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USMLE S1 > Haematology & Oncology > Flashcards

Haematology & Oncology Flashcards

1
Q

diagnosis

A

essential thrombocythaemia

or

IDA

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2
Q

define follicular lymphoma

A

neoplastic proliferation of small B cells (CD20+) that make follice-like nodules

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3
Q

cytoplasmic MPO +ve blasts suggests what pathology?

A

AML

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4
Q

who gets nodular sclerosing HL? and how does it present?

A

young girls - enlarging cervical LN or medastinal mass

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5
Q

what are the ocular complications of measles infection?

how do you prevent them?

A

keratitis and corneal ulceration

vitamin A supplementation

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6
Q

frequency of MGUS?

transformation rate to MM?

A

5% of people over 70

1% per year get MM

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7
Q

define myeloproliferative disorder

A

a neoplastic proliferation of mature myeloid leukocytes

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8
Q

what are these cells? what is the diesease?

A

smudge cells

chronic lymphocytic leukaemia

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9
Q

pathoG ‘owl-eye appearance’

A

Reed-Sternberg cell of HL

multilobed nuclei and prominent nucleoi

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10
Q

define Hodgkin’s lymphoma

A

neoplastic proliferation of Reed-Sternberg cells, which are large B cells (CD15+/CD30+)

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11
Q

most common cause of death in multiple myeloma

A

infection

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12
Q

tartrate-resistance acid phosphatase +ve staining cells suggests what pathology?

A

hairy B cell leukaemia

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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

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14
Q

BRCA1/2 mutation leads to overall lifetime risk of breast (%age)

A

breast - 70/80%

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15
Q

treatment of iron poisoning/haemochromatosis

A

IV deferoxamine, oral deferasirox

dialysis

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16
Q

pathoG - Pautrier microabscesses

A

mycosis fungoides

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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

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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)

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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

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20
Q

define polycythemia rubra vera

A

a neoplastic proliferation of mautre myeloid leukocytes, with an erythrocyte predominance

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21
Q

1 cause of basophilia

A

CML

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22
Q

define myelofibrosis

A

a neoplastic proliferation of mature myeloid leukocytes, predominantly megakaryocytes

also associated with JAK2 kinase mutation

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23
Q

anti-B19 IgM serum antibodies suggest what pathology?

A

recent previous parvovirus B19 infection

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24
Q

3 features of megaloblastic anaemia

A
  • Macrocytic anaemia
  • megaloblastic change in rapidly dividing cells
  • hypersegmented neutrophils
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25
Q

how does the t(14;18) translocation lead to lymphoma?

A

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

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26
Q

3 pathogens for non-EBV infectious mononucelosis

A
  1. CMV
  2. HIV
  3. toxoplasma
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27
Q

T-ALL surface markers

A

CD2 up to CD8

do not express CD10

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28
Q

name the pathoG cells

description of this smear?

diagnosis?

A

tear drop red cells - tapered at one end

leukoerythroblastic smear

myelofibrosis

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29
Q

define acute myeloid leukaemia

A

a neoplastic proliferation of immature myeloid leukocytes

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30
Q

how does pancreatic insufficiency affect absorbtion of a water-soluble vitamin?

A

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

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31
Q

what is the definitive diagnosis of EBV infectious mononucleosis?

A

serologic EBV viral capsid antigen

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32
Q

3 complications of EBV mononucleosis

A
  1. splenic rupture
  2. ampicillin rash
  3. dormancy in B cells leads to B cell lymphoma or recurrence
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33
Q

Rx Waldenstrom macroglobulinaemia

A

plasmapheresis

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34
Q

In Sickle cell, 5 complications of vaso-oclusion

A

1) dactylitis
2) autosplenectomy
3) acute chest syndrome
4) Pain crisis
5) Renal papillary necrosis (gross haematuria & proteinuria)

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35
Q

neoplastic cell detachment from adjactent cells of the primary is regulated by what molecular change?

A

decreased expression of E-cadherin

this releases a cell from its neighbours in the first step toward matastasis

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36
Q

pathoG - starry sky appearance

A

Burkitt lymphoma

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37
Q

microsomal cytochrome P450 monooxygenase

affect on development on cancer?

A

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

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38
Q

lympoid stem cells give rise to what cells?

