White cell disease Flashcards
Myeloperoxidase (MPO) is a marker of…
AML
PML-RARA
APL
t(15;17)
APL (PML-RARA)
Which FAB classification does APL belong to?
AML-M3
Pathogenesis and management of APL differentiation syndrome
Pathogenesis: release of inflammatory cytokines from malignant promyelocytes after ATRA –> capillary leak
Management: Dexamethasone, restart ATRA after resolution
Myeloblast vs Lymphoblast (5)
relatively low N:C ratio; very high
fine granules; agranular
fine chromatin; clumped
prominent nucleoli; indistinct
Auer rods
Cytogenetic studies for prognosis of ALL (3)
t(9;22) (poor)
t(12;21) (good)
hyperdiploidy (good)
Diagnostic criteria for Polycythaemia vera
Major:
- erythrocytosis
1. Hb > 18.5 / 16
2. Hct >49%
3. ↑ red cell mass
- BM briopsy: hyperceullar with trilineage growth
- JAK2
Minor:
- subnormal EPO
all majors, or major 1+2 + minor
Diagnostic criteria for essential thrombocytopenia
- Plt >450
- BM biopsy: megakaryocytic proliferation
- JAK2 / CALR / MPL
- ⨉ other MPN
Diagnostic criteria for PMF
Major:
- BM biopsy: reticulin +/- collagen fibrosis
- BM biopsy: megakaryocytic proliferation & atypia
- JAK2 / CALR / MPL
- ⨉ other MPN
Minor:
- leucoerythroblastosis
- ↑ serum LDH
- anaemia
- splenomegaly
all majors + 1 minor
Which MPN can directly transform into AML? (3)
CML, PV, PMF
t(9;22)
Philadelphia (Ph) chromosome / BCR-ABL1
CML
3 phases of CML (blast %)
- Chronic phase (blast <10%)
- Accelerated phase (blast 10~19%)
- Blast crisis (blast >=20%)
TKI for CML (1+3+1)
1st generation: Imatinib
2nd generation: Nilotinib 尼洛, Dasatinib 達沙, Bosutinib 博舒
3rd generation: Ponatinib 普納
Role of treatment of Ponatinib in CML
for T315I mutation
Role of treatment of hydroxyurea in CML
cytoreduction while awaiting confirmation of diagnosis
3 types of responses in treatment of CML
- Complete haematological response
- Complete cytogenetic response
- Molecular response
Major molecular response definition
3 log reduction (of BCR-ABL1 transcript) compared to international scale
Management for PV (4)
aspirin, venesection
[high risk] hydroxyurea, ruxolitinib
Management for ET (2)
aspirin, anagrelide
Assessment for PMF
DIPSS Plus scoring
Cytogenetics studies for prognosis of MDS
del 5q (good)
Risk stratification of MDS (4 parameters)
IPSS
1. dysplasia (single / multiple lineage)
2. % of blasts
3. del 5q
4. % of sideroblasts
PIG-A mutation
Paroxysmal nocturnal haemoglobinuria
BRAF V600E
Hairy cell leukaemia
Which haematological malignancy is associated with HTLV-1?
Adult T-cell leukaemia / lymphoma (ATLL)
Which haematological malignancy is associated with TCR rearrangement?
Adult T-cell leukaemia / lymphoma (ATLL)
Classification of Hodgkin lymphoma (4+1)
- Classical (CD30+)
a. Nodular sclerosing
b. Mixed cellularity
c. Lymphocyte rich
d. Lymphocyte depleted - Nodular lymphocyte predominant HL
Staging for Hodgkin lymphoma
Ann Arbor staging
t(14;18) (associated protein)
Follicular lymphoma
↑ Bcl-2
t(11;14) (associated protein)
Mantle cell lymphoma
↑ cyclin D1
MYD88
Lymphoplasmacytic lymphoma
t(8;14) / IGH-MYC fusion
Burkitt lymphoma
t(2;5) / NPM1-ALK fusion
Anaplastic T-cell lymphoma
Which blood cancer comes with DIC?
