Week 5 - WBC HAEMATOLOGY Flashcards
Reactive WBC Disorders, Leukemia, Lymphoma, MPD + MDS (114 cards)
1
Q
What are the 2 routine stains in haematology?
A
- Eosin stain
- taken up by eosinophil granules
- red/pink - Basic stain
- taken up by basophil granules
- blue
*neutrophils take up NEITHER
2
Q
What is the normal WBC range?
A
4-11 x 10^9/L
- neutrophils = 2-8 x 10^9/L
- lymphocytes = 1-4 x 10^9/L
- others = <1 x 10^9/L
3
Q
What are the physiologic changes in WBCs?
A
Infancy/Aged:
- lymphocytosis (incr. lymphocytes
- in infancy 60-70% of peripheral blood is lymphocytes
Pregnancy:
-leucocytosis (incr. leucocytes)
4
Q
When will you commonly see increased neutrophils and immature neutrophils?
A
Increased neutrophils
-acute infection/inflammation
Immature neutrophils
- LEFT SHIFT
- severe infection/inflammation
5
Q
What is Left Shift?
A
- an increase in the no. of immature leucocytes (typically increased neutrophil band cells) in peripheral blood
- seen in severe infection/inflammation (increase need for neutrophils)
6
Q
What are the toxic changes to neutrophils in acute infections?
A
- toxic granulations
- dohle bodies
- vacuolation
*suggestion of early marrow release
7
Q
What are the causes of lymphocytosis?
A
- viral infections **
- chronic infections
- immune reactions
- pertussis
- TB
8
Q
What are the only 2 bacterial conditions which cause a lymphocytosis?
A
pertussis + TB
9
Q
What is the difference in lymphocyte appearance between lymphocytosis and reactive lymphocytosis?
A
lymphocytosis:
-small, round, large nucleus, scanty cytoplasm
reactive lymphocytosis:
- activated T cells
- large, more cytoplasm, flowing between RBCs (v. fragile and large)
10
Q
When would you see reactive lymphocytosis?
A
viral infections
-e.g. EBV
11
Q
What are the causes of eosinophilia?
A
- allergy/hay fever
- hypersensitivity
- asthma
- parasites
- worminfestations
- hodgkin’s lymphoma
12
Q
What should you suspect if you see basophilia on a peripheral blood smear?
A
CML
- basophilia = v. rare
- chronic myeloid leukemia
13
Q
What is a common cause of leucocytopenia?
A
steroid therapy
14
Q
What is lymphoerythroblastic reaction and when is it seen?
A
- leucoblasts + erythroblasts in blood
- irrespective of number
- release of all (both WBC + RBC) types of immature cells from bone marrow
seen in:
-marrow fibrosis, malignant infiltration, severe hyperplasia or infection (increased stimulation of BM)
15
Q
What is leukemoid reaction and what are the causes?
A
- very high WBC counts
- severe and excessive leucocytosis with immature cells (leukemia-like)
Causes:
- severe infections (usually children)
- severe hemolytic anemia/crisis
- marrow infiltrations/metastasis (leucoerythroblastic reaction)
16
Q
What is neutropenia and agranulocytosis?
A
Neutropenia
- decreased neutrophils (<1.5 x 10^9/L)
- any condition
Agranulocytosis
- v. severe (<0.5 x 10^9/L)
- severe infections (life-threatening)
- decreased production –> marrow failure
- increased destruction –> immune, splenomegaly, septicemia, viral (HBV)
17
Q
What is pancytopenia and what are the causes?
A
-decr. ALL cell types (RBCs, WBCs, Plts)
Causes:
- BM suppression
- aplastic anemia
- megaloblastic anemia
- myelodysplastic syndromes
18
Q
What is reactive lymphadenitis?
A
-enlarged lymph nodes due to reaction to an infection or inflammation
19
Q
What are the clinical features of reactive lymphadenitis?
A
- enlarged LNs
- tender/painful
- mobile (not fixed)
- inflammation in the area
20
Q
What are the microscopic features of reactive lymphadenitis?
A
- follicle hyperplasia
- sinus histiocytosis
- granuloma in TB
- abscess in bacterial/cat-scratch disease
- tingible body macrophages –> eating away unwanted lymphocytes
21
Q
What are the types of myeloid neoplasms?
A
Acute myeloid leukemia (AML)
-neoplastic blast cells WITHOUT maturation
Myeloproliferative disorders (+CML) -neoplastic blasts mature along one or more cell lines
Myelodysplastic syndromes
- blasts mature in a dysplastic manner –> destruction
- increased abnormal cells in BM/decreased in blood
22
Q
What are the types of lymphatic/lymphoid neoplasms?