A

B cells –> plasma cells

T cells –> CD4 and CD8 cells

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39
Q

what is flutamide and what is it used for?

A

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

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40
Q

how do you stratify B-ALL prognosis? epidemiology?

A

by translocation

t(12;21) excellent prognosis, often in children

t(9;22) poorer prognosis more frequently in adults - known as Philadelphia+ ALL

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41
Q

a JAK2 kinase mutaion with elevated haematocrit suggests what?

A

polycthemia rubra vera

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42
Q

treatment for CML with t(9;22)? how does it work?

A

imatinib

blocks tyrosine kinase receptor activity

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43
Q

B-ALL surface markers (3)

A

CD10 CD19 CD20

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44
Q

how to determine clonality in B cell lymphoma?

A

kappa : lambda light chain ratio

3:1 in polyclonal reactive LAD, deranged in lymphoma (20-25:1)

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45
Q

what antimetabolite causes palmar-plantar eythrodysesthesia?

A

5-FU

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46
Q

complications of hereditary spherocytosis (2)

A
  1. pigment gallstones
  2. parvovirus B19 aplastic crisis
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47
Q

function of FFP

A

increase coagulation factors

use in DIC, cirrhosis

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48
Q

what are the side effects of methotrexate?

A

pulmonary fibrosis

myelosuppression

hepatotoxicity

mouth and GI ulcers

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49
Q

a CD34+ cell has what function?

A

haematopoetic stem cell for both lymphoid and myeloid cell lines

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50
Q

folate is absorbed in…

A

jejunum

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51
Q

define mantle cell lymphoma

A

neoplastic proliferation of small B cells (CD20+) that expands the mantle zone (the region immediately adjacent to the follicle)

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52
Q

>20% blasts in the bone marrow is defines what condition?

A

acute leukaemia

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53
Q

function of Bcl-2

A

blocks mitochondrial release of cytochrome C and inhibit apoptosis

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54
Q
A
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55
Q

marker of myeloblast (in AML)

A

myeloperoxidase (MPO) crystalised MPO results in Auer Rods forming, so pathoG for AML

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56
Q

haemophilia A, B and C

affected factor and inheritance patterns

A

A - VIII - XR

B - IX - XR

C - XI - AR

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57
Q

3 types of AML to remember

A

APML

acute monocytic leukaemia

acute megakaryoblastic leukaemia

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58
Q

all heretidary thrombosis syndromes (4)

A
  1. factor V Leiden
  2. protein C and S deficiency (inability to inactivate factor Va)
  3. antithrombin deficiency
  4. prothrombin gain of function mutation
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59
Q

causes of vitamin b12 deficiency (4)

A

1) pernicious anaemia
2) pancreatic insufficiency
3) damage to terminal ileum (*diphyllobothrium latum* tapeworm)
4) dietary deficiency in vegans (very unlikely)

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60
Q

define marginal zone lymphoma

associations (3)

A

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)

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61
Q

a mediastinal mass on CXR in teenagers with constituational symptoms suggests which CA?

A

acute lymphoblastic lymphoma , or T-ALL

lymphoma = forms a mass in the thymus

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62
Q

Down’s leukamia before age of 5

important negative finding

A

acute megakaryoblastic leukaemia

cells never stain +ve for MPO

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63
Q

what is the difference between myelodysplastic syndrome and acute myeloid leukaemia?

A

blast cell %age in bone marrow

both have hypercellular bone marrow with cytopenia

  • myelodysplasia is blasts < 20%*
  • AML is blasts > 20%*
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64
Q

cells of lymph node cortex

A

B cells

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65
Q

what antimetabolite drugs complexes with thymidylate synthetase and folic acid to block DNA synthesis?

A

5-fluorouracil

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66
Q

what do paclitaxel, vincristine and vinblastine do?

what part of cell cycle

A

microtubule assembly (vinca) and disassembly (placitaxel) inhibitors, arresting cells during mitosis

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67
Q

complications of paroxysmal nocturnal haemoglobinuria

A

1) iron deficiency anaemia - chronic loss of Hb
2) AML - develops in 10% of patients
3) thrombosis - intravascular platelet destruction

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68
Q

BRCA1/2 mutation leads to increase risk of ovarian CA as well as breast.

which has a bigger impact on ovarian CA?

