Haematology & Oncology Flashcards
1
Q
diagnosis
A
essential thrombocythaemia
or
IDA
2
Q
define follicular lymphoma
A
neoplastic proliferation of small B cells (CD20+) that make follice-like nodules
3
Q
cytoplasmic MPO +ve blasts suggests what pathology?
A
AML
4
Q
who gets nodular sclerosing HL? and how does it present?
A
young girls - enlarging cervical LN or medastinal mass
5
Q
what are the ocular complications of measles infection?
how do you prevent them?
A
keratitis and corneal ulceration
vitamin A supplementation
6
Q
frequency of MGUS?
transformation rate to MM?
A
5% of people over 70
1% per year get MM
7
Q
define myeloproliferative disorder
A
a neoplastic proliferation of mature myeloid leukocytes
8
Q
what are these cells? what is the diesease?
A
smudge cells
chronic lymphocytic leukaemia
9
Q
pathoG ‘owl-eye appearance’
A
Reed-Sternberg cell of HL
multilobed nuclei and prominent nucleoi
10
Q
define Hodgkin’s lymphoma
A
neoplastic proliferation of Reed-Sternberg cells, which are large B cells (CD15+/CD30+)
11
Q
most common cause of death in multiple myeloma
A
infection
12
Q
tartrate-resistance acid phosphatase +ve staining cells suggests what pathology?
A
hairy B cell leukaemia
13
Q
what does a tingible body macrophage do? when are these important?
A
tingible body marcophage = macrophage that phagocytoses the products of apoptosis in normal germinal centre of B cells that have not passed positive and negative selection
TBMs are present in normal, reactive LN germinal centres but not present in follicular lymphoma
14
Q
BRCA1/2 mutation leads to overall lifetime risk of breast (%age)
A
breast - 70/80%
15
Q
treatment of iron poisoning/haemochromatosis
A
IV deferoxamine, oral deferasirox
dialysis
16
Q
pathoG - Pautrier microabscesses
A
mycosis fungoides
17
Q
Treatment of aplastic anaemia
A
1) stop the offending agent
2) transfusion
3) marrow growth factors (EPO, GM-CSF and G-CSF)
4) some immunosupression
5) BM transplant
18
Q
what is fibronectin?
A
fibronectin - glycoprotein produced by fibroblasts and some epithelial cells, mediates binding of integrin to collagen (a.k.a. cells to ECM)
19
Q
define diffuse large B cell lymphoma
frequency? prognosis?
A
a neoplastic proliferation of large B cells (CD20+) that grow diffusely in sheets, without forming reognisable lymph node structures
most common NHL
poor prognosis
20
Q
define polycythemia rubra vera
A
a neoplastic proliferation of mautre myeloid leukocytes, with an erythrocyte predominance
21
Q
1 cause of basophilia
A
CML
22
Q
define myelofibrosis
A
a neoplastic proliferation of mature myeloid leukocytes, predominantly megakaryocytes
also associated with JAK2 kinase mutation
23
Q
anti-B19 IgM serum antibodies suggest what pathology?
A
recent previous parvovirus B19 infection
24
Q
3 features of megaloblastic anaemia
A
- Macrocytic anaemia
- megaloblastic change in rapidly dividing cells
- hypersegmented neutrophils
25
how does the t(14;18) translocation lead to lymphoma?
*BLC2* translocates to Ig heavy chain locus.
Ig heavy chain locus is constituatively expressed in B cells
Bcl-2 inhibits apoptosis of B cells undergoing somatic hypermutation/maturation in hugh numbers at the germinal centres
follicular lymphoma results
26
3 pathogens for non-EBV infectious mononucelosis
1. CMV
2. HIV
3. *toxoplasma*
27
T-ALL surface markers
CD2 up to CD8
do not express **CD10**
28
name the pathoG cells
description of this smear?
diagnosis?
tear drop red cells - tapered at one end
leukoerythroblastic smear
myelofibrosis
29
define acute myeloid leukaemia
a neoplastic proliferation of **immature myeloid** leukocytes
30
how does pancreatic insufficiency affect absorbtion of a water-soluble vitamin?
pancreatic enzymes are required for the cleavage of **R factor** from cobalamin for Vit B12 to be absorbed.
pancreatic insufficiency (chronic pancreatitis etc..) can lead to *megaloblastic anaemia*
31
what is the definitive diagnosis of EBV infectious mononucleosis?
serologic EBV viral capsid antigen
32
3 complications of EBV mononucleosis
1. splenic rupture
2. ampicillin rash
3. dormancy in B cells leads to B cell lymphoma or recurrence
33
Rx Waldenstrom macroglobulinaemia
plasmapheresis
34
In Sickle cell, 5 complications of vaso-oclusion
1) dactylitis
2) autosplenectomy
3) acute chest syndrome
4) Pain crisis
5) Renal papillary necrosis (gross haematuria & proteinuria)
35
neoplastic cell detachment from adjactent cells of the primary is regulated by what molecular change?
decreased expression of E-cadherin
this releases a cell from its neighbours in the first step toward matastasis
36
pathoG - starry sky appearance
Burkitt lymphoma
37
microsomal cytochrome P450 monooxygenase
affect on development on cancer?
