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FRACP > Oncology > Flashcards

Oncology Flashcards

1
Q

ALL
- Presentation/Sx

A

Ix:
- On FBE and film you have normochromic normocytic anaemia with BLASTS and reduced WCC and plt

Bone marrow failure

  • Anaemia: pallor
  • Thrombocytopaeani: purpura, bleeding
  • Leukopaenia: recurrent fever or infection

Blastic infiltration

  • Hepatosplenomegaly
  • Lymphadenopathy
  • Bone pain ++, limp
  • Testicular swelling (common site for spread)
  • Acute renal failure (TLS)
  • CNS symptoms (signs of raised ICP, papilloedema, retinal haemmhorage)
  • Mediastinal mass (T-ALL)
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2
Q

What is leukostasis

Which leukaemias is this associated this?

What organ systems are associated?

What is the main risk with this?

What is the mx?

A

High WBC (>300)

  • > hyperviscosity, relatively low normal WCC, Hb, plt count to blast ratio
  • > tissue hypoxia, DIC, risk of bleeding, risk of TLS

Associated with AML > ALL

Organs involved: CNS (alteration in conscious state) and lung (-> hypoxia)

Main risk: Haemmhoragic infarcts in brain

Mx:

  • Platelet, PRBC transfusion
  • Urgent cytoreductive tx with hydroxyurea
  • TLS prophylaxis w allopurinol
  • Hyperhydration
  • Start induction chemo
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3
Q

Tumour lysis syndrome

  • What is it?
  • Which leukaemia/lymphomas is this associated with?
  • Which blood cell is associated with leukaemia burden and cell death rate?
  • What blood changes does it result in?
  • Clinical consequences?
  • Mx
  • Monitoring?
A

Rapidly proliferating cancers: cell lysis and destruction -> releasing intracellular components into blood (K, Ph, Uric acid, H)

T-cell ALL > AML
-> HR is WCC >100 in acute leukaemias OR T/B cell lymphomas (Burkitt’s esp and bulky NHL)

LDH -> large tumour burden -> RF for TLS

Results in:
- Hyperuricemia (precipitates in kidneys)
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia (Ca binds with Ph and deposits in renal tubules)
- Acidosis
=> End-result is ARF

Clinically can lead to

  • AKI (uric acid nephropathy)
  • Cardiac arrhythmia (hyperK)
  • Seizure (hypoCa)
  • Sudden death

MX
Intermediate/Low risk
- Allopurinol
- Alkalinisation (bicarb)
- Hyper-hydration

High risk

  • Rasburicase
  • Hyper-hydration

Serial Monitoring + electrolyte mx
- UEC, CMP, uric acid

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4
Q

Mediastinal compression

  • what leukaemia is it associated with?
  • what causes it and what sx result from this?
  • What risk is associated?
  • Crucial ix
  • Major contra-indication?
A

Assoc w T cell ALL > AML + lymphoma (HL, BL, LL)

Results from vena cava compression and bronchtracheal compression

Results in facial oedema, dyspnoea, orthopnoea (don’t want to lie flat)

Assoc w sudden risk of sudden death (often assoc w pericardial effusion -> tamponade)

Ix - AP + lateral XR (?pericardial effusion)
Then needs urgent cardiac echo -> opportunistic pericardial tap for diagnosis and treatment (release of pressure)

Contra-indicated with GA due to cardiac and resp risk -> can make initial workup difficult

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5
Q

B ALL
1. NCI criteria (HR vs SR)

  1. addit Risk factors
A

NCI Criteria

  • standard risk: age 1-9 and WCC <50
  • high risk: age <1 or >10 OR WBC >50

Additional LR factors
• Rapid response to therapy
• cytogenetics

Additional HR factors
• T-cell immunophenotype
• Slow response to initial therapy
• CNS positive leukaemia
• Testicular disease
• cytogenetics

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6
Q

What cytogenetic abnormalities are considered favourable in B ALL?

Unfavourable?

A

Low risk:

  • Hyperdiploidy (>50)
  • Trisomies 4, 10, 17
  • t(12:21) = TEL AML1 (ETV6-RUNX1)

High risk:

  • t(9:22) = BCR ABL (Philadelphia chromosome, worst prognosis)
  • t(4;11) = infant ALL = MLL AF4
  • t(1:19)
  • Hypodiploidy
  • iAMP21 amplification
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7
Q

What is MRD in pre-B ALL and how does this impact prognosis?

A

MRD = ‘minimal residual disease’

How do the blasts respond to steroids (Intrathecal MTX) at various time points in treatments designates risk?

Induction: day 8 and day 29

End of consolidation

Risk stratification

  • Low risk: negative for blasts at end of induction and end of consolidation
  • Intermediate: positive for blasts and end of induction but negative at end of consolidation
  • Very high risk - positive for blasts at end of induction AND consolidation -> predictive of failure of tx -> often go straight to HSCT
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8
Q

Pre T ALL
Risk stratification

A
  1. *MRD* is the main prognosticating tool (at day 8, end induction (D29) and end consolidation)
    * Age and WCC NOT important
  2. Poor steroid response is higher risk
  3. Early relapse (<18mo) is higher risk
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9
Q

ALL
Backbone of tx (list stages)

A
  1. ‘Induction’ (of remission) - 29 days long
    +/- post induction intensification (tempo and intensity)
  2. ‘Consolidation’ (of remission) - intensive multi-agent chemo + CNS prophylaxis (high dose IT mtx)
  3. Intensification - 2-3 blocks of intensive multi agent chemo aimed at clearing submicroscopic or minimal residual disease
  4. Maintenance - 2 years as an O/P
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10
Q

ALL Induction

What is the purpose

What is the regime

A

Aim

  • Induce complete remission (no blasts with functional marrow)
  • MRD at day 29 compared with day 8 checks this.

Either 3 or 4 drug regimen:
3 drug: Vincristine, steroid and asparaginase
- More is better with dosing but have to balance w toxicity

4 drug: Add anthracycline (doxorubicin, daunorubicin)

  • Only used for B cell high risk disease and T-ALL
  • Has higher risk of toxicity (cardio toxicity)
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11
Q

ALL CNS prophylaxis

What is the purpose

What is the regime

A

Without this, blasts will stay in CNS and induce CNS relapse

High dose methotrexate (intrathecal -> directly into CSF)

+/- radiation (but generally high dose MTX is adequate)

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12
Q

ALL Maintenance

A

Long-term oral-based treatment that contains the disease

  • Oral 6MP
  • Vincristine
  • Steroid
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13
Q

‘Late effects’ of radiation tx

A
  1. Second tumour
  2. Endocrine dysfunction from cranial radiation and damage to HPA
  3. lung fibrosis
  4. Renal failure
  5. Bowel fibrosis
  6. Msk: osteonecrosis, fractures, spinal growth abnormalities, muscular hypoplasia
  7. Cardiomyopathy
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14
Q

Imatinib (Gleevac)

what is its use
MOA

A

Targeted therapy for use in philadelphia ALL (BCR ABL )

Works by blocking a protein called tyrosine kinase, which tells the leukaemia cells to grow and multiply. Without this signal, the cells die.

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15
Q

ALL: What to do when chemo does not work and there is no target for targeted tx?

