Haematology Flashcards
1
Q
background AML
A
epidemiology
- most common leukemia in elderly
- median age >60
aetiology
- most are idiopathic
- radiation
- benzenes
- alkylating chemotherapy agents
- topoisomerase II inhibitors
- accumulation of mutations with ageing
genes
- associated with bone marrow failure disorders
- > eg fanconis
- somatic cell chromosome aneuploidy
- > eg down syndrome
- cytogenetic abnormalities
- > unbalanced deletions (more common in treatment related)
- > balanced translocations
- > normal karyotype (more common in de novo than treatment related)
pathophys
- accumulation of blasts
- > unable to differentiate into mature neutrophils, platelets or RBCs
- > bone marrow failure
- little correlation in blast % and cytopenia
- > indicates secretion of inhibitory cytokines
- > rather than crowding out of marrow
2
Q
hx and exam AML
A
Hx
- risk factors
- bleeding/clotting
- > easy bruising/bleeding
- > past CVA/MI
- infection
- > fevers
- > systems review for infection
- anaemia
- > SOB
- > palpitations
- > dizziness
- > lethargy
- bone pain
Exam
- lymphocytopenia
- > fever
- > source of infection
- anaemia
- > pallor
- > tachypnea
- > tachycardia
- thrombocytopenia/cytosis
- > splenomegaly
- > petechiae/eccymoses
- invasion (myeloid sarcoma)
- > lymphadenopathy
- > hepatomegaly
- > leukemia cutis
- > gum hypertrophy
3
Q
CML background
A
epidemiology
- uncommon in children
- > median age >55
aetiology
- no family hx
- no cancer treatment risk etc
- radiation
- > increased with atomic bomb
- > not with chernobyl
pathophys
- philidelphia chromosome in >90%
- > balanced translocation between long arms of 9 and 22
- > formation of chimeric BCR-ABL1 gene product
- BCR-ABL1
- > codes for constitutively active tyrosine kinase
- > excess proliferation and reduced apoptosis of CML cells
findings
- indolent
- > fatigue
- > weight loss
- splenomegaly
- > early satiety
- > RUQ fullness
- blastic conversion late in coarse
- blood
- > leukocytosis or thrombocytosis
- > anaemia
- marrow
- > high M:E
- > blasts <5%
4
Q
ALL background
A
epidemiology
-most common neoplasm in kids
aetiology
- syndromes
- > down syndrome = 20x
- human T cell leukemia virus
- > adults
findings
- blood
- > leukocytosis (but often normal or down)
- > anaemia/neutropenia/thrombocytopenia
- marrow
- > blasts >90% of nucleated cells
5
Q
CLL background
A
epidemiology
- older age
- > median age >70
aetiology
- family hx strong
- no environmental exposures known
findings
- indolent
- blood
- > raised WCC with lymphocytosis
- > some lymphadenopathy or splenomegaly
complications
- cancers
- > skin cancers most common
- richters transformation
- > transformation to lymphoma
- > most commonly diffuse large b cell
6
Q
investigations leukemia
A
FBC -differential ->20% AML has leuckocytosis ->often anaemia in any leukemia -film ->myeloid blasts plus Auer rods = AML EUCs -hypokalaemia/hyperuricaemia ->tumour lysis syndrome -hypercalcaemia with boney invasion LFTs Coags -TT/fibrin degradation products/D dimer ->DIC in APML -fibrinogen ->decreased
marrow aspirate/biopsy
- > 20% blasts confirms diagnosis
- immunohistochemistry (ALL vs AML)
- > AML = + myeloperoxidase
- > ALL = + TdT
- immunophenotyping (flow cytometry) to subclassify
- > eg CD34/34 % expression
- cytogenetics for prognosis
- > 15:17 translocation = good prognosis
7
Q
AML prognosis and complications
A
prognosis
- long term survival is infrequent
- 5 year survival = 25%
complications (CD CLIPT)
- chemo
- > secondary cancers
- > cardiomyopathy
- DIC
- CNS leukemia
- leukostasis
- infection
- pancyopenia
- tumour lysis syndrome
- > hyperuricaemia
- > hyperkalaemia
- > hyperphosphataemia
- > AKI
8
Q
types of Hodgkins lymphoma
A
Classic (90%)
- immunophenotype
- > CD 15 +
- > usually CD30 +
- > never CD45+
- nodular sclerosing
- > most common/common in younger patients
- > nodular growth seperated by fibrous bands
- > less common RS cells
- > lacunar variant of RS common (multilobulated nuclei with abundant cytoplasm)
