Pediatric tumors

1. Pediatric tumors Dr Ramadas Nayak Professor & HOD Pathology Yenepoya Medical College Mangalore

2. Tumors and Tumor-like Lesionsof Infancy and Childhood • Only 2% of all malignant tumors occur in infancy and childhood. • Benign tumors are even more common than cancers.

3. Benign Tumors and Tumor-Like Lesions • Any tumor may occur in children • Hemangiomas • Lymphangiomas • Teratomas.

4. Malignant Tumors • Cancers of infancy and childhood differ biologically and histologically from their counterparts occurring later in life.

6. Small,round, blue cell tumours • Primitive appearance (not anaplastic or pleomorphic) • Sheets of small,round,blue cells (with dark nuclei,scantcytoplasm,indistinct borders.) • Frequent in pediatric tumors

7. Small Round Blue Cell Tumors • Differential diagnosis • Lymphoma • Neuroblastoma • Wilms tumor • Rhabdomyosarcoma • Ewings tumor • Diagnostic procedures • immunoperoxidase stains • electron microscopy • chromosomal analysis and molecular markers

8. Neuroblastoma

9. Neuroblastoma • Most important neuroblastic tumor • Most common extracranial childhood solid tumor. • Infants

10. Neuroblastoma • Sporadic and familial types: • Mostly occur sporadically, but 1% to 2% is familial.

11. Neuroblastoma Morphology Gross • Site: About 40% of neuroblastomas occur in the adrenal medulla.

12. Neuroblastoma -Morphology Gross • Size: Vary from minute nodules (as in situ lesions) to large tumors weighing 1 kg. • Majority are silent and regress spontaneously. • Sharply demarcated by a fibrous pseudo-capsule or infiltrate the surrounding structures (kidneys, renal vein, and vena cava, and aorta). • Cut section: Soft, and gray-tan. Large tumors may show areas of necrosis, cystic change and hemorrhage

13. Gross appearence of Neuroblastoma.

14. Neuroblastoma-Microscopy • Tumor cells: arranged in solid sheets. • The tumor cells appear as: • Small, primitive containing dark nuclei • Scant cytoplasm with poorly defined cell borders.

15. Neuroblastoma-Microscopy • Background: Shows a faintly eosinophilic fibrillary material (neuropil) • Homer-Wright pseudorosettes: consist of tumor cells concentrically arranged about a central space filled with neuropil may be seen.

16. Neuroblastoma

19. Neuroblastoma • Immunohistochemistry: Neuron-specific enolase positive • Electron microscopy: shows small, membrane-bound, catecholamine-containing secretory granules in the cytoplasm.

20. Neuroblastoma • Spread of Tumor • Local infiltration • Lymph node spread • Blood spread: Liver, lungs, bone marrow, and bones

21. Neuroblastoma-Clinical Course • Children below 2 years of age: Usually present as large abdominal masses, fever, and weight loss. • Older children: Symptoms develop due to metastases such as bone pain, respiratory symptoms, or gastrointestinal complaints.

22. Neuroblastoma-Laboratory Finding • Majority (~90%) of neuroblastomas, secrete catecholamines (similar to pheochromocytomas) → raised blood levels of catecholamines (hypertension is less frequent). • Raised urine levels of the metabolites vanillylmandelic acid [VMA] and homovanillic acid [HVA]. • Course: It is extremely variable

23. Neuroblastoma-Prognostic Factors • 1. Age and stage: Children younger than 18 months of age have excellent prognosis regardless of the stage. • 2. Morphology: Accordingly, tumors are divided into favorable and unfavorable histologic subtypes. • 3. Amplification of the N-MYC oncogene → high-risk category, irrespective of age, stage, or histology. • 4. Ploidy of the tumor cells: It is of prognostic value in children younger than 2 years and loses its prognostic significance in older children.

