Oncology Flashcards
craniopharyngioma
Suprasellar tumour
relatively benign
arises from floor of 3rd ventricle to the pituitary gland (infundibulum)
Usually age 10-15 years
Pressure effects- headaches, diplopia, visual disturbance, short stature, amenorrhoea
MRI look- may be single or multiple cysts filled with thick oily fluid high in protein, blood products, and/or cholesterol. >90% have calcification rimming
Rx- surgical resection and Rtx
Raised AFP
-Hepatocellular carcinoma
-Non seminomatous germ cell tumours - Embryonal tumours (poorly differentiated), dermoid
yolk sac tumour (endodermal sinus tumour, infantile embryonal tumour)
-Hepatoblastoma
Testable genetics
Ewings
- t(11:22)
Alveolar Rhabdomyosarcoma
- t(1;13)
- This is pathognomonic for this kind of rhabdo
- Alveolar is worse prognosis with 100% mortality (cf embryonal rhabdo)
Neuroblastoma
-MYCN amplification = poor prognosis
ATRT
- Loss INI1/SMARCB1.
- Poor prognosis
Li fraumeni syndrome
- Rare
- AD
- pre-disposes carriers to cancer development
- AKA sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome
- Germline loss of TP53
- Screening exam, bloods, whole body MRI, USS etc decreases mortality
VOD
If post HSCT occurs within 30 days. Occurs in 15% of ppl
- Hepatomegaly
- RUQ pain
- Jaundice
- Ascites
- Fluid overload
Risk factors:
- 1 young age
- prior liver disease
- abdominal radiation
- repeated transplants
- neuroblastoma
- familial Haemophagocytic lymphohistiocytosis
If severe form mortality
Rx:
Heparin, ursodeoxycolic acid
Consider defibrotide
Important translocations
Alveolar rhabdo (pathognomonic)
- t(1:13) or t (2;13)
- Terrible prognosis
t(8;14)
- may be burkitts lymphoma (Mature cells)
OR B-ALL (immature cell)
22q12 ESWR1
- sarcomas
- if t(11;22) in bone then it is Ewings
Infantile fibrosarcoma (age <1 year)
- t(12;15) is pathognomonic
- Infantile fibrosarcoma responds excellently to Tyrosine kinase inhibitors and spares children from mutilating surgeries
Small round blue tumours
H&E stain –> blue = nucleus
Large nucleus, small cytoplasm
Big nucleus = rapidly dividing
- EWINGS
- NEUROBLASTOMA
- WILMS
- RHABDOMYOSARCOMA
- LYMPHOMA
- Medulloblastoma
- Retinoblastoma
- Anaplastic hepatoblastic (NOT fetal or embryonal hepatoblastoma)
Wilms (nephroblastoma)
Embryonal tumour
Small round blue cells
Most common malignant renal tumour of childhood
6% of paediatric tumours
From infancy to 5 years. Very unlikely past then.
-Rarely dx <6months
-Best characterised gene is Wt1 deletion on 11p13
METS to LUNGS
95% unilateral
5% bilateral (at same time OR contralateral later in life)
90+ survival (unless anaplastic)
Can be syndromic or non syndromic
If known risk q3MONTHLY USS until age 8
If bilateral at same time -more aggressive chemo. Try to spare nephrons with surgery. If not remove –> dialysis 1-2 years –> transplant
20 years ESRF risk:
1% unilateral
12% bilateral
Sx: Unilateral large mass Abdo pain Fever Painless gross haematuria HTN in 25% (increased renin from tumour)
Complications: Bleed into tumour (with rapid enlargement) Anaemia Thrombus --> 5-10% can extend into IVC Acquired vWF deficiency
IX:
XR, USS, CT, MRI
USS is good to look at cystic vs solid, and differentiate from adrenal tumours
DDX:
Mesoblastic nephroma (<3 months, solid tumour, mostly benign)
Clear cell tumour (look for bone mets)
Rhabdoid tumour kidney (look for brain mets; poor prognosis, rare; often haematuria presenting complaint)
Prognostic factors:
Age (<2 =better), stage, tumour weight, loss of heterozygosity at 1p and 16q (poorer prognosis), anaplasia
Rx:
Low risk- actinomycin- D and vincristine
High risk: Actinomycin D, Vinc, Doxorubicin
Late effects: 2nd malignancy cardiac toxicity pulmonary disease renal failure
