Paediatric oncology

PAEDIATRIC PAEDIATRIC ONCOLOGYONCOLOGY

Dr. v veera ratnakar reddyDr. v veera ratnakar reddySenior resident fmmcSenior resident fmmc

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.the West.

Most malignant tumours in Most malignant tumours in children arise from children arise from hematopoietic,nervous and soft hematopoietic,nervous and soft tissues.tissues.

PEDIATRIC (VS) ADULT PEDIATRIC (VS) ADULT NEOPALSMSNEOPALSMS

Difference between adult & Difference between adult & Paed tumoursPaed tumours

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 Mass in the sacrum and

buttocksbuttocks Composed of elements of Composed of elements of

> 1 germ cell > 1 germ cell layer.mixture of layer.mixture of elements.elements.

Neural origin determines Neural origin determines the behaviourthe behaviour

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

Signs of Childhood CancerSigns of Childhood Cancer

CContinued, unexplained weight lossontinued, unexplained weight lossHHeadaches, often with early morning vomitingeadaches, often with early morning vomitingIIncreased swelling or persistent pain in bones, joints, back, or ncreased swelling or persistent pain in bones, joints, back, or legslegsLLump or mass, esp. in the abdomen, neck, chest, pelvis, or ump or mass, esp. in the abdomen, neck, chest, pelvis, or

armpitsarmpitsDDevelopment of excessive bruising, bleeding, or rashevelopment of excessive bruising, bleeding, or rash

CConstant/recurrent infectionsonstant/recurrent infectionsAA whitish color behind the pupil whitish color behind the pupilNNausea which persists or vomiting with or w/o seizureausea which persists or vomiting with or w/o seizure

CConstant tiredness or noticeable palenessonstant tiredness or noticeable palenessEEye or vision changes which occur suddenly and persistsye or vision changes which occur suddenly and persistsRRecurrent or persistent fevers of unknown originecurrent or persistent fevers of unknown origin

WHY DIFFICULT TO DIAGNOSE WHY DIFFICULT TO DIAGNOSE CHILDHOOD CANCER?CHILDHOOD CANCER?

Vague manifestationsVague manifestations

Childhood malignancies are rareChildhood malignancies are rare

Doctor’s reluctance to consider Doctor’s reluctance to consider cancer diagnosiscancer diagnosis

Pediatric Cancer SubtypesPediatric Cancer Subtypes

PREDISPOSING FACTORSPREDISPOSING FACTORS GeneticGenetic MutationsMutations Defects in DNADefects in DNA Neurocutaneous disordersNeurocutaneous disorders Immuno deficienciesImmuno deficiencies Chromosomal abnormalitiesChromosomal abnormalities Infections Infections E.B virus E.B virus HIVHIV Environmental Environmental ChemotherapyChemotherapy Ionising radiationIonising radiation Electromagnetic radiationElectromagnetic radiation

ACUTE LYMPHOBLASTIC ACUTE LYMPHOBLASTIC LEUKEMIALEUKEMIA

Classification:Classification: L1 – Predominantly small lymphoblasts L1 – Predominantly small lymphoblasts

with little cytoplasm.with little cytoplasm. L2 – Larger and pleomorphic with more L2 – Larger and pleomorphic with more

cytoplasm irregular nuclear shape cytoplasm irregular nuclear shape with prominent nucleus with prominent nucleus L3 – Have finely stippled and homogenous L3 – Have finely stippled and homogenous

nuclear chromatin, prominent nucleoli nuclear chromatin, prominent nucleoli deep blue cytoplasm with prominent deep blue cytoplasm with prominent vacuolation.vacuolation.

ALL-L1 TYPEALL-L1 TYPE



Clinical Features:Clinical Features:

Initially nonspecific – Anorexia, Initially nonspecific – Anorexia, Irritability and lethargy.Irritability and lethargy.