A 
Bone marrow (stem cell) transplant - use the immune system of a healthy donor to get rid of the leukaemic cells 
- Disease burden should be as low as possible before starting

Bispecific antibodies
- Recognise CD 19 and CD 3 on blasts -> engages T cells to fight the disease

Car T cells

  • engineered to specifically recognise blasts
  • can induce remission even in patients w neg MRD and high disease burden
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16
Q

Presenting sx/features of AML

*What features are different to ALL?*

A

*‘lumpy’ or ‘bleeding’* differentiates from ALL
>30% blasts on film (also ft Auer rods)

Bone marrow failure

  • *DIC*
  • Anaemia: pallor
  • Thrombocytopaeani: purpura, bleeding
  • Neutropaenia: recurrent fever or infections resistant to tx

Blastic infiltration

  • *Prominent EXTRAMEDULLARY DISEASE (not a feature of ALL)
  • > mass of leukaemia cells retro-orbital, skin or epidural location
  • > gingival hypertrophy*
  • Hepatosplenomegaly
  • Bone pain
  • CNS symptoms
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17
Q

What leukaemia is coagulopathy a complication of?

what is the typical IX findings for this?

A

APML (Acute promyelocytic leukaemia) which is a subclass of AML - t(15;17)

Results in DIC/fibrinolysis -> high risk of death from bleeding before 14 days

ix: Fibrinogen (low)
- D-dimer (elevated)
- Platelets (low)
- PT/APTT (high/prolongued)

Plt monitoring is critical, especially in first 15 days

  • Plts need to be 30-50
  • Fibrinogen > 1 (replace w FFP)
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18
Q

AML Risk assessment

A

Cytogenetics/molecular is critical risk factor

MRD early response

Down syndrome is favourable

Age and WCC are weak associations

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19
Q

AML treatment

A
  • Chemotherapy, but risk of relapse associated
  • -> induction, consolidation, further consolidation (no intensification or maintenance phases)
  • Bone marrow transplant, if relapse of AMT
  • > high risk of mortality (TRM) and late effects associated
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20
Q

Cytogenetic risk groups for AML (HR vs LR)

A

Low risk

  • t(8;21)
  • t(15;17) = APML
  • inversion of chromosome 16 = inv(16)

Poor/high risk

  • PR -7, -5 (monosomy 7 or 5)
  • 5q- (deletion of long arm of chromosome 5)
  • MRD >15%

Intermediate risk
- all others

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21
Q

Is T or B cell ALL higher risk?

A

T cell

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22
Q

What is the pathophys of renal impairment in TLS?

A

From precipitation of uric acid and phosphate in form of CaPh in the kidneys, causing tubular obstruction

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23
Q

What is spinal cord compression typically a complication of?

What are its classic presenting features?

Ix?

Mx?

A

*oncological emergency* caused by epidural mass compressing SC

Caused by:
Solid tumours
- Sarcomas
- Neuroblastoma
Hodgkin lymphoma
Mets

Sx

  • back pain (incr on vertebral percussion)
  • scoliosis, tenderness
  • incontinence/urinary retention
  • Change in sensation
  • acute paraplegia

Ix - urgent imaging

Mx

  • Dexamethasone
  • Chemo
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24
Q

Lymphoma
- what is it?

  • How are they different from leukaemias?
  • types
A

Solid tumours of lymphoid origin - lymph nodes or extranodal lymphoid tissues (thymus, tonsils, spleen, GIT, liver or skin)

  • Unlike leukaemias they do NOT originate from bone marrow and are not characterised first by their presence in the blood
  • 2 types:
    1. Hodgkin’s (40%)
    2. Non-Hodgin’s lymphoma (60%)
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25
Q

What are B symptoms and why are they important?

A

Fevers
Night sweats
Weight loss

Important as a prognostic tool in Hodgkin Lymphoma

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26
Q

Presentation of lymphoma

A

Regional lymphadenopathy

With 10-30% of patients also having constitutional sx (fevers, anorexia, body aches/pains, LOW, night sweats)

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27
Q

How is lymphoma staged (HD vs NHL)?

A

HD: Ann Arbor + B symptoms for ‘bulky disease’

NHL: Murphy + CNS involvement

Stages
I: Single LN

II: >= 2 lymph nodes on same side of diaphragm

III: Lymph nodes on both sides of diaphragm +/- spleen

IV: Diffuse/disseminated

  • > CNS or marrow involvement (Murphy)
  • > Lung, liver, marrow, or bone for Ann Arbor (< 25% in marrow)

Ann Arbor is also

  • A for absence of B sx
  • B for presence of B sx (worse prognosis)
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28
Q

Favourable vs unfavourable prognostic factors for Hodgkin lymhoma

A

Favourable:
- <10 yo
- Female
- Favourable subtypes (Lymphocyte predominant 10% and Nodular Sclerosing 50%)
Stage I non-bulky disease

Unfavourable:

  • >10yo
  • Male
  • B symptoms
  • Persistently elevated ESR
  • Lymphocyte Deplete histopathology (v rare but poor prognosis)
  • Stage IV/bulky disease (largest dimension > 10 cm)
  • Hypoalbuminaemia
  • Poor response to chemotherapy
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29
Q

What feature on histopath is classic of Hodgkin lymphoma?

A

Reed-sternberg cells
- Large cell with multiple or multilobated nuclei

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30
Q

Classic Hodgkins lymphoma presentation

A

Older child/adolescent
Insidious onset

Painless, non-tender, firm RUBBERY cervical or SUPRACLAVICULAR lymphadenopathy (90%)
(also axillary, inguinal)

Mediastinal mass (60%) -> may or may not be symptomatic (cough and dyspnoea or stridor)

Hepatosplenomegaly (25%)

B symptoms (fever, night sweats, LOW, fatigue, anorexia)

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31
Q

Inx workup for Hodgkins lymphoma

A
  1. Bloods - FBE, ESR (high), ferritin
  2. CXR - ?mediastinal mass (prognostic value)
  3. Excisional LN biopsy for diagnosis and histological classical
  4. BMA and biopsy to r/o advanced disease
  5. Staging CT + PET scan
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32
Q

In patients who relapse with Hodgkin lymphoma, which group has poorest prognosis and what is the prognosis

A

Relapse <1 yr of completion of tx
B symptoms
Extranodal disease (stage 4)

40-50% survival

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33
Q

What type of NHL is most common in the age groups
0-14?
adolescents and young adults?

A

0-14: Burkitt (40%)
15-19: DLBCL (37%)

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34
Q

What is non hodgkin lymphoma

How does it tend to progress

A

Malignant solid tumour characterised by undifferentiated lymphoid cells
- large cell, Burkitts, lymphoblastic, anaplastic

Spread: aggressive, rapid, diffuse, unpredictable (vs HL which is insidious)
-> can infiltrate BM and CNS

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35
Q

How do you differentiate lymphoblastic lymphoma (NHL) and ALL?

A

If >25% BM involvement, classified as ALL

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36
Q

In Diffuse large B cell lymphoma, what feature gives it a favourable prognosis and what gives it a poor prognosis?

A

Favourable: Germinal Centre B-Cell type

Poor: Activated B cell like and primary mediastinal B cell type

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37
Q

What are the different types of NHL ?

