What are the most common types of pediatric malignancies? Name the top 3.
1. Leukemia (40%)
2. Brain tumours (20%)
3. Lymphomas (15%)
What is the most common extracranial tumour in children?
What are the typical presenting features of leukemia?
Bone marrow failure
- Neutropenia: increased rate of infections
- Thrombocytopenia: easy bruising, gum bleeding etc.
- Gingival hypertrophy (esp. M4 AML)
- Hepatosplenomegaly (esp. ALL)
- Testicular enlargement -- painless (esp. ALL)
- Bone: bone pain, pathological fractures
- Skin: leukemia cutis
- Eyes: Roth spots, cotton wool spots, vision changes
- Weight loss
- Night sweats
>> "B symptoms"
- Diffuse pulmonary infiltrates
- Respiratory distress
- CNS bleeding
- Altered mental status
- Myocardial infarction
Metabolic effects aggravated by treatment
- Increased uric acid: nephropathy, gout
- Released phosphate
- Released procoagulants: DIC (esp. M3 AML)
If T-cell lymphoma --> thymic enlargement/lymphoma mediastinal mass can cause airway obstruction
What is the definition of acute leukemia?
Presence of 20% or more blast cells in the bone marrow aspirate at presentation
>> Usually <5%
What are the differential diagnosis of leukemia in children?
- Miliary TB
Langerhan's cell histiocytosis: look for skin rash
>> Characterized by cloncal proliferation of Langerhans cells (dendritics)
>> Painful bone swelling (esp. skull)
>> Rash: extensive eruptions on the skull, red papules in intertriginous areas
>> Diabetes insipidus is very common -- involvement of the hypothalamic-pit axis
What are the investigations helpful in the diagnosis for leukemia?
- Clotting profile in case of DIC (AML M3)
- Peripheral blood smear for blasts
>> Circulating blasts with Auer rods are pathognomonic for AML M3
- Baseline RLFT
- Serum hormone levels (not necessarily for leukemia)
>> AFP, B-hCG and LDH
:: Germ cell tumours
:: Germ cell tumours
>> Renin levels for Wilm's tumour
- Bone profile: primary bone tumours/metastasis
>> Increased PO4: released from blasts
>> Decreased Ca
Bone marrow aspirate
- AML >20%
- Morphologic, cytochemical and/or immunotypic features to establish lineage
Urine (not for leukemia)
- Catecholamines for neuroblastoma
- Bone scan: for bone metastasis
- CXR: for lung metastasis
- CT/PET-CT/MRI brain as indicated
- ECG and MUGA scan prior to chemotherapy (baseline for cardiotoxicity)
What is the treatment for AML?
M3 AML with t(15:17) translocation -- all-trans-retinoic acid and arsenic trioxide
1. Induction: cytarabine + daunorubicin
3. Supportive care: screening for infection + transfusion
>> Give allopurinol before chemotherapy to prevent gout
>> A total of 4-6 courses of induction and consolidation tx over 4-6 months
>> Each course is associated with 3-4 weeks of severe pancytopenia
Note: Treatment is much more aggresive in AML than in ALL, but
there is no evidence for CNS prophylaxis in AML
What is the management for ALL?
1. Induction: 4-5 weeks
2. Consolidation: 3-5 months
3. Maintenance treatment: up to 2-3 years
4. CNS prophylaxis: intrathecal methotrexate/irradiation
>> Intensive inpatient treatment for 6 months +
less intensive home maintenance treatment for up to 2-3 years
What is the prognosis for ALL?
5-year-survival rate: ~80%
- Good risk: 90%
- Intermediate risk: 70-80%
- Poor risk: 25%
What are the specific investigations to perform for neuroblastoma?
1. Urine catecholamines
2. Image-guided biopsy
3. For genetic markers for prognosis: n-myc amplification
4. Staging scans:
- Bone scan
- MIBG scan
- BM aspiration for Homer-Wright rosettes
What is the management for neuroblastoma?
1. Neo-adjuvant chemotherapy
2. Surgical debulking
3. Post-op chemotherapy
5. Autologous BM transplant
6. Target therapy
7. Differentiating agent: cis-retinoic acid
What is the most common cancer in the first year of life?
- Metastasis are common at presentation (>50%)
What is the most common age of presentation for leukemia?
Can occur at any age
Mean age of diagnosis: 2-5 years
What are the differential diagnoses for periorbital ecchymoses ("panda eyes")?
- Basal skull fracture: rule out child abuse
- Disseminated neuroblastoma
- Amyloidosis in multiple myeloma
What are the peak ages for Hodgkin lymphoma?
- 15-34 years
- >50 years
What is the common age of presentation in non-Hodgkin lymphoma?
What is the defining feature of Hodgkin lymphoma?
What are the classifications of non-Hodgkin lymphoma?
2. Large cell
>> T-cell VS. B-cell
>> Always do a CXR for any mediastinal masses
>> Rapidly growing tumour with distant metastases
What is the CHOP regimen and what is it used for?
Usually for Hodgkin lymphoma but can also be applied to non-Hodgkin lymphoma
O: Oncovin (Vincristine)
+ Rituximab in B-cell NHL
What is the prognosis for Hodgkin lymphoma?
>90% 5-year survival
What is the prognosis for non-Hodgkin lymphoma?
75-90% 5-year survival
What is the prognosis for AML?
50% 5-year event-free survival
What is the prognosis for stage 4 neuroblastoma?
40% 5-year event-free survival
What is the difference between allogenic and autologous bone marrow transplant?
- HLA (human leukocyte antigen) identical siblings
- Mismatched family donor
- Haplo-identical family donors (half-matched)
- Unrelated donor
- Patient's own bone marrow
- Used in AML
- Used in highly malignant solid tumours requiring high-dose chemotherapy that have potentially detrimental effects on the bone marrow (namely stage 4 neuroblastoma)
How is bone marrow transplant done?
Megadose chemotherapy +/-
total body irradiation to eradicate residual leukemic cells
>> infuse normal stem cells to reconstitute the bone marrow system
What are the indications for bone marrow/stem cell transplant in ALL?
- Early bone marrow relapse
- High risk (philadelphia chromosome, failed induction) ALL before relapse
What are some known specific side effects of asparaginase?
- Venous thrombosis
What is hyperleukocytosis?
Total WBC >100x10^9/L
- A common presenting feature of leukemia
- A MEDICAL EMREGENCY
>> Intracranial hemorrhage
>> Pulmonary leukostasis syndrome
>> Tumour lysis syndrome
>> Chest crisis
>> Myocardial infarction
What are the features of malignant lymphadenopathy?
>> Fluctuance, warmth or tenderness are more suggestive of benign nodes
Cancer is the second most common cause of death after injuries in children
after 1 year of age.