CYP450 metabolises forgein substances in the liver and endoplasmic reticulum of other tissues.
CYP450 can convert pro-carcinogens into carcinogens, increasing their association with developing cancer
38
lympoid stem cells give rise to what cells?
B cells --\> plasma cells
T cells --\> CD4 and CD8 cells
39
what is flutamide and what is it used for?
competitive androgen receptor blocker
used in prostate cancer - is a testosterone-dependent tumour. blocking androgen shrinks tumour
Improves symptoms like bone pain and urinary retention
40
how do you stratify B-ALL prognosis? epidemiology?
by translocation
t(12;21) excellent prognosis, often in children
t(9;22) poorer prognosis more frequently in adults - known as *Philadelphia+ ALL*
41
a JAK2 kinase mutaion with elevated haematocrit suggests what?
polycthemia rubra vera
42
treatment for CML with t(9;22)? how does it work?
imatinib
blocks tyrosine kinase receptor activity
43
B-ALL surface markers (3)
**CD10** CD19 CD20
44
how to determine clonality in B cell lymphoma?
kappa : lambda light chain ratio
3:1 in polyclonal reactive LAD, deranged in lymphoma (20-25:1)
45
what antimetabolite causes palmar-plantar eythrodysesthesia?
5-FU
46
complications of hereditary spherocytosis (2)
1. pigment gallstones
2. parvovirus B19 aplastic crisis
47
function of FFP
increase coagulation factors
use in **DIC****, cirrhosis**
48
what are the side effects of methotrexate?
pulmonary fibrosis
myelosuppression
hepatotoxicity
mouth and GI ulcers
49
a CD34+ cell has what function?
haematopoetic stem cell for both lymphoid and myeloid cell lines
50
folate is absorbed in...
jejunum
51
define mantle cell lymphoma
neoplastic proliferation of small B cells (CD20+) that expands the mantle zone (the region immediately adjacent to the follicle)
52
\>20% blasts in the bone marrow is defines what condition?
acute leukaemia
53
function of *Bcl-2*
blocks mitochondrial release of cytochrome C and inhibit apoptosis
54
55
marker of myeloblast (in AML)
myeloperoxidase (MPO) crystalised MPO results in Auer Rods forming, so pathoG for AML
56
haemophilia A, B and C
affected factor and inheritance patterns
A - VIII - XR
B - IX - XR
C - XI - AR
57
3 types of AML to remember
APML
acute monocytic leukaemia
acute megakaryoblastic leukaemia
58
all heretidary thrombosis syndromes (4)
1. factor V Leiden
2. protein C and S deficiency (inability to **inactivate** factor Va)
3. antithrombin deficiency
4. prothrombin gain of function mutation
59
causes of vitamin b12 deficiency (4)
1) pernicious anaemia
2) pancreatic insufficiency
3) damage to terminal ileum (\*diphyllobothrium latum\* tapeworm)
4) dietary deficiency in vegans (very unlikely)
60
# define marginal zone lymphoma
associations (3)
neoplastic proliferation of small B cells (CD20+) that expands the marginal zone
chronic inflammatory state (Hashimoto's, Sjogren's), or *H pylori* chronic gastritis (MALToma - subtype of marginal zone lymphoma)
61
a mediastinal mass on CXR in teenagers with constituational symptoms suggests which CA?
acute lymphoblastic *lymphoma* , or T-ALL
lymphoma = forms a mass in the thymus
62
Down's leukamia before age of 5
important negative finding
acute megakaryoblastic leukaemia
cells **never** stain +ve for MPO
63
what is the difference between myelodysplastic syndrome and acute myeloid leukaemia?
blast cell %age in bone marrow
both have hypercellular bone marrow with cytopenia
* myelodysplasia is blasts \< 20%*
* AML is blasts \> 20%*
64
cells of lymph node cortex
B cells
65
what antimetabolite drugs complexes with thymidylate synthetase and folic acid to block DNA synthesis?
5-fluorouracil
66
what do paclitaxel, vincristine and vinblastine do?
what part of cell cycle
microtubule assembly (vinca) and disassembly (placitaxel) inhibitors, arresting cells during mitosis
67
complications of paroxysmal nocturnal haemoglobinuria
1) iron deficiency anaemia - chronic loss of Hb
2) AML - develops in 10% of patients
3) thrombosis - intravascular platelet destruction
68
*BRCA1/2* mutation leads to increase risk of ovarian CA as well as breast.
which has a bigger impact on ovarian CA?
