Childhood cancers

Question 1

What is hemi hyperplasia?

Answer 1

Condition where one side of the body grows quicker than the other, hyperplastic cells rather than hypertrophy. Can predispose child to nephroblastoma so child is screened every 3-6months

Question 2

Child presents with easy bruising noticed over the last few weeks, also has bleeding from gums and appears pale

• Examination shows she is pale and bruised over bony prominences
• Abdo exam reveals hepatosplenomegaly
  
  • Concerning as if this was just infection the spleen tip might be palpable but nothing more
• Petechial spots appear when blood pressure cuff is removed

New history of bruising in the family rules out a familial coagulation disorder

Answer 2

Investigations

• FBC shows anemia, raised WCC, low platelets and blood film shows presence of lymphoblasts
  
  • Diagnostic of acute lymphoblastic leukemia
  • Child will be transferred to oncology unit for further tests such as bone marrow biopsy

Question 3

Palpable abdominal malignancies?

Answer 3

• Nephroblastoma, Wilm’s tumour, neuroblastoma
  
  • Nephroblastomas do not cross the midline

Question 5

Most common type of childhood cancer?

Answer 5

Leukaemia

• 25% childhood cancers worldwide
• In leukemia there is arrest at an early stage of haemopoietic cell development and therefore early lymphoid precursors aka blasts proliferate and replace normal bone marrow cells which reduces the production of normal blood cells

Question 6

Most common type of leukaemia diagnosed in children?

Answer 6

Acute lymphoblastic leukaemia

Caused by abnormal proliferation of immature lymphocytes – usually B cells – called blasts

• Much more common in children than adults – 55% patients are children and peak incidence is at 2-3 years and declines thereafter
• Children with certain genetic conditions are at higher risk

Question 7

Clinical features of acute lymphoblastic leukaemia

Answer 7

• Early symptoms often non-specific
  
  • Early bruising, easy bleeding e.g. when brushing teeth, lethargy
  • Symptoms occur due to the crowding out of other blood components e.g. thrombocytopenia occurs which accounts for the easy bruising and bleeding gums, anaemia occurs which accounts for the lethargy
• Bone pain may manifest as limp
• Hepatosplenomegaly
• Headaches, cranial nerve abnormalities and neck stiffness may indicate CNS involvement

Question 8

Diagnosis acute lymphoblastic leukaemia

Answer 8

• Suspected initially when FBC shows thrombocytopenia, anaemia and raised WCC (not WCC can also be normal or low)
• Lymphoblasts seen on blood film
• Bone marrow biopsy showing blasts confirms diagnosis and lumbar puncture indicated whether cells have entered CNS
  
  • Note – intrathecal chemo is given even if lumbar puncture does not indicate CNS involvement as lumbar puncture itself can facilitate entry of leukemic cells into CNS

Question 9

Management of acute lymphoblastic leukaemia

Answer 9

ALL is treated with chemo with several phases

Induction phase: achieves bone marrow remission I.e. normal blood count levels and no lymphoblast visible on blood film – at this stage there may still be residual disease

Consolidation phase: lasts several months, aim is to eliminate all leukaemic cells

Maintenance phase: lasts up to 3 years, aim is to prevent recurrence after remission

Management of CNS spread used to be managed with cranial irradiation but this has been replaced with intra thecal chemo because there is a high risk of neurotoxicity and brain tumours

• Radiation is used if there is a very high lymphoblast count or any clinical signs of CNS involvement e.g. facial palsy

Relapse occurs in 20%, some will go into remission again but some will need a stem cell transplant

Chemo is given by central line because it is an irritant so a child will have a Hickman line inserted, also allows for blood to be taken from this site so child doesn’t have to go through frequent venepuncture

• Prognosis
  
  • Good prognosis, 80-90% 5yr survival

Question 10

Acute myeloid leukaemia

Answer 10

• Results from abnormal proliferation of myeloblasts
• Abnormal cells leak into peripheral blood and infiltrate organs
• Second most common leukemia diagnosed in children – 15% cases
• Incidence highest in children <1year

Question 11

• Similar to those seen in ALL
• Bone pain and lymphadenopathy are less common than in ALL but organomegaly and haemorrhage are more common
• Formation of mediastinal masses due to infiltration of body tissues
  
  • Can lead to resp distress or superior vena cava syndrome: partial occlusion of the SVC
    
    • Most common presenting symptoms of SVC syndrome are face/neck swelling, distended neck veins, cough, dyspnea, orthopnea, upper extremity swelling, distended chest vein collaterals, and conjunctival suffusion
• Formation of abdominal masses can also occur, causing pain/ obstruction of GI or uro tract