A

BRCA1

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69
Q

what is the reversal agent for methotrexate toxicity?

A

folinic acid (leucovorin)

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70
Q

what is the mechanism of action of clopidogrel?

(and prasugrel, ticagrelor, ticlopidine)

A

ADP receptor blocker, P2Y12 sepcifically on platelets

blocking of receptors inhibits GpIIb/IIIa expression and plaelet aggregation

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71
Q

HbA2 is…

A

alpha2delta2

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72
Q

gastrectomy is risk factor for which anaemia? why?

A

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

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73
Q

4 Lab findings of intravascular haemolysis

A

1) LDH, unconj bili
2) haemoglobiinuria
3) haemosidinuria (delay of a few days)
4) decreased serum haptoglobin (Hb binding globin)

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74
Q

define mulitple myeloma

A

neoplastic proliferation of plasma cells within the bone marrow

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75
Q

what cell? disease?

pathoG cellular inclusion? what’s that made of?

A

bite cell

G6PD

Heinz body

disulphide bond formation leads to precipitation of Hb under oxidative stress

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76
Q

BRCA mutation is inherited in what pattern?

A

autosomal dominant

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77
Q

tumour angiogenesis is usually regulated by what growth factors?

A

VEGF

FGF-2

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78
Q

4 features/lab findings for folate deficiency, 1 negative finding

A
  1. megaloblastic anaemia 2. glossitis 3. decreased serum folate 4. increased serum homocysteine 5. normal methylmalonic acid (c/o VitB12 deficiency)
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79
Q

cause of lymph node paracortex hyperplasia?

A

viral infection

T cell zone is paracortex - so when CD8+ cells are needed these regions will expand…

typically EBV mononucleosis

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80
Q

what is the difference in target between dalteparin/enoxaparin and fondaparinux?

A

LMWH (dalte/enoxa) = predominantly on Xa

fonda = only Xa

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81
Q

HbA2 levels are slightly increased in what disease?

A

beta-thalassaemia minor

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82
Q

bone marrow biopsy

diagnosis?

A

myelofibrosis

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83
Q

heparin versus warfarin

administration, site of action, onset, mechanisms, duration, reversal, monitoring, obstetric consideration

A
  • 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
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84
Q

what is the effect on clotting tests of thrombolytics?

A

PT & PTT increase, no change in platelets

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85
Q

what do the ‘-tecans’ and ‘-posides’ do? what part of the cell cycle is affected?

A

topoisomerase inhibitors

  • tecan = topoisomerase I
  • poside = topoisomerase II

S and G2

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86
Q

examples of direct thrombin inhibitors

A

argatroban, dabigatran (only oral), bivalirudin

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87
Q

how does the t(8;14) translocation cause Burkitt lymphoma?

A

c-myc translocated to Ig heavy chain locus

Ig heavy chain constituatively expressed

c-myc oncogene promotes cell growth

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88
Q

decreased Fc receptors (CD16) on neutrophils suggests what?

A

immature neutrophils released from bone marrow in neutrophilic leukocytosis

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89
Q

complications of all myeloproliferative disorders

A
  1. hyperuricaemia and gout (purine degredation pathway)
  2. progression to marrow fibrosis (‘spent phase’)
  3. transformation to acute leukaemia
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90
Q

cancers associated with EBV infection

A

HL and NHL (Burkitt)

nasopharyngeal carcinoma

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91
Q

vitamin b12 is absorbed in…

A

ileum

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92
Q

3 ways to distinguish CML from acute infection?

A
  1. leukocyte alkaline phosphatease (LAP) -ve in CML
  2. basophils also present in CML
  3. t(9;22) present
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93
Q

2 causes of neutropenia

A

1) chemotherapy with alkylating agents 2) severe infection (gram negative sepsis)

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94
Q

proper function of cetuximab and panitumumab depend on normal function of what proto-oncogene?

A

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

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95
Q

what disease is this?

what is the important negative finding?

A

acute monocytic leukaemia

cells usually do not stain +ve for MPO

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96
Q

what is in cryoprecipitate (5 F’s)

when is it used

A

fibrinogen, factor VIII, factor XIII, vWF and fibronectin

coagulation factor deficiencies involving fibrinogen and factor VIII

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97
Q

vitamin b12 binds what in the duodenum? why not before?