A
Lymphatic leukemia
- ALL
- CLL
- Myeloma
Lymphoma
- non-hodgkins lymphoma
- hodgkins lymphoma
23
Q
What is leukemia?
A
- malignant WBCs in blood
- malignancy of blast cells in BM –> spread to blood + blood-related organs (liver, spleen, LNs)
- unkown etiology (radiation, viral ?)
- oncogenesis –> incr. division, decr. differentiation
- many subtypes –> gene-specific, Dx. + Tx.
24
Q
What are the common oncogenes in CML, AML, ALL, MPD?
A
CML –> BCR-ABL
AML –> RARA
ALL –> BCL2
MPD –> JAK2
25
What is the most common subtype of AML?
M3 --> promyelocytic leukemia
26
What is the most common subtype of ALL?
L1 --> small monomorphic
-CD10+ (pre-B lymphocytes)
N.B. FAB classification (L1, L2, L3)
27
What chronic leukemia is the most common clinically?
CLL
28
What are the clinical features of leukemia?
Decreased hemopoiesis:
- anemia (low RBCs)
- fever/infections (low WBCs)
- bleeding tendency (low plts)
Organ infiltration:
- bone/back pain
- hepatosplenomegaly
- lymphadenopathy
* BM, spleen, liver, LNs
29
What is CD10+?
- immature B cell marker
| - seen in L1 subtype of ALL (small monomorphic)
30
What age is ALL increased in and what are the clinical features?
- any age, common in CHILDREN
- growth failure, fever, anemia, PROMINENT lymphadenopathy, MINIMAL hepatosplenomegaly, bleeding
*LYMPHADENOPATHY marked
31
Why is there more prominent lymphadenopathy in ALL?
-malignancy of LYMPHOBLASTS --> increased spread to lymph nodes
32
What is the microscopy of ALL?
Lymphoblasts
| -plenty of large, round blast cells with little blue cytoplasm and NO granules
33
How do you differentiate between a normal lymphocyte and a lymphoblast (i.e. in ALL)?
- compare size to surrounding RBCs
- lymphoblasts > size than RBCs
- lymphocytes ~ size of RBCs
34
What age group is AML increased in and what are the clinical features?
- adults (40-60yrs common)
- anemia, fever, bleeding (same as ALL)
- moderate/prominent hepatosplenomegaly
- NO significant lymphadenopathy
- gum hypertrophy*
- increased infections --> candidiasis (oral thrush), gingivitis + hyperplasia, bruising --> purpura
35
What is the microscopy of AML?
Myeloblasts
| -plenty of large, round blast cells with more clear cytoplasm with granules and auer rods
36
What are Auer rods?
- seen on microscopy of AML
- granules join to form crystal-like structures within cytoplasm --> AUER RODS
- Dx. of AML
37
What is AML-M4 known as?
Myelomonocytic
| -cells present with pink cytoplasm (myeloblasts) and blue cytoplasm (monoblasts)
38
What is AML-M7?
Megakaryoblastic leukemia
- blasts
- abnormal megakaryocytes
- plenty of abnormal giant platelets
39
Briefly compare AML vs. ALL
ALL
- children increased
- increased lymphadenopathy/minimal hepatosplenomegaly
- scanty cytoplasm (lymphoblasts)
- NO granules
AML
- adults increased
- increased hepatosplenomegaly/NO lymphadenopathy
- more clear cytoplasm (myeloblasts)
- granules + AUER rods
*BOTH --> anemia, fever, bleeding, infections
40
Gum hypertrophy is typical of what leukemia?
AML
| -leukemic infiltration
41
What are some features of chronic leukemias?
CML + CLL
- later age
- chronic
- asymptomatic for many years
- slow + gradual progression
42
What is CLL (chronic lymphocytic leukemia) similar to?
Small lymphocytic lymphoma (SLL)
| -NHL
43
What are the features of CLL?
- similar to SLL (NHL)
- anemia, fever, bleeding --> slow over many yrs
- lymphocytosis + lymphadenopathy
- MASSIVE splenomegaly (over yrs) + mild hepatomegaly
- commonest = B cell (CD5+ --> T cell Ag); high BCL2 expression
- hypogammaglobulinemia --> non-functioning lymphocytes (despite increased no.)
44
What are the clinical phases of CLL?
Chronic (*commonest):
-slow progress (yrs)
Accelerated phase:
- high grade lymphoma/leukemia
- terminal phase after many yrs
- incr. mortality :(
45
What are the features on blood film of CLL?