Question 12

Diagnosis of acute myeloid leukaemia

Answer 12

• FBC will show normocytic anaemia with lower than normal reticulocyte count and thrombocytopenia, neutrophil count remains low
• Myeloblasts seen in peripheral blood film + auer rods
• Diagnosis confirmed with bone marrow biopsy

Question 13

Management of acute myeloid leukaemia

Answer 13

• AML treated with intensive induction chemo followed by consolidation chemo and bone marrow transplant if a match is available

Lower 5yr survival rate than ALL @60%

Question 14

Chronic myeloid leukaemia

Answer 14

• Caused by unregulated production of myeloid cells in bone marrow leading to excess of granulocytes – usually neutrophils
• Rare in children
• Starts with chronic phase where bloods are abnormal but child asymptomatic
• When symptoms appear they are usually non-specific
• Followed by an accelerated phase in which there is an increased number of myeloblasts in the blood
• FBC shows high level of granulocytes at various stages of maturation with normocytic anaemia and a high/ normal platelet count
• Chemo can control disease but bone marrow transplant is only cure

Question 15

What is lymphoma?

Answer 15

• Cancer of the lymphatic system
• Malignant proliferation of cells derived from B or T cells
• Malignant cells accumulate in lymphatic system and LNs causing solid tumour formation
• Lymphomas account for 11% childhood cancers
• M:F 2:1
• Hodgkins or non Hodgkins

Question 16

Hodgkins lymphoma

Answer 16

• Reed Stenberg cells
  
  • Giant, multinucleated cells usually derived from B cells
• Accounts for 45% cases of lymphoma in childhood
• Rare before 2yrs
• Sharp rise in cases during teenage years
• Linked to EBV
• Clinical features
  
  • Most common feature is painless lymphadenopathy which may be present for several months and typically above the clavicle but can be anywhere
  • Unexplained weight loss , fever and night sweats (drenching)
  • Mediastinal masses are common
• Diagnosis
  
  • Confirmed by presence of Reed Sternberg cells on LN biopsy
  • After diagnosis CT and PET to look for mets and confirm staging
• Management
  
  • Depends on the stage but in all cases involves a combination of chemo and radio
  • Responds well to treatment, 95% @5yrs
  • Mortality is higher from effects of treatment later on e.g. lung fibrosis or congestive heart failure rather than death related to cancer itself – important to tailor intensity of treatment to stage of disease

Question 17

Non Hodgkins lymphoma

Answer 17

• Most common
  
  • Mature B cell including Burkitt’s and diffuse large B cell
  • Lymphoblastic lymphoma
  • Anaplastic large cell lymphoma – cells express CD30 antigen which is an activation marker of B and T cells
  • EBV is also implicated in Burkitt’s lymphoma
• Clinical features
  
  • Depend on stage and type
  • Children present with enlarging, non-tender lymphadenopathy or due to mass compressing structures
    
    • Resp symptoms due to effusion or SVC syndrome
    • Abdo pain, constipation
  • Hepatosplenomegaly in 40%
  • Less common for fever, night sweats to be present - these are known as B symptoms and are more likely to occur in higher grade disease
• Diagnosis
  
  • Biopsy of mass or LN
  • Bone marrow biopsy to exclude leukemia and assist with staging
• Management
  
  • Combination chemo is standard
  • Prognosis good, 85% at 5yrs

Question 18

Second most common cancer type in children?

Answer 18

CNS tumours

• Almost always primary rather than mets
• 60% arise in cerebellum
• Main cause of death from childhood cancer
• Inherited conditions such as neurofibromatosis and tuberous sclerosis are associated with CNS tumours

Question 19

How are CNS tumours classified?

Answer 19

Accroding to cellular origin

• Gliomas arise from glial cells
• Embryonal tumours arise from neural crest cells
• Craniopharyngiomas are epithelial tumours that arise from remnants of Rathke’s pouch (embryological structure that forms the anterior pituitary)

Question 20

What are embryonal tumours

Answer 20

Embryonal tumours develop from cells that are left over from the early stages of our development

• Form in the brain and spinal cord
• Known as primitive neuroectoderm tumours and named according to location
• Fast growing
• Most are medulloblastomas which form in the cerebellum
• Mainly found in children

Question 21

What is craniopharyngiomas?

Answer 21

• 6-10% of all brain tumours in children
• Most commonly found in pituitary stalk and project into hypothalamus and press on optic chiasm
• Patients present with visual and endocrine disorders as tumour is near optic chiasm and pituitary
• Considered histologically benign – 99% @ 5 years
• Clinical features
  
  • Symptoms vary depending on size and location, effect on CSF flow etc
  • Clinical exam may show papilloedema indicating increase in ICP

Question 22

Symptoms of brain tumours in children

Answer 22

• < 5 years
  
  • Vomiting, headache (presenting as irritability because young children struggle to localise pain), abnormal gait, behavioral change, lethargy, abnormal eye movement or squint, increasing head circumference, developmental delay
• > 5 years
  
  • Vomiting, headache (persistent, recurrent, worse on waking, abnormal gait, lethargy, seizure, abnormal eye movement, blurred vision, deterioration at school

Question 23

Management of paediatric brain tumours

Answer 23

• Depends on type and location but standard is surgical removal/ chemo/ radio
• Radiotherapy is avoided in those <3yrs because it can damage developing brain

Question 24

What is neuroblastoma?

