Neoplasms of infancy and childhood

Neoplasms of infancy and childhood Benign>malignant Incidence of malignancy:1-15 yrs - 1.3 /10,000 /year but leading cause of death after accidents in the West. (developing countries??) Most malignant tumours in children arise from hematopoietic,nervous and soft tissues (adults –epithelial)

Difference between adult & Paed tumours Association between abnormal development (teratogenesis) & tumour induction. Prevalence of constitutional genetic abnormalities or syndromes that predispose to cancer Tendency of malignancy to undergo differentiation Improved survival

Benign tumours Hemangiomas “port wine stain” Lymphangiomas (cystic hygroma) Sacrococcygeal teratoma Naevi

Sacrococcygeal teratomas Germ cell neoplasm 1:40,000 live births Mass in the sacrum and buttocks Composed of elements of > 1 germ cell layer.mixture of elements. Neural origin determines the behaviour < 2 months-benign.

Small,round, blue cell tumours Primitive appearance (not anaplastic or pleomorphic) Sheets of small,round,blue cells (with dark nuclei,scant cytoplasm,indistinct borders.) May show features of organogenesis specific to the tissue of origin.

Neuroblastoma Embryonal malignant tumour Neural crest origin Neoplastic neuroblasts Site: adrenal medulla &sympathetic ganglia 7-10% of solid paediatric malignancies. Sporadic occurance. Rarely familial (bilateral,multifocal)

Pathology of neuroblastoma Site :Paravertebral, Posterior mediastinum, abdomen ,Adrenal 1/3 Gross appearance: Nodular, of varying size May be encapsulated or infiltrative Cut section: grey-tan, soft and friable Varigated,necrosis,hemorrhage, calcificaton,cystic change

Gross appearence of Neuroblastoma.

Microscopy of neuroblastoma Sheets of small,round,blue cells with dark nuclei,scant cytoplasm,indistinct borders. Mitosis++, Karyorrhectic debris + Pleomorphism +/- Homer-Wright rosettes, Neuropil. Maturation: Schwann cell, stroma &ganglion cell differentiation

Microscopy of neuroblastoma

Clinical features Abdominal mass, fever Blueberry muffin Wide metastasis Secrete catecholamines Vanillylmandelic acid (VMA)/Homovanillic acid (HVA) screening.

Prognosis Stage spread to regional lymph nodes,liver,lungs,bones etc Age :< 1 yr. Morphology –gangliocytic differentiation better MYCN (N myc) gene amplification-worse

Retinoblastoma Malignant tumour of the eye in childhood Neuroepithelial origin –posterior retina Familial,- 60-70%, associated with germ line mutation, heritable. Sporadic:30-40%,somatic gene mutation. Associated with Rb 1 gene Secondary malignancy –osteosarcoma

RB gene RB gene is on chromosome 13 RB gene function is the most critical checkpoint in the cell cycle and allows the cell to enter from G1 to S Tumour supressor gene If both RB genes are abnormal i.e. mutated or have a missing allele, it permits unregulated cell proliferation. Knudson’s two-hit hypothesis People with RB mutations are susceptibe to malignancies especially osteosarcoma

Morphology of retinoblastoma

Morphology of retinoblastoma Gross: occular masses. Microscopy: Sheets of small,round,blue cells with dark nuclei,scant cytoplasm,indistinct borders Flexner-Wintersteiner rosettes.

Behaviour Spread through optic nerve or to subarachnoid space to CNS, bone, lymph nodes. Cure with treatment Spontaneous cure Second malignancy

Wilms’ tumour (Nephroblastoma) Malignant neoplasm of embryonal nephrogenic elements Composed of embryonal elements Prevalence :1:10,000 2-5 yrs Good prognosis Associated with congenital malformations Tumour resembles developing kidney

Associated syndromes WAGR –Wilms tumour, Aniridia, Genitourinary anomalies,mental Retardation WT 1 gene Denys-Drash syndrome: Wilms tumour,intersexual disorders,glomerulopathy. WT1 gene Beckwith –Wiedemann syndrome(BWS) :Wilms tumour, overgrowth, visceromegaly,macroglossia. WT2

Cut surface :bulging,pale tan

Histopathology of Wilms tumour Components of Wilms tumour (triphasic) Blastema Immature epithelial- abortive tubules ,glomeruli Immature stroma (mesenchymal)

Clinical features 1-3 yrs Unilateral (sporadic),bilateral (familial) Large abdominal mass Hematuria Pain abdomen Hypertension Intestinal obstruction Pulmonary metastasis

In conclusion Childhood tumors are different from adult Small blue round cell tumors Associated with genetic abnormalities.