*BRCA1*
69
what is the reversal agent for methotrexate toxicity?
folinic acid (leucovorin)
70
what is the mechanism of action of clopidogrel?
(and prasugrel, ticagrelor, ticlopidine)
ADP receptor blocker, P2Y12 sepcifically on platelets
blocking of receptors inhibits GpIIb/IIIa expression and plaelet aggregation
71
HbA2 is...
alpha2delta2
72
gastrectomy is risk factor for which anaemia? why?
Fe2+ absorbed, Fe3+ is not. Fenton reaction keeps iron as Fe2+ in low pH. Without stomach, digested material in duodenum is higher pH so more Fe3+ and less absorption
73
4 Lab findings of intravascular haemolysis
1) LDH, unconj bili
2) haemoglobiinuria
3) haemosidinuria (delay of a few days)
4) decreased serum haptoglobin (Hb binding globin)
74
define mulitple myeloma
neoplastic proliferation of plasma cells within the bone marrow
75
what cell? disease?
pathoG cellular inclusion? what's that made of?
bite cell
G6PD
Heinz body
disulphide bond formation leads to precipitation of Hb under oxidative stress
76
*BRCA* mutation is inherited in what pattern?
autosomal dominant
77
tumour angiogenesis is usually regulated by what growth factors?
VEGF
FGF-2
78
4 features/lab findings for folate deficiency, 1 negative finding
1. megaloblastic anaemia 2. glossitis 3. decreased serum folate 4. increased serum homocysteine 5. normal methylmalonic acid (c/o VitB12 deficiency)
79
cause of lymph node paracortex hyperplasia?
viral infection
T cell zone is paracortex - so when CD8+ cells are needed these regions will expand...
typically EBV mononucleosis
80
what is the difference in target between dalteparin/enoxaparin and fondaparinux?
LMWH (dalte/enoxa) = predominantly on Xa
fonda = **only** Xa
81
HbA2 levels are slightly increased in what disease?
beta-thalassaemia minor
82
bone marrow biopsy
diagnosis?
myelofibrosis
83
heparin versus warfarin
administration, site of action, onset, mechanisms, duration, reversal, monitoring, obstetric consideration
* **Heparin** - IV/SC, blood, rapid (sec), IIa/Xa inhibitor, hours, protamine sulphate, PTT, does not cross placenta (safe)
* **Warfarin** - oral, liver, slow (C & S go first), inhibition of 2, 7, 9, 10 & C,S; vit K FFP PCC, PT and INR, teratogenic and crosses placenta
84
what is the effect on clotting tests of thrombolytics?
PT & PTT increase, no change in platelets
85
what do the '-tecans' and '-posides' do? what part of the cell cycle is affected?
topoisomerase inhibitors
- tecan = topoisomerase I
- poside = topoisomerase II
S and G2
86
examples of direct thrombin inhibitors
argatroban, dabigatran (only oral), bivalirudin
87
how does the t(8;14) translocation cause Burkitt lymphoma?
***c-myc*** translocated to Ig heavy chain locus
Ig heavy chain constituatively expressed
*c-myc* oncogene **promotes cell growth**
88
decreased Fc receptors (CD16) on neutrophils suggests what?
immature neutrophils released from bone marrow in neutrophilic leukocytosis
89
complications of all myeloproliferative disorders
1. hyperuricaemia and **gout** (purine degredation pathway)
2. progression to marrow fibrosis ('spent phase')
3. transformation to acute leukaemia
90
cancers associated with EBV infection
HL and NHL (Burkitt)
nasopharyngeal carcinoma
91
vitamin b12 is absorbed in...
ileum
92
3 ways to distinguish CML from acute infection?
1. leukocyte alkaline phosphatease (**LAP**) -ve in CML
2. **basophils** also present in CML
3. t(9;22) present
93
2 causes of neutropenia
1) chemotherapy with alkylating agents 2) severe infection (gram negative sepsis)
94
proper function of cetuximab and panitumumab depend on normal function of what proto-oncogene?
*KRAS*
these monoclonals are EGFR antagonists. If *KRAS* has an activating/oncogenic mutation then binding of these drugs doesn't properly inactivate the receptor and dysplastic proliferation continues.
Testing for the gene mutation is required before starting therapy
95
what disease is this?
what is the important negative finding?
acute monocytic leukaemia
cells usually **do not** stain +ve for MPO
96
what is in cryoprecipitate (5 F's)
when is it used
**f**ibrinogen, **f**actor VIII, **f**actor XIII, vW**F** and **f**ibronectin
coagulation factor deficiencies involving fibrinogen and factor VIII
97
vitamin b12 binds what in the duodenum? why not before?
intrinsic factor (IF) - made by gastric parietal cells vit b12 only cleaved from R-binder by pancreatic proteases
98
what do abciximab and eptifibatide bind to?