For each list the

  • predominant cell type (B or T)
  • Primary tumour site
  • sites for mets
A

Abnormal B cell lineage * most common *

  1. Burkitt’s lymphoma *most common in kids <10
    - Abdominal in developed world (pain, swelling, intussusception)
    - Head and neck in africa
    - Mets to CNS or BM
    * - Related to EBV infection
    - Endemic in Africa*
    - HR TLS
  2. Diffuse large B cell (DLBCL) *most common in older children and teens
    - Abdominal
    - mediastinal mass
    - Rarely mets

T cell lineage

  1. Lymphoblastic
    - Intra-thoracic (mediastinal mass +/- pleural effusion)
    - sub-diaphragmatic
    - Mets to CNS or BM
    - HR TLS
  2. anapaestic large cell lymphoma (ALCL)
    - Primary cutaneous skin deposits (erythematous, scaly, ulcerated lesions)
    - Systemic disease (mets to liver/spleen/lung/mediastinum rather than CNS/BM)
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38
Q

CLASSIC PRESENTATION of NHL

A

70% of children present with advanced stage disease (stage III or IV) – including extranodal disease with bone marrow and CNS involvement

B-symptoms less common and NOT prognostic

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39
Q

What types of NHL is TLS most common?

A

Small cell

  • Burkitt lymphoma (B lineage)
  • Lymphoblastic lymphoma (T lineage)
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40
Q

Tx for lymphoma (general)

Relapse mx

A

Chemotherapy

+/- Radiation therapy IF

  • emergency airway obstruction
  • CNS complications
  • local control
  • residual mass

+/- Surgery
- Biopsy
+/- excision

Relapse

  • Reinduction chemo
  • Then HSCT
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41
Q

Sx of superior vena cava syndrome

What is it caused by

A

Sx: facial oedema, dyspnoea, orthopnoea, coughing, stridor
- Positive pemberton’s sign (facial oedema and cyanosis, respiratory distress after 1 min of b/l arm evaluation).

Caused by compression of SVC, commonly caused by mediastinal mass (HL, DLBL, LL)

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42
Q

Prognosis of NHL

A

Local disease - 90-100%
Advanced disease: 70-95%

Favourable

  • stage 1 and II
  • Head/neck, peripheral nodes, GIT disease

Unfavourable

  • Stage 3 or 4
  • CNS or BM involvement
  • incomplete remission within first 2 months
  • Delay in tx
  • relapse of disease
  • pleural effusion
  • LDH >1000 , urate >0.39mmol/L (high tumour burden)
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43
Q

List 4 bone problems common in childhood cancer patients

A
  1. avascular necrosis (assoc w high-dose glucocorticoids and BMT)
  2. SUFE (incr risk with growth hormone deficiency, so in survivors of childhood cancer)
  3. Altered epiphyseal growth during chemo (usually catch up following chemo completion)
  4. Reduced bone mineral density
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44
Q

Invasive aspergillosis

RF for this

Presentaton

CT sign

Mx

A

Caused by aspergillus fumigatus

Invasive disease, originates in lungs

RF: immunocompromised (neutropaenic, SCID with neutrophil/macrophage dysfunction, CGD, prolonged high dose steroids, HIV, transplant)

Presentation; prolonged fever (often minimal other signs in immunocompromised host)

On CT: nodules
‘HALO sign’ - haemmhoragic nodule surrounded by ischaemia
‘air crescent’ - cavitation, usually heralds recovery
MRI - target sign
Need culture for definitive diagnosis

Mx - voriconazole first line (posaconasole an option but doses not established for paeds)

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45
Q

What does the galactomannan assay test for?

A

Aspergillus

  • ELISA based assay that looks for aspergillus cell wall component
  • Used for serial monitoring of infx
  • Caution: false negs
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46
Q

Li Fraumeni syndrome is assoc w which cancer and what mutation

A

p53 tumor suppressor gene mutation

AD inheritance

Solid and skin tumours diagnosed <45yo in multiple generations: Sarcomas (osteo- 15x in risk), leukaemias, gliomas; cancers of breast, bone, lung, brain

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47
Q

RB1 gene is assoc w which cancer and has what incr risk?

A

is a tumour suppressor gene

osteosarcoma 500-1000x incr risk
retinoblastoma

bladder cancer

small cell lung cancer

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48
Q

Presentation of osteosarcoma

Ddx?

A

Age at presentation related to pubertal growth spurt

  • Girls ~12yo
  • Boys ~16yo

Bone pain (night waking, limp)
Swelling/lump at tumour site
Loss of function
Pathological fracture

20% mets at diagnosis

DDx

  • Ewing sarcoma
  • Benign tumours of bone
  • Osteomyelitis
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49
Q

What is most common site for lesion in osteosarcoma?

Vs ewing sarcoma?

A

OsteosarcoMa: Metaphysis, KNEE

  • Distal femur - 50%
  • Prox tibia - 28%
  • prox humerus

Ewing: DIAPHYSIS (Shaft of long bones) and FLAT BONES

  • Pelvis - 26%
  • Ribs
  • Distal femur - 20%
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50
Q

Inx for staging osteosarcoma

A 
CT chest (look for mets to lungs - 80% of mets) 
Bone scan/PET (mets to distant bone)
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51
Q

Diagnosis of osteosarcoma (ix and features)

A
  1. Xray -> lytic, sclerotic or both regions within tumour
    - ‘Sunburst appearance’
    - Codman’s triangle
  2. MRI is standard for dx these days (defines intramedullary tumour extent, soft tissue component and its relation to vessels and nerves)
  3. Biopsy - verify diagnosis via histology
  4. CT chest - ?lung mets (most common site)
  5. PET/bone scan - ?distant bone mets
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52
Q

Genes associated with development of osteosarcoma

A

RB

p53

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53
Q

Tx of osteosarcoma

and relapses

A

Tx:

  1. Pre-operative chemo
    - ‘MAP’ (methotrexate, cisplatin, doxorubicin) -> main se is cardiac, renal, hearing dysfunction
  2. Surgery is mainstay - complete surgical removal of primary tumour AND mets
    +/- limb salvage surgery
  3. Radiation therapy is for in-operable tumours only as VERY high doses required
    - usually only pelvis, vertebral and base of skull primaries

Relapse
- Can be treated with chemo alone especially for lung mets only

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54
Q

What are the 2 most common bone tumours in children?
Where do they most commonly metastasise?

A
  1. Osteosarcoma (most common, 60% of malignant bone tumours)
    - > mets to lungs (80%), distant bone sites
  • > surgically managed w MAP
  • > presents in 2nd decade
  1. Ewing sarcoma
    - > mets to lung, distant bone sites, bone MARROW
  • > radiation sensitive
  • > median age 15 (but can be frmo age 0)
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55
Q

Xray findings for Ewings sarcoma vs osteosarcoma:

A
  • *Ew**ings:
  • Xray - ‘onion skin apperance’

OsteoSarcoma:

  • Xray -> Lytic, Sclerotic or both regions within tumour
  • > ‘Sunburst appearance’ = osteosuncoma
  • > Codman’s triangle
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56
Q

Ewing sarcoma - what is most common gene assoc?