APL
Which blood cancer often comes with monocytopenia?
Hairy cell leukaemia
Which blood cancer often comes with gum hypertrophy?
AML-M5 / AMoL
Which blood cancer comes often with CNS involvement?
ALL
Which blood cancer comes often with mediastinal involvement (2)?
T-ALL, nodular sclerosing classical HL
Which blood cancer often comes with serous effusion?
T-PLL
Which blood cancer often comes with skin involvement?
ATLL
Which blood cancer often comes with hypercalcaemia and bone lesions? (2)
ATLL, MM
Which blood cancer often comes with oropharyngeal involvement?
non-Hodgkin lymphoma
Which blood cancer often comes with massive splenomegaly? (3)
CMF, PMF, Hairy cell leukaemia
Which blood cancer often comes with plethora and erythromelalgia (2)?
PV, ET
Which blood cancers are associated with significant thrombotic and bleeding risk?
PV, ET
DDx of Lymphadenopathy (5)
(MIAMI)
Malignancies: lymphoma, metastasis
Infection
Autoimmune diseases
Miscellaneous: storage diseases (e.g. Gaucher disease)
Iatrogenic: drugs
DDx of pancytopenia (3+1)
- BM disorders
a. Malignancy: MDS, AA, PNH
b. Infiltration: leukaemia, lymphoma, carcinoma, TB
c. Iatrogenic: chemotherapy, RT, chloramphenicols - Hypersplenism
DDx of erythrocytosis (1+1+3)
- Pseudoerythrocytosis: dehydration, burns, stress…
- Primary: PV
- Secondary:
a. persistent hypoxia
b. renal hypoxia
c. ectopic EPO production
DDx of thrombocytosis (1+3)
- Primary: MPN
- Secondary:
a. anaemia / blood loss
b. inflammation (inc. infection, malignancy, autoimmune diseases)
c. post-splenectomy
Flow cytometer components (3)
- Fluidics system
- Optical system
- Computer / Electronic system
Functions of forward scatter, side scatter and gating in flow cytometry respectively
FS: assess cell size
SS: assess granularity
Gating: isolating single populations of interest within one sample
Immunophenotyping: markers for haematological progenitor cells (4)
CD34, CD45, TdT, HLA-DR
Immunophenotyping: myeloid markers (4)
MPO, CD13, CD33, CD117
(13 ⨉ 3 ⨉ 3=117)
Immunophenotyping: B-lymphoid markers (5)
CD10, 19, 20, 22, 79a
Immunophenotyping: T-lymphoid markers
CD2, cCD3, CD5, CD7
Blood cancer with CD20-, CD138+
Multiple myeloma
Blood cancer with CD5+, CD23+
CLL
Blood cancer with TRAP+
Hairy cell leukaemia
Blood cancer with CD7-, CD25++
ATLL
Blood cancer with CD30+, CD15+
Classical Hodgkin lymphoma
Lymphoma with CD30-, CD20+
Non-classical Hodgkin lymphoma
Lymphoma with CD10+
FL, BL
Lymphoma with CD3+, CD30+, ALK+
Anaplastic T-cell lymphoma
Acute leukaemia definition
> =20% blast in BM
Which acute leukaemia is associated with Down syndrome?
