■ Focussed oncore presentationsand teaching diagnostictechnique If you’re new here… ■ By medical students, for medical students Welcome to ■ Reviewed by doctorsto ensure accuracy Teaching ■ We’ll keepyouupdatedabout our Things! upcoming events viaemail and groupchats!What are the main haematological malignancies? Leukaemias ■ Acute myelocytic leukaemia (AML) ■ Chronic myelocytic leukaemia (CML) ■ Acute lymphoblastic leukaemia (ALL) ■ Chronic lymphoblastic leukaemia (CLL) Lymphomas ■ Hodgkin’s lymphoma ■ Non-Hodgkin’s lymphoma Other Disorders: ■ Multiple Myeloma ■ Myelodysplasia ■ Myeloproliferative disordersNormal PhysiologyLeukaemia Harish BavaWhat is Leukaemia? ■ Abnormal proliferationof theWBCs ■ Split into: – M(thrombocytes,erythrocytes, basophils,neutrophils,eosinophils, monocytes) – Lymphoblasticleukaemia – abnormal proliferation oflymphoid cells (B cells, T cells,NK cells)Normal PhysiologyPathophysiology ■ AML – Associated witht(15;17),fusionof PMLand RAR-alphagenes – Leads to anaccumulationof immaturemyeloblasts ■ CML – Associated withPhiladelphia chromosomet(9;22) – ResultsinBCR-ABL fusion gene– resultsinuncontrolled tyrosine kinaseactivity – Leads to overproductionof matureand immaturegranulocytesPathophysiology ■ ALL – No knownchromosomal abnormality – Gcellswithin bonemarrowoliferationof immaturelymphoid precursor – Typicallyseeninyoungchildren – aged 2 to 5 ■ CLL – Clonal proliferation of small,mature incompetentB lymphocytes – Most commonleukaemia inadults – Has aslow progressionSymptoms ALL(2-5 years) CLL (>65 years) ■ Fatigue, pallor ■ Often asymptomatic,incidental ■ Fever,infections finding onblood test ■ Bsymptoms ■ Easy bruising, bleeding ■ Bonepain ■ Bleeding,infections ■ Lossof appetite,weight lossClinical Signs ALL(2-5 years) CLL (>65 years) ■ Lymphadenopathy ■ Incidental lymphocytosis ■ Hepatosplenomegaly ■ Painless lymphadenopathy ■ Mediastinal mass ■ Hepatosplenomegaly ■ Petechiae, purpura ■ Pallor ■ Testicular swelling ■ CNS involvement – cranial nervepalsies, meningismSymptoms AML(>60 years) CML (30-60 years) ■ Fatigue, weakness, pallor ■ Bsymptoms ■ Fever,infections ■ Lethargy ■ Gingival hyperplasia ■ Abdominal fullness ■ Menorrhagia,leg bruises ■ Early satiety ■ BonepainClinical Signs AML(>60 years) CML (30-60 years) ■ Pallor ■ Massivesplenomegaly ■ Petechiae/ecchymoses ■ Hepatomegaly ■ Gingival hypertrophy ■ Gout ■ Leukostasissymptoms– headache,dyspnoea,vision changesBlood Tests ALL(2-5 years) CLL (>65 years) ■ Anaemia ■ Lymphocytosisof mature ■ Thrombocytopenia lymphocytes ■ Thrombocytopenia ■ Neutropenia ■ Lymphoblasts ■ Anaemia ■ ReducedimmunoglobulinsBlood Tests AML(>60 years) CML (30-60 years) ■ Anaemia ■ Anaemia ■ Thrombocytopenia ■ Granulocytes at different ■ Neutropenia stages ofmaturation ■ Leucocytosis ■ Myeloblasts ■ Thrombocytosis ■ Decreased leukocytealkaline phosphatase(LAP)SBA A70year oldmalepatient presentsto thegeneralpractitionerfor annual reviewofhis someroutinebloodtests andthewhitecell count is foundto be12.8x10^9/L(normalrange 3-10x10^9/L), with85% lymphocytes. Whichof thefollowing bloodfilmfindings is consistentwiththemost likely diagnosis? 1. Leukemiclymphoblasticcells 2. Auerrods 3. Rouleauxformation 4. Maturemyeloidcells 5. Smudge cellsSBA A70year oldmalepatient presentsto thegeneralpractitionerfor annual reviewofhis someroutinebloodtests andthewhitecell count is foundto be12.8x10^9/L(normalrange 3-10x10^9/L), with85% lymphocytes. Whichof thefollowing bloodfilmfindings is consistentwiththemost likely diagnosis? 