pathology course haematology 2
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Pathology Course Haematology 2. Kindly sponsored by:. What will be discussed. Tuesday: Anaemia, coagulation, thrombosis Thursday: Haematological malignancies Paraproteinaemias Myelodysplastic / myeloproliferative disorders. General tips for written exams. Don’t focus too much on - PowerPoint PPT PresentationTRANSCRIPT
Pathology Course Haematology 2
Kindly sponsored by:
What will be discussed
Tuesday: Anaemia, coagulation, thrombosis
Thursday: Haematological malignancies Paraproteinaemias Myelodysplastic / myeloproliferative disorders
General tips for written exams
Don’t focus too much on Eponymous syndromes Nitty gritty facts e.g. chromosomal translocations
Do WebCT questionsSome questions will be hard / strangeUnderstanding is key
Acute Leukaemia
Acute Leukaemia
Neoplastic process of bone marrow and blood‘Acute’ therefore rapidly progressive and
fatalImmature blasts > 20% BM cells
Signs/symptoms: BM failure: anaemia, thrombocytopenia, neutropenia Organ infiltration: hepato/spleno-megaly,
lymphadenopathy, bone pain, gum hypertrophy
Aetiology
Ionising radiation – radiotherapyCytotoxic drugs – chemotherapyBenzenePre-leukaemic disorders e.g. MDS/MPDDown’s
Significnatly increased risk of AML/ALL Also, Down’s neonates often develop transient
abnormal myelopoeisis Resembles AML Resolves spontaneously after a few weeks
Acute Lymphoblastic Leukaemia
Childhood (ALL)Symptoms as previously mentioned
Lymphadenopathy +++ CNS involvement +++ Testicular enlargment Thymic enlargement
High WCC (accumulation of lymphoblasts)Ph+ve t(9;22) – poor prognosis
ALL: Treatment
Chemotherapy: (memory aid: I Can Cure Mankind) Remission Induction Consolidation CNS treatment Maintenance
Supportive Blood products, fluids, electrolyes
Acute Myeloid Leukaemia
Adulthood (risk increases with age) and under 2’s
Signs/symptoms as before Lymphadenopathy less common
Subtypes M3: Acute promyelocytic leukaemia DIC M5: Skin/gum infiltration +
hypokalaemia
AML: Lab
High WCCAuer rods and granulesMyeloperoxidase and Sudan black +ve
AML: Treatment
Chemotherapy Similar principles to ALL but… No CNS prophylaxis or maintenance needed
ATRA for M3Consider allo-SCT in young
Chronic Myeloid Leukaemia
Chronic Myeloid Leukaemia
A myeloproliferative diseaseOften diagnosed on routine bloodsNow very successfully treated in the majority
CML: Presentation
40-60 years peak (middle-aged)May be asymptomaticAnaemiaWeight loss, low grade fever, night sweatsMassive splenomegaly (down to RIF)Gout (raised urate – hypermetabolism)
CML: Lab
Huge WCC > 100 (neutrophilia)Hypercellular BM with spectrum of mature
and immature cells in the blood Malignant cells proliferate excessively but retain
ability to differentiate into mature cellsPh+ve in 80%; t(9;22)PCR for BCR-ABL
Monitor disease and therapeutic response
CML: Phases & Treatment
Chronic Phase< 5% blasts in BM/bloodWBC slowly increasesOver 3-4 years
Rx = Imatinib BCR-ABL tyrosine kinase inhibitor
CML: Phases & Treatment
Accelerated phase > 10% blasts in BM/bloodIncreasing manifestations e.g. splenomegalyUp to a yearLess responsive to therapy
CML: Phases & Treatment
Blast phase> 20% blasts in BM/bloodResembles an acute leukaemiaCourse = monthsTreatment similar to AML
Chronic Lymphocytic Leukaemia
Chronic Lymphocytic Leukaemia
A lymphoproliferative disease Others include ALL, MM and Waldenstrom’s
Also often an incidental finding on routine bloods
Disease of the elderly
CLL & SLL
Chronic lymphocytic leukaemia and small lymphocytic lymphoma
Same underlying disease, different presentation
CLL is primarily located in BMSLL is primarily located in lymph nodes
CLL: Presentation
> 40 years, elderlyMay be asymptomaticSymmetrical painless lymphadenopathyAnaemia, thrombocytopenia, neutropeniaWt loss, low grade fever, night sweatsHepato/Spleno-megaly (less prominent)Ass w/ autoimmunity
AIHA (Coomb’s +ve) + ITP = Evan’s syndrome
CLL: Lab
High WCC with lymphocytosis > 5 (high % lymphocytes)
Low serum Ig‘Smear cells’Prognostic factors
LDH raised = bad Hypermutated Ig gene = good
CLL: Stages & Treatment
Binet Staging A, B & C
Stage A < 3 groups of enlarged LN No treatment required
Stage B & C > 3 groups of LN, patient becomes more symptomatic Rx: 1st line is chlorambucil
