Neoplasms of infancy Neoplasms of infancy and childhoodand childhood

Neoplasms of infancy and Neoplasms of infancy and childhoodchildhood

Benign>malignant Benign>malignant Incidence of malignancy:1-15 yrs - Incidence of malignancy:1-15 yrs -

1.3 /10,000 /year but leading 1.3 /10,000 /year but leading cause of death after accidents in cause of death after accidents in the West. (developing countries??)the West. (developing countries??)

Most malignant tumours in Most malignant tumours in children arise from children arise from hematopoietic,nervous and soft hematopoietic,nervous and soft tissues (adults –epithelial) tissues (adults –epithelial)

Difference between adult & Paed Difference between adult & Paed tumourstumours

Association between abnormal Association between abnormal development (teratogenesis) & development (teratogenesis) & tumour induction.tumour induction.

Prevalence of constitutional genetic Prevalence of constitutional genetic abnormalities or syndromes that abnormalities or syndromes that predispose to cancerpredispose to cancer

Tendency of malignancy to undergo Tendency of malignancy to undergo differentiationdifferentiation

Improved survival Improved survival

Benign tumoursBenign tumours

Hemangiomas “port wine stain”Hemangiomas “port wine stain” Lymphangiomas (cystic hygroma)Lymphangiomas (cystic hygroma) Sacrococcygeal teratomaSacrococcygeal teratoma NaeviNaevi

Sacrococcygeal teratomasSacrococcygeal teratomas

Germ cell neoplasmGerm cell neoplasm 1:40,000 live births1:40,000 live births Mass in the sacrum and buttocksMass in the sacrum and buttocks Composed of elements of > 1 germ Composed of elements of > 1 germ

cell layer.mixture of elements.cell layer.mixture of elements. Neural origin determines the Neural origin determines the

behaviourbehaviour < 2 months-benign.< 2 months-benign.

Small,round, blue cell tumoursSmall,round, blue cell tumours

Primitive appearance (not anaplastic Primitive appearance (not anaplastic or pleomorphic)or pleomorphic)

Sheets of small,round,blue cells (with Sheets of small,round,blue cells (with dark nuclei,scant dark nuclei,scant cytoplasm,indistinct borders.)cytoplasm,indistinct borders.)

May show features of organogenesis May show features of organogenesis specific to the tissue of origin.specific to the tissue of origin.

NeuroblastomaNeuroblastoma

Embryonal malignant tumour Embryonal malignant tumour Neural crest origin Neural crest origin Neoplastic neuroblastsNeoplastic neuroblasts Site: adrenal medulla &sympathetic Site: adrenal medulla &sympathetic

gangliaganglia 7-10% of solid paediatric 7-10% of solid paediatric

malignancies.malignancies. Sporadic occurance.Sporadic occurance. Rarely familial (bilateral,multifocal)Rarely familial (bilateral,multifocal)

Pathology of neuroblastomaPathology of neuroblastoma

Site :Paravertebral, Posterior Site :Paravertebral, Posterior mediastinum, abdomen ,Adrenal 1/3mediastinum, abdomen ,Adrenal 1/3

Gross appearance:Gross appearance:

Nodular, of varying sizeNodular, of varying size

May be encapsulated or infiltrativeMay be encapsulated or infiltrative

Cut section: grey-tan, soft and friable Cut section: grey-tan, soft and friable

Varigated,necrosis,hemorrhage, Varigated,necrosis,hemorrhage, calcificaton,cystic changecalcificaton,cystic change

Gross appearence of Gross appearence of Neuroblastoma.Neuroblastoma.

Microscopy of neuroblastomaMicroscopy of neuroblastoma

Sheets of small,round,blue cells with Sheets of small,round,blue cells with dark nuclei,scant dark nuclei,scant cytoplasm,indistinct borders.cytoplasm,indistinct borders.

Mitosis++, Karyorrhectic debris +Mitosis++, Karyorrhectic debris +

Pleomorphism +/-Pleomorphism +/-

Homer-Wright rosettesHomer-Wright rosettes, Neuropil., Neuropil.

Maturation: Schwann cell, stroma Maturation: Schwann cell, stroma &ganglion cell differentiation&ganglion cell differentiation

Microscopy of neuroblastomaMicroscopy of neuroblastoma

Clinical featuresClinical features

Abdominal mass, feverAbdominal mass, fever Blueberry muffinBlueberry muffin Wide metastasisWide metastasis Secrete catecholaminesSecrete catecholamines Vanillylmandelic acid Vanillylmandelic acid

(VMA)/Homovanillic acid (HVA) (VMA)/Homovanillic acid (HVA) screening.screening.