1. Leukemiclymphoblasticcells 2. Auerrods 3. Rouleauxformation 4. Maturemyeloidcells 5. SmudgecellsOther Investigations ALL(2-5 years) CLL (>65 years) ■ Bonemarrowbiopsy ■ Blood filmshowssmudgecells – Hypercellular,heavily – Cellsdamaged asthefilm is packedwithlymphoblasts madeasit lacks ■ Blood film cytoskeletal protein ■ Immunophenotyping – Blast cells ■ PositivePeriodicAcid-Schiff – Key investigation (PAS)staining – Identifyantibodies ■ Lymph NodeBiopsy ■ Immunophenotyping – To differentiatewhether – Richter’sTransformation theoriginis T orB cellOther Investigations AML(>60 years) CML (30-60 years) ■ Blood film– blast cells ■ Blood film- >20%blast cells ■ Bonemarrowbiopsy ■ Bonemarrowbiopsy – Hypercellular marrow – Marrow hyperplasia – Presenceof blasts – Increased fibrosis – Auer rods – Granulocyticpredominance ■ Philadelphia chromosomeis diagnosticHistology ALL(2-5 years) CLL (>65 years) ■ Largelymphoblasts - promin■ Smudgecells nucleiHistology AML(>60 years) CML (30-60 years) ■ Auer rods with ■ Myeloblasts,maturemyeloid myeloperoxidasestain cells, multiplebasophilsPrognosis ALL (2-5 years) CLL (>65 years) ■ Cure rate 70-90% with chemo alone ■ Veryvariabledisease ■ Factorsaffecting prognosis: ■ Poor prognostic factors: – Age <1 and >10 – Diseasestage – Male sex – Atypical lymphocyte – CNS Disease morphology – WCC >50x10 9 – Malesex – ast(9:22)enetic features(such – T-ALL – worsethanB-ALL – Incompleteresponseto therapy ■ Protectivefactors: – Hyper-diploidblastcellsPrognosis AML (>60 years) CML (30-60 years) ■ 3-yearsurvival rate 20% ■ Mediansurvival is5-6years ■ 30% cured with chemo ■ Prognostic factors: – Age – Poor cytogenetics – Response tofirst dose of chemoSBA A67-year-old malepresentstohis haematologist.Last year it wasnotedhe had enlargedcervical lymphnodes and hepatosplenomegaly. Hecomplains of ongoing fevers,weight loss and night sweats.Afull blood count showsa lymphocytosis andanaemia.Hisplatelet count isinnormal range.Hehas had several chest infections over thelast 6 months.On blood film hehas smudge cells.Hecomplains of enlarginglymphnodesoverthelast few weeks. Giventhemost likely underlyingdiagnosis, what complicationhasoccurred? 1. Localspread 2. Burkitt’slymphoma 3. Richter’stransformation 4. Hodgkin’slymphoma 5. ColdautoimmunehaemolyticanaemiaSBA A67-year-old malepresentstohis haematologist.Last year it wasnotedhe had enlargedcervicallymph nodesand hepatosplenomegaly.He complainsof ongoing fevers, weight loss andnight sweats.Afull blood count showsa lymphocytosisand anaemia.His platelet count isinnormal range.Hehashadseveral chest infectionsover thelast 6months.Onblood film hehassmudgecells.Hecomplainsof enlarginglymph nodes over the lastfewweeks. Giventhemost likely underlyingdiagnosis, what complicationhasoccurred? 1. Localspread 2. Burkitt’slymphoma 3. Richter’stransformation 4. Hodgkin’slymphoma 5. ColdautoimmunehaemolyticanaemiaComplications CLL Richter’sTransformation ■ Anaemia ■ Leukaemiacellsenter lymph ■ Hypogammaglobulinemia nodeand changeinto high- grade, fast-growing non- ■ Warm autoimmune haemolytic Hodgkin’slymphoma anaemia ■ Becomevery suddenly unwell ■ Transformation tohigh-grade lymphoma (Richter’s ■ Indicatedby: transformation) – Lymph nodeswelling – Fever without infection – Weight loss – Night sweats – Nausea – Abdominal painTreatment ■ Treatments for all leukaemiainvolvechemotherapy ■ Theonly treatment to beawareof isfor CML: – CML involvesuncontrolledtyrosinekinaseactivity – Tyrosinekinase inhibitorsareused ■ E.g. imatinib ■ Induce haematological remission in 90% of casesOther associated syndromes ■ Myelodysplastic syndrome – Often aprecursor toAML – Characterised bydysplasticchanges inbloodcell precursors ■ Myeloproliferativedisordersand myelofibrosis – Megakaryocyte proliferation – Replacement