TUMOURS OF INFANCY & CHILDHOOD

1. TUMOURS OF INFANCY & CHILDHOOD

2. Small Round Blue Cell Tumours • Diverse group of tumors that are primitive in appearance • often lack any particular morphologic features that would allow precise identification. • Designation usually reserved for neoplasms of childhood, adolescents & young adults • approx 20% of solid tumors in children

3. H&E stain 100x

4. Small round blue cell tumors • Retinoblastoma • Neuroblastoma • Hepatoblastoma (embryonal) • Nephroblastoma (blastema) • Ewing sarcoma • Lymphoma • Rhabdomyosarcoma • Medulloblastoma

5. Retinoblastoma

6. What is Retinoblastoma? • “Retinoblastoma is a disease that causes the growth of malignant tumors in the retinal cell layer of the eye.” • It is the most common eye tumor in children. • Untreated, retinoblastoma is almost always fatal.

7. The Prevalence of Retinoblastoma • Retinoblastoma is a childhood disease. • There is no known sex or racial predilection. • “Retinoblastoma can be either a hereditary or non-hereditary disease

8. A white reflex (spot) on the pupil of the eye. UNILATERAL Bilateral Trilateral with pinealoblastoma Retinoblastoma

9. What Causes Retinoblastoma? • Retinoblastoma is caused by a mutation on the 13th chromosome – RB gene

10. retinoblastoma • Nodular masses, satellite seedings • Undifferentiated areas • Differentiated structures FLEXNER-WINTERSTEINER rosettes Homer-wright rosettes

11. H&E stain 400x

12. NEUROBLASTOMA

13. Neuroblastoma • A common tumor of neural crest origin • 10% of childhood tumours • By far the commonest congenital tumour(>60%) • Average diagnosed age: 2 y (90%, 5 y) (< 1 y: 40% ) Spontaneous / therapy-induced regression or differentiation into ganglioneuroblastoma/ benign ganglioneuroma

14. GROSS • Solid, circumscribed or multinodular mass • Deep red, hemorrhagic with glistening gray-white tissue • Cut section shows yellow areas of coagulative necrosis are often present, possible cyst formation • GNB and GN have white tan tissue, hemosiderin deposition and calcification

15. Neuroblasts • Neuroblasts may be in a spectrum of completely undifferentiated to complete differentiation into ganglion cells

16. MICROSCOPY • Variable mixtures of small primitive neuroblasts with round to oval hyperchromatic or densely speckled nuclei and little cytoplasm - BLUE • Tumor cells are separated by pink fibrillar matrix (‘neuropil’) composed of cell processes • Fibrovascular septa often divided into lobules • IHC: Neuron Specific Enolase (NSE)

17. Diagnosis • Lab: • VMA (vanilyllmandelic acid): Urine Image: • CT scan: determine tumor extent • Tc 99bone scan: evaluate bone metastases • Bone marrow

18. HEPATOBLASTOMA

19. Hepatoblastoma • Epithelial – fetal - embryonalROUND CELL! mesenchymal

20. NEPHROBLASTOMA(Wilms’ tumour)

21. Introduction • Wilms’ tumor, or nephroblastoma, is the most common primary malignant renal tumor of childhood, • 6% of all pediatric malignant disease. • This embryonal tumor develops from remnants of immature kidney.

22. Wilms tumor was named after German surgeon Max Wilms, who published the first review of the disease in 1899. • The National Wilms Tumor Study Group (NWTSG) established in1969.

23. Etiology • The etiology essentially remains unknown. • The tumor may arise in 3 clinical settings, • The settings for WT are: Sporadic Familial Association with genetic syndromes

24. Familial WT occurs in 1-2% of all cases. Analysis of families with WT has shown that the predisposition is caused by an autosomal dominant trait with incomplete penetrance.

25. Genetic syndromes that predispose to WT • Beckwith-Wiedemann syndrome (WT, macroglossia, gigantism, umbilical hernia, Hemihypertrophy, Congenital aniridia) • WAGR syndrome (WT, aniridia, genitourinary malformations, mental retardation) • Denys-Drash syndrome (WT,pseudohermaphroditism, glomerulopathy) • Trisomy 18 mutation

26. Molecular Genetics • Based on the model developed originally for retinoblastoma, Knudsen and Strong proposed that WT results from 2 mutational events based on loss of function of tumor suppressor genes.(WT1 & WT2 genes)

27. Diagnosis • A palpable, smooth abdominal mass is present on physical examination in more than 90% of children. • Other presenting signs and symptoms are gross hematuria, fever, and/or abdominal pain. • hypertension in about 25% of patients • Congenital anomalies

28. MICROSCOPY • The classic histologic pattern is composed of epithelial, blastemal, and stromal elements (triphasic). • Approximately 90% of all renal tumors have this so-called favorable histology (FH). • 3-7% of tumors are characterized by anaplastic changes and is also referred to as unfavorable histology (UH). • If diffusely anaplastic throughout the tumor, predicts for poor outcome.

29. LEUKEMIA

30. LEUKEMIA • ALL (acute lymphoblastic leukemia) - lymphoblasts - 85% B cell origin

31. LYMPHOMA

32. Burkitt’s lymphoma • 1. African – endemic - EBV - jaw 2. Sporadic • HIV • Very aggressive • Small noncleaved cells

33. RHABDOMYOSARCOMA

34. Rhabdomyosarcoma • Head & neck, genito-urinary • Embryonal • Alveolar • pleomorphic

35. EWING’S SARCOMA

36. Ewing’s sarcoma • 10-15 yrs • Femur, pelvis • Xray- periosteal reaction “onion-skin” layering

37. MEDULLOBLASTOMA

38. Demography • Cerebellar tumor - cerebellar vermis • 10-20% of primary CNS neoplasms in children • Peak age of incidence is 5 years • Most tumors occur in first 10 years of life • 2:1 male to female ratio

39. Tumor Characteristics • Embryonal neuroepithelial tumor • Highly cellular, soft friable tumors • Little cytoplasm - BLUE • Degrees of glial or neuroblastic differentiation - primitive cell of origin with bipotential capacity • Desmoplastic - tumors with a large stromal component