GpIIb/IIIa receptor preventing aggregation
99
HbF is...
alpha2gamma2
100
what is the mechanism for boney deformity in beta-thalassaemia major?
chronic haemolysis
erythropoetic stimulation
hyperplastic haematopoetic marrow cell invasion of bone, liver and spleen (extramedullary haematopoesis)
dysregulation of boney archetecture - cortical thinning and limited longitudinal growth
101
what type of receptor is human epidermal growth factor receptor 2 (HER2)?
what biologic agent targets this?
tyrosine kinase
trastuzumab, Herceptin - inhibitor
102
What are these cells? what is the dieasea?
reactive CD8+ T cells (large nucleus and too much cytoplasm)
infectious mononucleosis
103
what is the mechanism for desmopressin use in bleeding disorder?
DDVAP - increases vWF release from endothelium and circulating factor VIII
104
function of platelets
clinical use
increase platelet count, indicated when \< 50,000 plts
thrombocytopenia, qualitative platelet bleeding disorder
105
invasion through the basement membrane and access to the vasculature is mediated by what neoplastic molecular process?
expression and secretion of proteolytic enzymes such as **matrix** **metalloproteinase** and **cathepsin D protease**
final step in metastasis
106
Down's association with leukaemia after the age of 5
ALL
107
DDx (3) painless LAD
chronic inflammation
metastatic carcinoma
lymphoma
108
does heparin or warfarin cross the placenta?
Warfarin - not that it should be used anyway because it it teratogenic
109
major difference between UFH and LMWH?
LMWH = better bioavailability, longer half life (2 - 4 x); subcut administration without lab monitoring
UFH = reversible
110
2 causes of monocytosis
1) chronic inflammatory state (AI or infection) 2) malignancy
111
function of packed red cells
cinical use
increase Hb and O2 binding capacity
severe aneamia and blood loss.
112
screening test for sickle cell gene
metabisulphite - causes any degree of HbS to sickle and appear in blood film
sickle cell trait otherwise would not have sickle shaped RBCs or target cells
113
what is the major complication of cyclophosphamide/ifosfamide?
how can this be prevented?
**haemorragic cystitis** - breakdown product of cyclophosphamide is toxic to uroepithelial cells
prevention with pretreatment of **mesna** (2-mercaptoethanesulfonate), binds and inactivates the toxic products in the urine
114
haemoglobin A2 levels are highly increased in what disease?
beta-thalassaemia major
115
what is the main role of IkappaB? how is it inactivated?
inhibition of **NFkappaB**, so inhibition of transcription of pro-inflammatory genes (cytokines, acute phase reactants, cell adhesion molecules)
activation of TLRs, mitogens or pro-inflammatory cytokines --\> **IkappaB kinase** --\> **phosphorylation** of IkappaB --\> **uqibuitination** and disinhibtion of NFkappaB
116
presenting FBC findings for acute leukaemia (3)
1. anaemia
2. thrombocytopenia
3. neutropenia
117
define a chronic leukaemia
a neoplastic proliferation of mature circulating lymphocytes
118
why do you get bone marrow fibrosis is myelofibrosis?
megakaryocytes expanding massively and producing PDGF causing fibroblast proliferation and fibrosis
119
Rx PRV
1. blood letting
2. hydroxyurea
120
t(9;22) classically associated with what cancer?
CML
also associated wtih adult onset, poor prognosis B-ALL
121
symptoms of hyperviscosity??
1. blurry vision and headache
2. venous thrombosis (Budd Chiari syndrome)
3. Flushed face
4. itching after bathing, due to concomitant increase in mast cell
122
biochemical compostion of Auer rods?
myeloperoxidase (MPO)
123
Rx for hariy cell leukaemia.
how does this work?
2-CDA (cladribine)
adenosine deaminase inhibitor... adenosine accumulates in B cells leading to cell death
124
what is the margianted pool?
neutrophils attached to the pulmonary vasculature at rest that can be released into the circulation secondary to infection/necrosis
125
what cell? disease?
spherocyte
hereditary spherocytosis, drug-/infection-induced haemolytic anaemia
126
osteoblastic boney mets suggests what primaries (3)?
