Cancer in Children II Flashcards
Neuroblastoma:
how does it often present at diagnosis? [1]
Metastatic disease in >50% cases at diagnosis; spreads via lymphatics and blood stream
Neuroblastoma is a tumour of which body system? [1]
Which organs does it usually occur in? [2]
Tumour of the sympathetic nervous system, usually arising in the adrenal gland or sympathetic ganglia
Which oncogenes are involved with neuroblastoma? [3]
MYCN amplification, ALK & PHOX2B
What is the difference betwen molecular pathology of neuroblastoma between high risk, low risk and hereditary patients? [3]
High risk patients
* Have high MYCN amplification; ATRX & ALK mutations
* Near-diploid/near-tetraploid karyotype, complex chromosome aberrations
* Deletions in 1p and 11q
Low risk:
* Numerical chromosome gains (e.g. spontaneous chromosomes)
Hereditary
* Germline ALK mutations
How do patients with Acute Lymphoblastic Leukaemia (ALL) present [3]
Where does infiltration of ALL usually occur? [4]
- bruising or bleeding due to thrombocytopaenia
- pallor and fatigue due to anaemia
- infection due to neutropenia
- Infiltratration to the liver, spleen, lymph nodes and mediastinum common at diagnosis
Tx for neuroblastoma? [3]
How would Tx be elevated for high risk patients? [2]
Which gene and drug can you use / target for targeted therapy? [2]
Surgery, chemotherapy, radiation therapy
High risk disease: high-dose chemotherapy and stem cell transplantation
Targeted therapy– crizotinib against ALK mutations
Immunotherapy
In children, what are the three major types of ALL? [3]
In children ~80% are CD19+, CD10+ “B-cell precursor ALL”
ALL paedatric leaukames can be traced back to what process? [1]
haematopoiesis - in children particularly linked to lymphoid lineage
Which comes first Pro-B or Pre-B? [1]
What are Pro-B and Pre-B cells characterised by on their cell surfaces? [3]
Pro-B then Pre-B
ProB cells are characterized by cell surface marker CD19+
PreB cells are characterized by cell surface markers CD19+ and CD10+
What are the distinctive cell abnormalites that often occur in Pro-B cells and Pre-B cells? [2]
There are distinctive cell abnormalities:
Pro-B (CD19+, CD10-) always have translocation of MLL gene translocated
Pre-B always have translocation of chromosomes 12 & 22
How do Pro-B ALL cells appear histologically? [1]
Lots of pre-cursor cells
What is the molecular pathway of ALL?
Incidence of subtypes varies with age
Explain the two step model that causes ALL
Step 1: developmental error in utero
Step 2: Dysregulated immune response to infection (This occurs in patients who
carry a covert pre- leukaemic clone and have a deficit of infectious exposures in infancy; children who are born by C-section may not be exposed to microbes during the birth canal)
What is the prognosis for patients with:
Pro-B ALL? [1]
Pre-B ALL [1]
Pro-B ALL / MLL translocation: unfavourable for children
Pre-B ALL: ETV6-RUNX1 translocation: more favourable
What are the treament phases for ALL? [4]
Induction
Consolidation; CNS-directed treatment
Maintenance
Bone marrow transplantation