A

intrinsic factor (IF) - made by gastric parietal cells vit b12 only cleaved from R-binder by pancreatic proteases

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98
Q

what do abciximab and eptifibatide bind to?

A

GpIIb/IIIa receptor preventing aggregation

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99
Q

HbF is…

A

alpha2gamma2

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100
Q

what is the mechanism for boney deformity in beta-thalassaemia major?

A

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

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101
Q

what type of receptor is human epidermal growth factor receptor 2 (HER2)?

what biologic agent targets this?

A

tyrosine kinase

trastuzumab, Herceptin - inhibitor

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102
Q

What are these cells? what is the dieasea?

A

reactive CD8+ T cells (large nucleus and too much cytoplasm)

infectious mononucleosis

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103
Q

what is the mechanism for desmopressin use in bleeding disorder?

A

DDVAP - increases vWF release from endothelium and circulating factor VIII

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104
Q

function of platelets

clinical use

A

increase platelet count, indicated when < 50,000 plts

thrombocytopenia, qualitative platelet bleeding disorder

105
Q

invasion through the basement membrane and access to the vasculature is mediated by what neoplastic molecular process?

A

expression and secretion of proteolytic enzymes such as matrix metalloproteinase and cathepsin D protease

final step in metastasis

106
Q

Down’s association with leukaemia after the age of 5

107
Q

DDx (3) painless LAD

A

chronic inflammation

metastatic carcinoma

lymphoma

108
Q

does heparin or warfarin cross the placenta?

A

Warfarin - not that it should be used anyway because it it teratogenic

109
Q

major difference between UFH and LMWH?

A

LMWH = better bioavailability, longer half life (2 - 4 x); subcut administration without lab monitoring

UFH = reversible

110
Q

2 causes of monocytosis

A

1) chronic inflammatory state (AI or infection) 2) malignancy

111
Q

function of packed red cells

cinical use

A

increase Hb and O2 binding capacity

severe aneamia and blood loss.

112
Q

screening test for sickle cell gene

A

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
Q

what is the major complication of cyclophosphamide/ifosfamide?

how can this be prevented?

A

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
Q

haemoglobin A2 levels are highly increased in what disease?

A

beta-thalassaemia major

115
Q

what is the main role of IkappaB? how is it inactivated?

A

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
Q

presenting FBC findings for acute leukaemia (3)

A
  1. anaemia
  2. thrombocytopenia
  3. neutropenia
117
Q

define a chronic leukaemia

A

a neoplastic proliferation of mature circulating lymphocytes

118
Q

why do you get bone marrow fibrosis is myelofibrosis?

A

megakaryocytes expanding massively and producing PDGF causing fibroblast proliferation and fibrosis

119
Q

Rx PRV

A
  1. blood letting
  2. hydroxyurea
120
Q

t(9;22) classically associated with what cancer?

A

CML

also associated wtih adult onset, poor prognosis B-ALL

121
Q

symptoms of hyperviscosity??

A
  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
Q

biochemical compostion of Auer rods?

A

myeloperoxidase (MPO)

123
Q

Rx for hariy cell leukaemia.

how does this work?

A

2-CDA (cladribine)

adenosine deaminase inhibitor… adenosine accumulates in B cells leading to cell death

124
Q

what is the margianted pool?

A

neutrophils attached to the pulmonary vasculature at rest that can be released into the circulation secondary to infection/necrosis

125
Q

what cell? disease?

A

spherocyte

hereditary spherocytosis, drug-/infection-induced haemolytic anaemia

126
Q

osteoblastic boney mets suggests what primaries (3)?

A
  1. prostate
  2. small cell lung CA
  3. Hodgkin lymphoma
127
Q

most common cause of death in Sickle cell children

A

infection with encapsulated organisms

128
Q

Associated conditions with Immune haemolytic anaemia (IHA)

A

1) SLE 2) CLL 3) drugs - penicillin and cephalosporins

129
Q

pathoG wordy description?

what’s the disease? what cell type is this?

A

hairy cytoplasmic processes

hairy cell leukaemia

mature B cell

130
Q

diagnosis?

