Oncology

Question 1

ewing sarcoma prevalence

Answer 1

second most common primary bone cancer in children
rare <100 cases diagnosed in UK
more commonly affects male
10-20’s

Question 2

ewing sarcoma pathophysiology

Answer 2

small, round
blue cell tumour
in majority of cases - genetic mutation - translocation between chromosome 11 and 22 resulting in formation of a fusion gene which does for fusion protein. This is a transcription factor that upregulates cell proliferation…uncontrolled cell turnover

Question 3

ewing sarcoma bonesc

Answer 3

flat bones - tibia, fibula, femur, pelvis, ribs

Question 4

clinical features ewing sarcoma

Answer 4

misinterpreted as growing pains or sports injuries
unexplained bony lump - urgent x ray within 48 hrs

Question 5

x ray ewing sarcoma

Answer 5

urgent referral for an appt within 48 hrs for specialist assessment

Question 6

hx ewing sarcoma

Answer 6

bone pain - progressive, worse at night, OTC analgesia not work
restricted ROM
fatigue
weight loss

Question 7

examination ewing sarcoma

Answer 7

Tender palpable mass
Fever
Increased susceptibility to fracture – this can often be how Ewing sarcoma is diagnosed

Question 8

ddx ewing sarcoma

Answer 8

Tendonitis
Osgood-Schlatter disease
Trauma
Slipped epiphysis

Question 9

investigations ewing sarcoma

Answer 9

FBC, UE, LFT, ESR, CRP, ALP, bone profile - all elevated, anaemia, leucocytosis
X ray - destructive, diaphyseal lesion with layered periosteal calcification
MRI/CT - staging
bone biopsy - definitive

Question 10

management ewing sarcoma

Answer 10

combination of chemo, surgery and radio
chemo - neoadjuvant and adjuvant, VDC/IE regime
surgery - limb sparing with resection and metal implant or autologous bone graft, may require amputation
radio - not every pt, before surgery to shrink tumour

Question 11

poor prognostic factors ewing sarcoms

Answer 11

Metastatic disease at diagnosis
Large tumour size (≥200ml in volume or ≥8cm in diameter)
Primary tumour located in the axial skeleton, especially the pelvis
Histological response of less than 100%

Question 12

complications ewing sarcoma

Answer 12

metastatic disease - lungs, other bones and bone marrow
recurs later in life at around 30% of individuals
60% live at least 5 yrs

Question 13

nephroblastoma definition

Answer 13

aka wilm’s tumour
most common renal tumour affecting children

Question 14

epidemiology nephroblastoma

Answer 14

80 children per year in UK
pre school age group
female more

Question 15

pathophysiology nephroblastoma

Answer 15

arise from nephrogenic rests - embryonal remnants
also mutations of common tumour suppressor genes

Question 16

risk factors nephroblastoma

Answer 16

WAGR (Wilm’s tumour, Aniridia, Genitourinary malformations, and Retardation), Denys-Drash and Beckwith-Wiedemann

Question 17

hx nephroblastoma

Answer 17

abdo mass/swelling
pain
fever
haematuria

Question 18

exam nephroblastoma

Answer 18

abdo distention with unilateral or b/; mass

Question 19

ddx nephroblastoma

Answer 19

PCKD
hydronephrosis
neuroblastoma

Question 20

investigations nephroblastoma

Answer 20

FBC, UE, urine dip
USS
CT/MRI
biopsy - defintiive
risk scoring (1-5)

Question 21

management nephroblastoma

Answer 21

healthy BP
avoid contact sports
stage 1 and 2 - just surgery
chemo before surgery
surgery - nephrectomy

Question 22

prognosis nephroblastoma

Answer 22

even with mets 85% of pts expected to be cured
effects of chemo - cardiotoxicity

Question 23

neuroblastoma origins

Answer 23

derived from neural crest cells - typically arising from adrenal glands or abdominal sympathetic chain

Question 24

neuroblastoma epidemiology

Answer 24

90 children per year in UK
most common solid tumour in children

Question 25

neuroblastoma pathophysiology

Answer 25

Like most cancers of infancy, neuroblastoma arises from poorly differentiating embryonic cells (blasts), in this case from the neural crest. Neural crest cells are derived from developing ectoderm, and normally migrate throughout the body to form a range of structures including the sympathetic nervous system and adrenal medulla. When this migration is stalled, neural crest cells have the potential to acquire mutations that eventually lead to a neuroblastoma. Whilst familial cases of neuroblastoma are rare, neuroblastoma tumours are associated with a specific profile of acquired genetic mutations, in particular of the MYCN and ALK oncogenes, as well as loss-of-function of the tumour suppressor PHOX2B

Question 26

risk factors neuroblastoma

Answer 26

It’s incidence is therefore more likely if the child has other neurocristopathies, such as Hirschsprung’s Disease or Congenital Central Hypoventilation Syndrome

Question 27

hx neuroblastoma

Answer 27

abdo distention fatigue weight loss creased catecholamine secretion (sweating, agitation) or metastasis (bone pain that prevents sleep, recurrent infections). Compression of the sympathetic nervous system can occasionally lead to urinary incontinenc arise from thoracic portion - SOB, CP

Question 28

examination neuroblastoma

Answer 28

dense abdo swelling HTN and tachycardia periorbital bruising - mets to skull base bluberry muffin rash recurrent infection thrombocytopenic purpura

Question 29

ddx neuroblastoma

Answer 29

cysts (hepatic, polycystic kidney disease), hyperplasia (pyloric stenosis, hepatomegaly, splenomegaly) or neoplasia (Wilms’ tumour, lymphoma, rhabdomyosarcoma, hepatoblastoma).