CML CLL
Middle-aged
Massive splenomegaly
Neutrophilia
Ph+ve, BCR-ABL fusion gene
Imatinib Rx
Older
AID
Lymphocytosis
Smear cells
Chlorambucil Rx
CML vs CLL
Lymphoma
Lymphoma
Neoplastic tumour of lymphoid tissue Lymph nodes Spleen, MALT Rarely anywhere –
skin, testes, breast
1. Hodgkin’s – 20%2. Non- Hodgkin’s –
80%
Hodgkin’s lymphoma
M>FBimodal incidenceEBV associatedSpreads to adjacent lymph nodes – often
involves single LN groupAssymetrical painless lymphadenopathyConstitutional symptoms (Pel-Ebstein fever in
a minority)Pain after alcohol in affected nodes
Presentation CXR
nk
NormalMediastinal mass: Cough & resp infections SVC syndrome Dysphagia
Hodgkin’s: lab
CD15 & CD30Reed-Sternberg cell: binucleate / multinucleate
cell on background of lymphocytes
Subtypes Nodular sclerosing – most common
Staging
Stage I: 1 lymph node regionStage II: 2+ LN region; same side of diaphragmStage III: 2+ LN regions; opposite sides of
diaphragmStage IV: Extranodal sites, e.g. liver/BM
A: No constitutional symptomsB: Constitutional symptoms
Treatment
Combination chemotherapy ABVD – adriamycin, bleomycin, vinblastine,
dacarbazine 2-4 cycles in I/II, 6-8 cycles in III/IV
Radiotherapy Sometimes used alongside chemo against bulky areas
Intensive chemo + autologous SCT Relapsed patients
ESR used for progress and monitoring
Non-Hodgkin’s Lymphoma
• All lymphomas other than Hodgkin’s• Approximately 40 different subtypes
Mature/ImmatureHistology
High grade Very aggressive – Burkitt’s Aggressive – Diffuse Large B-Cell, Mantle Cell
Low grade Indolent – Follicular, Marginal Zone, Small Lymphocytic
Lineage B-Cell: All of the above T-Cell
Non-Hodgkin’s Lymphoma
Presentation varies significantly from subtype to subtype Painless lymphadenopathy Often involves multiple sites Constitutional symptoms No pain after alcohol
Staging as per Hodgkin’s
Burkitt’s Lymphoma
Very aggressiveThree variants
Endemic – most common malignancy in equatorial Africa; EBV associated; jaw involvement and abdominal masses
Sporadic – found outside of Africa, EBV associated, less commonly affects jaw
Immunodeficiency – HIV/Post-Tx patients; not EBV associated
Histology ‘Starry-sky’ appearance
t(8;14) translocation; c-myc oncogene overexpressionTreatment – chemotherapy (rituximab)
Diffuse Large B-Cell Lymphoma (DLBCL)
Middle-aged and elderlyAggressive• Richter’s transformation: leukaemias
DLBCLHistology
Sheets of large lymphoid cellsTreatment
Rituximab-CHOP
Mantle Cell Lymphoma
Middle-agedAggressive
Disseminated at presentation Median survival 3-5 years
Histology ‘Angular nuclei’
t(11;14) translocationDysregulation of cyclin D1Tx similar to DLBCL
Follicular Lymphoma
ElderlyIndolent
Median life expectancy 12-15 years Mostly incurable
Histology ‘Follicular pattern’, ‘Nodular appearance’
t(14;18) translocationTreatment
Watch and wait Rituximab-CVP
MALT lymphomas
Mucosal Associated Lymphoid Tissue Marginal Zone NHL
Middle agedChronic antigen stimulation
H. Pylori gastric MALT lymphoma Sjogren’s syndrome parotid lymphoma
Treatment Remove antigenic stimulus e.g. H pylori triple therapy Chemotherapy
T-Cell Lymphomas
Adult T-Cell leukaemia/lymphoma HTLV-1 infection
Enteropathy associated T-cell lymphoma Long standing coeliac disease
Cutaneous T-cell lymphoma
Anaplastic large cell lymphoma Children and young adults Aggressive Large ‘epitheloid’ lymphocytes
Peripheral T-Cell Lymphoma Middle aged and elderly Aggressive Large T cells
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A routine medical of a 33 year old footballer reveals: Hb 9.9, WCC 130. Blood film shows spectrum of myeloid precusors including a few blast cells. He admits to having frequent night sweats and blurred vision. Cytogenetic analysis shows Ph chromosome t(9;22)
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A routine medical of a 33 year old footballer reveals: Hb 9.9, WCC 130. Blood film shows spectrum of myeloid precusors including a few blast cells. He admits to having frequent night sweats and blurred vision. Cytogenetic analysis shows Ph chromosome t(9;22)
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A 5 year old girl presents with failure to thrive, recurrent fever and bruising. Immunophenotyping reveals the presence of CD10.
