Oncology Flashcards
How common is cancer before age 15?
1/500
What is the most common cancers in kids <15 and kids >15?
<15: leukaemia, CNS, lymphoma, neuroblastoma
> 15: lymphoma, germ cell tumour, leukaemia, CNS tumour, melanoma, sarcoma, thyroid
What proportion of kids <7 have enlarged ant or posterior cervical nodes (or both)?
= adenopathy
At least 70%!
In most kids, cervical, axillary and inguinal nodes are palpable and small
What size are lymph nodes considered enlarged?
> 15-20mm for cervical nodes; otherwise
>10mm (epitrochlear: if >5mm, inguinal: if >15mm)
Which lymph node groups warren further investigation?
Posterior auricular, epitrochlear, supra-clavicular
How many weeks until non-cancerous lymph nodes return to normal size?
2-3 weeks in most cases
Fever and localised cervical lymphadenopathy?
Oral antibiotics: anti-staph, anti-strep, anaerobic if dental source suspected. Give 7 days - if not responded, or fluctuant or >20mm -> Ix further
What are features of malignant lymphadenopathy?
Increase in size
Chronic ie still large after 2 weeks
Firm, rubbery, matted
Non-tender
Which cancers are associated with generalised adenopathy?
ALL, AML, Lymphoma, Neuroblastoma
What is the most common symptom of superior mediastinal syndrome? Is this a medical emergency?
Dyspnoea when supine
Yes - need immediate transfer to hospital
Common unreported symptoms of mediastinal tumours?
Cough
Dyspnoea
Orthopnoea
Stridor
If orthopnoea or tracheal caliber <50% of normal, what is the biggest concern?
Sedation / anaesthetic risk!
- Raise head of bed
- Place prone
An anterior & posterior mediastinal mass is what until proven otherwise?
Anterior: leukaemia (usually T cell) or lymphoma
Posterior: neuroblastoma or PNET
- need MRI spine to rule out extension in spinal canal - risk of cord compression
What is the most common solid tumour in paeds?
Brain tumours
Is increased ICP common in brain tumour?
Is neuro abnormalities on examination common in brain tumours?
Yes - most brain tumour are located in spots that interfere with normal circulation of CSF
Yes - 95% have abnormalities on detailed examination
What are the indications for neuroimaging? / symptoms of concern
- Early morning HAs or wake from sleep
- HA associated with, and often improved by, vomiting
- HA and abnormal neurology
- Papilloedema, reduced acuity
- Short stature
- Enlarged HC
- Diabetes insipidus
- Neurofibromatosis
- Previous cranial irradiation
HA
Which childhood cancers present with bone pain?
- waking from sleep
- function impaired but no trauma
- no cause found in 2 weeks
- associated mass
Bone cancers
- pain usually intermittent at first and increasing severity over time
Leukaemia
- limp, refusal to walk
- can present as leukaemia arthiritis
Metastatic lesions to bone:
ie stage IV neuroblastoma
Diagnosis of neuroblastoma?
- most common solid tumour in infants
Calcified abdominal mass
MIBG scan: radioactively labelled compound taken up by catecholaminergic cells
Urine catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA), metaiodobenzylguanidine (MIBG)
If fever and bone pain, what are the key differentials?
Osteomyelitis
Malignancy, often Ewing’s sarcoma
A palpable abdominal mass is more likely to be benign or malignant?
Benign
- faeces, aorta, bladder distention, hydronephrotic kidney
- but take into account rest of history and examination for red flags
If a renal mass is present on U/S, what further structures need to be U/Sed to rule out tumour thrombus extension?
IVC and heart
Autoimmune haemolytic anaemia can be a paraneoplastic manifestation of which malignancy?
Lymphoma
Immune thrombocytopenic purpura can be associated with which malignancy?
Hodgkin lymphoma
WCC >50 can occur in which other conditions?
Septicaemia
Mumps, varicella, pertussis, adenovirus, CMV
> 100 has been reported in preterm infants whose mothers received steroids in pregnancy
What proportion of neonates with T21 develop TAM?
- transient abnormal myelopoiesis
- high WCC, blasts
- low Hb, low Pl
- hepatosplenomegaly
- usually spontaneously resolves
- 20-30% develop leukaemia AML
- GATA1 somatic mutation
10%
Conditions with increased risk of malignancy?
Wiskott-Aldrich syndrome: leukaemia, lymphoma
Conditions assoc with eosinophilia?