A

follicular lymphoma

131
Q

treatment of hereditary spherocytosis

A

splenectomy

132
Q

complications of CLL (3)

A
  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
Q

what cancer are nitrosoureas used for mainly and why?

A

brain CA as crosses the BBB

134
Q

pathogenesis of splenomegaly in myelofibrosis

A

fibrosis in the bone marrow reduces haematopoetic potential

resulting extramedullary haematopoesis, mainly in the spleen

135
Q

what is CD55?

A

delay-activating factor

GPI mutation means you don’t anchor CD55(DAF) in PNH, complement-mediated intravascular haemolysis

136
Q

pure red cell aplasia is associated with which cancers (2)?

A

thymoma

lymphocytic leukaemia

…IgG-/cytotoxic T cell-mediated autoimmune inhibition of only erythrogenesis

137
Q

CD5+/CD20+ cells are found in what pathology? when is this normal?

A

they are naive B-cells found in CLL

is normally found on physiologic T cells

138
Q

WBC count reference range

A

5,000 - 10,000 cells/microL

139
Q

what do alkylating and platinum agenst do?

A

cell-cycle independent drugs.

form cross-links between DNA

140
Q

Hx mutliple thromboses, PTT normal and unaffected by exogenous protein C

diagnosis?

A

factor V Leiden

because protein C should usually break down factor V and stop thromboses, but the mutation renders it resistant

141
Q

diagnosis? explanation?

A

multiple myeloma

increased circulating protein decreases charge between RBCs allowing rouleaux formation

142
Q

what is the difference between CLL and hairy cell leukaemia?

A

HCL = neoplastic proliferation of mature B cells

CLL = neoplastic proliferation of naive B cells

143
Q

main cause of death in paroxysmal nocturnal haemoglobinuria

A

thrombosis of hepatic, portal or cerebral veins destroyed platelets release cytoplasmic contents into the serum inducing thrombosis

144
Q

what happens to a multiple myeloma cell treated with proteasome inhibitor?

A

accumulation fo toxic intracellular proteins, build up of pro-apoptotic proteins

apoptosis

145
Q

epidemiology (age) of AML?

A

50 - 60 year olds

146
Q

screening test for G6PD deficiency

A

blood smear with Heinz preparation highlights precipitated haemoglobin that otherwise wouldn’t be seen on H&E slide

147
Q

what is the monospot test? (3 points)

A

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
Q

cells of lymph node paracortex

149
Q

myeloid stem cells give rise to what cells?

A

erythroblasts –> RBCs

myeloblasts –> neutrophils, basophils, eosinophils

monoblasts –> monocytes

megakaryoblasts –> megakaryocytes –> platelets

150
Q

osteoclastic boney metastases suggests what primaries?

A
  1. MM
  2. Non-Hodgkin lymphoma
  3. Non-small cell lung CA
  4. Kidney (RCC)
  5. melanoma
151
Q

effect of elevated steroids on white cell count

A

neutrophilia steroids impair adhesion of neutrophils to pulmonary vasculature, releasing the marginated pool into circulation

152
Q

define CML

A

neoplastic proliferation of mature myeloid leukocytes, predominantly granulocytes

basophils are classically elevated

153
Q

marker of either type of lymphoblast (in ALL)

A

TdT - a DNA polymerase

TdT is absent in blasts from myeloid lineage and in mature lymphocytes

154
Q

what are the slow and fast reversal options for warfarin?

A

slow - vitamin K

fast - FFP or prothrombin complex concentrate (PCC)

155
Q

complications of blood transfusion

A
  1. hyperkalaemia (lysed RBCs)
  2. hypocalcaemia (citrate added which chelates Ca++)
  3. 2ary haemochromatosis
  4. transfusion reaction
  5. infection transmission (low risk)
156
Q

AL amyloidosis associated with primary malignancy?

A

multiple myeloma

157
Q

how is leuprolide used in cancer?

A

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
Q

define Burkitt lymphoma

A

a neoplastic proliferation of intermediate sized B cells (CD20+)

association with EBV

159
Q

AML translocation

160
Q

disease?

name of cell?