Pallor, bleeding, petechiae and Pallor, bleeding, petechiae and fever lymphadenopathy, fever lymphadenopathy, splenomegaly, hepatomegaly, bone splenomegaly, hepatomegaly, bone pain and arthralgia pain and arthralgia

Rarely headache and vomitingRarely headache and vomiting

DiagnosisDiagnosis

Anemia, thrombocytopenia, Anemia, thrombocytopenia, WBC WBC count count

Presence of blast cells on peripheral Presence of blast cells on peripheral smear smear

Bone marrow – Leukemic Bone marrow – Leukemic lymphoblastslymphoblasts

Differential diagnosisDifferential diagnosis

Aplastic anemiaAplastic anemia MyelofibrosisMyelofibrosis Infections mononucleosis Infections mononucleosis

TreatmentTreatment

Remission inductionRemission inductionContinuationContinuation

VincristineVincristine 6 6

mercaptopurine mercaptopurine PrednisonePrednisone MethotrexateMethotrexate Asparginase Asparginase ReinforcementReinforcement Vicristine and Vicristine and

prednisoneprednisone Prognosis overall cure rate 80% Prognosis overall cure rate 80% Chromosomal transactions t(22:9), t (4:10) – poor Chromosomal transactions t(22:9), t (4:10) – poor

prognosisprognosis

Acute myeloid leukemiaAcute myeloid leukemia

Clinical features:Clinical features: Anemia, Thrombocytopenia and Anemia, Thrombocytopenia and

neutropenianeutropenia Pallor, fatigue, petichae, epistaxisPallor, fatigue, petichae, epistaxis Chloromas may occurChloromas may occur Investigation:Investigation:

25% myeloblasts in bone harrow 25% myeloblasts in bone harrow F.A.B. Classifications into 7 typesF.A.B. Classifications into 7 types

Classification:Classification:

Myeloblastic, no maturation Mo & M1Myeloblastic, no maturation Mo & M1 Myeloblastic, some maturation M2Myeloblastic, some maturation M2 Hypergranular promyelocytic M3Hypergranular promyelocytic M3 Myelomonocytic M4Myelomonocytic M4 Monocytic M5Monocytic M5 Erythroleukemia M6Erythroleukemia M6 Megakaryocytic M7Megakaryocytic M7

Treatment:Treatment:

Anthracycline and Anthracycline and

cystosine arabinosidecystosine arabinoside Antibiotics & antifungalsAntibiotics & antifungals

Hodgkins diseaseHodgkins disease

PathologyPathology Reed Sternberg Reed Sternberg

cell is the Hallmark cell is the Hallmark featurefeature

4 Histologic subtypes:4 Histologic subtypes:

Lymphocyte predominantLymphocyte predominant

Nodular sclerosing Nodular sclerosing

Mixed cellularMixed cellular

Lymphocyte depletedLymphocyte depleted

Clinical featuresClinical features

Painless, firm, cervical or Painless, firm, cervical or supraclavicular adenopathy is the supraclavicular adenopathy is the most common presenting sign. most common presenting sign. Rarely hepatosplenomegalyRarely hepatosplenomegaly

Less commonLess common: : Pruritus, lethargy and Pruritus, lethargy and anorexia anorexia

ANN ARBOR STAGINGANN ARBOR STAGING

Stage 1Stage 1 ::Single lymphnode or a single Single lymphnode or a single extralymphatic site or organ.extralymphatic site or organ.

Stage 2Stage 2 : : 2 or more lymphoid regions on the 2 or more lymphoid regions on the same side of diaphragm or localized involvement same side of diaphragm or localized involvement of a ELS.of a ELS.

Stage 3Stage 3 : : Lymphnode on both sides of Lymphnode on both sides of diaphragm, may be ccompanied by involvement diaphragm, may be ccompanied by involvement of spleen or ELS.of spleen or ELS.

Stage 4Stage 4 ::Diffuse or disseminated involvementDiffuse or disseminated involvement Also stage A & B- Presence of fever, night Also stage A & B- Presence of fever, night

sweats & weight loss sweats & weight loss

DiagnosisDiagnosis

CBC CBC Chest & ABD. CTChest & ABD. CT ESR, S.ferritin ESR, S.ferritin Gallium scan Gallium scan LFTLFT Bone marrow biopsy Bone marrow biopsy Chest X-rayChest X-ray

TreatmentTreatment

MOPP or ABVDMOPP or ABVD

Six cycles minimumSix cycles minimum

Prognosis:Prognosis: 70-90%70-90%

one year old child brought one year old child brought with the swelling in the b/l with the swelling in the b/l

orbital region with orbital region with excessive cry. o/e mass excessive cry. o/e mass palpable in the rt lumbar palpable in the rt lumbar region extending in to the region extending in to the

iliac area diagnosis??iliac area diagnosis??

Gross appearence of tumour.Gross appearence of tumour.