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A 5 year old girl presents with failure to thrive, recurrent fever and bruising. Immunophenotyping reveals the presence of CD10.
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A 64 year old woman receiving long-term chemotherapy for lymphoma presents with worsening bone pain, recurrent fever and night sweats. Blood film shows blast cells and Aeur rods.
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
A 64 year old woman receiving long-term chemotherapy for lymphoma presents with worsening bone pain, recurrent fever and night sweats. Blood film shows blast cells and Aeur rods.
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
An 85 year old lady with a painless swelling in her neck. After undergoing several investigation, she is told that there is cancer present but it is very slow growing. She is advised that she will be followed up regularly but no intervention is necessary at present.
Question Time!
A. CMLB. AMLC. ALLD. NormalE. CLLF. Mantle Cell LymphomaG. Hodgkin’sH. Follicular Lymphoma
An 85 year old lady with a painless swelling in her neck. After undergoing several investigation, she is told that there is cancer present but it is very slow growing. She is advised that she will be followed up regularly but no intervention is necessary at present.
Multiple Myeloma
Multiple Myeloma
Neoplasia of plasma cells of BMProduction of monocloncal Ig (IgG most
common) = paraproteinaemia
Middle aged – elderlyIncreased incidence in Afro-Caribbeans
Multiple Myeloma: Presentation
Multiple Myeloma: Presentation
Calcium high Thirst, abdo pain, constipation, stones, confusion
Renal failure Light chain obstruction of tubules Chains in urine = Bence Jones protein
Anaemia Infiltrate of plasma cells in BM Tiredness (also easy bleeding and infection)
Bone pain Osteoperosis, osteolytic lesions, wedge compression fractures
Multiple Myeloma: Lab
Dense narrow band on serum electrophoresisRouleax on blood filmESR very highBence Jones protein in urine> 10% plasma cells in BM
Multiple Myeloma: Treatment
Supportive for CRAB symptoms Bisphosphonates EPO
Chemotherapy Melphalan
Proteosome inhibitor: Bortezomib is 2nd line
Lenalidomide 3rd line
MGUS & Smouldering Myeloma
Monoclonal gammaglobinopathy of unknown significance
<10% plasma cells in BM (>10 % = MM)Incidental findingProgresses to MM at rate of 1-2%/year
Smouldering Myeloma>10% plasma cells in BM but no CRAB
Waldenstrom’s Macroglobinaemia
Older menLymphoplasmacytoid cells in BMIgM paraproteinaemiaUnlike myeloma, similar to NHL –
lymphadenopathy, wt loss, fatigueHyperviscosity syndrome – blurred vision,
headachesPlasmapheresis for hyperviscosity
MDS, MPD & ‘The Rest’
Myelodysplastic Syndromes
Group of progressive disorders where clonal proliferation of abnormally maturing stem cells occurs Cytopenias Hypercellular BM Dysplasia: Defective RBCs, WBCs, platelets e.g.
ringed sideroblasts Leukaemia transformation risk (AML)
ElderlySymptoms and signs relate to each cytopeniaBy definition, pts have < 20% blasts
>20% blasts = acute leukaemia
MDS: Treatment
Supportive – transfusions, EPOBiological ModifiersChemotherapy: hydroxyureaAllogenic SCT
PrognosisDepends on International Prognostic Scoring SystemMortality rule of 1/3: infection, bleeding, acute
leukaemia
Aplastic Anaemia
Inability of BM to produce adequate blood cells AA typically refers to anaemia i.e. just RBCs, but these
pts have a pancytopeniaSymptoms and signs relate to each cytopenia
Patients typically present with bleeding problemsAA closely linked to
Leukaemia Paroxysmal nocturnal haemoglobinuria
Aplastic Anaemia
Classification
Primary Idiopathic (70%) Inherited (10%) – see next slide
Secondary (10-20%) Radiation, drugs, viruses, immune
Inherited AA / BM Failure Syndromes
Fanconi Anaemia AR Presents at 5-10 years Skeletal abnormalities, short stature, renal
malformations, microopthalmia, skin pigmentation AML risk
Schwachman-Diamond Syndrome AR Skeletal abnormalities, short stature, endocrine
panreactic dysfynction, hepatic impairment AML risk
Inherited AA / BM Failure Syndromes
Dyskeratososis Congenita X linked Triad: skin pigmentation, nail dystrophy, leukoplakia
Diamond-Blackfan Syndrome Pure red cell aplasia; normal WCC and platelets Presents at 1 yr Dysmorphology
Myeloproliferative disorders
Group of conditions characterised by clonal proliferation of one or more haemopoietic component
1. Polycythaemia vera – RBCs2. Essential thrombocythaemia – platelets3. Idoiopathic myelofibrosis – WBCs Associated with JAK2 mutations (PRV)
Polycythaemia
Absolute polycthaemia Red cell mass raised Primary
PRV, familial Secondary