A

t(11;22)

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57
Q

Ewing sarcoma tx

  • Initial
  • Relapse
A

Initial TX
Local tx
- Pre-op chemotherapy
- Surgery (if feasible - often difficult
- AND Radiotherapy (quite effective, much more so than for osteosarcoma)

Mets
- whole-lung irradiation

Relapse

  • Very poor prognosis (vs osteosarcoma - good prognosis with just surgical mx)
  • Combination of chemo, surgery/radiotherapy for local control
  • Palliation
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58
Q

Rhabdomyosarcoma
what are the most common subtypes

A

Most common soft tissue sarcoma and THIRD msot common solid tumour (after NB > Wilms) in children
- tumour of primitive mesenchymal tissue from which skeletal muscle arises

  • peaks age ~5 and ~15
  • Can arise rfom anywhere there is muscle. More common in parameninges, GU, orbit, extremities

SUBTYPES
1. Embryonal most common (70-75%) - spindle and/or small round blue cell tumour

  • younger patients
  • better prognosis
  • main sites: trunk, extremities, GU/bladder, head/neck, nasopharyngeal,
  1. Alveolar (20-25%) - poor prognosis
  • more common in older children
  • main sites: trunk, extremities
  • PAX3 (do better) or PAX7 (do worse) - FOX01 fusion protein
  1. Botryoid
    - Main sites: GIT, head, neck
  2. Pleomorphic - adult form, worst prognosis
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59
Q

Mutations and syndromes assoc w alveolar rhabdomyosarcoma

A

t (2;13) - PAX3-FOXO1 fusion
t (1;13) - PAX7-FOXO1 fusion

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60
Q

Diagnosis and staging of rhabdomyosarcoma

A

Imaging:

  • CT/MRI of primary site (with regional LNs)
  • CT chest (mets to lungs)
  • Bone scan +/- PET
  • BBMATs (mets to BM)

Molecular:

  • CSF (in parameningeal tumours)
  • BIOPSY of primary tumour and of sentinel LN if metastatic disease

Staging

  • HR is metastatic
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61
Q

Prognostic features of rhabdomyosarcoma

A
  • Age (age <1 and >10 unfavourable)
  • Tumour size (>5cm unfavourable)
  • Tumour site (parameningeal, extremities, bladder/prostate unfavourable)
  • Completeness of surgical resection
  • LN involvement is unfavourable

Mets is HR - do poorly

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62
Q

Tx of rhabdomyosarcoma

A

Surgery - up front if clear margins and no danger of functional impairment (this is rare; often done after neoadjuvant chemo)

Chemo - for mets and local control

  • VAC (vincristine, actinomycin-d and cyclophsphamide)
  • Biologics

Radiotherapy for local control if unclear margins - 3months into tx

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63
Q

Mainstays of treatment of rare sarcomas

A

Tx with surgery is KEY
Radiation tx is standard for large or residual tummours
Most have moderate/poor responses to chemo (ifosfamide/doxorubicin)
Molecular typing with biopsy is important
Trial of targeted therapies

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64
Q

Presenting features of brain tumours

A

INFANTS

  • Vomiting, irritability, lethargy, FTT
  • Increased HC
  • Sun setting eyes, papilloedema
  • Bulging fontanelles

Older children

  • Morning headaches
  • Early morning vomiting
  • Visual changes, strabismus
  • Seizures
  • Focal neurological sx (CN palsies)
  • Change in personality
  • Change in gait
  • ‘Learning disability’
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65
Q

Sx of infratentorial tumours

VS sx of supratentorial tumours

A

Intratentorial tumours (50-60%):

  • 1-11yo
  • Truncal unsteadiness, ataxia, CN palsies
  • CNVI (long course) - double vision and unable to move eye laterally
  • Then CVII - facial drop, unequal smile

Supratentorial tumours

  • <1yo
  • Seizures, hemiparesis, visual field defects
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66
Q

Wilm’s tumour

  • what is it
  • where does it often metastasise to?
  • Main affected age
  • survival
  • inheritance
A

Primary malignant renal tumour
Mets to lungs, regional LN, liver

75% cases in children <5yo (mean age 3)

90% survival after 5 years (or 50% if anaplastic stage II or above)

Mutation of gene WT1 (located on 11p13)

67
Q

What syndromes is Wilm’s tumour commonly associated with?

A
  1. WAGR syndrome (deletion of WT1=11p13)
    - aniridia, GU abnormalities, mental retardation
  2. Denys-Drash syndrome (triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms’ tumor)
  3. Beckwith Wiedemann syndrome
    - organomegaly, macroglossia, hemihypertrophy, omphalocele
  4. Isolated hemihytrophy
  5. NF1
  6. Urogenital malformations
  7. Perlman syndrome
    - macrocephaly
    - deep rooted eyes and ears
    - macrosomia
    - organomegaly
  8. Sotos syndrome
68
Q

Triad of sx in Wilm’s tumour

Ix

A

Can be asymptomatic

  1. Painless palpable abdo mass
    - Unilateral in 95% of cases (note, usually DOESN’T cross midline; calcification UNcommon)
  2. Painless heamaturia
  3. HTN (due to incr renin activity)
    +/- abdo pain, coagulopathy (acquired deficiency of vWF)

NOTE constitutional sx not that common

Ix

  • Abdominal USS, CT or MRI and CXR (lung mets)
  • > ‘claw sign’ on CT
  • Does NOT need bx for diagnosis as imaging is diagnostic alone

Tx

  • Initial chemo then nephrectomy
  • Radiotherapy if lung mets or disease recurrence post nephrectomy
69
Q

What is the most common solid renal tumour identified in the neonatal period
How is it diagnosed and what is its treatment

A

Mesoblastic nephroma
- prenatal USS diagnosis

Tx with radical nephrectomy
-> Local recurrence uncommon

70
Q

Neuroblastoma
What is it?
Age range

A

Tumour comprised of neural crest cells (SNS) within adrenal medulla (most common site) or sympathetic chain

  • Most common sites: 65% abdomen, 20% chest

Most common <2yo (mean age 22mo), rare >5yo

71
Q

What mutation is associated with mets/has impact on staging in Neuroblastoma?

A

n-MYC amplification >10 copies has 35% chance of metastatic disease

72
Q

Conditions associated with neuroblastoma

A
  • Turner syndrome
  • Hirschsprung’s
  • Congenital central hypoventilation syndrome
  • NF1
  • Noonan syndrome
  • Beckwith Wiedemann syndrome and hemihypertrophy
73
Q

Sx of neuroblastoma

A
  1. Constitutional sx: LOW, pallor, malaise
  2. *Paraneoplastic manifestations*
    - Opsoclonus-myoclonus (dancing eyes) -#1

- Cerebellar ataxia

  • Lambert-Eaton myasthenic syndrome (resembles GBS)
  • Encephalomyelitis
  • Hypothalamic syndrome
    3. Catecholamine production -> sweating, hypertension, intractable diarrhoea (VIP)
  1. Mass effect depending on location of tumour (can arise anywhere in SNS; abdo most common due to adrenals)
    - PAINFUL abdominal mass -> swelling, CROSSES MIDLINE, calcifications common
    - Lungs -> breathing difficulties
    - Spine -> cord compression -> back pain, bladder/bowel dysfunction sensory deficits
    - Neck -> SVC syndrome, adenopathy, Horner’s syndrome
    - Bone mets -> bone pain and fractures (LIMP)
    - Bone marrow mets -> anaemia, thrombocytopaenia, neutropaenia
    - Orbital mets -> Proptosis and periorbital ecchymoses (or ‘RACCOON EYES’
74
Q

Ix and diagnosis: Neuroblastoma

A

a. Primary site imaging – CT/MRI
b. Tissue and/or BM biopsy = histology, molecular
d. MIBG scan (radio-isotope that detects presence of neuroectoderm derived tumours - neuroblastoma, phaeochromocytoma)
e. Bone scan (if non-MIBG avid) +/- PET (can metastasise to BM, LN)
f. Urine catecholamines (HVA and VMA) – 90% sensitivity in children >1 year
- —> = Homovanillic acid and vanillylmandelic acid

—-> ddx for elevated urine catecholamines is phaeochromocytoma however those pts tend to be older and have HTN

75
Q

What are poor prognostic markers in Wilm’s disease?

A

Prognosis dermined by: Histology, stage, tumour size and child’s age

  • Favourable histology = 90% survival
  • Anaplastic or clear cell histology = POOR PROGNOSIS 50% survival
76
Q

PHOX2B
ALK
BARD1 gene

Are mutations assoc w which cancer?