1. prostate
2. small cell lung CA
3. Hodgkin lymphoma
127
most common cause of death in Sickle cell children
infection with encapsulated organisms
128
Associated conditions with Immune haemolytic anaemia (IHA)
1) SLE 2) CLL 3) drugs - penicillin and cephalosporins
129
pathoG wordy description?
what's the disease? what cell type is this?
hairy cytoplasmic processes
hairy cell leukaemia
mature B cell
130
diagnosis?
follicular lymphoma
131
treatment of hereditary spherocytosis
splenectomy
132
complications of CLL (3)
1. hypogammaglobulinaemia (B cells are naive so don't produce Ig)
2. AIHA - when B cells *do* try to make Ig they do a bad job and end up killing the body's own RBCs
3. **Richter** transformation to diffuse large B-cell lymphoma (presentation with an acutely enlarging lymph node or spleen)
133
what cancer are nitrosoureas used for mainly and why?
brain CA as crosses the BBB
134
pathogenesis of splenomegaly in myelofibrosis
fibrosis in the bone marrow reduces haematopoetic potential
resulting extramedullary haematopoesis, mainly in the spleen
135
what is CD55?
delay-activating factor
GPI mutation means you don't anchor CD55(DAF) in PNH, complement-mediated intravascular haemolysis
136
pure red cell aplasia is associated with which cancers (2)?
thymoma
lymphocytic leukaemia
...IgG-/cytotoxic T cell-mediated autoimmune inhibition of **only** erythrogenesis
137
CD5+/CD20+ cells are found in what **pathology**? when is this normal?
they are naive B-cells found in CLL
is normally found on physiologic T cells
138
WBC count reference range
5,000 - 10,000 cells/microL
139
what do alkylating and platinum agenst do?
cell-cycle independent drugs.
form cross-links between DNA
140
Hx mutliple thromboses, PTT normal and unaffected by exogenous protein C
diagnosis?
factor V Leiden
because protein C should usually break down factor V and stop thromboses, but the mutation renders it resistant
141
diagnosis? explanation?
multiple myeloma
increased circulating protein decreases charge between RBCs allowing rouleaux formation
142
what is the difference between CLL and hairy cell leukaemia?
**HCL** = neoplastic proliferation of mature B cells
**CLL** = neoplastic proliferation of naive B cells
143
main cause of death in paroxysmal nocturnal haemoglobinuria
thrombosis of hepatic, portal or cerebral veins destroyed platelets release cytoplasmic contents into the serum inducing thrombosis
144
what happens to a multiple myeloma cell treated with proteasome inhibitor?
accumulation fo toxic intracellular proteins, build up of pro-apoptotic proteins
## Footnote
**apoptosis**
145
epidemiology (age) of AML?
50 - 60 year olds
146
screening test for G6PD deficiency
blood smear with Heinz preparation highlights precipitated haemoglobin that otherwise wouldn't be seen on H&E slide
147
what is the monospot test? (3 points)
test for IgM that react with horse or sheep RBCs (heterophile antibodies)
positive in EBV infectious mononucleosis, but not in CMV mono.
Turns positive 1 week after EBV infection
148
cells of lymph node paracortex
T cells
149
myeloid stem cells give rise to what cells?
erythroblasts --\> RBCs
myeloblasts --\> neutrophils, basophils, eosinophils
monoblasts --\> monocytes
megakaryoblasts --\> megakaryocytes --\> platelets
150
osteoclastic boney metastases suggests what primaries?
1. MM
2. Non-Hodgkin lymphoma
3. Non-small cell lung CA
4. Kidney (RCC)
5. melanoma
151
effect of elevated steroids on white cell count
neutrophilia steroids impair adhesion of neutrophils to pulmonary vasculature, releasing the marginated pool into circulation
152
define CML
neoplastic proliferation of mature myeloid leukocytes, predominantly granulocytes
*basophils* are classically elevated
153
marker of either type of lymphoblast (in ALL)
TdT - a DNA polymerase
TdT is absent in blasts from myeloid lineage and in mature lymphocytes
154
what are the slow and fast reversal options for warfarin?
slow - vitamin K
fast - FFP or prothrombin complex concentrate (PCC)
155
complications of blood transfusion
1. hyperkalaemia (lysed RBCs)
2. hypocalcaemia (citrate added which chelates Ca++)
3. 2ary haemochromatosis
4. transfusion reaction
5. infection transmission (low risk)
156
AL amyloidosis associated with primary malignancy?
multiple myeloma
157
how is leuprolide used in cancer?
luprolide - GnRH agonist.