A

macrocytic anaemia - folate/B12

macro-ovalocyte

162
Q

APML translocation, disruption, effect, complication

A

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
Q

DDx lymph node follicular hyperplasia (2)

A

HIV infection (hyperplasia of CD4+ follicular dendritic cells)

rheumatoid arthritis

164
Q

treatment of immune haemolytic anaemia

A

1) stop offending drug 2) steroids 3) IVIG 4) splenectomy

165
Q

scalp rash, lytic bone lesions (skull), diabetes insipidus, exopthalmus

A

Hans-Schuller-Christian disease

langerhans cell histiocytosis - children older than 3 y/o

malignant

166
Q

principles of treating AIP

medication?

A

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
Q

how does infection cause neutropenia?

A

severe Gram-negative infection leads to movement of neutrophils into tissues resulting in decreased circulating numbers

168
Q

iron is absorbed in…

169
Q

what cancers spread to bone?

A

prostate, breast, kidney, thyroid, lung

(lead kettle; PB/KTL)

170
Q

pathogens for infectious mononucleosis

A

EBV (more common) CMV (less common)

171
Q

what anti-nausea medication is best for chemo adjunct and why? what receptor does it affect?

A

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
Q

HbA is…

A

alpha2beta2

173
Q

what is the target of hydroxyurea?

A

ribonucleotide reductase

stops nucleotide synthesis

174
Q

what is it? diagnosis?

A

Birbeck granule

Langerhans cell histiocytosis

175
Q

lymph node structure from out to in

A

cortex, paracortex and medulla

176
Q

which HL has the best prognosis?

A

lymphocyte-rich HL

177
Q

what is this?

what is the associated inherited condition?

what are other signs/symptoms associated with this?

A

right renal angiomyolipoma (benign)

Tuberous Sclerosis (autosomal dominant)

skin [ash-leaf patch, facial angiofibroma], brain [subependymal hamartoma, cortical tubers], heart [cardiac rhabdomyoma]

178
Q

what is the enzyme that activates azathioprine?

A

HGPRT, into 6-MP

179
Q

what are the two targets of heparin?

A

thrombin (IIa) and factor Xa

180
Q

what HL has the worst prognosis?

who gets it?

A

lymphocyte-depleted

elderly and HIV +ve

181
Q

define essential thrombocythaemia

A

a neoplastic proliferation of mature myeloid leukocytes, predominantly platelets

also associated with a JAK2 mutation

182
Q

conditions inducing HbS sickling

A

1) hypoxaemia 2) acidosis 3) dehydration 4) high 2,3-BPG

183
Q

what are the major mediators of neoplastic cachexia?

A

TNF-alpha

IL-1beta

IL-6

184
Q

what is a Howell-Jolly body?

disease?

A

HJB is a nuclear remnant found in RBCs from maturation

hyposplenia or asplenia

splenic macrophages usually removes these from physiologic red cells

185
Q

what cell? diagnosis?

A

acanthocyte - spur cell

cholesterol dysregulation (liver disease, abetalipoproteinaemia)

186
Q

what is mutated?

name of cells?

disease

A

RBC membrane proteins (e.g. spectrin)

elliptocyte

hereditary elliptocytosis

187
Q

trimethoprim mechanism

A

inhibitor of bacterial dihydrofolate reductase (DHFR)

188
Q

methotrexate mechanism

A

inhibitor of mammalian dihydrofolate reductase (DHFR)

189
Q

which is the most common subtype of ALL?

190
Q

in the setting of CLL, development of generalised lymphadenopathy indicates what?

A

infiltration of the B cells into the lymph nodes.

goes from CLL to small lymphocytic lymphoma

191
Q

Rx paroxysmal nocturnal haemoglobinuria

mechanism

A

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
Q

pathoG phrase and diagnosis

explain what is happening

A

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
Q

what is a lacunar cell? where do we find it?

A

lacunar - from ‘lake’

RS cell sat in lake-like spaces seen as clearing on histology.

nodular sclerosing hodgkin’s lymphoma

194
Q

what is the difference between fresh frozen plasma and cryoprecipitate?

A

FFP = all coagulation factors

cyroprecipitate = only cold-soluble factors VIII, fibrinogen, vWF, vitronectin

195
Q

what is cytarabine used for? and what is the main side effect?

