1. Belgorod State National Research University Department: Pathological Anatomy. Topic: Childhood Tumors. Compiled by: N. K. Gaur

2. Small,Round, Blue Cell Tumors in Childhood.  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.

4. 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)

7. 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, calcification, cystic change

8. 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.

9. Microscopy of Neuroblastoma.

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

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

12. 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

13. 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

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

16. Morphology of retinoblastoma.

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