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RACP Paediatrics Divisional Written Examination 2023 > Oncology > Flashcards

Oncology Flashcards

1
Q

Which chemotherapy agents cause 2nd malignancy?

A

Cyclophosphamide (leukaemia/lymphoma, bladder cancer)

Etoposide (AML)

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2
Q

What are the side effects of asparaginase?

A

Pancreatitis, hyperglycaemia, hypertriglyceridaemia, fatty liver disease, allergies, increased risk of thrombosis (reduced antithrombin III) and haemorrhage (decrease in fibrinogen and clotting factors), encephalopathy.

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3
Q

What are the side effects of cyclophosphamide?

A

Alopecia, hyperpigmentation, myelosuppression (nadir 7-14 days), haemorrhagic cystitis, sterility (in males for 5-10 yrs post treatment), lung fibrosis, SIADH, second malignancy

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4
Q

What are the side effects of doxirubicin?

A

Cardiotoxicity (dilated cardiomyopathy), myelosuppression, necrosis on extravasation

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5
Q

What are the side effects of vincristine?

A

Neurotoxicities (peripheral neuropathy, ptosis, jaw pain, voice hoarseness, ataxia), extravasation injury/phlebitis, mucositis, alopecia, constipation. Uncommonly can progress to paralytic ileus, intestinal necrosis and perforation.
Myelosuppression, but is minimal compared to other agents (nadir 7-10 days).

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6
Q

What are the side effects of 6-mercaptopurine?

A

Myelosuppression, hepatic necrosis, pancreatitis, lymphoma

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7
Q

Which chemotherapy agents in particular require adequate hydration?

A

Cyclophosphamide - risk of haemorrhagic cystitis (metabolite acrolein is toxic to the bladder epithelium).

Methotrexate - risk of renal failure from precipitation in the renal tubules

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8
Q

What class and mechanism of doxirubicin?

A

Anthracycline drug class, which -
Commonly used in leukaemia, lymphoma and various other malignancies. Echocardiogram surveillance due to the risk of dilated cardiomyopathy.

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9
Q

What class and mechanism of etoposide?

A

Works by inhibiting topoisomerase, which usually unwinds coiled DNA for replication. Etoposide binds the topoisomerase to the DNA, leading to DNA damage and apoptosis of rapidly dividing cancer cells.

Commonly used in leukaemia, lymphoma and Ewing’s sarcoma.

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10
Q

What class and mechanism of cyclophosphamide?

A

An alkylating agent (nitrogen mustard type). Forms DNA and RNA cross-links, inhibiting protein synthesis and leading to cell apoptosis.

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11
Q

Side effects of bleomycin?

A

Dose-limiting toxicity is an interstitial pneumonitis due to oxidative damage that can lead to pulmonary fibrosis (can be life-threatening). Not myelosuppressive.

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12
Q

Criteria for myelodysplastic syndrome?

A

Cytopoenia in 1 or more lineage (most commonly erythrocytes), dysplastic cells on film and <20% blasts in blood and bone marrow (>20% blasts is diagnostic of AML, end of the spectrum).

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13
Q

Differentials for testicular tumours?

A
  • Seminomatous germ cell tumour; 20% cause elevated b-HCG, but pure seminomas do not cause elevated AFP
  • Non-seminomatous germ cell tumour (embryonal carcinoma, yolk sack carcinoma, choriocarcinoma, teratomas, mixed germ cell tumours); raised AFP +/- b-HCG in 80-85% cases
  • Leydig cell tumours (less common, 2% testicular tumours); often present at an earlier age (6-10 yo) with precocious puberty, b-HCG/AFP is NOT raised
  • ALL; rarely presents as painless testicular enlargement, testicular relapse in T-ALL > B-ALL
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14
Q

Prognostic factors for medulloblastoma?

A
  • Age: <18 mo at diagnosis has better prognosis
  • Genomic typing: whole Chr gains with no segmental aberrations has better prognosis (common sites of segmental aberrations with worse prognosis are 1p deletion, 11 q deletion and/or 17 q gain)
  • Amplification of N-myc oncogene: has a worse prognosis
  • Shimada histology rating: indicates the degree of neuroblast differentiation, such that a lower Shimada rating indicates a better prognosis compared to a higher Shimada rating.
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15
Q

Regarding lymphadenopathy, what raises suspicion of malignancy?

A
  • Systemically unwell / B-symptoms
  • Supraclavicular nodes ( leukaemia, lymphoma, histiocytosis, germ cell tumours, neuroblastoma)
  • Generalised lymphadenopathy
  • Fixed and non-tender “matted” nodes, esp. if >2 cm
  • Elevated LDH and/or persistently elevated inflammatory markers (ESR, CRP)
  • Abnormal CXR
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16
Q

How to differentiate between osteosarcoma and Ewing sarcoma on XR?