- > mixed inflammatory background
- mixed cellularity
- > elderly patients infected with HIV
- > diffuse or vaguely nodular growth
- > absent of prominent fibrous bands
- > RS more common
- > mixed inflammatory background
- lymphocyte rich
- > usually nodular growth
- > RS cells common
- > inflammatory background is mainly lymphocytes
- lymphocyte depleted
- > least common
- > hypocellular with fibrosis and necrosis
- > lots of RS cells
Nodular lymphocytic predominant (10%)
- immunophenotype
- > CD45 +
- > CD15 -
- > rarely CD30+
- lymphocytic and histiocytic cells
- > polylubulated nuclei
- > nucleus appears exploded as popcorn cell
- nodular growth
- background = b cells, t cells, dendritic cells
9
Q
hx and exam Hodgkins lymphoma
A
hx
- onset
- > usually insidious (weeks/months)
- B symptoms (40%)
- > fevers
- > drenching night sweats
- > weight loss >10% over 6 months
- lymphadenopathy (non tender)
- > cervical most common
- > mediastinal (cough, sob, retrosternal pain)
- > axillary
- > step wise progression
- generalised pruiritis
- other
- > pel epstein fevers
- > alcohol induced joint pain
- > hepato/splenomegaly symptoms
- > bone pain
- > skin changes
- PMHx
- > previous malignancy
- > chemo/radiation
- > HIV/immunosuppression
- > EBV
- > fmhx
exam
- lymph nodes
- > all including waldeyers ring
- > size, site, number, firmness, mobility
- hepatosplenomegaly
10
Q
types of non Hodgkins lymphoma
A
Aggressive b cell
- diffuse large b cell
- > most common (1/3rd)
- > related to EBV infection, immunosuppression and autoimmune disease
- > large, atypical lymphocytes with prominent nucleoli
- burkitts
- > rare in adults
- > common in children
- > homogenous staining of b cells with pale macrophages gives starry night appearance
Indolent b cell
- follicular lymphoma
- > second most common
- > nodules of small lymphocytes
- gastric MALT
Aggressive T cell
-angioimmunoblastic
Indolent T cell
- Adult T cell
- > associated with human t lymphotropic virus 1
11
Q
non Hodgkins lymphoma hx and exam
A
hx
- risk factors
- > family hx
- > past malignancies, chemo, radiation
- > pesticides and hair dyes
- > EBV, HTCLV
- autoimmune diseases
- B symptoms
- > more common in aggressive
- lymphadenopathy
- > non step wise progression
- > waxing and waning in indolent
- extranodal
- > GI most common = distress/bowel obstruction
- > lungs = SOB/cough
- > hepatosplenomegaly= abdodiscomfort
- > CNS = ataxia
- > bone pain
exam
- lymph nodes
- pallor (anaemia
- petichiae/purpura (thrombocytopenia)
- extranodal
- > skin
- > jaundice/hepatosplenomegaly
- > EDCSS = neuro signs
12
Q
investigations lymphoma
A
FBC -anaemia -thrombocytopenia EUC -treatment LFTs -treatment -ddxs Prognostic -ESR -albumin -lactate dehydrogenase
excisional lymph node biopsy
- occasionally core, never aspirate
- > diagnosis requires RS/LH cell with appropriate background mileui
- classic = RS or variant (eg lacunar)
- > two nucleoli in seperate nuclear lobes
- > owls eye
- NLP= HS
- > popcorn cell
IMMUNOPHENOTYPING
immunohistochemistry
- classic
- > CD15+ mostly
- > CD30+ almost always
- > CD45-
flow cytometry
- > PDL-1 expressed by some RS
- > ligand for immune checkpoint receptors
STAGING
FDG PET CT
-staging
CONSIDER:
bone marrow biopsy
- Stage 1A and 2A
- > unnecessary as low risk of marrow involvement
- Stage 3 and 4
- > PET CT more sensitive so can be avoided
13
Q
staging lymphoma
A
lugano classification
- stage 1
- > one lymph node region
- > single extra lymphatic organ site (1E)
- stage 2
- > involvement of two or more lymph node regions on same side of diaphragm
- > contiguous limited involvement of extralymphatic organ (IIE)
- stage 3
- > involvement of lymph regions above and below diaphragm
- stage 4
- non contiguous involvement of extralymphatic tissue
for treatment
- 1 and 2 = early stage
- 3 and 4 = advanced stage
further notation
- b symptoms
- > A = absent
- > B = present
- bulky disease = X
- E only relevant to early stage
non-hodgkins
- no record of b symptoms
