1. Solid tumors of Childhood Sariu Ali: Introduction, CNS Tumors, Neuroblastoma Mohammed Farhan: Neproblastoma, Retinoblastoma, sarcomas, others

2. Introduction More than 11 million people are diagnosed with cancer anually. <2% occur in children Second commonest cause of death in children (5-14 yo) in developing countries Adults tumors are epitheilai in orifgin

4. Astrocytoma

5. Glioma

9. Primary central nervous system (CNS) tumors are second most frequent malignancy in childhood and adolescence.

10. Mortality among this group approaches 45%.

13. Astrocytomas

14. Brain stem gliomas

15. Epandymoma

16. Optic glioma

17. PrirmitiveNeuroendocrine Tumors (PNET)/ Medulloblastoma

18. Craniopharyngioma

19. Pineal region tumors

20. Choroid plexus tumors

21. germ cell tumors

23. CNS Tumors Tumor locations The relative frequency of brain tumor histologic types and the anatomic distribution are shown.

24. CNS Tumors Age related differences

25. CNS Tumors Clinical presentations Clinical symptoms depend upon: Age, location, and type of tumor and grade Increased intracranial pressure :secondary to obstruction of CSF at aqueduct :hydrocephalus (infants), headache, papilledema, vomiting

27. >100 histological categories and subtypes

28. 5 types account for 80%

29. juvenile pilocyticastrocytoma

30. Medullobalstoma/PNET

31. Diffuse Astrocytoma

32. Epandymoma

34. occur throughout the CNS

36. the classic site of presentation is the cerebellum

37. The classic neuroradiologic findings of JPA are the presence of an enhancing nodule within the wall of a cystic mass

39. CNS Tumors WHO grading commonly used for astrocytoma The WHO-grading scheme is based on the appearance of certain characteristics: atypia,mitosis, endothelial proliferation and necrosis.

41. PE (careful neurological examination, visual fields and a fundoscopic examination)

42. MRI

43. Serum and CSF ß-HCG, a-FP for germ cell tumors

44. LP: medulloblastoma/PNET, ependymoma, germ cell tumors that spread to the leptomeningesLP contraindicated if newly dx’d hydrocephalus d/t CSF outflow obstruction or infratentorialtumors

45. CNS Tumors Management Treatment – Multimodal

47. Approximately 600 new cases in the U.S. annually

48. Slightly more common in males than females.

49. Median age at diagnosis is approximately 22 months, 89% of new patient diagnoses occurring under the age of 5 years.

52. Cervical/thoracic disease more common in infants <1 yo, adrenal disease more common in >1 yo.

53. In patients less than 1 yo, local tumor only (39%), regional lymphatic spread (18%), metastases (25%), IV-S (18%).

55. Neuroblastoma Clinical Features

56. 9 months female Failure to thrive Periorbitalecchymosis “Raccoon Eyes” Dysconjugate gaze Dilated fixed pupils T1 MRI extensive mets to base of skull Sphenoid/temporal/zygomatic bones Raccoon eyes caused by obstruction palpebral vessels by mets around eyes Delayed diagnosis: Child abuse/Trauma

58. Bone (55.7%)

59. Lymph node (30.9%)

60. Liver (29.6%)

61. Intracranial/orbital (18.2%)

62. Lung (3.3%)

64. Neuroblastoma International Neuroblastoma Staging System(INSS)

65. Neuroblastoma

66. Neuroblastoma Diagnostic Evaluation

67. CATECHOLAMINE METABOLISM TYROSINE Tyrosine Hydroxylase DOPA HOMOVANILLIC ACID (HVA) DOPA Decarboxylase DOPAMINE Monamine oxidase Catechol-O-methyltransferase Dopamine -Hydroxylase NOREPINEPHRINE Phenylethanolamine N-Methyltransferase NB Lack this enzyme VANILLYLMANDELIC ACID (VMA) EPINEPHRINE Catechol- O-Methyltransferase METANEPHRINE

70. Located on distal short arm of chromosome 2.

71. MYCN is a protooncogene normally expressed in developing nervous system and other tissues. MYCN dimerizes with Max, and releases the transcriptional repression mediated by Max homodimers.

72. Amplification usually results in 5-400 copies of the gene, with corresponding increases in protein expression. Co-amplified genes.

74. Neuroblastoma Principle of initial Management Surgery, chemotherapy, and radiotherapy. Depending on the anticipated clinical behavior of the tumor in individual cases considering stage, age, and tumor pathobiology. Surgery Goal: If performed prior to therapy: Establish the diagnosis. Provide tissue for biologic studies. (MYCN, Genomics) Stage the tumor surgically. Attempt to excise the tumor without injury to vital structures. In delayed primary or second-look surgery, the surgeon will determine response to therapy and remove residual disease when possible. Radiation Treatment Neuroblastoma is a radiosensitive tumor. May play role as adjunct to primary therapy with surgery and/or chemotherapy, for palliation of symptomatic lesions, relief of cord compression, or as preparative regimen for BMT.

75. Neuroblastoma Management Low-risk : surgery Intermediate-risk : surgery + chemotherapy ± radiotherapy High-risk: chemotherapy +surgery + radiotherapy

76. References Nelson Text book of Peadiatrics 17th edition Hand book of Hospital peadiatrics 2nd edition Illustrated text book of paediatrics 3rd edition National Cancer unit (US) paediatric oncology unit report CNS malignancies Emed

77. Thank You