A

acute leukaemis (AML) and lymphoma.

causes pancytopenia and megaloblastic anaemia
(as you would expect if it’s stopping leukaemia)

196
Q

what is cilostazol(/dipyridamole)?

how do they affect clotting?

A

phosphodiesterase inhibitors

increase cAMP in platelets, inhibiting aggregation.

197
Q

what is this?

DDx

A

basophilic stippling

lead/arsenic poisoning, sideroblastic anaemia, myelodysplastic syndrome

198
Q

Rx follicular lymphoma

criteria for treatment

A

rituximab (CD20 antibody) or chemotherapy

if they are symptomatic

199
Q

splenomegaly due to cellular expansion in the red pulp with lymphocytosis suggests what CA?

A

hairy B cell leukaemia

whereas usually other white cell infiltrates into the spleen will expand in the white pulp.

200
Q

function of BRCA1 and BRCA2 genes?

A

DNA repair enzymes

201
Q

classify Hodgkin’s lymphoma

A

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
Q

follicular lymphoma complication

presentation

A

transformation to large B-cell lymphoma

presentation - acutely enlarging single lymph node on a background of generalised LAD

203
Q

pathoG - cerebriform nuclei

A

mycosis fungoides that has neoplastic T cells spreading through the circulation - now called Sezary syndrome

204
Q

how does the t(11;14) translocation cause mantle cell lymphoma?

A

translocation of cyclin D to Ig heavy chain locus

Ig heavy chain constituatively expressed

overexpression of cyclin D promotes G1/S phase progression

206
Q

pathologic fracture in adolescent

biopsy shows CD1a+/S100+ cells with numerous eosinophils infiltrating

disease?

A

eosiophilic granulma

a benigin langerhans cell histiocytosis

207
Q

how does kidney disease result in a bleeding disorder?

A

chronic kidney disease leads to an accumulation of uraemic toxins

uraemic toxins impair platelet aggregation and adhesion - qualitative disorder

208
Q

what are these cells? describe the features?

A

blasts of acute leukaemia

large, immatue, punched out nuclei

209
Q

neoplastic proliferation of CD4+ T cells in the epidermis forming microabscesses

A

mycosis fungoides

210
Q

diagnosis?

A

chronic myeloid leukaemia

211
Q

skin rash, cystic skeletal defects in infant

A

Letterer-Siwe disease (a langerhans cell histiocytosis)

malignant

children < 2 years old

212
Q

what cell is pathologic in ATLL?

what is the microbiology association?

A

mature CD4+ T cells

HLTV-1 - Japan and Carribean

213
Q

treatment for neutropenia secondary to chemotherapy

A

GM-CSF and G-CSF

214
Q

3 causes of neutrophilia

A

1) bacterial infection 2) tissue necrosis 3) high cortisol state

215
Q

diagnostic test hereditary spherocytosis

A

osmotic fragility test - increased fragility of spherocytes in hypotonic solution because less membrane available to expand total volume of cell

216
Q

most common cause of death in Sickle Cell adults

A

acute chest syndrome

217
Q

vitamin b12 binds what in the mouth?

A

R-binder once cleaved from animal protein by amylase

218
Q

mixed cellularity HL is associated with what cell type?

important cytokine?

A

eosinophils

associated with IL-5

219
Q

epidemiology of myeloproliferative disorder

A

disease of late adulthood

220
Q

2 causes of lymphocytic leukocytosis

A

1) virus infection (CD8+ T cells) 2) bordetella pertussis - lymphocytosis-promoting factor stops lymphocytes from leaving the blood to enter lymph node

221
Q

transformation in CML leads to what?

A

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
Q

mixed boney metastases suggests what primaries (2)?

A

gastrointestinal

breast

223
Q

Rash, generalised LAD and HSM

lytic bone lesions with hypercalaemia

lymphocytosis

what disease?

224
Q

Hb Barts is…

225
Q

painless swollen lymph node that gets bigger and smaller over a long time, no other symptoms

A

follicular lymphoma - non-hodgkin

226
Q

6 features/lab findings of vitamin b12 deficiency

A

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
Q

three phases of CML

A
  1. accelerated (spleen getting acutely bigger)
  2. chronic (enlarged spleen)
  3. transformation (to acute leukaemia)
228
Q

what consideration should be made in a patient with diabetes and beta-thalassaemia minor?