Syndromes associated with Wilm’s
WAGR syndrome
- WT1 DELETIONS (11p13)
- Wilms
- Anirida (100%) = no iris. PAX6 del
- GU
- Retardation
Denys-Drash Syndrome
- WT1 MISSENSE
- Nephropathy (early onset renal failure)
- male hermaphrodism
Beckwith Wiedeman
- 11p15
- Wilms and hepatoblastoma
- Organomegaly, macroglossia, hemihypertrophy
FWT1 and FWT2
Doxorubicin
ADD
Sarcoma- soft tissue
Soft tissue malignancy
- Rhabdomyosarcoma most common
- Others include liposarcoma, fibrosarcoma, leiomyosarcoma etc
- Rhabdomyosarcomas are chemo SENSITIVE
- The rest are chemo RESISTANT and are treated with resection and radiation
Rhabdomyosarcoma
Most common soft tissue malignancy in children
- Embryonal (unless alveolar) skeletal muscle
- Small round blue cells
- embryonal (60%) - NO translocations
- Alveolar 25-40% (translocations 1;13 or 2;13) and are most often in trunk and extremities and have poor prognosis
- chemosensitive
- 3.5% of childhood cancers
- Can occur anywhere but usually head and neck (including face, nasopharynx, midle ear, sinuses etc)
- more likely alveolar in older children
- Can disseminate early + LUNG METS
- Alveolar METS everywhere incl BONE MARROW
- Associated with neurofibromatosis and Li-Fraumeni syndrome
Sx:
- Mass (may be painful)
- Secondary sx from pressing on structures (anywhere from nose bleeds to cranial nerve palsies). Can often present with similar to common childhood conditions
- If in extremities usually noticed after trauma and mistaken for haematoma
- Can get vaginal rhabdo (grape like mass bulging through vaginal orifice)
Ix:
CT and MRI
Staging - bone scan, chest CT, BMA, biopsy
RX:
- pre-operative chemo
- resection
- post -op chemo (vinc, cyclophosphamide)
- +/- irradiation depending on stage and site
Survival:
Embryonal - 40-90%, still curable if mets
Alveolar 0-60% incurable if mets
Risk factors:
Older = bad
Histology and staging (mets and site)
Late effects:
- Impaired bone growth from radiation
- second malignancy
- Infertility from CYCLOPHOSPHAMIDE
Osteosarcoma
Malignant bony tumour
- Most likely to occur in second decade
- Highest risk during adolescent growth spurt
- INCREASED risk if has had hereditary retinoblastoma or Li-Fraumeni syndrome (TP53), previous Rtx
- Can be primary or secondary (previous RTX to bony areas!)
- Chemosensitive
-Site = METAPHYSES of long bones
SX:
- local pain and swelling + limp
- often hx of trauma
- Bloods are often normal, may have raised ALP or LDH
- XR changes –> sunburst pattern (new bony formation), SCLEROTIC destruction (blastic), may have some lytic
- Histology + spindle cell-producing osteoid
- Genetics - TP53 found in 3-10% (Li-fraumeni)
Mets: Lung + bones
DDX:
Ewing’s, osteomyelitis
Rx:
- Chemo (doxorubicin, cisplatin, HDmtx, ifosphamide
- Surgery of primary tumour
- Resect lung mets
- laregly RESISTANT to Rtx
Prognosis:
W/o mets at least 70%
with mets <20%
Late effects:
SNHL
Cardiac toxicity (anthracyclines)
Ewings Sarcoma
Malignant bony tumour
- Most likely to occur in second decade
- Chemo sensitive
- Ewing >osteosarcoma if <10 year of age
Site: DIAPHYSES of long bones, flat bones
METS TO LUNGS and BONE MARROW
Sx: Local pain, fever, swelling, weight loss
XR- primarily LYTIC tumour, multi-laminar periosteal reaction/elevation (onion-skinning)
Histo –> small round blue cells
t(11;22) found in 90% DIAGNOSTIC
IX:
- MRI + 2x CT guided biopsy from andt least 2 sites
- staging with CT chest
DDX:
- osteomyelitis
- eosinophilia granuloma
- neuroblastoma
- rhabdomyosarcoma
- lymphoma
Rx:
Chemo
RTX SENSITIVE +/-surgery
Prognosis:
w/o mets 60% cured
with mets 20-30% cured
Late effects:
- cardiotoxicity
- secondary osteosarcoma from Rtx
- Late relapses (as long as 10 years!)