- plenty of normal looking lymphocytes
| - SMUDGE CELLS --> smeared/crushed cells from smearing blood as cancer cells are fragile (v. characteristic of CLL)
46
When would you see smudge cells?
CLL peripheral blood smear
47
What chromosome is characteristically affected in CML?
Philadelphia chromosome
| -translocation of 22 onto 9
48
What is the difference between CLL + SLL (NHL)?
CLL
-increased leukemic lymphocytes in BLOOD
SLL/NHL
-increased leukemic lymphocytes in LYMPH NODES
49
What is the commonest type of CLL?
B CELL:
- CD5+ (T cell Ag)
- high BCL2 gene expression
50
Why is there hypogammaglobulinemia in CLL depite an increased no. of lymphocytes?
They are NON-FUNCTIONING
| -produce monoclonal Abs which are of NO use physiologically
51
What oncogene is mutated in CML commonly?
BCR-ABL fusion gene activation
| -Breakpoint Cluster Region - Ableson Leukemia gene --> carcinogenesis (uncontrolled blast cell proliferation)
52
True or False?
| There is marked left shift in CML
True
53
What are the key features of CML?
Marked leucocytosis (>50 x 10^9/L)
- ALL cells
- not just blast cells --> marked left shift
Marked hepatosplenomegaly
Basophilia --> v. characteristic
54
What are the 3 clinical phases of CML?
Chronic
-slow progress (yrs)
Accelerated
-rapid progress (mths)
Blast Crisis
-acute leukemia (wks)
55
What is Blast Crisis?
- clinical phase of CML
- pt. deteriorates within weeks
- blast cells over proliferate and take over from previous variety of immature/mature cells (Left Shift)
- acute leukemia (decr. mature/incr. immature)
56
What is multiple myeloma?
- leukemia of PLASMA CELLS (B lymphocytes)
- HYPERGAMMAGLOBULINEMIA*
- old age, males increased
57
What condition would you see a perinuclear halo and what is it resulted from?
Multiple myeloma
- perinuclear halo is at region of golgi apparatus
- B cells loaded with immunoglobulins (monoclonal Ab --> not useful)
58
Why is there an increased risk of infarctions, visual difficulties and even blindness in multiple myeloma?
- hypergammaglobulinemia from increased monoclonal Ab
- increased gamma globulin --> STICKY substance
- blood becomes thick + viscous --> infarctions, visual disturbance, blindness (obstruction to small vessels)
59
What is the pathogenesis of punched out lytic bone lesions + fractures in multiple myeloma?
- leukemia in BM
- production of osteolytic enzymes
- increased osteolysis
60
True or False?
| CML is a type of MPD
True
61
What is the commonest pathogenesis of lymphoid neoplasms?
- commonly related to EBV infection
- overexpression of BCL2 (ANTIAPOPTOTIC GENE)
- t(14;18) --> BCL2 + IgM --> B cell neoplasia
- continuous proliferation of unneeded B lymphocytes
62
What are the general clinical features of lymphoid neoplasms?
- fever, anemia, infections
- lymphadenopathy, splenomegaly
- BM infiltration + bleeding ONLY in high-grade neoplasms (unlike leukemias)
63
How are lymphoid neoplasms diagnosed?
Immunophenotyping
- T/B cell Ag commonest --> to differentiate between T cell or B cell lymphomas
- CD5 --> CLL
Genetic
- BCL2
- TdT (ALL)
64
Where do the commonest lymphomas arise from (commonest starting cell)?
```
Germinal Centre (GC) B cells:
=overproliferation due to BCL2 mutation (antiapoptotic gene)
```
65
Clinically, what is the commonest type of lymphoma?
Non-Hodgkin's lymphoma
- 62.4%
- out of NHL --> Diffuse B cell Lymphoma = commonest
66
What is the common infection implicated in the development of lymphoid neoplasms?
EBV
67
What is Hodgkin's lymphoma and what is the characteristic microscopic feature?
- malignancy of germinal centre B cells
- double peak (young + late age)
- REED STERNBERG (RS) CELLS**
68
What is significant about the fever in Hodgkin's lymphoma?
Cyclic Pel-Ebstein Fever (like malaria)
- 2-3 days
- only in 30% of cases
69
What are the clinical Sx of Hodgkin's lymphoma?
- wt. loss
- sweating
- fever (cyclical --> Pel-Ebstein)
- weakness
- anorexia
70
What are the 2 types of symptom classification for hodgkin's lymphoma?
A --> absence of Sx.
| B --> fever, night sweats, wt. loss, etc.
71
Why is staging important in Hodgkin's lymphoma and outline what it is?