24. Retinoblastoma

25. Retinoblastoma • Malignant tumourof the eye in childhood • Neuroepithelial origin –posterior retina

26. Retinoblastoma • Familial: 60-70%, associated with germ line mutation, heritable. • Sporadic:30-40%,somatic gene mutation. • Associated with Rb1 gene • Secondary malignancy –osteosarcoma

27. RB gene • RB gene is on chromosome 13 • RB gene function is the most critical checkpoint in the cell cycle

28. RB gene • Tumour suppressor 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 susceptible to malignancies especially osteosarcoma

30. Morphology of retinoblastomaGross • Ocular masses.

31. Morphology of retinoblastomaMicroscopy • Sheets of small, round,bluecells with dark nuclei, scant cytoplasm,indistinct borders • Flexner-Wintersteiner rosettes.

32. Morphology of retinoblastoma

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

34. Wilms Tumor (Nephroblastoma)

35. Wilms Tumor (Nephroblastoma) • Most common primary renal tumor of childhood. • Highly malignant primary embroynal tumor. • Age group: Most common between 2 and 5 years of age, and more than 95% occur below 10 years of age.

36. Wilms Tumor (Nephroblastoma) Pathogenesis and Genetics • In most (90%) cases, the Wilms tumor is sporadic and unilateral. • About 5% to 10% are bilateral

37. Wilms Tumor (Nephroblastoma) Pathogenesis and Genetics • Mutation in tumor suppressor genes. • These include Wilms tumor associated genes 1 (WT1) and WT2. • WT1 gene is located in the chromosome 11p13.

38. Wilms Tumor (Nephroblastoma) • In about 5% of cases, it arises in three congenital syndromes at an early age and often bilaterally. • 1. WAGR (for Wilms tumor, aniridia, genital anomalies, and mental retardation) syndrome. • 2. Denys-Drash syndrome (Wilms tumor, intersexual disorders, glomerulopathy) is associated with mutations of the WT1 gene. • 3. Beckwith-Wiedemann syndrome (BWS) is associated with Wilms tumor and WT2 gene imprinting abnormalities.

39. Wilms Tumor (Nephroblastoma) Morphology • Gross • Usually large, single, round, well-circumscribed mass. • Usually unilateral but 10% is either bilateral or multicentric. • Cut section: • Tumor is soft, bulging, homogeneous, and tan to gray. • Foci of hemorrhage, cyst formation, and necrosis may be seen

40. Wilms Tumor (Nephroblastoma) Microscopy • Tumor shows three major components, which resemble normal fetal tissue. • These cells attempt to recapitulate different stages of nephrogenesis.

41. Wilms Tumor (Nephroblastoma) Microscopy • The three types of cells are: • 1. Blastemal component • 2. Immature stromal (mesenchymal) component • 3. Immature epithelial component:

42. Wilms Tumor (Nephroblastoma) Microscopy • 1. Blastemal component: consists of small, round to oval blue cells with scanty cytoplasm. • Cells are arranged in sheets, nests and trabeculae.

44. Wilms Tumor (Nephroblastoma) Microscopy • 2. Immature stromal (mesenchymal) component: • It consists of undifferentiated fibroblast-like spindle cells. • They may show smooth muscle, skeletal muscle or fibroblast differentiation.

45. Wilms Tumor (Nephroblastoma) Microscopy • 3. Immature epithelial component: • Epithelial cells show differentiation in the form of • small abortive (embryonic) tubules or • immature glomeruli.

47. Wilms Tumor (Nephroblastoma) Microscopy • Classically, the tumor shows triphasic (all three cell types) combination, although the percentage of each component varies. • Occasionally they contain only two elements (biphasic) or even only one (monophasic).

48. Wilms Tumor (Nephroblastoma) • Anaplasia: • presence of cells with large, hyperchromatic, pleomorphic nuclei and atypical mitotic figures. • Do not respond to chemotherapy.

49. Wilms Tumor (Nephroblastoma)Clinical Features • Abdominal mass. • Hematuria • Pain in the abdomen • Intestinal obstruction, and • Pulmonary metastases

50. Wilms Tumor (Nephroblastoma) • Spread • Local spread: It spreads to perirenal soft tissues. • Lymphatics: It spreads to regional lymph nodes. • Hematogenous: Lungs, liver and peritoneum.