Disease states (renal Ca, hypoxia - COPD), high altitude raised EPO
Relative (pseudo) polycythaemia Red cell mass normal – plasma volume reduced Dehydration, burns, vomiting, diarrhoea Cigarette smoking, alcohol, HTN, obesity
Polycythaemia rubra vera (PRV)
MPD where erythroid precursors dominate BM JAK2 point mutations
Symptoms/signs Hyper-viscosity/volaemia/metabolism plethoric (red
nose), gout, splenomegaly Histamine release aquagenice pruritus (e.g. hot shower)
and peptic ulcersLab
Raised Hb, HCT Low serum EPO (cf secondary polycythaemia) Platelets, WCC may also be raised
Tx: venesection, hydroxycarbamide, aspirin
Idiopathic myelofibrosis
MPD where abnormal stem cells fibrosis of BM JAK2 mutation in 50%
Symptoms/signs Related to cytopenias Hepatomegaly, massive splenomegaly Weight loss, fever
Lab findings Tear drop poikilocytes, leucoerythroblasts Abnormally shaped RBCs, nucleated RBCs, immature myeloid cells BM: fibrosis, dry tap appearance
Treatment Supportive with blood products, splenectomy Cytoreductive therapy if platelet count is high: hydroxycarbamide
Essential thrombocythaemia
MPD where megakaryocytes dominate BMSymptoms/signs
Thrombosis (stroke and MI) and haemorrhage Erythromelalgia – extremities become blocked
painfully inflamed and hyperemicLab
Platelet count >600 x 109
Large platelets and megakaryocyte fragments BM – increased megakaryocytes
Tx: aspirin, angrelide, hydroxycarbamide
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 74 year old man is being investigated following a crush fracture of his T8 verterbra. He is found to have a monoclonal band on serum electrophoresis and free light chains in his urine.
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 74 year old man is being investigated following a crush fracture of his T8 verterbra. He is found to have a monoclonal band on serum electrophoresis and free light chains in his urine.
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 74 year old woman presents to her GP complaining of headaches and itchiness that is much worse after a warm bath. OE she has a normal CV and respiratory system. While palpating the abdomen, the doctor feels a vague fullness in the left upper quadrant. A full blood count shows Hb 22.1g/dl
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 74 year old woman presents to her GP complaining of headaches and itchiness that is much worse after a warm bath. OE she has a normal CV and respiratory system. While palpating the abdomen, the doctor feels a vague fullness in the left upper quadrant. A full blood count shows Hb 22.1g/dl
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 25 year old man presents to his GP complaining of a mass in his neck. The mass is generally painless, although it occasionally aches after alcohol. He admits to losing a significant amount of weight over the last month and also complains of excessive sweating and general itching. A biopsy of the mass reveals the presence of Reed-Sternberg cells.
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 25 year old man presents to his GP complaining of a mass in his neck. The mass is generally painless, although it occasionally aches after alcohol. He admits to losing a significant amount of weight over the last month and also complains of excessive sweating and general itching. A biopsy of the mass reveals the presence of Reed-Sternberg cells.
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 65 year old man on long term oxygen therapy for COPD is found to have a Hb of 18.4 g/dL
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
A 65 year old man on long term oxygen therapy for COPD is found to have a Hb of 18.4 g/dL
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
An 83 year old man is referred for bone marrow aspiration after presenting with heaptomegaly and splenomegaly. No marrow could be aspirated on the first attempt. Trephine biopsy is successfully performed and histology reveals hypercellular marrow containing many abnormal megakaryocytes.
Question Time!
A. CMLB. DehydrationC. Essential ThrombocytopeniaD. Hodgkin’sE. MGUSF. Multiple MyelomaG. MyelofibrosisH. Non-hodgkin’s I. Osteoperosis J. PRV K. Secondary polycythaemia L. Waldenstrom’s macroglobinaemia
An 83 year old man is referred for bone marrow aspiration after presenting with hepatomegaly and splenomegaly. No marrow could be aspirated on the first attempt. Trephine biopsy is successfully performed and histology reveals hypercellular marrow containing many abnormal megakaryocytes.
The END!
Go through the Blood Transfusion lecture
Understanding is key
Any questions email:[email protected]@imperial.ac.uk