A

Neuroblastoma

77
Q

Horner syndrome features

What is it associated with

A

Unilateral ptosis (droopy eyelid), miosis (constricted pupil) and anhidrosis (inability to sweat)

Associated w thoracic or cervical primary tumour -> compression of symptathetic innervation to eye

78
Q

What is the significance of LDH and ferritin in Neuroblastoma

A

High ferritin and LDH are prognostic for WORSE/POOR OUTCOMES

79
Q

Opsoclonus-Myoclonus
what is it?

Is assoc w what tumours

Tx and general prognosis

A

3 features:
o Opsoclonus = ocular motility disorder, with spontaneous, arrhythmic, conjugate saccades occurring in all directions
o Myoclonus = brief, shock-like involuntary movements caused by muscular contractions or inhibitions
o Ataxia +/- other cerebellar signs

ASsoc w neuroblastoma of lower stage and favourable prognosis

Tx - immunological tx has some benefit but often left w long-term neurological deficits. Resection of neuroblastoma does NOT improve sx.

80
Q

Acute side effects of chemotherapy

A

Nausea and vomiting

  • > chemoreceptor trigger zone in brainstem is OUTSIDE BBB -> activated by chemo drugs -> stimulates vomiting centre
  • Tx is antiemetic medications

Mood changes

Allopecia (hair cells also have turn over so indiscriminately targeted)

Mucositis - oral and perianal ulceration

Diarrhoea, constipation

Gonadal dysfunction can be long-term SE

  • Anovulation, premature menopaue
  • Decr spermatogenesis, azoospermia

Peripheral neuropathy (alkylating agents that target the ‘M phase of cell life)

Bone marrow - myelosuppression (suppression of N, plt, erythrocyte production)

  • > Febrile neutropaenia -> septic work-up + prophylactic abx +/- G-CSF for neutrophil production
  • > Thrombocytopaenia -> give plt transfusion if <20 or 10
  • > Anaemia -> give PRBC if sx or Hb<70
81
Q

Cell cycle

Check points in cycle

A

G0 - resting cell, quiescence
G1 - growth 1 phase
S - synthesis phase: chromosomes duplicate (DNA replication)
G2 - growth 2 phase
M - mitosis phase: cell divides into 2 identical daughter cells which can re-enter cell cycle (G1) or go back to G0 phase

Check points

  • G1 checkpoint: ensures no problem in DNA
  • G2 checkpoint: ensure no problems before it enters mitosis
  • M checkpoint
82
Q

Oncogenes - what are they, give examples x2

A

Oncogene activation lead to uncontrolled cell growth
-> allow cells to bypass checkpoints in cell cycle

Ex:

  • Bcr-abl (ALL, CLL)
  • RAS gene
  • MYCN gene amplification (neuroblastoma)
83
Q

Alkylating agents

How do they work
Give examples

A

INHIBIT DNA SYNTHESIS - anti proliferative
Bind via alkyl groups to DNA causing cell arrest

ex:
Cisplatin
Cyclophosphamide
Ifosphamide
Busulfan

SE

  • N&V
  • Myelosupression
  • Haemorrhagic cystitis (give Mesna + IV hydration)
  • Secondary malignant (AML, MDS)
  • Sterility/infertility
  • Lung fibrosis
  • SiADH
  • Nephrotoxic (Ifosfamide -> Fanconi)
84
Q

Anti metabolites

How do they work
Give 2 examples

A

Disrupts DNA/RNA metabolism/production interrupting S phase of cell cycle

ex: 6MCP
6TG

85
Q

Anthracyclines

How do they work
Give example

A
  1. Inhibit topoisomerase II (important enzyme in helping to unwind and relax supercoils in DNA to enable DNA replication in S phase)
  2. Inhibit helicase (unwinds 2DNA strands in S phase)
    ex: Doxorubicin and daunorubicin

SE

  • Cardiotoxicity (echos to monitor for this)
  • Necrosis on extravasation
  • Myelosuppression
  • Secondary malignancy
86
Q

Topoisomerase inhibitors

How do they work
Give example

A

Inhibit topoisomerase I (important enzyme in helping to unwind and relax supercoils in DNA to enable DNA replication in S phase)
ex: camptothecin, etoposide

87
Q

Vinca alklyloids - MOA, Ex, S/E

A

Inhibit microtubule formation in M phase of mitosis
-> leads to cell cycle arrest and apoptosis

Ex: Vincristine and Vinblastine

SE

  • Constipation
  • Peripheral neuropathy
  • Jaw pain
  • Ptosis
  • Extravasation injury

NOTE minimal myelosuppression with vincristine (do get it with vinblastine though)

88
Q

Febrile neutropenia

A

High risk for this :
AML treatment
ALL induction, delayed intensification
Lymphoma induciton
Transplant
Re-induciton chemo for any relapse

Ix: FBE, UEC
BC x2
Group and hold
VBG
Urine MCS
+/- other

89
Q

Indication and Ix for invasive fungal infection

A

Fevers >72hrs or recurrent fevers

a. CT of lungs + sinuses (>2 years)
b. Bronchoscopy + BAL if pulmonary infiltrates on CT
c. Fungal cultures from blood, BAL and other sterile sites
d. Galactomannan +/- aspergillus PCR on blood and BAL fluid

90
Q

Chronic myelogenous leukamia

What causes it

Tx for this

A

99% due to philadelphia chromosome t((9;22) (q34;q11) -> BCR-ABL fusion

Tx

  1. Imatinib (first generation); dasatinib (second generation)
    - > Inhibits BCR-ABL tyrosine kinase used in adults and children
    - > Second generation TK inhibitors improved remission rates
  2. Hydroxyurea: helps to return WCC to normal whilst waiting for response to TK inhibitor
  3. Allogenic Stem cell transplant -> 80% cure
91
Q

Types of tumours under infratentorial and supratentorial cranial subgroups

A

*Low grade gliomas are most common type of brain tumour in children

Infratentorial (posterior fossa, cerebellum and brain stem)

  • Medulloblastoma - 2nd most comomn
  • Ependymoma - 3rd most common
  • Brain stem glioma *

Supratentorial

  • Gliomas *
  • Teratomas
  • PNET
  • Choroid plexus

Both
- Astrocytoma * (cerebellar or midline)

92
Q

Brain tumours - Mx

A

Surgery

Chemotherapy - mainstay of tx

Radiotherapy for local tx

  • Vol and dose varies depending on histology and age
  • try to avoid when possible
93
Q

Small round blue cell tumours

A

Medulloblastoma

Neuroblastoma

Hepatoblastoma

NHL - Lymphoblstic lymphoma

REtinoblastoma

Rhabdomyosarcoma

Ewing’s sarcoma

94
Q

Embryonal tumour NOS
(formerly known as PNET
????)