*as it is CONTINUOUSLY/CONTIGUOUSLY SPREADING from LN --> LN
stage I --> single or one region LN
stage II --> 1 group of LNs (ABOVE diaphragm)
stage III --> multiple groups of LNs (incl. BELOW diaphragm)
stage IV --> involvement of liver, spleen or BM (high-grade)
72
Which cells are malignant in hodgkin's lymphoma?
Reed-Sternberg Cells
| -rest of the cells are reactive inflammatory cells --> lymphocytes, neutrophils, macrophages, eosinophils
73
What region lymphadenopathy is typical in Hodgkin's lymphoma?
Mediastinal lymphadenopathy
| -compresses trachea --> cough
74
What is the relationship between alcohol + hodgkin's lymphoma?
Alcohol-induced pain (LN pain)
- rare
- but if present --> v. characteristic
75
What is the pathogenesis of hodgkin's lymphoma?
- RS cells = malignant
- reactive inflammatory cells = non-malignant (lymphocytes, neutrophils - inflammation, macrophages, eosinophils --> fibroblasts --> fibrosis)
- spread via nearby LNs (no metastasis unlike NHL)
76
What is the commonest type of hodgkin's lymphoma?
Nodular Sclerosis
-characterised by malignant RS cells, inflammation + FIBROSIS --> extensive fibrosis forming nodules which form fibrous septa
77
Outline classification of hodgkin's lymphoma
1. nodular sclerosis --> most common*
2. mixed cellularity
3. lymphocyte-rich
4. lymphocyte depletion
5. nodular lymphocytic predominance
```
(1-->4 = classical HL - EBV + Ig Tran. mutation)
(5 = NO EBV or Ig Tr. mutation; popcorn cells)
```
78
What do RS cells look like and how are they related to prognosis?
- binucleate, large, 'owl-eye' shaped nuclei --> scary looking
- increased RS cells (malignant cells) = poor prognosis
79
What is the microscopy of nodular sclerosis HL?
- nodular, fibrous septa
- reactive inflammatory cells --> eosinophils, lymphocytes, neutrophils, plasma cells, etc.
- RS cells**
80
How can you differentiate between NHL + HL on microscopy?
NHL --> uniform cells; NO RS cells
| HL --> mixed RS cells + inflammatory cells
81
What are popcorn cells?
- RS cell variant
- significantly clear cytoplasm, uninucleated
- seen in Nodular Lymphocytic Predominance (NLP) Hodgkin's (non-classical hodgkins)
82
What are the clinical features of NHL?
- fever, anemia, infections, lymphadenopathy, splenomegaly (+/-)
- NO RS cells/eosinophilia **
83
How does the spread of NHL differ to HL?
- NHL has a random spread between LNs (can spread to distal nodes randomly)
- HL has a contiguous pattern of spread between LNs
*NHL staging is thus DIFFICULT
84
Which cell type is commonest in NHL?
B cell
| -T cell + histiocytic also possible, unlike HL (ALL B cells)
85
What is small lymphocytic lymphoma + large lymphocytic lymphoma?
SLL --> low grade --> CLL
LLL --> high grade --> ALL
* 2 main types of NHL
- bigger cell size = higher grade = worse prognosis
86
True or False?
| -NHL can be diffuse or follicular on microscopic appearance
True
87
What would low, intermediate and high grade NHL appear like on microscopy?
Low
-uniform SMALL cells
Intermediate
-MIXED small + large cleaved cells
High
-LARGE cells
88
What is the difference between diffuse NHL + follicular NHL with regards to grading?
```
Follicular = low-grade (well differentiated)
Diffuse = high-grade
```
* BUT --> cell size still matters (i.e. diffuse vs. follicular is NOT the only determining factor for grading NHL)
- small cells = low grade
- large cells = high grade
89
What is Burkitt's lymphoma?
- B cell lymphoma
- children/young
- large cell --> high grade
- endemic in Africa (sporadic elsewhere)
- MYC-IgH translocation - 14 - EBV*
- surface B cell marker + IgM
- common on facio-maxillary region
90
What is microscopy of Burkitt's lymphoma?
- larger, dark blast cells
- lipid vacuoles (same as ALL type L3)
- plenty of scattered macrophages
**STARRY SKY --> characteristic appearance
91
What is the most common type of plasma cell neoplasm?
