Oncology Flashcards
ewing sarcoma prevalence
second most common primary bone cancer in children
rare <100 cases diagnosed in UK
more commonly affects male
10-20’s
ewing sarcoma pathophysiology
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
ewing sarcoma bonesc
flat bones - tibia, fibula, femur, pelvis, ribs
clinical features ewing sarcoma
misinterpreted as growing pains or sports injuries
unexplained bony lump - urgent x ray within 48 hrs
x ray ewing sarcoma
urgent referral for an appt within 48 hrs for specialist assessment
hx ewing sarcoma
bone pain - progressive, worse at night, OTC analgesia not work
restricted ROM
fatigue
weight loss
examination ewing sarcoma
Tender palpable mass
Fever
Increased susceptibility to fracture – this can often be how Ewing sarcoma is diagnosed
ddx ewing sarcoma
Tendonitis
Osgood-Schlatter disease
Trauma
Slipped epiphysis
investigations ewing sarcoma
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
management ewing sarcoma
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
poor prognostic factors ewing sarcoms
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%
complications ewing sarcoma
metastatic disease - lungs, other bones and bone marrow
recurs later in life at around 30% of individuals
60% live at least 5 yrs
nephroblastoma definition
aka wilm’s tumour
most common renal tumour affecting children
epidemiology nephroblastoma
80 children per year in UK
pre school age group
female more
pathophysiology nephroblastoma
arise from nephrogenic rests - embryonal remnants
also mutations of common tumour suppressor genes
risk factors nephroblastoma
WAGR (Wilm’s tumour, Aniridia, Genitourinary malformations, and Retardation), Denys-Drash and Beckwith-Wiedemann
hx nephroblastoma
abdo mass/swelling
pain
fever
haematuria
exam nephroblastoma
abdo distention with unilateral or b/; mass
ddx nephroblastoma
PCKD
hydronephrosis
neuroblastoma
investigations nephroblastoma
FBC, UE, urine dip
USS
CT/MRI
biopsy - defintiive
risk scoring (1-5)
management nephroblastoma
healthy BP
avoid contact sports
stage 1 and 2 - just surgery
chemo before surgery
surgery - nephrectomy
prognosis nephroblastoma
even with mets 85% of pts expected to be cured
effects of chemo - cardiotoxicity
neuroblastoma origins
derived from neural crest cells - typically arising from adrenal glands or abdominal sympathetic chain
neuroblastoma epidemiology
90 children per year in UK
most common solid tumour in children
neuroblastoma pathophysiology
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
risk factors neuroblastoma
It’s incidence is therefore more likely if the child has other neurocristopathies, such as Hirschsprung’s Disease or Congenital Central Hypoventilation Syndrome
hx neuroblastoma
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
examination neuroblastoma
dense abdo swelling
HTN and tachycardia
periorbital bruising - mets to skull base
bluberry muffin rash
recurrent infection
thrombocytopenic purpura
ddx neuroblastoma
cysts (hepatic, polycystic kidney disease), hyperplasia (pyloric stenosis, hepatomegaly, splenomegaly) or neoplasia (Wilms’ tumour, lymphoma, rhabdomyosarcoma, hepatoblastoma).
investigations neuroblastoma
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
staging neuroblastoma
international neuroblastoma risk group (INRG)
1, 2A, 2B, 3, 4, 4S
management neuroblastoma
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
prognosis neuroblastoma
5 year survival rate is 67%
if diagnosed before 1 year of age - 82%
1-5 yrs old - 43%
good prognostic factors neuroblastoma
younger age at diagnosis
female
lesser tumour stage at diagnosis
MYCN mutation absent
complication neuroblastoma
relapse which is often resistant to tx
OMA syndrome - autoimmune condition, leading to opsoclonus, myoclonus, ataxia, confusion and irritability
SVC syndrome definition and causes
results from compression or obstruction of major vessels
life-threatening
most common causes - anterior mediastinal masses secondary to lymphomas and leukaemias, also from thrombosis
SVC syndrome presentation
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
SVC syndrome investigations
CXR - mediastinal widening, pleural effusion
CT chest
echo - pericardial effusion
bloods - FBC, UE, blood film, LDH
SVC syndrome management
A-E assesment
haem and onc consultants
avoid giving fluid via cannula in upper limbs
spinal cord compression definition
can lead to permanent loss of sensory, motor and/or autonomic function
acute complication of mets - undiagnosed cancer
SSC causes
Tumour extension through the vertebral foramina into the epidural space (most common)
Intradural metastases
Crush fractures from bony vertebral metastases or extended steroid use
investigation SSC
MRI spine
presentation SSC
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
management SSC
surgical - NBM, catheter, cord decompression
medical - dexamethasone, analgesia, laxatives
tumour lysis syndrome definition
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
tumour lysis syndrome presentation
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
investigations TLS
bloods - FBC, UE, bone profile, urate
fluid balance
daily weight
management TLS
prevention - allopurinol
treatment - hyperhydration so high urine output, rasburicase, dialysis
febrile neutropenia define
Fever defined as a single temperature of on one occasion. Neutropenia is characterised as an absolute neutrophil count of <0.5 x109/L9
hx febrile neuropenia
recent blood tests
recent chemo
myelosuppression
shaking chills, rigor
previous isolation of gram neg bacteria
recent tx with antimicrobial therapy
febrile neutropenia exam
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
investigations febrile neutropenia
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
febrile neutropenia management
empirical abx within 1hr of arrival - tazocin +/- gentamicin +/- teicoplanin
repeat cultures
osteosarcoma prevalence
most common childhood primary bone cancer
in teens and young adults and adults >50
more common in males
and afro-caribbean
osteosarcoma pathophysiology
DNA mutations occur in rapidly diving osteoblasts leading to malignant transformation
- metaphysis of long bones
osteosarcoma types
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
risk factors osteosarcoma
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
clinical features osteosarcoma
pain at tumour site
intermittent, worsens at night, resistant to analgesia
lump, warm and tender
mobility issues
fatigue, weight loss, headaches
ddx osteosarcoma
Secondary bone tumours (this is more likely in adults than in children)
Benign bone tumours
Infection (e.g. osteomyelitis)
investigations osteosarcoma
X ray - Bone destruction
New bone formation
Periosteal swelling
Soft tissue swelling
definitive - biopsy of affected area
management sarcoma
surgery and chemo (doxorubicin, cisplatin and high dose methotrexate +/- mifamurtide)
amputation may be required
prognosis osteosarcoma
poor
5 year survival rate 60%
as late diagnosis and aggressive
complications osteosarcoma
pathological fractures
mets
CNS tumour
primary - originate from brain
secondary - spread from other parts
brain tumours epidemiology
400 young people per year in UK
10 diagnosed per week
boys more
most common groups of CNS tumours
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%]
risk factors CNS tumours
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)
clinical features CNS tumour
delayed milestones
neurodevelopmental delay
differential education attainment
headache
polyuria/dipsia
seizures
altered GCS
examination CNS tumours
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
ddx CNS tumours
migraine or tension headache
meningitis
IC haemorrhage/stroke
investigations CNS tumours
MRI first choice
management CNS tumours
analgesia, antiemetics, anticonvulsants, fluid/diet, steroids
surgical resection
radiotherapy
cehmo
proton therapy or stem cell transplants
fetility support and neuro-rehab
complications CNS tumours
epilepsy and seizures
sleep disturbance
effects on puberty.fertility
hearing loss
impaired growth
cognitive impairment
secondary malignancy
prognosis CNS tumours
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%