of bonemarrow withfibroustissue – Canoftenprogress to AMLSBA A60 yearoldmalepresents withweight loss, nightsweats andgeneralisedfatigue.He respiratory tract infections andaurinary tract infection,whichhe has never hadbefore. Onexamination, massivehepatosplenomegaly isobserved.Thereareno other significant abnormalities.Aperipheral bloodfilmis ordered, whichis shownbelow.Whichof these myeloproliferativedisorders is this patient mostlikely tobe suffering from? 1. Chroniceosinophilicleukaemia 2. Polycythaemiarubravera 3. CML 4. Myelofibrosis 5. EssentialthrombocythemiaSBA A60 yearoldmalepresents withweight loss, nightsweats andgeneralisedfatigue.He respiratory tract infections andaurinary tract infection,whichhe has never hadbefore. Onexamination, massivehepatosplenomegaly isobserved.Thereareno other significant abnormalities.Aperipheral bloodfilmis ordered, whichis shownbelow.Whichof these myeloproliferativedisorders is this patient mostlikely tobe suffering from? 1. Chroniceosinophilicleukaemia 2. Polycythaemiarubravera 3. CML 4. Myelofibrosis 5. EssentialthrombocythemiaMyelofibrosis ■ Presentsinelderly people with symptomsof anaemia – fatigue – Also massivesplenomegaly – dueto haematopoiesis inliver and spleen – Also weight loss, night sweats etc ■ Closely associated with geneticmutations - JAK2 ■ Blood filmtypically shows tear-shaped polikilocytes ■ Bonemarrowbiopsy -->characteristic‘dry tap’SBA A 60-year-old male patient isundergoing a pre-operative review prior to an elective hernia repair.A routine full blood count reveals a haemoglobin of 192 g/L(normal range 130-170 g/L) and platelet count of 490 x 10^9/L(normal range 150-400 x 10^9/L).The patient has no past medical history of note and is asymptomatic at present. The patient isa non-smoker and drinksalcohol socially. On physical examination there is mild splenomegaly,and the patient is noted to have a red complexion. Which of the followinginvestigation findings are consistent with the most likely diagnosis? 1. Increasedcell mass,low serumerythropoietin,JAK2mutation present 2. Increasedred cell mass,low serum erythropoietin, JAK2mutation absent 3. Increased red cell mass,raised serumerythropoietin,JAK2 mutation absent 4. Increasedred cell mass,raised serumerythropoietin,JAK2 mutation present 5. Normal redcell mass,decreasedplasma volume, normal serum erythropoietinSBA A 60-year-old male patient isundergoing a pre-operative review prior to an elective hernia repair.A routine full blood count reveals a haemoglobin of 192 g/L(normal range 130-170 g/L) and platelet count of 490 x 10^9/L(normal range 150-400 x 10^9/L).The patient has no past medical history of note and is asymptomatic at present. The patient isa non-smoker and drinksalcohol socially. On physical examination there is mild splenomegaly,and the patient is noted to have a red complexion. Which of the followinginvestigation findings are consistent with the most likely diagnosis? 1. Increased cellmass,lowserumerythropoietin,JAK2 mutation present 2. Increasedred cell mass,low serum erythropoietin, JAK2mutation absent 3. Increased red cell mass,raised serumerythropoietin,JAK2 mutation absent 4. Increasedred cell mass,raised serumerythropoietin,JAK2 mutation present 5. Normal redcell mass,decreasedplasma volume, normal serum erythropoietinOther JAK2mutations ■ PolycythaemiaRubraVera – Clonal proliferation leading to overproductionof RBC,neutrophils and platelets – Typicallypresentswithpruritus after a hot bath ■ Essential thrombocytosis – Overproductionof platelets – Typicallypresentswitha burningsensationinthehands ■ All JAK2 mutations – treat withhydroxycarbamideand aspirin – Reducesplatelet