Constant GnRH (not pulsatile) inhibits LH, inhibits testosterone from leydig cell, decreases DHT.
decreases testosterone signalling to prostate CA & mets, improving symptoms of this testosterone-dependent tumour
158
define Burkitt lymphoma
a neoplastic proliferation of intermediate sized B cells (CD20+)
association with EBV
159
AML translocation
t(15;17)
160
disease?
name of cell?
macrocytic anaemia - folate/B12
macro-ovalocyte
161
162
APML translocation, disruption, effect, complication
**t(15;17)**
retanoic acid receptor (**RAR**) dysfunction
inability of cell to mature - accumulation of promyelocytes (many Auer rods)
**DIC** --\> coagulation cascade triggered by Auer rods
163
DDx lymph node **follicular** hyperplasia (2)
HIV infection (hyperplasia of CD4+ follicular dendritic cells)
rheumatoid arthritis
164
treatment of immune haemolytic anaemia
1) stop offending drug 2) steroids 3) IVIG 4) splenectomy
165
scalp rash, lytic bone lesions (skull), diabetes insipidus, exopthalmus
Hans-Schuller-Christian disease
langerhans cell histiocytosis - children older than 3 y/o
malignant
166
principles of treating AIP
medication?
want to decrease Succinyl CoA conversion to ALA which is the toxic build up product.
ALAS is induced by CYP450 so avoid all enzyme-inducing drugs (antiepileptics, griseofulvin, rifampin)
**glucose and haeme** are downregulators of ALAS - haeme/dextrose IV acutely
167
how does infection cause neutropenia?
severe Gram-negative infection leads to movement of neutrophils into tissues resulting in decreased circulating numbers
168
iron is absorbed in...
duodenum
169
what cancers spread to bone?
prostate, breast, kidney, thyroid, lung
| (**lead kettle**; PB/KTL)
170
pathogens for infectious mononucleosis
EBV (more common) CMV (less common)
171
what anti-nausea medication is best for chemo adjunct and why? what receptor does it affect?
ondansetron, 5-HT3 blocker
blocks vagus-mediated stimuli from gut and central serotonin neurotransmisison from area postrema
**area postrema** - is the _chemosensitive_ trigger zone. sends signal to NTS for integration with vesibular and ocular input.
172
HbA is...
alpha2beta2
173
what is the target of hydroxyurea?
ribonucleotide reductase
stops nucleotide synthesis
174
what is it? diagnosis?
Birbeck granule
Langerhans cell histiocytosis
175
lymph node structure from out to in
cortex, paracortex and medulla
176
which HL has the best prognosis?
lymphocyte-rich HL
177
what is this?
what is the associated inherited condition?
what are other signs/symptoms associated with this?
right renal angiomyolipoma (benign)
Tuberous Sclerosis (autosomal dominant)
**skin** [ash-leaf patch, facial angiofibroma], **brain** [subependymal hamartoma, cortical tubers], **heart** [cardiac rhabdomyoma]
178
what is the enzyme that activates azathioprine?
HGPRT, into 6-MP
179
what are the two targets of heparin?
thrombin (IIa) and factor Xa
180
what HL has the worst prognosis?
who gets it?
lymphocyte-depleted
elderly and HIV +ve
181
define essential thrombocythaemia
a neoplastic proliferation of mature myeloid leukocytes, predominantly platelets
also associated with a JAK2 mutation
182
conditions inducing HbS sickling
1) hypoxaemia 2) acidosis 3) dehydration 4) high 2,3-BPG
183
what are the major mediators of neoplastic cachexia?
TNF-alpha
IL-1beta
IL-6
184
what is a Howell-Jolly body?
disease?
HJB is a nuclear remnant found in RBCs from maturation
hyposplenia or asplenia
splenic macrophages usually removes these from physiologic red cells
185
what cell? diagnosis?
acanthocyte - spur cell
cholesterol dysregulation (liver disease, abetalipoproteinaemia)
186
what is mutated?
name of cells?
disease
RBC membrane proteins (e.g. spectrin)
elliptocyte
hereditary elliptocytosis
187
trimethoprim mechanism
inhibitor of bacterial dihydrofolate reductase (DHFR)
188
methotrexate mechanism
inhibitor of mammalian dihydrofolate reductase (DHFR)
189
which is the most common subtype of ALL?
B-ALL
190
in the setting of CLL, development of generalised lymphadenopathy indicates what?
infiltration of the B cells into the lymph nodes.
goes from CLL to small lymphocytic *lymphoma*
191
Rx paroxysmal nocturnal haemoglobinuria
mechanism
**eculizumab**
PNH is complement mediated intravascluar haemolysis. (GPI anchor mutation so decay-accelerating factor cannot protect RBC membranes)
drug inhibits terminal complement cascade, protecting RBCs,
192
pathoG phrase and diagnosis
explain what is happening
starry sky - Burkitt lymphoma
high cytoplasmic to nuclear ratio stains dark blue (night sky).
such rapid proliferation leads to cell death in the tumour and tingible body macrophage infiltration to phagocytose the debris (bright star)
193
what is a lacunar cell? where do we find it?
lacunar - from 'lake'
RS cell sat in lake-like spaces seen as clearing on histology.
nodular sclerosing hodgkin's lymphoma
194
what is the difference between fresh frozen plasma and cryoprecipitate?