A

Rare - 3-5% paed brain tumours

Mean onset 5.5yo (20% <3yo)

Histologically similar to medulloblastoma but do much worse

95
Q

Side effects
Asparaginase

A

Anaphylaxis!! (common)
Pancreatitis and Hepatotoxicity
Hyperglycaemia
Coagulopathy (thrombosis, bleeding, DIC)
-> Central sinus thrombosis

96
Q

SE doxorubicin (and other anthracyclines)

A

Cardiotxicity
VESICANT - extravasation burns
Radiation recall dermatitis

97
Q

]What drug is CI with vincristine and why

A

Azoles CI (incr vinc toxicity)

98
Q

6-MP
MOA and S/E

A

MOA - purine antagonist, inhibits purine synthesis

SE:

  • Hypoglycaemia
  • Myelosuppression
  • Hepatic necrosis
  • Pancreatitis
99
Q

MOA and SE of bleomycin

A

Binds to DNA -> induces strand breakage

Lung fibrosis
Myelosuppression

100
Q

SE bulsulphan

A

Seizures

101
Q

SE Cytarabine (ara-C)

A

FEVER/PYREXIA (‘ara-C fever’)
N&V
Mucositis
Myelosuppresion

102
Q

Etoposide MOA and SE

A

MOA - inhibits topoisomerase II -> decr coiling of DNA -> DNA strand breakage and degradation

SE:

  • Secondary AML (1% risk)
  • Alopecia
  • Mucositis
  • Myelosuppression
103
Q

Ifosfamide SEs

A

Fanconi syndrome (proximal RTA)

104
Q

Procarbazine SE

A

Sterility

105
Q

Chemotx agents that cause minimal/no myelosuppression

A
  1. Vinca alkaloids – vincristine, vinblastine
  2. Asparaginase
  3. Bleomycin
  4. Steroids
106
Q

Allogenic vs autologous transplant

Advantages of autologous

A

Autologous = patient receives their on cells (their own marrow is harvested before ablation, then purged f malignant cells, cryopreserved and then reinfused into child after marrow-ablation OR for solid tumours can harvest peripheral blood stem cells with G-CSF)

  • > Less rejection and GVHD
  • > But more chance of tumour relapse

Allogeneic = cells collected from a relative or unrelated donor who is HLA matched (preferably HLA matched sibling)
-> More chance of rejection and GVHD (conditioning with radio and chemotx is used to minimise chance of this)

107
Q

Indications for BMT

A
  1. Malignancy
    - ALL HR disease
    - AML HR disease
    - CML
  2. Immunodeficiencies
    - SCID/DiGeorge
    - Wiskott-Aldrich
    - HyperIgM
  3. Bone marrow failure
    - Severe aplastic anaemia (Fanconi, Blackfan diamond)
    - Congenital neutropenias
    - Congenital amegakaryocytic thrombocytopenia
    - Thalassaemia, sickle cell disease
    - HLH
  4. Storage disorders
    - ex: leukodystrophies
108
Q

Cx of HSCT

Allogenic vs autologous

A

Allogenic

  1. Feb neut
  2. VOD (onset <30 days of transplant)
  3. GVHD (acute <100 days, chronic >100 days post transplant)
  4. Graft failure
  5. infx

Autologous

  1. Feb neut
  2. Graft failure
  3. Secondary neoplasm from high-dose chemo used in conditioning
  4. Engraftment syndrome
  5. infx
109
Q

Hepatic veno-obstructive syndrome or Veno-occlusive disease

Cause
MOA
Presentation
Ix
Tx

A

Cx of myelo-ablative HSCT (first 20 days)

MOA - endothelial damage due to radio or chemotx -> obstruction of hepatic venules and sinusoids -> outflow tract obstruction

Onset within 30 days of transplant
Clinical triad
1. Weight gain (Ascites and fluid retention)
2. Painful hepatomegaly (RUQ pain)
3. Jaundice

Ix

  • Thrombocytopaenia refractory to platelets
  • Transaminitis
  • Conjungated bilirubinaemia

Tx
- Defibrotide

110
Q

Clinical manifestations and biopsy findings of ACUTE GVHD

A

Note >30 but <100 days post transplant (generally)

SKIN

  1. Erythema, pain , blistering (pruritic MACROPAPULAR rash)
  2. Biopsy: apoptotic bodies in the basal layer of the epithelium

LIVER

  1. Cholestatic hepatitis = Jaundice + deranged LFTs
  2. DDX – drug toxicity, VOD, infection
  3. Biopsy: bile duct destruction with apoptotic bodies

GUT

  1. N+V, (bloody) diarrhoea, abdominal pain
  2. DDx – infection, drug toxicity (ATB, MMF)
  3. Biopsy: apoptotic bodies in the base of crypts
111
Q

Pathogenesis of acute GVHD

A

Essentially is an inflammatory reaction where DONOR’S T-CELLS attack host cells (host’s MHC Ags)
= Type 4 hypersensitivity reaction

Inflammatory process thought to begin in GIT

112
Q

Grading of GVHD

Impact on prognosis?

A

Grades 0-4

Based on

  • Skin: % BSA of rash
  • Liver: Bilirubin level
  • GIT: volume of diarrhoea

Prognosis

  • Steroid-refractory GVHD has dismal prognosis
  • Grade 3 - survival rate 25%
  • Grade 4 - survival rate 5%
113
Q

Tx acute GVHD

A

*Steroids are the mainstay of treatment (remembering that GVHD is an immune-induced phenomenon caused by donor T cells attacking host MHC Ags = Type 4 HS rxn)*

PREVENTION
- Immunosuppression: Cyclosporine + MTX

Tx
Grade 1 (mild cutaneous)
- Optimise immunosuppression (up dose of cyclosporine)
- Topical steroids to rash

Grade 2 or higher

  • STEROIDS 1-2mg/kg is gold standard/first line
  • Steroid-refractory GVHD has dismal prognosis
114
Q

Tx chronic GVHD

A

Further Immunosuppression:

  • Steroids (pred)
  • Cyclosporin
  • Mycofenolate
  • Azathioprine
115
Q

Definition and clinical effects of chronic GVHD

A

>100 days post HSCT
Biggest RF is acute GVHD

Can be limited (skin and/or liver) or extensive in terms of organ involvement

i. Skin rash - hyper pigmented nodules, lichenoid, erythema, hypo pigmented then scleroderma-like
ii. Joints – arthritis/effusion/ stiffness/ contracture
iii. GIT – malabsorption/ stricture
iv. Liver – obstructive jaundice, chronic change to cirrhosis
v. Conjunctivae – dry, sicca syndrome
vi. Mucosal surfaces – dry, ulcers, lichen planus
vii. Bronchial tree – bronchiolitis obliterans

116
Q

Engraftment syndrome
What is it
How does it present

A

Non-infectious complication of autologous HCT (7-10%)

Similar presentation to acute GVHD but mild sx
- Usually cutaneous rash and signs of capillary leak syndrome (noncardiogenic pulmonary oedema with hypoxia, weight gain = PERDS = Peri-engraftment resp distress syndrome)

117
Q

Presentation
- FTT, emanciation, hyperkinesia, euphoria

?brain tumour

A

Diencephalic syndrome

Tumour in hypothalamus

118
Q

Rituximab - mechanism of action

What is it used to treat?

A

Anti-CD20 monoclonal Ab
(note CD-20 is an Ab on IMMATURE B cells)

Used in Non Hodgkins Lymphoma (Burkitts)

119
Q

Bloom syndrome

A

Cancer predisposition syndrome
- Due to defect in DNA repair mechanism

Sx
Photosensitive telangiectatic erythema
Short stature
Incr risk of leukaemia, lymphoma, solid tumours

120
Q

What is greatest risk factor for fungal infections in a pt undergoing chemotherapy?