– risk of cardiac disease
Leukaemia, Hodking’s lymphoma
Primary immunodeficiency syndrome (Wiskott-Aldrich syndrome), Omenn syndrome (severe SCID), absent radii syndrome
Disseminated malignancies, ie leukaemia with WCC >100 & esp acute promyeloctic leukaemia (APL and Retinoic Acid Receptor A translocation), can lead to what blood condition?
& cure of this malignancy?
DIC
Retinoic acid and arsenic
t(8;21) (16;16)
inv(16)
= good risk genetics
What impact can penicillin have on platelet function?
Can cause platelet dysfunction and increase bleeding
Supra or infra-tentorial: where are 70% of paed brain tumours located?
Infra-tentorial = posterior fossa
(cerebellum or 4th ventricle mostly)
- usually pilocytic astrocytoma (commonly seen, low grade), medulloblastoma (most common malignant brain tumour in paeds), ependymoma, brainstem glioma
What is the most common childhood malignancy & prognosis?
ALL
85% cure
Is hyperdiploidy (increased number of chromosomes) or hypodiploidy (less chromosomes; haploid is close to half) associated with best prognosis?
Hyperdiploidy is better prognosis
Which type of Leukaemia has worst prognosis?
B cell (mature B cell lymphoblast, Burkitt cell) = t(8;14)
&
t(9;22) philedelphia chromosome;
T cell;
11q23 (MLL gene) rearrangement; persistent MRD; age <1 or >10, CNS disease, WCC >50 at presentation, hypodploidy (<44 chromosomes)
What is JMML and is it aggressive or benign and which age group commonly affected?
Which 2 conditions increase risk?
Presentation?
Juvenile myelomonocytic leukaemia Aggressive Infants/toddlers Noonan's NF1 Massive splenomegaly, elevated Hb F
What has helped increase survival with CML?
TKIs
NHL is more common age 10? And is it common with AIDS?
> 10
Yes most common malignancy in AIDS
NHL is characterised into 3 groups:
- Lymphoblastic
- usually T cell
- 30% of cases
- anterior mediastinal mass, SVC syndrome, TLS (renal failure) - Small non-cleaved cell (Burkitt and non-Burkitt)
- 50% cases
- most are intra-abdominal - can present with obstruction, usually ileocaecal - Large cell
- 25%
Is the lymphadenopathy fast or slow?
Fast!
What is the most common presentation of Hodgkin’s?
Mostly above the diaphgram
Painless LN enlargement, most often cervical or supra-clavicular
- subacute and slow
- B symptoms = fever 38 for 3 consecutive days, night sweats, unexplained weight loss
- ant mediastinal mass
- high ESR, ferritis, eosinophilia
Lymphocyte-predominant and nodular sclerosing are best or worst prognosis in Hodgkin’s?
Best
Worst is lymphocyte-depleted type
What type of cancer is neuroblastoma?
- most common malignant tumour of infancy
- most common solid tumour outside CNS
primitive sympathetic ganglion cells
- Adrenal gland neuroblastoma often present with?
- Neuroblastoma in cervical ganglia?
- Thoracic?
- Pelvic?
- Paraspinal?
- Abdominal mass: firm, irregular, non tender
or pain
& commonly:
- anorexia
- vomiting
- change in bowel habits
- Horner syndrome, heterochromia
- Dysphagia, dyspnoea, cough
- Difficult defecation or urination
- Back pain, paraplegia, urinary / faecal retention
Paraneoplastic syndromes with Neuroblastoma?
Hypertension: stretching of renal artery - angiotensin effect
Flushing, hypertension: catecholamine effect
Watery diarrhoea, abdominal distention: vasoactive intestinal peptide effect
Opsoclonus-myoclonus syndrome
Progressive cerebella ataxia
Worse prognosis genetics in neuroblastoma?
high N-myc amplication (MYCN oncogene)
trisomy 17q
Conditions associated with Wilm’s tumour?
Denys-Drash syndrome (germline mutation in WT1 gene): pseudohermaphroditism, glomerulopathy / renal failure, 95% chance of Wilm’s tumour)
WAGR syndrome (WT1 mutation): Wilm’s tumour, Aniridia (absent iris), Genetic / Urinary tract abnormalities, mental Retardation
WT2: Beckwith-Wiedermann gene (11q15 - is near WT2) - fetal overgrowth syndrome, increased risk of solid tumours:
macroglossia, hemihypertrophy, visceromegaly, mild microcephaly, omphalocele, facial nevus flammeus, characteristic earlobe crease, and renal medullary dyslalia
If aniridia or hemi-hypertrophy, need 3 monthly renal U/S until age 6!