A

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
Q

what is the reversal agant for heparin and how does it work?

A

protamine sulphate

positively charged molecule that binds heparin in the circulation

230
Q

characteristic of immature neutrophil

A

decreased Fc receptor (CD16) concentration causes - bacterial infection or tissue necrosis

231
Q

clinical features of waldenstrom macroglobulinaemia

A

generalized LAD

hyperviscosity - headache and retinal haemorrhage/stroke

bleeding - deranged platelet function due to viscous serm

IgM-containing M spike on SPEP

232
Q

HbH is…

233
Q

cause of lymph node sinus histiocyte hyperplasia?

A

LN draining site of cancer

234
Q

caldribine is an analog of what nucleotides?

A

purine - inhibits DNA polymerase and induces strand breaks

235
Q

high serum IL-6 suggests what pathology?

A

multiple myeloma

236
Q

what part of the cell cycle is arrested by bleomycin?

A

G2 - double check and repair

bleomycin induces DNA strand breakage by free radical formation

237
Q

an abnormal eosin-5-maleimide binding test suggests what disease?

A

hereditary spherocytosis

238
Q

splenomegaly, dry tap and absent lymphadenopahty suggests what pathology?

A

Hairy B cell leukaemia

239
Q

classify Burkitt lymphoma

A

African - involves jaw

sporadic - involves abdomen

240
Q

3 causes of eosinophilia

A

1) allergic reactions - type I hypersensitivity 2) parasite/helminth infection 3) Hodgkin lymphoma - overproduction of IL-5

241
Q

what is integrin? clinical significance?

A

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
Q

3 consequences of Ig light chain overproducation in MM

A
  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
Q

which antimetabolites reduce DNA synthesis by stopping dTMP production?

A

5-FU (thymidylate synthetase) and methotrexate (dihydrofolate reductase)

244
Q

what cancer is cladribine used for?

A

hairy cell leukaemia

245
Q

what is the pathogenesis of heparin-induced thrombocytopenia?

A

IgG antibodies versus heparin::Platelet-Factor 4 (PF4) complex

Immune complex activates platelets, leading to thrombosis and thrombocytopenia

246
Q

neoplastic cell atatchment to the basement membrane is mediated by what molecular process?

A

expression of laminin and other adhesion molecules.

this middle (2nd of 3) step in metastasis buys the cells time to access vasculature

247
Q

4 causes of lymphopenia

A

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
Q

what are the three neurotransmitter targets modulated by anti-emetics for chemotherapy-induced emesis?

A

serotonin (5-HT3) antagonist

dopamine antagonist

neurokinin 1 antagonist

249
Q

APML Rx

A

all-trans retanoic acid (ATRA) causes blasts to mature through activation of RAR

250
Q

pelger huet cells

A

congenital - lamin B receptor mutation

aquired - myelogenous leukaemia, myelodysplastic syndrome

251
Q

what is the usual causes of paroxysmal cold haemoglobinuria?

A

viral infection (measles, VZV)

syphilis

252
Q

what happens in paroxysmal cold haemoglobinuria?

A

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
Q

what is the management for PNH?

A

Vit B12/folate suppliments

prophylactic vaccines/antibodies

Mab = eculizumab (targets complement C5)

254
Q

what is the management for chronic autoimmune thrombocytopenic purpura?

A

IVIG, steroids, splenectomy

255
Q

what is the target INR or 1st episode DVT/PE or atrial fibrilaiton

256
Q

what is the target INR for recurrent DVT/PE or mechanical prosthetic valve?

257
Q

what cells proliferate and expand in the blood in infectious mononucleosis?

A

reactive, atypical CD8+ T cells

258
Q

what are the principles of multiple myeloma treatment?

A
  • supportive
    • bisphosphonates etc
  • chemotherapy
    • melphalan, borzetomib (proteasome inhibitor), lenalidomide/thalidomide
  • +/- allo-HSC transplant
  • steroids
    • dex or pred
259
Q

what is the treatment for essential thrombocytopenia?

A

aspirin

anagrelide - decreases production of plts from megakaryocytes

hydroxycarbamide

USMLE S1 (16 decks)

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