A

Prolonged neutropaenia

121
Q

Denys Drash Syndrome

genetics

sx

A

Point mutation in 11p13 (mutation in WT1 gene)

  1. Congenital nephropathy
    Mesangial sclerosis
  2. Wilm’s tumour (90%)
  3. Male pseudohermaphroditism (Denis vs Denys)
122
Q

Pilocytic astrocytomas

  • Where do the majority of these tumours lie?
  • What condition is associated?
  • Presentation
  • What is the metastatic potential/outcomes like?
  • ## Appearance on MRI and histology
A

Type of low grade glioma (largest group of CNS tumours; pilocytic is most common of these)

  • Location: infratentorial region - Cerebellum (2/3 in posterior fossa, most of the optic pathway tumours)
  • Associated with NF1 (20% of pts with NF1)
  • Present with ataxia or signs of ICP as the mass blocks the 4th ventricle thus preventing CSF drainage
  • Slow growing -> indolent course (stabilise or even regress); low metastatic potential with good outcomes
  • Survival is ~90%, better w NF1
  • MRI - contrast enhancing nodule within the wall of a CYSTIC mass
  • Histology - Rosenthal fibres

Treatment: observe (low grade, can stabilise/regress), surgery +/- chemo (if non resectable) +/- radiiotx

123
Q

Patient with NF1 has a locally aggressive tumour in the PA of the optic nerve and chiasm region - what tumour is this?

A

Pilocytic astrocytoma

Could also be a low grade glial tumour

124
Q

Medulloblastoma

What is it

Presentation

MRI ft

Histo ft

Prognosis

A

EMBRYONAL NEUROEPITHELIAL TUMOUR
-> all arise in cerebellum/posterior fossa

Most common MALIGNANT brain tumour in children (20% of all CNS tumours)

1/3 metastatic on presentation

Presentation - Male, age 3-9; short symptomatic course (ataxia, headaches, nausea, vomiting, drowsiness) with evidence of hydrocephalus

MRI - Homogenous, contrast-enhancing midline or paramedian mass (cerebellum)

Histology - Small round blue cell tumour

Prognosis - 60-80% 5 yr survival on average (less if metastatic; depends on resection, stage, histo, molecular markers)

125
Q

Medulloblastoma - what genetic markers are assoc w low, intermediate and high risk?

A
  1. WNT1 = good (100% cure rate)
  2. SHH = intermediate
  3. MYC amp, p53 = bad
126
Q

Hepatoblastoma

Age
Presentation
Met sites
Tumour markers
Mx
Prognosis
Main differential

A

Age - <3 years (mean 1 yo); most common extracranial solid tumour in children

Presentation - large asymptomatic RUQ mass in a well child; may be pale but systemic sx uncommon
+/- precocious puberty if Beta-HCG secreting tumour

Mets -> to regional LN and lungs

Ix

  • AFP elevated (60% of pts)
  • Anaemia and thrombocytosis
  • * bili and LFTs often normal *
  • Plain AXR
  • Abdo USS
  • CT/MRI (assess resectability and incl chest to assess for mets)
  • Bx: small round blue cell tumour

Mx - cure requires 100% complete surgical resection -> systemic chemo (pre-op chemo required if initially unresectable)

Prognosis

  • Low-stage resectable: >90%
  • If unresect at diagnosis - 60%
  • Metastatic disease - 25%

Main differential is HCC

  • HCC usually occurs in teenage age group in pts with pre-existing cirrhosis (33%)
  • Also tend to present more commonly w systemic features
  • Poorer prognosis than HB and higher relapse rates
127
Q

What syndromes are associated with hepatoblastoma?

A
  • Familial adenomatous polyposis
  • Beckwith-Wiedemann syndrome
  • Hemihypertrophy
  • Li-Fraumeni syndrome (p53 germline mutation)
  • Goldenhar sydnrome
  • T18, T21
128
Q

Familial adenomatous polyposis

What causes it?

What does it lead to?

When does it typically present?

A
  1. Most common genetic polyposis syndrome
  2. Mutation in APC (adenomatous polyposis coli)
  3. Pre-cancerous lesions within surface epithelium of intestine
  4. Polyps generally develop late in the 1st decade of life or in adolescence (mean age of presentation is 16 yr)
  5. At time of diagnosis: 5 or more polyps are present in the colon and rectum.
  6. By young adulthood : number typically increases to hundreds or even thousands
129
Q

NF 1 and 2

Inheritance
Mutation
what types of cancers does it cause (1 vs 2)

A

i. AD, defect in tumour suppressor genes NF1 and NF2
ii. Proliferation of cells of neural crest origin -> neurofibromas
iii. NF1 = neurofibroma, optic glioma, pilocytic astrocytoma, acoustic neuroma, meningioma, phaeochromocytoma, sarcoma (rhabdomyosarcoma)
iv. NF2 = bilateral acoustic neuromas, meningiomas

130
Q

Beckwith wiedemann syndrome

What is it
What tumours does it predispose to

A

Overgrowth disorder, predisposition to tumour development

  • Hemihypertrophy
  • Macroglossia
  • Omphalocele/abdo wall defects
  • Visceromegaly
  • Hyperinsulinism /hypoglycaemia

Tumour risk = Wilms and hepatoblastoma most common, also neuroblastoma, adrenocortical carcinoma and rhabdomyosarcoma + others

131
Q

Craniopharyngoma

  • Derived from?
  • Presenting features/age
  • MRI features
  • Mx
A
  • Derived from pituitary gland embryonic tissue (remnant of Rathke’s pouch) in sella turcica, often locally invasive upwards into optic chiasm/optic nerves
  • Third most common CNS tumour after glioma and medulloblastoma and is the most common suprasellar tumour in childhood
  • Presents age 5-14
  • Presents with endocrine abnormalities (growth failure, pubertal delay, hypothyroid) and visual disturbance (bitemporal hemianopia), headache, vomiting
  • MRI – heterogeneous lesion with solid and cystic components
  • Mx: surgical resection +/- radiate
132
Q

Retinoblastoma

  • Cause
  • Presentation
  • Diagnosis
  • Tx
  • Potential for metastasis/prognosis
A

Most common intraocular tumour in kids

Cause - requires 2 hits to develop the disease:

  1. Hereditary (multifocal, all the bilateral tumours but may be unilateral) = AD, loss of function of RB1 gene (Tumour suppressor gene) in order to cause phenotypic disease
    - > patients younger (<5mo)
  2. Sporadic (unifocal, unilateral)

Most common presentation is

  • Mean age 2 with leukocoria (white eye reflex)
  • NEW Strabismus (squint)
  • Decr visual acuity
  • Orbital inflammation, proptosis, orbital pain, pupil irregularity, hyphaema with advanced disease

Dx - opthalmoscopy, CT, MRI (?optic nerve invovlement)

Tx - enucleation (removal of eye) if unilateral
- If bilateral, chemo first then limited resection bilaterally to preserve sight

  • 90% 5 yr survival if treated
  • Metastastic spread occurs ~6mo, via optic nerve to CNS, death within years if untreated
133
Q

Risk factors for GVHD

A

HLA typing
Related vs unrelated donors (siblings are donors of choice, twin best; unrelated next best)
Umbilical cord transplants > BMT or PBSCT
Age
In vitro T cell depletion of graft

NOTE - ABO blood group compatibility is NOT a RF

134
Q

What are long-term side effects of childhood cancer survivors who required HSCT?

A 
#1 - gonadal dysfunction (65%) 
#2 - Growth disturbance (25%) - multifactorial causes (CS use, bone dysplasia from chemo, malnutrition) 
#3 Primary hypothyroidism (10%), often subclinical
135
Q

Following curative therapy, which primary malignancies are most commonly associated with a future second malignant neoplasm?

A

Retinoblastoma > Hodgkin > soft tissue sarcomas

136
Q

What does southern blot procedure identify?

A

DNA

  • separated by gel electrophoresis
  • can assess for amplified DNA (-> tumour)
137
Q

Shwachman Diamond Syndrome

Main features

What malignancy risk?