Question 30

investigations neuroblastoma

Answer 30

the products of catecholamine breakdown - homovanilic acid and vanillymandelic acid in urine - both raised bone marrow and skin biopsies USS MRI CXR if thoracic MIBG scan - definitive test

Question 31

staging neuroblastoma

Answer 31

international neuroblastoma risk group (INRG) 1, 2A, 2B, 3, 4, 4S

Question 32

management neuroblastoma

Answer 32

if <18mths old - likely to regress to nothing or benign ganglioma older children - surgery is preferred, L1 - curative, if L2 - adjuvant chemo or radio novel immunotherapies clinical trials - proto-oncogene inhibitor anti-emetics analgesia

Question 33

prognosis neuroblastoma

Answer 33

5 year survival rate is 67% if diagnosed before 1 year of age - 82% 1-5 yrs old - 43%

Question 34

good prognostic factors neuroblastoma

Answer 34

younger age at diagnosis female lesser tumour stage at diagnosis MYCN mutation absent

Question 35

complication neuroblastoma

Answer 35

relapse which is often resistant to tx OMA syndrome - autoimmune condition, leading to opsoclonus, myoclonus, ataxia, confusion and irritability

Question 36

SVC syndrome definition and causes

Answer 36

results from compression or obstruction of major vessels life-threatening most common causes - anterior mediastinal masses secondary to lymphomas and leukaemias, also from thrombosis

Question 37

SVC syndrome presentation

Answer 37

reduced venous return from head and neck to heart airway compression - reduced TLC - face and neck oedema distention of neck and thoracic veins plethora headaches dizziness - dyspnoea hoarse voice cough oropharyngeal obstruction orthopnoea

Question 38

SVC syndrome investigations

Answer 38

CXR - mediastinal widening, pleural effusion CT chest echo - pericardial effusion bloods - FBC, UE, blood film, LDH

Question 39

SVC syndrome management

Answer 39

A-E assesment haem and onc consultants avoid giving fluid via cannula in upper limbs

Question 40

spinal cord compression definition

Answer 40

can lead to permanent loss of sensory, motor and/or autonomic function acute complication of mets - undiagnosed cancer

Question 41

SSC causes

Answer 41

Tumour extension through the vertebral foramina into the epidural space (most common) Intradural metastases Crush fractures from bony vertebral metastases or extended steroid use

Question 42

investigation SSC

Answer 42

MRI spine

Question 43

presentation SSC

Answer 43

Unexplained, persistent back pain which wakes the child from sleep, restricts movement and/or does not resolve with simple analgesia Limb weakness/paraesthesia Progressive weakness below the level of the suspected lesion Bladder dysfunction/incontinence Constipation or overflow diarrhoea

Question 44

management SSC

Answer 44

surgical - NBM, catheter, cord decompression medical - dexamethasone, analgesia, laxatives

Question 45

tumour lysis syndrome definition

Answer 45

overwhelming cell lysis...mass release of intracellular cell content into circulation..metabolic abnormalities if suffer with acute lymphoblastic leukaemia, non-hodgkin lymphoma or high proliferative malignancies - high risk of TLS

Question 46

tumour lysis syndrome presentation

Answer 46

hyperuricaemia - Oliguria or anuria, crystal formation in urine, hypertension, renal insufficiency hyperkalaemia - nausea, slow/irregular pulse, muscle weakness, cardiac arrythmias hyperphosphataemia - not obvious hypercalcaemia - Muscle cramps, facial twitch, paraesthesia, seizures, ECG abnormalities

Question 47

investigations TLS

Answer 47

bloods - FBC, UE, bone profile, urate fluid balance daily weight

Question 48

management TLS

Answer 48

prevention - allopurinol treatment - hyperhydration so high urine output, rasburicase, dialysis

Question 49

febrile neutropenia define

Answer 49

Fever defined as a single temperature of on one occasion. Neutropenia is characterised as an absolute neutrophil count of <0.5 x109/L9

Question 50

hx febrile neuropenia

Answer 50

recent blood tests recent chemo myelosuppression shaking chills, rigor previous isolation of gram neg bacteria recent tx with antimicrobial therapy

Question 51

febrile neutropenia exam

Answer 51

LOOK FOR SOURCE Oropharynx – consider mucositis, hepatic stomatitis, candidiasis ENT – take viral nasopharyngeal and throat swabs for extended viral screen. Upper gastrointestinal – painful swallowing may suggest herpetic or candidal oesophagitis. Abdominal – signs of colitis or typhlitis (caecal inflammation causing tenderness of the right lower quadrant) Perineum – always ask about perianal discomfort Central venous line sites – examine for erythema, swelling, tenderness or tracking along the line site Skin exam – look for rashes, examine bone marrow aspirate sites