Monoclonal Gammopathy of Undetermined Significance (MGUS)
- chronic plasma cell neoplasm
- v. slow growing (benign)
- <3gm/dL of monoclonal gammaglobulins = diagnostic
- may develop into myeloma; plasma cytic lymphoma
- amyloidosis due to increased immunoglobulin production
92
Compare HL vs. NHL
HL:
- avg age 28; double peak at 25 + 60yrs
- <10% of all lymphomas
- cervical, chest + mediatinal LNs (85%); extranodal (4%), contiguous spread; mesenteric + waldeyer ring involvement uncommon
- B cells affected with RS cells present
- more likely to have systemic (B) Sx.
- early Dx, predictable, better prognosis
NHL:
- avg age 67yrs
- >60% of all lymphomas
- multiple sites, chest (40%), extranodal (23%) +BM; non-contiguous spread; mesenteric + wladeyer ring involvement common
- B cells commonly affected, but T cells, histiocytes + NK cells can also be affected
- less likely to have systemic (B) Sx.
- less predictable, early spread, good --> worse prognosis
93
True or False?
| Mesenteric + waldeyer ring involvement is common in HL
False
| -common in NHL
94
What is the commonest mutation seen in MPD and explain its role in the pathogenesis of MPD? What is the exception?
JAK2 activation on 9p
-exception = CML --> BCR-ABL mutation
*JAK2 activation causes increased tyrosine kinase activity, PDGF mutations --> growth factor hypersensitivity
95
What are the 4 conditions that constitute MPDs?
1. polycythemia vera (PV) --> RBC maturation
2. CML --> WBC maturation
3. essential thrombocythemia (ET) --> Plt maturation
4. myelofibrosis (MF) --> fibroblast* maturation
- as a result (secondary to) one of the other 3 conditions
*N.B. mixed = common
96
True or False?
| MPD can transform to acute leukemia
True
97
What are the outcomes of MPD?
1. acute leukemia (AML)
2. myelofibrosis (after yrs) --> scarring of BM
(3. death by MPD) :(
98
True or False?
| -in PV, EPO is required for RBC maturation
False
- PV = neoplastic due to JAK2 mutation
- growth factor (EPO)-independent proliferation
99
What happens to serum EPO in PV?
Decreases
| -due to increased serum RBCs from growth factor-independent proliferation
100
What are the clinical features of PV?
- red skin/flushing
- hypercellular marrow
- hepatosplenomegaly
- high viscosity blood --> vascular stenosis --> infarctions
- bleeding - BV damage; plt. abnormality
101
Why is primary myelobrosis common in ET?
-plts. release PDGF which stimulates fibroblasts and causes fibrosis/scarring of marrow
102
Why is there increased bleeding in ET?
- JAK2 tyrosine kinase activation
| - increased plts --> large + abnormal --> therefore non-functioning --> bleeding
103
What is primary myelofibrosis?
- end result of PV, ET and other MPDs
- JAK2 tyrosine kinase activation
- increased marrow fibrosis due to PDGF + TGF-beta from neoplastic stem cells + megakaryocytes
**fibroblasts = non-neoplastic
104
Why is there massive hepatosplenomegaly in primary myelofibrosis?
-increased extramedullary hemopoiesis as the whole BM is scarring
105
What characterisitic RBC feature is seen in myelofibrosis?
Teardrop RBCs
106
What are Myelodysplastic syndromes (MDSs) AKA?
- refractory anemia
| - pre-leukemia
107
What is the common mutation seen in MDS and what does it result in?
- deletions of 5q
| - excess proliferation of functional + structurally abnormal DYSPLASTIC cells (MDS)
108
What is the main difference between MPD + MDS?
MPD
-functionally abnormal but structurally normal cells
MDS
- functionally + structurally abnormal dysplastic cells
- majority cells destroyed in marrow
- ineffective myelopoiesis
- peripheral pancytopenia --> anemia, infections, bleeding
109
What is the commonest cell line affected in MDS?
RBCs = most common
-anemia --> v. common in pts. with MDS
Sx. = fever, anemia, bleeding (like leukemia)
110
What is the FAB classification of MDS?
1. RA: - refractory anemia; only RBCs affected (<1% BM blasts)
2. RARS: - RA with ring sideroblasts - iron deposits around nucleus of erythroblasts (<1% blasts)
3. RAEB: - RA with excess blasts (in BM); faster developing/higher grade disease (1-5% blasts)
4. RAEB-T: - RAEB in transformation (5-30% blasts)
* >30% blasts = leukemia
111
What % of blasts is diagnostic for leukemia?
>30%
112
What are the 2 known pathogenetic mechanisms for lymphomas?
EBV + BCL2 mutation
113
True or False?
| transformation to AML is more common in MDS than MPD
True
114
True or False?
| peripheral pancytopenia is typical of MPD
False
| -typical of MDS