A

inherited disorder of ribosomes leading to BM failure
mutation in SBDS gene

FTT
PanCytopaenia -> recurrent infections (GCSF, stem cell transplant)
Pancreatic exocrine dysfunction -> malnutrition -> growth failure (enzyme replacements)
Abnormalities of bone

elevated risk of developing myelodysplastic syndromes (MDS) or leukemia, typically acute myeloid leukemia.

138
Q

Gorlin syndrome - what cancers does it predispose to?

A

Medulloblastoma
Multiple BCC

139
Q

What would anti-NMDA receptor encephalitis be secondary to in a young girl?

A

Ovarian teratoma (LP -> dx with pelvic ultrasound)

140
Q

What antimicrobial do you use to treat candidaemia?

A

Fluconazole -> amphotericin if in blood and immunocompromised (as sometimes resistant to fluconazole)

141
Q

What is first line treatment for prolongued fever + neutropaenia?

A

Think fungal inx
-> amphotericin is BROAD spectrum

-> Fluconazole if low risk (narrower spectrum, covers

142
Q

What tumour is associated with ROHHAD (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) syndrome

A

neuroblastoma

143
Q

What cancer is the best example of the “two hit” hypothesis for cancer development?

A

Retinoblastoma
Due to loss of heterozygosity of retinoblastoma gene (RB1) i.e. need 2 hits to develop retinoblastoma

144
Q

Tumour suppressor genes
What are they, how can they lead to cancer and give examples

A

Tumour suppressor genes normally restrict proliferation of cells
-> encode proteins which inhibit progression of cell cycle or induce DNA repair and cell apoptosis in case of abnormal cells

INACTIVATION of these genes can lead to unregulated cell growth nd proliferation

Examples

  • RB1 gene (retinoblastoma, osteosarcoma)
  • WT1 gene (Wilm’s tumour)
  • p53
  • APC
145
Q

Methotrexate MOA

Toxicity

CI drugs

A

Folic acid antagonist
- inhibits dihydrofolate reductase (competitively)

Toxicity (incr w bactrim; same MOA)

  • Severe enteritis and mucositis
  • Liver damage, dermatitis, stomatitis
  • myelosuppression
  • renal impairment (renal metabolism)

Rescue/antidote to toxicity
- folonic acid

CI - cyp450

  • PPIs
  • Azoles
  • Penicillins
146
Q

MOA - rasburicase vs allopurinol and their role in TLS management

A

Allopurinol = prevention
-> Inhibits xanthine oxidase so prevents formation of NEW uric acid

Rasburicase = treatment 
-\> = Uricate oxidase, rapidly breaks down serum uric acid to allantoin which is less nephrotoxic and water-soluble so able to be excreted)
147
Q

What is hte most common long-term effect of CNS irradiation?

A

GH deficiency

148
Q

What is the reason patients with Wilms tumour get coagulopathy?

What do they recieve pre-op to manage this?

A

5-10% get acquired VWF/factor 8 deficiency
-> need DDAVP (desmopressin) pre-op (pre-nephrectomy)

149
Q

Conditions assoc w rhabdomyosarcoma

A

NF1
Beckwith Wiedemann syndrome
Li-Fraumeni (p53)

150
Q

What chemotherpay agent is CI in case of pericardial effusions?

A

MEthotrexate -> rare SE of this is pericarditis and pericardial effusion

Also avoid doxirubicin/duanorubicin

151
Q

Tumour cells of Osteosarcoma vs Ewing sarcoma

A

Osteosarcoma - Spindle cells

Ewing sarcoma - Small round cells

152
Q

Blasts and auer rods on blood film =?

A

AML

153
Q

Intussusception and abdominal mass = ? cancer

A

Burkitt lymphoma

154
Q

What is langerhans cell histiocytosis?

Clinical features

Ix

Mx

A

Infiltration with langerhans cells (skin histiocytes with Ag presenting function, CD1 positive) and subsequent immune reaction to the langerhans cells

Clinical ft:

  • skeletal involvement 80% (femur, ribs, pelvis, skull, orbit) - painful
  • skin rash (resistant to tx); face, neck, scalp, creases, back and nappy area
  • chronically draining infected ears
  • lymphadenopathy, hepatosplenomegaly
  • Can also have lung, endocrine, GIT, CNS involvement

Lytic lesions on xray, punched out skull lesions

Tx

  • if single system only involved- observe; topical tx, analgesia, steroids . consider chemo to arrest progression of bone lesion
  • if multisystem: chemo then SCT if necessary
155
Q

HLH

What is it?
Cuases

Presentation
Ix

Tx/prognosis

A

Disorder of immune dysregulation
- Cytotoxic T cells and/or NK cell dysregulation resulting in inflammation and destruction of self-tissue and phagocytosis of other immune cells

  • “cytokine storm” from excessive secretion by uncontrolled activated CTL and NK cells that in turn hyperactivate macrophages

Causes

  • Primary/familial/sporadic form due to mutation in perforin gene (CD8 and CD56 T cells)
  • Seconddary to infections (classically EBV in children), lymphoma, X-linked agammaglobulinaemia, autooimmune (systemic JIA, SLE)

Presents <4yo
Fevers
Splenomegaly
Pancytopaenia
High TGL or Low fibrinogen
Haemophagocytosis on histology
May have elevated LFTs, high ferritin

Tx:

  • chemo then HSCT
  • fatal without HSCT
156
Q

What is this?

A

Hodgkin lymphoma (reed sternnberg cells)

157
Q

What is Kasabach-Merritt Phenomenon?

A
  • Ft: Giant hemangiomas and consuptive coagulopathy; haemolytic anaemia, thrombocytopaenia etc
  • Essentially these fast-growing vascular tumors [kaposiform hemangioendothelioma (KHE) or tufted angioma (TA)] trap and destroy platelets, interfering with blood clotting -> DIC
158
Q

What condition are LCH lesions of the skull associated with?

A

Diabetes insipidus

159
Q

Dinutuximab

MOA and indication for use

A

Anti-GD2 Ab

Targeted against GD2 which are expressed in NB cells

160
Q

What is trilateral RB?

A
  • unilateral or bilateral hereditary retinoblastoma (Rb)
  • associated intracranial neuroblastic tumor w pineal (most commonly) or suprasellar (near pituitary gland and 3rd ventricle) involvement
161
Q

Posterior fossa syndrome - what is it?

How does it present

A

Complication of tumour resection from posterior fossa (eg medulloblastoma )

Occurs in ~20% of cases

Mutism

Emotional lability, irritability

Weakness of limbs, hypotonia

162
Q

6mo with large supratentorial mass

  • cystic and subtle area of calcification
  • three weeks after initial GTR, it has regrown back to its original size?

What is the diagnosis?

What is the assoc molecular genetics?

A

ATRT (atypical teratoid/rhabdoid tumours)

INI1 mutation (loss) -> inactivation of SMARCB1

  • Usually occurs before age 2
  • occurs anywhere in brain and spine
  • short clinical history
  • highly malignant
  • disseminated disease in 20%
  • poor prognosis
163
Q

Diffuse intrinsic pontine glioma

Triad of sx

Age of presentation

Prognosis

A

Presents 5-10yo

Glimoa in pons

  1. Presents w CN palsies (CN6),
  2. Cerebellar signs: ataxia
  3. UMN signs (incr tone, hyperreflexia, clonus, upgoing plantars)

Generally poor prognosis (survival <10% longterm)

FRACP (21 decks)

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