PrognosisPrognosis

Stage Stage spread to regional lymph spread to regional lymph

nodes,liver,lungs,bones etcnodes,liver,lungs,bones etc Age :< 1 yr.Age :< 1 yr. Morphology –gangliocytic Morphology –gangliocytic

differentiation better differentiation better MYCN (N myc) gene amplification-MYCN (N myc) gene amplification-

worseworse

RetinoblastomaRetinoblastoma

Malignant tumour of the eye in childhoodMalignant tumour of the eye in childhood Neuroepithelial origin –posterior retinaNeuroepithelial origin –posterior retina Familial,- 60-70%, associated with germ Familial,- 60-70%, associated with germ

line mutation, heritable.line mutation, heritable. Sporadic:30-40%,somatic gene mutation.Sporadic:30-40%,somatic gene mutation. Associated with Rb 1 gene Associated with Rb 1 gene Secondary malignancy –osteosarcoma Secondary malignancy –osteosarcoma

RB geneRB gene RB gene is on chromosome 13RB gene is on chromosome 13 RB gene function is the most critical RB gene function is the most critical

checkpoint in the cell cycle and allows checkpoint in the cell cycle and allows the cell to enter from the cell to enter from

G1 to SG1 to S Tumour supressor geneTumour supressor gene If both RB genes are abnormal i.e. If both RB genes are abnormal i.e.

mutated or have a missing allele, it mutated or have a missing allele, it permits unregulated cell proliferation. permits unregulated cell proliferation.

Knudson’s two-hit hypothesisKnudson’s two-hit hypothesis People with RB mutations are People with RB mutations are

susceptibe to malignancies especially susceptibe to malignancies especially osteosarcoma osteosarcoma

Morphology of retinoblastomaMorphology of retinoblastoma

Morphology of retinoblastomaMorphology of retinoblastoma

Gross: occular masses.Gross: occular masses. Microscopy: Sheets of Microscopy: Sheets of

small,round,blue cells with dark small,round,blue cells with dark nuclei,scant cytoplasm,indistinct nuclei,scant cytoplasm,indistinct bordersborders

Flexner-Wintersteiner rosettes.Flexner-Wintersteiner rosettes.

Behaviour Behaviour

Spread through optic nerve or to Spread through optic nerve or to subarachnoid space to CNS, bone, subarachnoid space to CNS, bone, lymph nodes.lymph nodes.

Cure with treatmentCure with treatment Spontaneous cureSpontaneous cure Second malignancy Second malignancy

Wilms’ tumour (Nephroblastoma)Wilms’ tumour (Nephroblastoma) Malignant neoplasm of embryonal Malignant neoplasm of embryonal

nephrogenic elements nephrogenic elements Composed of embryonal elementsComposed of embryonal elements Prevalence :1:10,000 Prevalence :1:10,000 2-5 yrs2-5 yrs Good prognosisGood prognosis Associated with congenital Associated with congenital

malformationsmalformations Tumour resembles developing kidneyTumour resembles developing kidney

Associated syndromesAssociated syndromes WAGR –Wilms tumour, Aniridia, WAGR –Wilms tumour, Aniridia,

Genitourinary anomalies,mental Genitourinary anomalies,mental RetardationRetardation

WT 1 geneWT 1 gene Denys-Drash syndrome: Wilms Denys-Drash syndrome: Wilms

tumour,intersexual tumour,intersexual disorders,glomerulopathy. WT1 genedisorders,glomerulopathy. WT1 gene

Beckwith –Wiedemann Beckwith –Wiedemann syndrome(BWS) :Wilms tumour, syndrome(BWS) :Wilms tumour, overgrowth, overgrowth, visceromegaly,macroglossia. WT2visceromegaly,macroglossia. WT2

Cut surface :bulging,pale tanCut surface :bulging,pale tan

Histopathology of Wilms tumourHistopathology of Wilms tumour

Components of Components of Wilms tumour Wilms tumour (triphasic)(triphasic)

BlastemaBlastema Immature Immature

epithelial- abortive epithelial- abortive tubules ,glomerulitubules ,glomeruli

Immature stroma Immature stroma (mesenchymal)(mesenchymal)

Clinical featuresClinical features 1-3 yrs1-3 yrs Unilateral (sporadic),bilateral Unilateral (sporadic),bilateral

(familial)(familial) Large abdominal massLarge abdominal mass HematuriaHematuria Pain abdomenPain abdomen HypertensionHypertension Intestinal obstructionIntestinal obstruction Pulmonary metastasisPulmonary metastasis

In conclusionIn conclusion

Childhood tumors are different from Childhood tumors are different from adultadult

Small blue round cell tumorsSmall blue round cell tumors Associated with genetic Associated with genetic

abnormalities.abnormalities.