43. Cancer in Children Flashcards
Cancer is the leading cause of death in children under 15 (UK) - what are the most common malignancies in children?
What are some health and quality-of-life issues faces by cancer survivors?
What are 4 common malignancies origionating in developing tissues and organ systems which are usually diagnosed before 5 years?
Why are they more common in childhood i.e. why do tumours in childhood need much fewer mutations to become tumours?
0-14yrs: leukemia most common (almost 1/3), then 1/4 CNS. 15-19yrs: lymphoma, then carcinoma, myeloma and CNS.
Psychosocial, growth and development, organ function, fertility and reproduction, cancer (recurrant/subsequent).
Acute lymphoblastic leukemia, Wilms’ tumour, retinoblastoma, neuroblastoma.
Arise in cells naturally undergoing rapid developmental growth, with fewer brakes on their proliferation than adult cells. Also tumor precursor cells are negotiating crucial developmental checkpoints that’re susceptible to corruption -> incomplete/abnormal cellular maturation.
Acute lymphoblastic leykaemia (ALL):
a) clinical presentation
b) cellular origins
c) molecular pathology
d) treatment
a) most common malignancy, present with bruising/bleeding (thrombocytopaenia), pallor/fatigue (anaemia), infection (neuropenia). Infiltration to liver/spleen/LN/mediastinum common. Clonal expansion of immmature lymphocytes (lymphoblasts).
b) can be traced to all haematopoiesis.
c) specific genetic alterations are associated with phenotypic subtypes of ALL, subtype incidence varies with age, certain ones found in babies who contract ALL in a few years: MLL and TEL-AML1 translocations.
d) corticosteroids, methotrexate, bone marrow transplantation…
Wilms’ Tumour:
a) clinical presentation
b) cellular origins
c) molecular pathology
d) treatment
a) tumor of kidney (nephroblastoma), <5y, asymptomatic abdominal mass with no metastasis, spreads by growth/via lymphatics/blood, heritable, often bilateral (indicates genetic predisposition), can be associated with Wilms’ tumor, aniridia, genito-urinary abnormalities, metal retardation, BWS.
b) pluripotent embryonic renal precursors: blastema, epithelia, stroma. Closely resembles developing nephrogenic mesenchyme. Expresses markers of early kidney development.
c) inactivated WT1 (tumor supressor gene) which normally has key role in ureteric branching and epithelial induction of metanephtic pathways (with WNT). If don’t have WT1 = constant proliferation of tissue and less differentiation.
d) chemo then surgery, combo chemo, counselling if genetic predisposition suspected (if bilaterl tumours).
Retinoblastoma:
a) clinical presentation
b) cellular origins
c) molecular pathology
d) treatment
a) retinal tumour, usually <5y, 30% heritable, bilateral or multifocal, germline mutation of RB1, white pupil when light shone into it, eye pain/redness, vision problems.
b) cone precursor cells, signalling pathways promote cell survival after loss of RB1 -> constant proliferation of cone cells. Normally phosphorylation of RM1 releases E2F, inducing G1-S transition, but if no RB1, then G1-S transition goes ahead.
c) v few genetic changes, loss of RB1 key, MYCN activation and MDM2 amplification leads to inactivation of p53 pathway (apoptosis).
d) cryotherapy, laser therapy, thermotherapy, chemo, surgery +/- radiation
Neuroblastoma:
a) clinical presentation
b) cellular origins
c) molecular pathology
d) treatment
a) tumour of sympathetic NS usually arising in adrenal gland/sympathetic ganglia, metastatic in >50% cases at diagnosis, spreads via LN and blood, high and low extremes of risk.
b) from sympatho-adrenal lineage of neural crest during development, originates from incompletely comitted precursor cell. Key genes: MYCN, ALK, PHOX2B.
c) High risk = MYCN amplification, ARTX and ALK mutations, complex chromosome aberrations. Low risk = numerical chromosome gains. Hereditary = germline ALK mutations.
d) surgery, chemo, radiation, SC transplants, crizotinib against ALK mutations, immunotherapy.
What are some high-risk groups for developing cancer in childhood?
Tumor diagnosed in prenatal period suggests genetic predisposition syndrome e.g. Wilms’ tumour, familial retinoblastoma/neuroblastoma. Bilateral/multifocal associated with congenital malfomations. Cancer in close relatives. Same rare tumour in >1 family member, or different types in family members. Genetic counselling essential.