FFP = all coagulation factors
cyroprecipitate = only cold-soluble factors VIII, fibrinogen, vWF, vitronectin
195
what is cytarabine used for? and what is the main side effect?
acute leukaemis (AML) and lymphoma.
causes pancytopenia and megaloblastic anaemia
(as you would expect if it's *stopping* leukaemia)
196
what is cilostazol(/dipyridamole)?
how do they affect clotting?
phosphodiesterase inhibitors
increase cAMP in platelets, inhibiting aggregation.
197
what is this?
DDx
basophilic stippling
lead/arsenic poisoning, sideroblastic anaemia, myelodysplastic syndrome
198
Rx follicular lymphoma
criteria for treatment
rituximab (CD20 antibody) or chemotherapy
if they are symptomatic
199
splenomegaly due to cellular expansion in the red pulp with lymphocytosis suggests what CA?
hairy B cell leukaemia
whereas usually other white cell infiltrates into the spleen will expand in the white pulp.
200
function of BRCA1 and BRCA2 genes?
DNA repair enzymes
201
classify Hodgkin's lymphoma
based on the population of reactive myeloid cells that are attracted to the RS cells and form the bulk of the tumour
1. nodular sclerosis (70%)
2. lymphocyte-rich
3. mixed cellularity
4. lymphocyte-depleted
202
follicular lymphoma complication
presentation
transformation to large B-cell lymphoma
presentation - acutely enlarging single lymph node on a background of generalised LAD
203
pathoG - cerebriform nuclei
mycosis fungoides that has neoplastic T cells spreading through the circulation - now called Sezary syndrome
204
how does the t(11;14) translocation cause mantle cell lymphoma?
translocation of **cyclin D** to Ig heavy chain locus
Ig heavy chain constituatively expressed
overexpression of cyclin D promotes **G1/S phase progression**
205
206
pathologic fracture in adolescent
biopsy shows CD1a+/S100+ cells with numerous eosinophils infiltrating
disease?
eosiophilic granulma
a benigin langerhans cell histiocytosis
207
how does kidney disease result in a bleeding disorder?
chronic kidney disease leads to an accumulation of uraemic toxins
uraemic toxins impair platelet aggregation and adhesion - qualitative disorder
208
what are these cells? describe the features?
blasts of acute leukaemia
large, immatue, punched out nuclei
209
neoplastic proliferation of CD4+ T cells in the epidermis forming microabscesses
mycosis fungoides
210
diagnosis?
chronic myeloid leukaemia
211
skin rash, cystic skeletal defects in infant
Letterer-Siwe disease (a langerhans cell histiocytosis)
malignant
children \< 2 years old
212
what cell is pathologic in ATLL?
what is the microbiology association?
mature CD4+ T cells
HLTV-1 - Japan and Carribean
213
treatment for neutropenia secondary to chemotherapy
GM-CSF and G-CSF
214
3 causes of neutrophilia
1) bacterial infection 2) tissue necrosis 3) high cortisol state
215
diagnostic test hereditary spherocytosis
osmotic fragility test - increased fragility of spherocytes in hypotonic solution because less membrane available to expand total volume of cell
216
most common cause of death in Sickle Cell adults
acute chest syndrome
217
vitamin b12 binds what in the mouth?
R-binder once cleaved from animal protein by amylase
218
mixed cellularity HL is associated with what cell type?
important cytokine?
eosinophils
associated with IL-5
219
epidemiology of myeloproliferative disorder
disease of late adulthood
220
2 causes of lymphocytic leukocytosis
1) virus infection (CD8+ T cells) 2) bordetella pertussis - lymphocytosis-promoting factor stops lymphocytes from leaving the blood to enter lymph node
221
transformation in CML leads to what?
**2/3 AML**
**1/3 ALL**
because the mutation driving the transformation will be at the level of the CD34+ haematopoetic stem cell which can give rise to either leukaemia
222
mixed boney metastases suggests what primaries (2)?
gastrointestinal
breast
223
Rash, generalised LAD and HSM
lytic bone lesions with hypercalaemia
lymphocytosis
what disease?
ATLL
224
Hb Barts is...
gamma4
225
painless swollen lymph node that gets bigger and smaller over a long time, no other symptoms
follicular lymphoma - non-hodgkin
226
6 features/lab findings of vitamin b12 deficiency
1) megaloblastic anaemia 2) glossitis 3) subacute degeneration of spinal chord 4) decreased serum vitamin B12 5) increased serum homocyteine 6) increased serum methylmalonic acid (c/o folate def)
227
three phases of CML
1. accelerated (spleen getting acutely bigger)
2. chronic (enlarged spleen)
3. transformation (to acute leukaemia)
228
what consideration should be made in a patient with diabetes and beta-thalassaemia minor?
beta-thal minor - increase in HbA2 to compensate.