AML-M7 (acute megakaryoblastic leukaemia)
Classification scheme of acute leukaemia (2)
- WHO
- FAB
Investigation findings for AML
Peripheral blood film: myeloblasts
BM aspirate & trephine biopsy: hypercellularity
Immunophenotyping
Cytogenetics: PML-RARA / t(15;17)
Molecular studies for prognosis in AML (3)
FLT3-ITD (poor)
NPM1 (good)
CEBPA (good)
Chemotherapy for AML
- Remission induction: Cytarabine (7d) + Anthracyclin (3d)
- Consolidation
Management for APL
All-trans-retinoic acid (ATRA), Arsenic trioxide, Ascorbic acid
Chemotherapy steps for ALL
remission induction + consolidation + maintenance
Investigation findings for CML
CBC: WCC >200, basophilia
Peripheral blood film: complete spectrum of immature white cells
BM trephine biopsy:
- hypercellularity, with granulopoietic dominance
- ↑ hypolobated megakaryocytes
Cytogenetics: Ph+ / BCR-ABL1 fusion
Investigation findings for MDS
CBC: pancytopenia, ↑ RDW
BM aspirate:
- blast cells
- ring sideroblasts…
- pseudo-Pelger Huet anomaly… (hypolobuted, hypogranulated, hypersegmented)
- hypolobulated megakaryocytes
BM trephine biopsy: hypercellularity
Congenital aplastic anaemia (2+1)
Multi-lineage: Fanconi’s anaemia, Dyskeratosis congenita
Single-lineage: Diamond-Blackfan syndrome
Aetiology of secondary aplastic anaemia
Iatrogenic: chemotherapy, radiation, drugs
Industrial: benzene
Infectious
Immune: SLE
Pathogenesis of paroxysmal nocturnal haemoglobinuria
PIG-A mutation –> ↓ GPI anchor –> CD55, CD59 cannot link to red cells –> complement attack –> intravascular haemolysis
Diagnosis of paroxysmal nocturnal haemoglobinuria
Flow cytometry
Management for paroxysmal nocturnal haemoglobinuria
Eculizumab
(Anti-C5 : “E””C”ulizumab)
Investigation findings for CLL
WCC: monoclonal B cells
Peripheral blood film: small lymphocytes, smear cells, smudge cells
BM aspirate: lymphocytosis
Immunophenotyping: CD5+, CD23+, light chain restriction
Genetics studies for prognosis of CLL (3)
del 13q14 (good)
trisomy 12 (intermediate)
del 17p / TP53, del 11q23 / ATM (poor)
Staging methods for CLL (2)
- Binet staging (A~C)
- RAI staging (0~IV)
Management for CLL
asymptomatic: watchful waiting
symptomatic: chemotherapy +/- targeted therapy
Targeted therapy for CLL (3)
Rituximab, Ibrutinib, Venetoclax
Name for the transformation from CLL to (…)
Richter transformation
(DLBCL)
Hodgkin’s lymphoma vs Non-Hodgkin’s lymphoma (prevalence, stage during presentation, spread, extranodal diseases)
Prevalence: (1:9)
Stage: early; later
Spread: contiguous nodal groups; remote
Extranodal diseases: fewer; more
MC lymphadenopathy in lymphoma (Describe the features of the lymph nodes)
cervical
non-tender, multible, rubbery, asymmetrical
Ann Arbor staging
- single LN region
- > 1 regions, same side of diaphragm
- both sides of diaphragm
- > = 1 extra-lymphatic organs
MC blood cancer
Multiple myeloma
Classifications of plasma cell dyscrasia (3)
- MGUS (serum M-protein <30 and BM plasma cells <10%)
- Smouldering myeloma
- Multiple myeloma (BM plasma cells >10% and >=1 CRAB features)
Specific investigations for multiple myeloma (serum 3 + urine)
Serum protein electrophoresis
Serum immunofixation electrophoresis
Serum FLC ratio
Bence Jones proteins
MC M proteins
IgG (>IgA > FLC)
Prognostic studies for multiple myeloma (1+3)
Good: hyperdiploidy
Poor: del 13q, ↑ serum albumin, ↑ serum β2-microglobulin
Which white cell disease shows raindrop skull?
Multiple myeloma
Describe Reed Sternberg cells
large atypical lymphoid cells with Owl-eye appearance of nuclei & inclusion-like nucleoli