Rhabdomyosarcoma in kids <3is associated with which conditions?
Li-Fraumeni syndrome (inactivation of p53 gene)
Costello syndrome / faciocutaneoskeletal syndrome increases risk of which malignancy?
Rhabdomyosarcoma
Localised bone pain is the most common presenting sign of bone cancer (osteosarcoma or Ewing’s sarcoma). Where is the most common sites?
Distal femur
Proximal tibia
Which cancers have “small, blue, round cells”?
Ewing's sarcoma Rhabdomyosarcoma Neuroblastoma Lymphoma Leukaemia
Where do bony cancers commonly metastasise to?
- 20% have mets at diagnosis
Lungs
Bone
What are the 2 most common presentations of retinoblastoma?
- Leucocoria (>50% have it, large tumour or caused retinl detachment)
- Strabismus (when tumour in macula, loss of central vision and eye may drift)
30% of retinoblastomas are bilateral on presentation. They have worse prognosis because of high incidence of second malignancy, most commonly?
- Osteosarcoma
- PNET pineal gland = Germline mutations in RB1 can lead to “trilateral” retinoblastoma that includes bilateral ocular disease along with an intracranial component that is located in the pineal gland.
What 3 conditions is hepatoblastoma associated with?
(Age <5 usually, high alpha-fetoprotein that parallels disease activity, can metastasise to lungs)
- nil alpha-fetoprotein is a poor prognostic sign as assoc with small cell anaplastic histologic variant that poorly responds to therapy
- Beckwith-Wiedermann syndrome
- Familial adenomatous polyposis
- Low birth weight
What is hepatocellular carcinoma associated with?
Hepatitis B or C infection, especially if perinatally acquired
- occurs in very young or older adolescents
Most common adverse effects:
Alkylating agents (cyclophosphamide, ifosfamide): decreased fertility
Anthracyclines: cardiomyopathy
Asparaginase: pancreatitis, coagulation abnormalities, anaphylactic reaction
Bleomycin: pulmonary fibrosis
Cisplatin: ototoxicity, renal toxicity
Cyclophosphamide: hemorrhagic cystitis, syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Etoposide: secondary leukemia (AML)
Ifosfamide: Fanconi renal tubular acidosis, hemorrhagic cystitis
Vincristine/vinblastine: neurotoxicity (peripheral neuropathy), constipation
Ifosphamide / cytarabine: neurotoxicity
Etoposide and vinblastine are M-phase dependent.
Ifosfamide and cisplatin are cell cycle phase non-specific.
Prednisolone has activity in the S phase only.
Carboplatin - uncommonly myelosuppressive
Cyclophosphamide - commonly myelosuppressive, nausea and vomiting, alopecia, haemorrhagic cystitis,
Doxorubicin (adriamycin) - commonly myelosuppressive, nauesea and vomiting, alopecia, mucositis
Etoposide (VP-16) - commonly myelosupressive, nausea and vomiting
Vincristine - uncommonly myelosuppressive, peripheral neuropathy, jaw pain, alopecia.
Although carboplatin is uncommonly myelosuppressive, the least toxic is vincristine.
Vincristine primarily causes neuropathy, including constipation, myalgias, arthralgias, and cholestasis.
Ifosfamide is similar to cyclophosphamide, although it has a higher incidence of hemorrhagic cystitis, which requires the use of 2-mercaptoethane sulfonate sodium (MESNA). Patients near the end of therapy occasionally develop the Fanconi syndrome of electrolyte wasting.
Etoposide can result in pancytopenia as well as anaphylactic reactions and is implicated in the development of second malignancies, particularly acute myeloblastic leukemia and myelopsuppresion.
Vincristine: constipation, paralytic ileus, intestinal necrosis/perfo, impact with empty rectum. Need prophylactic aperients
In ALL, 3 most important prognostic features?
Age
WCC >50 on presentation (high proliferation of tumour cells - often with lymphadenopathy and hepatosplenomegaly)
Response to treatment
What is the most common tumour in infancy?
Neuroblastoma
Hodgkin’s lymphoma is commonly associated with anterior or posterior mediastinal mass?
Anterior
Which tumour is infra-tentorial and contrast enhancing?
Medulloblastoma
Glioblastoma multiforme and oligodendroglioma are less common and are typically located supratentorially.
Which tumours associated with NF1?