A
  • Osteosarcoma - typically medullary and cortical bone destruction with wide zone of transition and aggressive “subburst” periosteal reaction; typically affects metaphyses of long bones in appendicular skeleton (femur > tibia/humerus)
  • Ewing sarcoma - typically poorly defined “moth eaten” destructive/permeative lucent lesions with “onion skin” periostitis and large soft tissue component; sclerotic changes in 30% of cases; affects long bones (femur > tibia/humerus) as well as flat bones (pelvis > ribs/scapula); if involving diaphysis/epiphysis more likely Ewing’s than osteosarcoma.
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17
Q

What are the side effects of ciclosporin?

A

Gingival hyperplasia, hirsutism, elevated bilirubin/transaminases, nephrotoxicity (acute dose-related renal insufficiency, nephrotic syndrome) and neurotoxicity (tremor, headache).

18
Q

What are the side effects of ifosfamide?

A 
Similar to cyclophosphamide... but more renal nephrotic effects? dunno *INCOMPLETE
metabolic acidosis (hypophosphataemia, low bicarb, proteinuria, glucosuria, borderline Na/K)
19
Q

Histopathology findings with neuroblastoma?

A

A “small round blue cell tumour” - blue on staining due to a large nucleus and minimal cytoplasm. Pathognomonic pseudorosette formation.

20
Q

Oncologic associations with NF1?

A
  • Optic glioma
  • Soft tissue sarcoma (neurofibromosarcoma, rhabdomyosarcoma)
  • Phaeochromocytoma
  • Breast cancer risk increased in women <50
21
Q

What are the common side effects of mycophenolate?

A

Abdominal pain, anorexia, constipation, diarrhoea, dyspepsia, GI haemorrhage, vomiting.

22
Q

What are the types of “small round blue cell tumours” ?

A
  • Neuroblastoma
  • Medulloblastoma
  • Retinoblastoma
  • Peripheral primitive neuroectodermal tumours (pPNETs)
  • Soft tissue sarcomas incl. rhabdomyosarcoma
  • Ewing’s sarcoma
  • Wilm’s tumour (nephroblastoma)
  • Non-Hodgkin’s lymphoma
  • Megakaryoblastic leukaemia
23
Q

Characteristic molecular genetic findings in Ewing’s sarcoma?

A

Chromosomal translocations on chromosome 22 affecting the EWSR1 gene are characteristic, of which t(11;22) is seen in 90% of cases.

24
Q

What class and mechanism of bleomycin?

A

Cell-cycle specific glycopeptide antibiotic that arrests rapidly dividing cells at the early G2 stage.

25
Q

What class and mechanism of cytarabine?

A

Cell-cycle specific pyrimidine analogue that inhibits DNA polymerase leading to arrest of DNA synthesis at the S stage.

26
Q

What class and mechanism of asparaginase?

A

Cell-cycle specific enzyme that depletes leukemic cells of asparagine thereby arresting growth at the G1 stage.

27
Q

Role/mechanism of rasburicase in managing tumour lysis syndrome (TLS)?

A

Used in the treatment and prevention of TLS in high-risk patients. Unlike allopurinol, rasburicase can break down uric acid that is already present - it does this as a urate oxidase by promoting catabolism of uric acid to water soluble allantoin

28
Q

Diagnosis of Hogdkin’s lymphoma?

A

Lymphadenopathy (often in teens), B symptoms (LOW, fever, night sweats), with lymph node biopsy showing Reed-Sternberg cells with a surrounding infiltrate of lymphocytes, eosinophils, macrophages, plasma cells and fibroblasts.

Reed-Sternberg cells are germinal centre B-cells that can’t synthesise Ig but instead secrete a range of cytokines important in the maintenance of the heterogeneous lymph node infiltrate.

29
Q

Late complications of radiotherapy?

A
  • Cataracts
  • Short stature - radiation to pituitary and impaired GH secretion, radiation to axial skeleton and reduced growth of the vertebral column
  • Learning difficulties - memory, concentration, processing, planning, organisation, problem solving and social skills.
30
Q

Side effects of cytarabine?

A

Mucositis, phlebitis, diarrhoea, oesophagitis/GI ulceration, deranged LFTs, ocular toxicity, pulmonary toxicity, neurotoxicity (dysarthria, nystagmus, ataxia, somnolence). Fever is common.

31
Q

What class and mechanism of cytarabine?

A

Cytarabine is an antimetabolite - a pyrimidine nucleoside analogue of cytidine.

32
Q

Prevention of high dose metothrexate (MTX) toxicity?

A
  • Hyperhydration - high urinary flow reduces [MTX] in renal tubules
  • Urinary alkalisation - improves MTX solubility, will otherwise precipitate in pH <7
  • Folinic supplementation - provides reduced folate and bypasses enzyme blockage of dihydrofolate reductase, thereby reducing toxicity to normal cells.

NB - allopurinol has no role (as in TLS)

33
Q

Hemihypertrophy is associated with increased risk of which tumours?