count and thromboticriskLymphoma Harish BavaWhat is lymphoma? ■ Lymphomaisamalignant proliferationof lymphoid cells,formingsolid tumoursin lymphnodes or other lymphatictissues includingthespleen, bonemarrow and other extra-nodal sites ■ Classifiedaseither Hodgkin’slymphoma or non-Hodgkin’s – Hodgkin’scharacterised by presenceof Reed-Sternberg cells – Non-Hthgkin’sis every othertypeof lymphoma ■ 6 most common cause of cancer in UK ■ low-graderther classifiedinto T-cell orB-cell lymphoma and high-grade orPathophysiology Hodgkin’s Non-Hodgkin’s ■ Malignant proliferationof ■ Malignant proliferationof lymphocytesin lymphnodes or lymphocytesin lymphnodes or other lymphatictissues other lymphatictissues ■ Localised to asinglegroupof ■ Multiplelymphnodegroups lymphnodes involved ■ Contiguousspread ■ More extra-nodal involvement ■ Non-contiguousspread ■ Commonly affects BcellsEpidemiology and Risk Factors Hodgkin’s Non-Hodgkin’s ■ EBV ■ Elderly >75 ■ HIV ■ Caucasians ■ Immunosuppression ■ EBV ■ Cigarettesmoking ■ Familyhistory ■ Immunodeficiency (transplant, HIV, diabetes) ■ Commonin30s and 70s ■ Autoimmunedisease(SLE, Sjogren’s, coeliac) ■ Pesticides, solventsClinical Features Hodgkin’s Non-Hodgkin’s ■ Cervical/supraclavicular ■ Painless lymphadenopathy lymphadenopathy – Non-tender,rubbery, – Painless,non-tender, asymmetrical asymmetrical ■ Bsymptoms ■ Alcohol-induced lymphnode ■ Extra-nodal disease painischaracteristic – Dyspepsia, dysphagia ■ Bsymptoms – Pancytopenia,bone pain ■ Mediastinal mass – cancause – CNS palsies SVCOTypes of Non-Hodgkin’s Lymphoma ■ Burkitt’s lymphoma – High-gradeBcell lymphoma – Associated withc-myc genet(8;14) – StronglyimplicatedwithEBVinfectionif endemic/Africanform – Commonly seeninyoung or immunosuppressed patients ■ Waldenstrom’s macroglobulinaemia – Secretionof monoclonal IgM paraprotein ■ Paraprotein – fragments of antibodies producedby plasma cells/B cells – Commonly seeninolder men ■ DiffuseLargeB cell lymphoma – Most commonnon-HodgkinlymphomaSBA A32-year-old manpresentsto hisgeneral practitioner witha2-monthhistory of alump inhis neck.Hethinksthis lumpisslowly getting bigger.Hefeels well, isotherwiseasymptomaticand hashad norecent infectionsor illnesses.Onexamination,a3-cmlymphnodeis felt intheleft anteriorchain. It isrubbery,withnotetheringtothesurroundingskinandnooverlying skin changes. Whichof thefollowing investigationsismost likely to confirm the diagnosis? 1. Excisional lymphnodebiopsy 2. Acid fast bacilli culture 3. Monospot test 4. PET 5. FNAof affected lymphnodesSBA A32-year-old manpresentsto hisgeneral practitioner witha2-monthhistory of alump inhis neck.Hethinksthis lumpisslowly getting bigger.Hefeels well, isotherwiseasymptomaticand hashad norecent infectionsor illnesses.Onexamination,a3-cmlymphnodeis felt intheleft anteriorchain. It isrubbery,withnotetheringtothesurroundingskinandnooverlying skin changes. Whichof thefollowing investigationsismost likely to confirm the diagnosis? 1. Excisional lymphnodebiopsy 2. Acid fast bacilli culture 3. Monospot test 4. PET 5. FNAof affected lymphnodesInvestigations Hodgkin’s Non-Hodgkin’s ■ Lymph Nodebiopsy ■ Lymphnodebiopsy ■ CT CAP ■ CT PET ■ FBC: ■ FBC – Normocyticanaemia – HighLDH – Showsnormocytic anaemia – Neutropenia – HighLDH(showing – Thrombocytopenia increased cell turnover) ■ Bonemarrow biopsy – For Waldenstrom’s ■ Positivecoombstest – Shows infiltrationof lymphoma – Haemolyticanaemia cellsintobone marrow – MonoclonalIgM paraproteinaemiaHistology ■ Hodgkin’s – ReedSternbergcells – Large, multinucleated cellsHistology ■ Burkitt’s lymphoma – Starrysky appearance – Lymphocytesheetsinterspersed withmacrophagesHistology ■ Waldenstrom’s – Rouleauxformation ■ Due toparaproteinsmaking cells stick together ■ Note: This is not specific to Waldenstrom’s andcan be causedby many thingssuch asmultiple myeloma andchronic inflammationStaging for Hodgkin’s Lymphoma ■ AnnArbour staging – There iscontiguous, localised spread ■ I – Single lymphnode ■ II– 2 or morelymphnodeson samesideof diaphragm ■ III – nodeson bothsidesof diaphragm ■ IV– spread beyond lymph nodes ■ A= no system symptoms other thanpruritus ■ B= Bsymptoms(poor prognosis)Prognostic Factors Hodgkin’s Non-Hodgkin’s ■ Age >45 ■ RaisedLDH ■ StageIV ■ Bsymptoms ■ Bsymptoms ■ Lymphadenopathy ■ Hb<10.5 ■ Anaemia ■ Lymphocytes <600 ■ Oldage ■ Albumin<40 ■ HighLDHTreatment ■ Treatment for all lymphoma involveschemotherapy ■ Another important factor isvaccinations ■ Thisisto reducetherisk of certaininfectionsSBA A 70 year old man presents to his GP with What is themost likely diagnosis? chronic back pain, which has been worsening over a period of about 5 years. The GP orders A– Paget’sdiseaseof thebone some blood tests which return the following B – Chronic KidneyDisease results; ↓Haemoglobin (Hb) C– Waldenstrom’s macroglobulinaemia Normal mean corpuscular volume (MCV) Normal mean corpuscular haemoglobin (MCH) D – PolycythaemiaRubraVera Normalwhite cell count (WCC) E– MultipleMyeloma Normalplatelet count ↑Urea ↑Creatinine ↑Calcium (Ca2+) Normalalkaline phosphatase (ALP)SBA A 70 year old man presents to his GP with What is themost likely diagnosis? chronic back pain, which has been worsening over a period of about 5 years. The GP orders A– Paget’sdiseaseof thebone some blood tests which return the following B – Chronic KidneyDisease results; ↓Haemoglobin (Hb) C– Waldenstrom’s macroglobulinaemia Normal mean corpuscular volume (MCV) Normal mean corpuscular haemoglobin (MCH) D – PolycythaemiaRubraVera Normalwhite cell count (WCC) E–MultipleMyeloma Normalplatelet count ↑Urea ↑Creatinine ↑Calcium (Ca2+) Normalalkaline phosphatase (ALP) Multiple Myeloma Harish BavaWhat is multiple myeloma? ■ Haematological malignancycharacterised byabnormal plasma cell proliferationinthebonemarrow – Plasma cell dyscrasiaof post-germinal B cells – TypicallyIgGandIgA – Also called paraproteins ■ Secondmost commonhaematological cancerintheelderly populationwith noknowngeneticcomponentPathophysiology ■ MM cancer cells secretecytokinesthat inhibit osteoblast production, increase osteoclasticactivity and amplifybreakdownof bone – Leads to anincreaseincalcium in the blood – Leads to easier fracturesandlytic lesionsinthebone ■ Increased proliferationof plasmacells – Therefore,reduced RBC production → anaemia ■ Depositionof paraproteinsinthekidney → Renal failure – Therefore,lessEPOproductionClinical signs and symptoms CRABBIpneumonic ■ Calcium – hypercalcaemia – Moans (painful bones),stones (renal stones), groans(GIsymptoms, Psychiatricmoans(fatigue,psychosis etc.) ■ Renal failure ■ Anaemia ■ Bonepathology – Bonepain,pathological fractures ■ Bleeding ■ Infection – Recurrent infectiondueto leukopeniaand immunoparesis(low levels of functional IgG)Investigations ■ FBC,U&Es,urinedip →anaemia,hypercalcaemia,renal impairment,Bence- Jones proteinonurinemicroscopy ■ Bonemarrowbiopsy →>10%plasma cells ■ X-Ray of skull –‘rain-drop’ skull showinglytic lesions ■ MRISkeletal survey for bone lesions ■ Blood film– Rouleaux'sformationManagement ■ Treatment involveschemotherapy and radiotherapy of neoplasticplasma cells ■ Treatingcomplications: – Bisphosphonates for bone – Dialysis – EPOand dietary supplements – Anti-coagulation duetoincreased viscosity of blood THANKS FOR WATCHING! Reviewed by DrCatherine Kwok