Malignant Disease

Question 1

Wilm’s tumour: definition

Answer 1

Wilms’ nephroblastoma is one of the most common childhood malignancies. It typically presents in children under 5 years of age, with a median age of 3 years old.

Question 2

Wilm’s tumour associations

Answer 2

• Beckwith-Wiedemann syndrome (overgrowth e.g. macrosomia, with higher risk of cancer)
• as part of WAGR syndrome with Aniridia, Genitourinary malformations, mental Retardation
• hemihypertrophy
• around one-third of cases are associated with a loss-of-function mutation in the WT1 gene on chromosome 11

Question 3

Features of Wilms’ tumour (signs and histological)

Answer 3

• abdominal mass (most common presenting feature)
• painless haematuria
• flank pain
• other features: anorexia, fever
• unilateral in 95% of cases
• metastases are found in 20% of patients (most commonly lung)

Question 4

Referral for Wilms’ tumour

Answer 4

• children with an unexplained enlarged abdominal mass in children - possible Wilm’s tumour - arrange paediatric review with 48 hours

Question 5

Wilm’s tumour mx

Answer 5

Surgery (nephrectomy) and chemotherapy (may be post-operative or pre-operative)

Subsequent management is dependent on histological findings

Radiotherapy in more advanced disease

5% have bilateral disease

More than 80% of patients are cured

Question 6

ALL epidemiology

Answer 6

80% childhood leukaemia

2-5 years of age

Male>female

Question 7

Features of ALL

Answer 7

BM failure:

• anaemia = lethargy, pallor
• neutropenia = frequent or severe infections
• thrombocytopenia = easy bruising, petechiae

other features:

• bone pain (2o to BM infiltration)
• splenomegaly
• hepatomegaly
• fever (50%) cases
• testicular swelling

Question 8

Types of ALL

Answer 8

• common ALL (75%), CD10 present, pre-B phenotype
• T-cell ALL (20%)
• B-cell ALL (5%)

Question 9

ALL prognostic factors

Answer 9

• ge < 2 years or > 10 years
• WBC > 20 * 10⁹/l at diagnosis
• T or B cell surface markers
• non-Caucasian
• male sex

Question 10

How do we manage ALL?

Answer 10

Supportive:

• fluid (UO 100mL/hour)
• allopurinol/rasburicase = prevent tumour lysis syndrome
• transfusion = low platelet count, bleeding
• prophylactic abx, antifungals, antivirals
• prophylactic haematopoietic GFs e.g. CSF (filgrastim) = in those at risk of febrile neutropenia
• norethisterone = female patients to suppress periods and thrombocytopenia

Correct anaemia before tx

NO CNS Disease in newly diagnosed:

induction chemotherapy = prednisolone, vincristine, anthracyclines (doxorubicin, daunorubicin).

• dexrazone = prevent cardiotoxcitiy from doxorubicin
• rituximab (CD20+ ALL)
• imatinib (TKI) = for Philadelphia chromosome +ve patients

CNS involvement

• Intrathecal methotrexate alone or w/ cytarabine + hydrocortisone (TRIPLE)
• Consolidation therapy with high-dose cytarabine (HDC) or high dose methotrexate (HDM) to ensure good blood-brain penetration

Maintenance therapy

• remission when leukaemic blasts eradicated and normal marrow function restored

Relapse, refractory, residual disease

• high-dose chemotherapy w/wo total body irradiation followed by BM transplantation

Question 11

Retinoblastoma: average age of diagnosis and pathophysiology

Answer 11

Retinoblastoma is the most common ocular malignancy found in children. The average age of diagnosis is 18 months.

Pathophysiology

• autosomal dominant
• caused by a loss of function of the retinoblastoma tumour suppressor gene on chromosome 13
• around 10% of cases are hereditary

Question 12

Retinboblastoma features and ix

Answer 12

• absence of red-reflex, replaced by a white pupil (leukocoria) - the most common presenting symptom
• strabismus
• visual problems

ix

• MRI and examination under anaesthetic
• tumours are frequently multifocal

Question 13

Retinoblastoma mx

Answer 13

save life, save eye, save vision

frequent eye exams under anaesthesia to assess response to tx

Gross vitreous seeding present (tumour cells floating within vitreous cavity)

• 1st line = enucleation (eye removal without resection of lids or extra ocular muscles)
• infilitration of iris, ciliary body/sclera = adjuvant chemotherapy (carboplatin, etoposide, vincristine)

minimal/no vitreous seeding present

• 1st line = systemic chemotherapy (carboplatin, etoposide, vincristine)
• PLUS = focal therapy (cryotherapy, laser therapy)

FHx of retinoblastoma/detected at birth

• usually treated by laser alone
• followed up with an examination under anaesthesia every month for at least 1 year

Vitreous seeding after chemotherapy and/or focal therapy

• 1st line = external beam radiotherapy

Prognosis

• most patients cured (90%)
• many visually impaired
• significant risk fo 2o malignancy (sarcoma) among survivors of hereditary retinoblastoma