A

Wilms, hepatoblastoma, adrenal carcinoma

E.g. Beckwith Wiedemann syndrome

34
Q

Which syndromes are associated with increased risk of Wilms tumour?

A
  • Beckwith-Wiedeman syndrome - variety of 11p15.5 chromosomal anomalies with 3-5% risk of Wilms tumour (associated hemihypertrophy, macroglossia, visceromegaly)
  • WAGR syndrome - contiguous gene deletion syndrome that consists of *Wilms tumour, *Aniridia (abnormal iris), *Genitourinary abnormalities (cryptorchidism, streak ovaries, bicornate uterus, ambiguous genitalia), and *Renal impairment and mental Retardation; constitutional deletion of Chr 11p13 where the Wilms tumor and aniridia genes are located.
  • Denys-Drash syndrome - typically due to missense mutation in WT1 gene (associated male pseudo-hermaphrodism, early-onset renal failure characterised by mesangial sclerosis)
  • Other: Pearlman syndrome, Sotos syndrome, neurofibromatosis, von Willebrand disease, other genitourinary anomalies (hypoplasia, fusion and ectopia of the kidney, dupications of the collecting systems, hypospadias and cryptorchidism).
35
Q

Common culprit medications for radiation recall?

A

Radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration. Most often due to adriamycin, doxorubicin or daunorubicin.

36
Q

Cytogenetic prognostic factors for ALL?

A

Better prognosis/low-standard risk:

  • Age >1 yo and <10 yo at diagnosis
  • WBC <50,000 at diagnosis
  • Hyperdiploidy (blasts containing >50 Chr) with trisomies of Chr 4,10,17 have greater chance of cure than children without these trisomies
  • POSITIVE for t(12;21) - this is TEL-AML1 rearrangement and has excellent prognosis
  • NEGATIVE for t(9;22) - the Philidelphia chromosome in 4% cases
  • NEGATIVE for t(4;11)

Worse prognosis/high risk:

  • Age <1 yo and >10 yo at diagnosis
  • WBC >50,000 at diagnosis
  • Hypodiploidy
  • t(9;22) generally have very poor chance of cure even with intensive chemotherapy
  • Infants with t(4;11) have poor chance of cure with conventional chemotherapy
37
Q

Hallmarks of tumour lysis syndrome (TLS)?

A
  • Hyperphosphataemia
  • Hypocalcaemia
  • Hyperkalaemia (often rapid)
  • Hyperuricaemia (due to catabolism of released nucleic acids)
  • Acute renal injury - elevated Cr
38
Q

Which chemotherapy agent is the least toxic to bone marrow?

A

Both carboplatin and vincristine are uncommonly myelosuppressive, however vincristine is the least toxic.

39
Q

Side effects of calcineurin inhibitors?

A

Common SEs of cyclosporine and tacrolimus:

  • Gingival hyperplasia
  • Hirsutism
  • Nephrotoxicity
  • Hypertension
  • Hypercholesterolaemia
  • Neurotoxicity - tremor, headache, paraesthesiae
  • LFT derangement
  • Electrolyte derangement - hypomagnesaemia, hyperkalaemia
  • Diarrhoea
40
Q

Common changes on peripheral blood smear, flow cytometry and immunohistochemistry to differentiate leukaemias?

A
  • AML: myeloblasts have large nuclei with prominent nucleoli and variable amounts of cytoplasm; auer rods present; immunohistochemistry is negative for CD3/CD19; commonly stain positive with myeloperoxidase.
  • B-cell ALL: morphology on smear varies (small cells/scant cytoplasm/indistinct nucleoli versus larger cells/moderate cytoplasm/multiple nucleoli); negative for cell marker CD3, positive for cell marker CD19 and cytoplasmic markers CD79a/CD22; auer rods negative in all types ALL; negative myeloperoxidase staining.
  • T-ALL: morphology similar to B-ALL; auer rods negative in ALL; positive for cell marker CD3 and negative for B-cell antigens; negative myeloperoxidase staining.
  • Mixed picture acute leukaemia (MPAL): both myeloid and lymphoid markers.
41
Q

What is trephine used for?

A

Trephine = core of bone with marrow, to see architecture of bone marrow as well as cells. It is used to confirm the lack of erythroid progenitors in bone marrow (as opposed to infiltration) in diagnosis of aplastic anaemia.

Whilst not required for diagnosis, it may also be used in AML to look for high risk features (myelodysplasia, fibrosis, etc.). BMA/trephine would only be required in megaloblastic anaemia if there was failure to respond to B12/folate therapy.

42
Q

Prognosis for Hodgkin’s lymphoma based on histopathology?

A

Better prognosis:

  • Lymphocyte-predominant
  • Nodular sclerosing

Intermediate prognosis:
* Mixed cellularity

Worst prognosis;
* Lymphocyte-deplete

RACP Paediatrics Divisional Written Examination 2023 (25 decks)

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