Optic pathway gliomas are typically low-grade gliomas causing unilateral visual disturbance and are often seen in neurofibromatosis type 1.
What is the most rapidly proliferating tumour, and highest risk of TLS?
Burkitt lymphoma is the most rapidly proliferating tumor and caries a high risk of tumour lysis syndrome upon initiation of chemotherapy.
What is the most rapidly proliferating tumour, and highest risk of TLS?
Burkitt lymphoma is the most rapidly proliferating tumor and caries a high risk of tumour lysis syndrome upon initiation of chemotherapy.
ALL
Management of TLS?
2L/m2 iv fluids, no potassium, allopurinol or rasburicase (if not G6PD deficient), closely monitor UEC/CMP
Folate is needed for synthesis of which nucleoside?
Thymidine - which is required for DNA synthesis
Folate also needed for purine base synthesis
Which are the live vaccines? ie contraindicated during treatment (until 6 months after finishing treatment)
Rotavirus
MMR
Varicella
- inactivated vaccines may be less effect but not contraindicated
What is cytarabine? and what is a common side effect?
Cytarabine is an antimetabolite. It is a pyrimidine nucleoside analogue of cytidine
Fever
What is 6MP? (6 mercaptopurine)
purine antimetabolite and interferes with purine synthesis impairing lymphocyte proliferation.
Child on chemotherapy exposed to someone with chicken pox. Next step?
ZIG should be administered within 96 hours of exposure (passive immunity) - if can’t, then for IVIG
What cancer accounts for most common mediastinal mass?
Neuroblastoma (Neuroblastomas are malignant tumors of neural crest cells that can arise anywhere throughout the sympathetic nervous system)
Thymoma is rare in kids but may present with which neurological condition?
Myasthenia gravis
Alkylating agents are particularly risky for developing secondary malignancies. Such a medication is?
Cyclophosphamide
Germ cell tumours or germinomas & pineal tumours secrete which cancer markers?
bHCG
AFP
Which cancer is most common in 15-19 year olds?
Hodgkin lymphoma
In Hodgkin lymphoma, B sx (fever >38 unexplained persistent or recurrent in past 1/12, night sweat recurrent drenching in pat 1/2, LOW >10% in 6/12 prior), are associated with good or bad prognosis?
Poor prognosis
Advanced stage and bulky disease often
EBV is associated with which malignancies?
B cell: Burkitt’s lymphoma, Hodgkin’s lymphoma
Gastric cancers
Nasopharyngeal
Some T cell lymphoma
HHV8 is an oncogenic virus, associated with which cancers?
Karposi’s sarcoma
Castleman’s disease
HIV is associated with?
NHL
KS
Leimyosarcoma
Cervical and anal cancer
HPV is associated with?
cervical vulvar vaginal penile anal oropharyngeal
Is CMV associated with malignancy?
No
Isolated hemihypertrophy is associated with?
Phaeochromocytoma
Mechanism of action
A. Etoposide inhibits the enzyme topoisomerase II, which unwinds DNA, and by doing so causes DNA strands to break. It is used as a form of chemotherapy for cancers such as Ewing’s sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.
B. Vincristine. Tubulin is a structural protein that polymerizes to actin microtubules. The cell cytoskeleton and mitotic spindle, among other things, are made of microtubules. Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests mitosis in metaphase. Therefore, the vinca alkaloids affect all rapidly dividing cell types including cancer cells, but also those of intestinal epithelium and bone marrow.
C. Cyclophosphamide. The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. Phosphoramide mustard forms DNA crosslinks between and within DNA strands at guanine N-7 positions. This is irreversible and leads to cell death. Cyclophosphamide has relatively little typical chemotherapy toxicity to bone marrow, liver and GIT as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium.
D. Doxorubicin. The exact mechanism of action of doxorubicin is complex and still somewhat unclear, though it is thought to interact with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription.
E. Cisplatin. Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis.
Craniopharyngioma vs pituitary adenoma?
A craniopharyngioma presents with raised ICP (headaches) and pituitary dysfunction (usually as growth failure).
A pituitary adenoma presents with overgrowth and hyperpituitarism.
Worse prognosis cytogenetics in ALL?
t(9;22)
t(4;11)
hypodiploidy
Good prognosis cytogenetics in ALL?
hyperdiploid with trisomy 4, 10 or 17
rearrangement (12;21) = TEL-AML1
TLS meds, allopurinol vs rasburicase action?
