Neoplasms of infancy and childhood Neoplasms of infancy

Neoplasms of infancy and childhood

Neoplasms of infancy and childhood n n n 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 n n 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 n n Hemangiomas “port wine stain” Lymphangiomas (cystic hygroma) Sacrococcygeal teratoma Naevi

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

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

Retinoblastoma n n n 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 n n n 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 G 1 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 n n n Gross: occular masses. Microscopy: Sheets of small, round, blue cells with dark nuclei, scant cytoplasm, indistinct borders Flexner-Wintersteiner rosettes.

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

Wilms’ tumour (Nephroblastoma) n n n n 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 n n n WAGR –Wilms tumour, Aniridia, Genitourinary anomalies, mental Retardation WT 1 gene Denys-Drash syndrome: Wilms tumour, intersexual disorders, glomerulopathy. WT 1 gene Beckwith –Wiedemann syndrome(BWS) : Wilms tumour, overgrowth, visceromegaly, macroglossia. WT 2

Cut surface : bulging, pale tan

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

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

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