Answer 24

• Tumour originating in neural crest part of the sympathetic NS
• Third most common childhood cancer and most common solid tumour in those <1 year
• Incidence highest in first year of life
• Very rare in children >5 years
• 50% occur in adrenal glands but can grow anywhere in sympathetic NS e.g. abdomen, chest
• By time of diagnosis 50% have metastasised

Question 25

Clinical feature of neuroblastoma

Answer 25

* Depend on affected site * Abdomen: distension, constipation, pain * Thorax: SOB, Horner's syndrome, SVC syndrome * Spinal cord: leg weakness, loss of ability to walk or crawl * Orbital bone: bruising around eyes * Endocrine: HTN, diarrhoea * Skin: blueberry muffin * Eyes: rapid eye movements

Question 26

Diagnosis of neuroblastoma

Answer 26

* Requires histo confirmation from biopsy or bone marrow aspirate * CT and bone marrow aspirate to detect mets

Question 27

Management of neuroblastoma

Answer 27

* Depends on risk category assigned to patient * Low risk: surgical excision of tumour * Intermediate: surgery + chemo * High risk: surgery, chemo, radio + high dose chemo + peripheral blood stem cell rescue

Question 28

What is retinoblastoma

Answer 28

Embryological tumour of retinal cells 3% childhood cancers 40% cases: mutation in RB1 * If mutation present tumour more likely to be bilateral * No mutation present, tumour likely to be unilateral

Question 29

Clinical features of retinoblastoma

Answer 29

* Leukocoria (white pupil) is 1^st sign usually * Noted in flash photography of child * Can also present with squint

Question 30

Diagnosis of retinoblastoma

Answer 30

* Diagnosed on clinical appearance and examination is carried out under anesthetic * Biopsy is not needed * USS and MRI may be needed to stage

Question 31

Management of retinoblastoma

Answer 31

* Aim is to treat tumour while preserving vision * Small tumours treated with cryotherapy or laser * Local radio can be applied to eye * Larger tumours may require removal of eye * Excellent prognosis – 99% at 5yrs

Question 32

What is nephroblastoma?

Answer 32

* Embryonal tumours of kidney * 90% of renal tumours * Rare, accounts for 6% childhood cancers * Peaks 1-3yrs * 5% bilateral * 10% associated with other conditions e.g. Beckwith Wiedemann syndrome and hemi hyperplasia

Question 33

Clinical features of neprhoblastoma

Answer 33

* 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 34

Diagnosis of nephroblastoma

Answer 34

* Initial investigation is USS which identifies a tumour * CT or MRI to determine stage * Histological examination after nephrectomy * Transcutaneous biopsy not recommended as may cause mets

Question 35

Management of nephroblastoma

Answer 35

* Nephrectomy = 1^st line followed by chemo * If bilateral, masses are removed in attempt to preserve some kidney function * Radiotherapy if disease is advanced * 85% @5yrs

Question 36

Child with an unexplained large abdominal mass - what to do?

Answer 36

Refer for paeds review within 48hrs - possible Wilm's tumour

Question 37

What is rhabdomyosarcoma?

Answer 37

* Type of connective tissue tumour arising from primitive muscle cells * Incidence peaks at 3 years * Presents with hard, swelling typically in head/ neck, chest or abdo wall * Biopsy to confirm diagnosis * Management via surgical excision + chemo + radio * Worst prognosis of childhood cancers * 5 year survival = 70%

Question 38

What is osteosarcoma?

Answer 38

* Most common bone tumour in children * Arises from primitive mesenchymal bone-forming cells * Incidence increases with age of child ad peaks during teenage growth spurt * Rare in those \<5 * Common tumour location = metaphyses of long bones – usually distal femur * Child may be asymptomatic, some present with pathological fracture * Management: surgical resection + chemo * Amputation may be needed * Metastasises easily * Poor prognosis – 70% at 5yrs in localised disease \<30% if mets

Question 39

What is Ewing's sarcoma?

Answer 39

* Primitive neuroectodermal tumour of connective tissue * Rare * Most common in bones of leg and pelvis but can be anywhere * Peak incidence late adolescence * Can cause onion skin appearance on x-ray * Management: chemo 1^st line * 2/3 @ 5 years