Translocations in cancer
Results in two DNA binding domains (target genes) fused together and two regulatory domains (on and off switches) together instead of one binding and one regulatory together.
Because missing regulatory domain switch stays ON
= Mutant transcription factor –> cancer
Retinoblastoma
Embryonal tumour
- most common intra-ocular cancer in childhood
- 4% malignancies
- Most cases <5 years old, median age 2
- At least 2/3 unilateral
- Hereditary and sporadic
- Hereditary associated with younger age and bilateral retinoblastoma
- Loss of function of RB1 gene on chromosome 13
- Small round blue cell tumour with rosette formation
- Generally presents with leukocoria or strabismus
- Advancing disease results in orbital inflammation, redness and pupillary distortion
- pain if glaucoma present
Can MET to CSF and spinal cord
AT RISK of trilateral tumour (pineal ) tumour which can occur at the same time or any time after (presetns with HEADACHES AND VI NERVE PALSY
DDX:
Other causes of leukocoria –> ROP, coats disease, cataract, persistent hyperplastic primary vitreous
IX:
Dx made based on ophthalmological findings (under GA) as imaging is not diagnostic and biopsy is contraindicated
Orbital USS, CT and MRI useful for staging
Rx:
Focal chemo (etoposide, vincristine, carboplatin)
If too large then enucleation of the eye
If bilateral - focal chemo to reduce size + focal laser photocoagulation or cryotherapy
+/-irradiation (significant deformity + increased risk of 2ndary tumour)
Prognosis - good >95%
Continue routine examination of eyes until age 7
If spread outside orbit, prognosis is poor
Those with RB1 mutation increased risk of secondary tumours, esp if exposed to radiation
Late effects: Usually related to Rtx - cataracts -poor orbital growth deformities - lacrimal dysfunction - late retinal vascular injury
Neuroblastoma
Most comon extra cranial solid tumour
- 8-10% childhood malignancies
- median age dx 22 months with 90% dx by 5 year old
- Can occur at any site of sympathetic nervous tissue. about 50% adrenals, the rest along sympathetic ganglion
- mets more likely if >1 year old
- mets lymph nodes, long bones, skull, bone marrow, liver and skin
- lung and brain mets are RARE
- Associated with neural crest disorders such as hirschsprungs, NF1 and central hypoventilation syndrome
- Associated with Beckwith wiedemann syndrome or isolated hemihypertrophy
3 types of risk
- High risk and malignant and aggressive (local/mets)
- MYCM AMPLIFICATION
- 70% survival
- HIGH dose chemo 13-18 months –> causes aplastic anaemia so need autologous stem cell rescue + surgery + radiation +/- MIBG radioactive isotope, chimeric (immune therapy), retinoic acid - Intermediate risk local or metastatic <18 month
- 95% survuval
- 2-8 cycles mod chemo +surgery
- No transplant, no chimeric, rarely radiation - Low risk, localised and STAY that way
- 97-99% survival
- small ones in babies usualy resolve spontaneously
- larger ones cured with resection
Sx:
Can present with syndrome (see slide)
Great mimicker so can be non-specific and hard to dx
-metastatic disease can present with systemic sx, bony pain, cytopenia, proptosis, periorbital ecchymoses,.