Resulting microcytic erythrocytes have a shorter half life than normal red cells
the HbA1c will be falsely lowered b/c of high cell turnover
229
what is the reversal agant for heparin and how does it work?
protamine sulphate
positively charged molecule that binds heparin in the circulation
230
characteristic of immature neutrophil
decreased Fc receptor (CD16) concentration causes - bacterial infection or tissue necrosis
231
clinical features of waldenstrom macroglobulinaemia
generalized LAD
hyperviscosity - headache and retinal haemorrhage/stroke
bleeding - deranged platelet function due to viscous serm
IgM-containing M spike on SPEP
232
HbH is...
beta4
233
cause of lymph node sinus histiocyte hyperplasia?
LN draining site of cancer
234
caldribine is an analog of what nucleotides?
purine - inhibits DNA polymerase and induces strand breaks
235
high serum IL-6 suggests what pathology?
multiple myeloma
236
what part of the cell cycle is arrested by bleomycin?
G2 - double check and repair
bleomycin induces DNA strand breakage by free radical formation
237
an abnormal eosin-5-maleimide binding test suggests what disease?
hereditary spherocytosis
238
splenomegaly, dry tap and **absent** lymphadenopahty suggests what pathology?
Hairy B cell leukaemia
239
classify Burkitt lymphoma
African - involves jaw
sporadic - involves abdomen
240
3 causes of eosinophilia
1) allergic reactions - type I hypersensitivity 2) parasite/helminth infection 3) Hodgkin lymphoma - overproduction of IL-5
241
what is integrin? clinical significance?
transmembrane receptor that binds cytoskeletal stuctures (e.g. actin) to fibronectin. Important in regulating cellular adherance to the basement membrane/other cells/ECM
variable expression/mutation of integrin is associated with **metastatic potential** of dysplastic cells.
*e.g. (malignant) melanoma*
242
3 consequences of Ig light chain overproducation in MM
1. primary AL amyloidosis
2. Bence-Jones protein aggregation in the urine
3. myeloma kidney --\> renal failure (Ig light chain deposition in the tubules)
243
which antimetabolites reduce DNA synthesis by stopping dTMP production?
5-FU (thymidylate synthetase) and methotrexate (dihydrofolate reductase)
244
what cancer is cladribine used for?
hairy cell leukaemia
245
what is the pathogenesis of heparin-induced thrombocytopenia?
IgG antibodies versus heparin::Platelet-Factor 4 (PF4) complex
Immune complex activates platelets, leading to thrombosis and thrombocytopenia
246
neoplastic cell atatchment to the basement membrane is mediated by what molecular process?
expression of **laminin** and other adhesion molecules.
this middle (2nd of 3) step in metastasis buys the cells time to access vasculature
247
4 causes of lymphopenia
1) Immunodeficiency (Di George or HIV) 2) High cortisol - apoptosis of lymphocytes 3) Autoimmune (e.g. SLE) 4) radiation damage (lymphocytes most sensitive cell to radiation in whole body)
248
what are the three neurotransmitter targets modulated by anti-emetics for **chemotherapy-induced emesis**?
serotonin (5-HT3) antagonist
dopamine antagonist
neurokinin 1 antagonist
249
APML Rx
all-trans retanoic acid (ATRA) causes blasts to mature through activation of RAR
250
pelger huet cells
congenital - lamin B receptor mutation
aquired - myelogenous leukaemia, myelodysplastic syndrome
251
what is the usual causes of paroxysmal cold haemoglobinuria?
viral infection (measles, VZV)
syphilis
252
what happens in paroxysmal cold haemoglobinuria?
production of anti-RBC IgG that bind RBCs in the cold.
complement-mediated intravascular haemolysis on rewarming
self-limiting, as IgG dissociates from RBCs at higher temperature
253
what is the management for PNH?
Vit B12/folate suppliments
prophylactic vaccines/antibodies
Mab = **eculizumab** (targets complement C5)
254
what is the management for chronic autoimmune thrombocytopenic purpura?
IVIG, steroids, splenectomy
255
what is the target INR or 1st episode DVT/PE or atrial fibrilaiton
2.0-3.0
256
what is the target INR for recurrent DVT/PE or mechanical prosthetic valve?
2.5-3.5
257
what cells proliferate and expand in the blood in infectious mononucleosis?
reactive, atypical CD8+ T cells
258
what are the principles of multiple myeloma treatment?
* **supportive**
* bisphosphonates etc
* **chemotherapy**
* melphalan, borzetomib (proteasome inhibitor), lenalidomide/thalidomide
* **+/- allo-HSC transplant**
* **steroids**
* dex or pred
259
what is the treatment for essential thrombocytopenia?
aspirin
anagrelide - decreases production of plts from megakaryocytes
hydroxycarbamide