- > no effect on prognosis
- usefulness
- > haematogenous spread more common = less utility
- > no difference in treatment between stage 3 and 4
- > main use is identifying patients with early disease
- > hodgkins spreads by contiguous lymphatic involvement
14
Q
prognosis hodgkins lymphoma
A
Early stage (unfavourable/favourable)
- ME3 (German Hodgkins Study Group)
- > unfavourable = 1 of following
- > Mediastinal mass large
- > ESR >30 w B symptoms, >50 no B symptoms
- > 3 or more sites
- favourable with treatment
- > survival at 5 years >97%
Advanced stage (International prognostic score)
- HAM LAW 4
- > Haemoglobin
- > Albumin
- > Male gender
- > Lymphocytosis
- > Age >60
- > WCC
- > stage 4
- freedom from progression =
- > 5 factors = 42%
- > 0 factors = 84%
15
Q
prognosis non hodgkins
A
IPS (LEAPS 369)
- for DLBC with rituximab
- > Lactate dehydrogenase
- > Extranodal involvement
- > Age >60
- > Performance (ECOG)
- > Stage 4
- 3 year survival
- > 5 factors = 60%
- > 0 factors = 90%
16
Q
treatment lymphoma
A
non hodgkins
- RCHOP for 6 cycles
- > rituximab
- > cyclophosphamide
- > doxorubicin hydrochloride
- > vincristine
- > prednisone
- radiation therapy
hodgkins
- DBVD
- > doxorubicin
- > bleomycin
- > vinblastine
- > dacarbazine
- early = DBVD + radiation
- advanced = just DBVD
- > no benefit from radiation
17
Q
hodgkins vs non hodgkins lymphoma
A
epidemiology
- non-hodgkins 10x more common
- hodgkins
- > bimodal
- > 20’s and 80’s
- non hodgkins
- > risk increases with age
risk factors
- hodgkins
- > EBV
- > family hx
- non hodgkins
- > chemo, radiation, pesticides, hair dyes
- > EBV, HTCLV
- > immunosuppression and autoimmune
path
- hodgkins
- > monoclonal expansion of mature b cells
- non hodgkins
- > disease of progenitor or mature B or T cells
clinical presentation
- in general
- > hodgkins = indolent
- > non hodgkins = acute with aggressive or waxing waning with indolent
- > both lymphadenopathy and B symptoms
- differences
- > non hodgkins = non stepwise progression and extranodal involvement more common
- > hodgkins = pel epstein fevers, alcohol induced pain, involvement of mediastinum
diagnosis
- investigations similar
- > bone marrow biopsy in non hodgkins but not usually hodgkins
- both by biopsy
- hodgkins
- > RS or LH with background milleu
- non hodgkins
- > histological typical patterns
- > immunophenotyping for T or B cell origin
- > genotyping for monoclonality and typical mutations
staging
- both lugano classification
- > more useful in hodgkins
treatment
- both chemotherapy
- > but different agents
- both radiation
prognosis
->non hodgkins generally much worse
18
Q
ddx splenomegaly
A
CHINA
- congestive
- > CCF
- > cirrhosis
- haematological
- > haemolytic anaemia
- > sickle cell
- infection
- > malaria
- > EBV
- > CMV
- > HIV
- neoplasia
- > CML (CLL)
- > lymphoma
- > myelofibrosis
- autoimmune
- > amyloidosis
- > sarcoid
- > RA (feltys)
Massive = M’s
- cMl
- myelofibrosis
- malaria
19
Q
Platelet disorders
A
I’M FluID
- Immune thrombocytopaenia
- Microangiopathic haemolytic anaemias
- > HUS
- > TTP
- > DIC
- Functional defects due to
- > liver disease
- > uraemia
- Inherited diseases
- > Bernard Soulier
- Dysproteinaemias and myeloproliferative disorders
20
Q
disorders vessel wall
A
Sick Vessels Can Haemorrhage
- Steroids/cushings
- Vasculitis
- Collagen (Ehlers, marfans, scurvy)
- Henloch Shonlein Purpura
21
Q
Coagulation in chronic liver disease
A
Bleeding:
Thrombocytopenia -portal hypertension -decreased thrombopoeitin -DIC Decreased FII,VII,IX,X and fibrinogen -hepatocyte failure -vitamin k DIC Dysfibrinogenaemia Systemic fibrinolysis
Clotting: Altered blood flow Damage to vessel walls DIC Decreased protein C, S and antithrombin -hepatocyte failure -vitamin K
22
Q
ddx bleeding disorder
A
Von Willebrand Platelet disorders (I'M FluID) Vessel wall (Sick Vessels Can Haemorrhage) Coagulation disorders -Haemophilia A, B and acquired -Factor XI deficiency Vitamin K -deficiency -enzyme disorder Liver disease