Allopurinol inhibits xanthine oxidase which block metabolism of xanthine and hypoxanthine to uric acid. This decreases the formation of new uric acid, however does not reduce acid concentration prior to treatment. If there is pre-existing hyperuricaemia, rasburicase is the preferred hypouricaemic agent. Allopurinol may interact with other drugs. It may also lead to deposition of xanthine crystals in the renal tubules causing renal failure.
Uricase (Rasburicase) or uric oxidase catalyses the oxidation of uric acid to a water soluble compound allantoin. It is not present in humans. It is well tolerated and lowers serum uric acid and is effective in preventing and treating hyperuricaemia and tumour lysis syndrome.
Cause of precocious puberty in a boy with hepatoblastoma?
Ectopic b-hCG production may cause precocious puberty in boys with hepatoblastoma.
Approximately 10% of hepatoblastomas secrete ectopic b-hCG. hCG, through its LH-like action, causes Leydig cell stimulation in the testes. In turn, testosterone levels reach those of a normal adult, and secondary sexual characteristics develop together with premature skeletal maturity.
The testes usually do not significantly enlarge – as Leydig cells only constitute about 25% of testicular volume; Sertoli cell hyperplasia or spermatogenesis is dependent on FSH.
Therefore boys with precocious puberty secondary to hCG production by tumours typically have only mildly enlarged testes, discordant with their degree of pubertal development.
Approximately 4% of boys with precocious puberty have hCG-producing tumours.
The most frequent cause is hepatoblastoma, followed by mediastinal teratoma, intracranial germ cell tumours, and, last, presacral and retroperitoneal carcinomas.
Trephine BM aspirate (to see architecture) needed in which condition?
Asplastic anaemia
Hepatic GVHD
GVHD of the liver can be acute or chronic but often occurs with the presence of GVHD in other target organs such as the skin and gut. Hepatic GVHD is caused by immunologic reaction to bile duct epithelium, leading to a non-suppurative cholangitis.
Onset typically occurs at the time of donor engraftment (days 14–21 after SCT).
Acute hepatic GVHD can present both early (days 14–21) and late (>day 70) after allogeneic SCT. In chronic hepatic GVHD, serum aminotransferase levels are not as markedly elevated and cholestasis is more prominent with marked rises in serum conjugated bilirubin, GGT, and ALP levels.
Post transplant VOD:
VOD or SOS secondary to sinusoidal endothelial damage and subsequent thrombotic/fibrotic occlusion of hepatic sinusoids and venules. There is a clinical syndrome of:
Jaundice and hyperbilirubinaemia
Right upper quadrant pain, generally with tender hepatomegaly.
Weight gain and ascites
When do infant clotting factors (vit K dependent: 2, 7, 9, 10) reach adult values?
- low at birth
Age 6 months
Haemophilia inhibitor
Inhibitors are a complication of haemophilia. The inhibitors are antibodies (primarily IgG) directed against the specific deficient factor. This occurs in: 25-30% of patients with severe haemophilia A; and 3-5% of patients with severe haemophilia B.
Development of an inhibitor, usually occurs early in treatment, shortly after replacement therapy has been initiated (within first 50 exposure days of factor given). Inhibitors are more likely in severe disease.
The presence of an inhibitor does not lead to a marked increase in bleeding events, but inhibitors can make bleeding episodes more difficult to control.
Inhibitor activity is measured by the Bethesda assay (diagnoses inhibitor presence and quantifies the antibody titre)
Management is with factor VIII replacement therapy, with minimal change in the factor VIII dose.. Inhibitor eradication (immune tolerance induction), requires routine administration of the deficient factor to reset the patient’s immune system.
PRES syndrome
This question requires knowledge regarding the risk factors and radiological features of posterior reversible encephalopathy syndrome (PRES). Chemotherapeutic agents and hypertension are both risk factors for PRES. Vision loss suggests the region of cerebral ischaemia involves the occipital lobes which is typical, but not invariable, in PRES. The lack of diffusion restriction indicates vasogenic oedema rather than cytotoxic oedema that is again classic, but again not invariable, in PRES (cytotoxic oedema can be seen).
What are the two types of immune system?
Innate and adaptive
What are the three types of white cells involved in immune function?
- Granulocytes
- Lymphocytes
- Monocytes -> tissue macrophages
What are granulocytes and what are 3 types of granulocytes?
Cytoplasm contains granules of substances involved in inflam/allergic reactions
a) neutrophils
b) eosinophils
c) basophils -> mast cells