Question 52

investigations febrile neutropenia

Answer 52

Bloods – FBC, U+Es, CRP, venous blood gas, lactate Blood cultures Urine/Stool culture Sputum culture Imaging – chest and/or abdominal x-ray or CT Swab – nasal/throat/ski

Question 53

febrile neutropenia management

Answer 53

empirical abx within 1hr of arrival - tazocin +/- gentamicin +/- teicoplanin repeat cultures

Question 54

osteosarcoma prevalence

Answer 54

most common childhood primary bone cancer in teens and young adults and adults >50 more common in males and afro-caribbean

Question 55

osteosarcoma pathophysiology

Answer 55

DNA mutations occur in rapidly diving osteoblasts leading to malignant transformation - metaphysis of long bones

Question 56

osteosarcoma types

Answer 56

steoblastic, chondroblastic and fibroblastic The osteoblastic subtype arises from the most highly differentiated cells, the fibroblastic subtype arises from the least differentiated cells, and the chondroblastic subtype is somewhere in between

Question 57

risk factors osteosarcoma

Answer 57

Li-Fraumeni syndrome- an autosomal dominant germline mutation affecting the p53 protein (a tumour suppressor protein). RB1 mutation- this affects the retinoblastoma protein, causing hereditary retinoblastoma. Osteosarcoma is the most common tumour caused by this mutation, aside from retinoblastoma itself. Other genetic conditions include Rothmund-Thomson Syndrome, Bloom Syndrome, Werner Syndrom

Question 58

clinical features osteosarcoma

Answer 58

pain at tumour site intermittent, worsens at night, resistant to analgesia lump, warm and tender mobility issues fatigue, weight loss, headaches

Question 59

ddx osteosarcoma

Answer 59

Secondary bone tumours (this is more likely in adults than in children) Benign bone tumours Infection (e.g. osteomyelitis)

Question 60

investigations osteosarcoma

Answer 60

X ray - Bone destruction New bone formation Periosteal swelling Soft tissue swelling definitive - biopsy of affected area

Question 61

management sarcoma

Answer 61

surgery and chemo (doxorubicin, cisplatin and high dose methotrexate +/- mifamurtide) amputation may be required

Question 62

prognosis osteosarcoma

Answer 62

poor 5 year survival rate 60% as late diagnosis and aggressive

Question 63

complications osteosarcoma

Answer 63

pathological fractures mets

Question 64

CNS tumour

Answer 64

primary - originate from brain secondary - spread from other parts

Question 65

brain tumours epidemiology

Answer 65

400 young people per year in UK 10 diagnosed per week boys more

Question 66

most common groups of CNS tumours

Answer 66

Astrocytoma (low and high grade gliomas that develop from glial cells) [40%] Medulloblastoma (usually develop in the posterior fossa/cerebellum) [13%] Ependymoma (formed from cerebrospinal fluid (CSF) producing ependymal cells) [7%] Craniopharyngioma (found at the base of the brain close to the pituitary gland) [5%] Germ cell tumours (arising from germ cells, usually found close to the pituitary gland and the pineal gland) [4%] Choroid plexus tumours (develop from network of ependymal cells) [2%]

Question 67

risk factors CNS tumours

Answer 67

Personal or family history of a brain tumour, leukaemia, sarcoma, and early onset breast cancer Prior therapeutic CNS irradiation Neurofibromatosis 1 and 2 Tuberous sclerosis 1 and 2 Other familial genetic syndromes (such as von Hippel-Lindau)

Question 68

clinical features CNS tumour

Answer 68

delayed milestones neurodevelopmental delay differential education attainment headache polyuria/dipsia seizures altered GCS

Question 69

examination CNS tumours

Answer 69

General examination: Child’s behaviour, consciousness level and alertness Visual symptoms: diplopia, reduced visual acuity/visual fields, abnormal eye movement/fundoscopy Motor signs: abnormal gait or coordination, swallowing difficulties, weakness Delayed growth Delayed, arrest or precocious puberty Increased head circumference if under 2 years old

Question 70

ddx CNS tumours

Answer 70

migraine or tension headache meningitis IC haemorrhage/stroke

Question 71

investigations CNS tumours

Answer 71

MRI first choice

Question 72

management CNS tumours

Answer 72

analgesia, antiemetics, anticonvulsants, fluid/diet, steroids surgical resection radiotherapy cehmo proton therapy or stem cell transplants fetility support and neuro-rehab

Question 73

complications CNS tumours

Answer 73

epilepsy and seizures sleep disturbance effects on puberty.fertility hearing loss impaired growth cognitive impairment secondary malignancy

Question 74

prognosis CNS tumours

Answer 74

The 5-year survival in England for all Brain and spinal tumours in children is 73% Low grade astrocytoma has a survival rate of about 95% High grade (anaplastic) astrocytoma has a survival rate of about 25% Ependymoma has a survival rate of about 80% Medulloblastoma, it is more than 60%