-localised disease can present as asymptomatic or mass-related sx such as spinal cord compression, bowel obstruction and SVC syndrome
Dx:
- Imaging - plain film, CT, MRI
- Tumour markers such as catecholamine metabolites (HVA and VMA) in urine is elevated in 95% cases and helps to confirm dx
- biopsy gold standard but dx can be made if small round blue cells in bone marrow and urine catecholamines are high
- Staging - CT chest and abdomen, bone scan and at least 2x BMA
Neurobolastoma risk:
- met vs local
- easy to resect vs not
- age (older = worse. cut off age 18 months)
- histology
- genetics = MYCN amplification and 11q missing are bad
Syndromes associated with neuroblastoma
HORNER SYNDROME
- neuroblastoma originating in superior cervical ganglion
- Unilateral ptosis, myosis, ahydrosis
- Sx DO NOT resolve with tumour resection
OPSOCLONUS-MYOCLONUS-ATAXIA syndrome
- paraneoplastic syndrome of autoimmune origin
- myoclonic jerking and random eye movement +/-ataxia
- usually associated with lower risk tumour
- may not resolve with tumour removal
- can be progressive
SWEATING and HTN
- catecholamine release from tumour
NEUROCRISTOPATHY SYNDROME
- when neuroblastoma associated with other neural crest syndrome such as hirschsprungs, and congenital hypoventilation syndrome
- Germline mutation of PHOX2B
KERNER-MORRISON SYNDROME
- tumour secreation of vasointestinal peptides causing intractable secretory diarrhoea
- tumours generally biologically favourable
PEPPER SYNDROME
- massive involvement of the liver with mets disease +/- respiratory involvement
HUTCHINSON SYNDROME
- irritability and limp in young child associated with bony and bone marrow mets.
Chimeric (Ch14.18) monoclonal antibody
- targets “GD2” which is present on healthy and unhealthy nerve cells
- antibody dependent cellular cytotoxicity (ADCC)
- attacks healthy nerves = ++pain. need morphine and ketamine
- causes physiological instability, fever, oedema
Hepatoblastoma
Most common liver malignancy of childhood
<1% malignancies of childhood (liver tumours account for 1%, hepatoblastomas about 65% of this)
- usually in children <3 years
- Alterations in APc/beta-catenin pathway
-Environment predisposition LBW <1000g (38 x relative risk) –> not high enough to screen for
- 15% have genetic predisposition
- -> BWS
- -> FAP
- -> Li-fraumeni, T18, NF-1, ataxia telangectasia, fanconi anaemia, TS
Ix:
AFP raised (non-specific as high in HCC and GCTs) –> but used for monitoring response
Can also have raised BHCG
Biopsy gold standard
RX:
1. resection key to cure (as much as 85% is fine with regeneration in 3-4 months!)
2. chemo in most Cisplatin/carboplatin (also treats mets) + sodium thiosulpahte (protects against SNHL)
vinc and doxorubicin
3. Transplant if unable to resect
+/- post-transplant chemotherapy
The ONLY CONTRAINDICATION to TRANSPLANT:
persistence of viable extrahepatic disease after chemo
Prognosis:
- > 90% with low staged with surgery and post chemo
- 60% if unresectable tumour
- 25% if pulmonary mets
Sodium thiosulphate
- antidote for cyanide poisoning
- infuse soon after giving cisplatin prptects against SHNL w/o compromising efficacy of Rx
Germ cell tumours
- tumour that begins in cells that give rise to eggs or sperm
- can occur almost anywhere in the body and can be malignant or benign
- 1/3 arise in gonads
- 2/3 are extragonadal as arise from aberrant migration and occur in the MIDLINE
- appearance may mimic any cell in embryo (yolk) or extra embryonic (chorion)
-types include teratoma (mature and immature) --> benign Germinoma embryona carcinoma endodermal sinus tumour (raised AFP) choriocarcinoma (raised BHCG)
Primary sites:
- Gonadal - testes 25% (adolescents), ovaries 10% (adolescents
- CNS–> pineal, suprasellar, rare and aggressive
- cervical –> rare, teratomas/infants
- MEDIASTINAL –> 5% (adolescents) associated with KLINFELTERS
- Retroperitoneal 10% infants/children
- SACROCCOYGEAL 50% infants/children
Sx: present as mass lesions
If in CNS presents often as diabetes insipidus in adolescents. Or as precocious puberty or panhypopit
RX:
1. Surgery
2. Cisplatin/carboplatin if cannot be resected
+/-radiation (intracranial chemo +radiation as cannot resect
Teratoma
GCT
- derived from more than one germ layer
- cell of origin is totipotent so can resemble anything
- tumour components resemble normal tissues