Microscopy of HPEMicroscopy of HPE

NeuroblastomaNeuroblastoma Most frequent diagnosed Most frequent diagnosed

neoplasm in infants neoplasm in infants C/FC/F- May develop at any site - May develop at any site

of sympathetic nervous tissueof sympathetic nervous tissue involvement – hard fixed involvement – hard fixed

mass, may produce spinal or mass, may produce spinal or neural root compression.neural root compression.

Cervical involvement- Cervical involvement- Horner’s syndromeHorner’s syndrome

Fever, Irritability, FTI, bone Fever, Irritability, FTI, bone pain, Hypertensionpain, Hypertension

Opsoclonus- MvoclonusOpsoclonus- Mvoclonus


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.

DiagnosisDiagnosis CT, MRI CT, MRI massmass

Tumor markers Tumor markers HVA, HVA, VMAVMA

BiopsyBiopsy

TreatmentTreatment

Surgical excisionSurgical excision

Chemotherapy- Cisplatin, Chemotherapy- Cisplatin, Doxorubicin, vincristine, Doxorubicin, vincristine, cyclophospamidecyclophospamide

RadiotherapyRadiotherapy

Wilm’s tumorWilm’s tumor

Pathology- usually a solitary growth Pathology- usually a solitary growth in any part of either kidneyin any part of either kidney

Stage1: Limited to kidneyStage1: Limited to kidney Stage2: Beyond kidneyStage2: Beyond kidney Stage3: Confined to abdomenStage3: Confined to abdomen Stage4: haematogenous extensionStage4: haematogenous extension Stage5: B/L rental involvement Stage5: B/L rental involvement

C/FC/F Abdominal or flank massAbdominal or flank mass ½ have ½ have abdominal pain abdominal pain

or vomiting hypertensionor vomiting hypertension

Diagnosis-Diagnosis- USG, CTUSG, CT Chest X-ray, CTChest X-ray, CT

Treatment- Treatment-

U/L tumor – surgical removalU/L tumor – surgical removal

Vincristine, actinomycin & Vincristine, actinomycin & doxorubicindoxorubicin

Radiotherapy Radiotherapy

3 ½ yr old female child 3 ½ yr old female child brought with c/o sudden brought with c/o sudden

onset abd distension rapidly onset abd distension rapidly growing in size on day 1 growing in size on day 1

Day 3Day 3 5 th day5 th day

Non Hodgkins lymphoma Non Hodgkins lymphoma

3 Histologic subtypes 3 Histologic subtypes –– LymphoblasticLymphoblastic

Large cellLarge cell

Small non cleavedSmall non cleaved


Lymphoblastic – Intrathoracic tumor- Lymphoblastic – Intrathoracic tumor- dyspnea, chest pain, dysphagia, pleural dyspnea, chest pain, dysphagia, pleural effusioneffusion

Large cell – many sitesLarge cell – many sites SNCL – abdominal tumor – ABD. Pain, SNCL – abdominal tumor – ABD. Pain,

distension, bowel obstruction, intestinal distension, bowel obstruction, intestinal bleeding, perforation may involve CNS or bleeding, perforation may involve CNS or bone marrowbone marrow

Also classified into 4 stagesAlso classified into 4 stages

InvestigationsInvestigations

CBC, S.electrolytes, uric acid, CO+, CBC, S.electrolytes, uric acid, CO+, PO4, LDHPO4, LDH

LFT LFT Spinal fluid cytologySpinal fluid cytology Chest X – ray + CT Chest X – ray + CT Gallium scan ABD X – ray + CT Gallium scan ABD X – ray + CT Bone marrow aspirate & biopsyBone marrow aspirate & biopsy

TreatmentTreatment

Surgical excision may precedeSurgical excision may precede

CHOP – 6 cyclesCHOP – 6 cycles

OrOr

3 cycles + 6m – 6mp + mtx3 cycles + 6m – 6mp + mtx

Case scenerio Case scenerio 2 yr old child presented with slow 2 yr old child presented with slow

growing mass started in the lateral growing mass started in the lateral canthal region n now attained the canthal region n now attained the size as shown in figure. size as shown in figure. Histopathology showing the Histopathology showing the following . Fundus examination following . Fundus examination shows the following . What might be shows the following . What might be differential diagnosis?differential diagnosis?

Morphology of Morphology of retinoblastomaretinoblastoma

Fundus examination Fundus examination

RetinoblastomaRetinoblastoma

C/F- Leukocoria, strabismus, orbital C/F- Leukocoria, strabismus, orbital infalmn, paininfalmn, pain

Diagnosis Diagnosis Opthalmology – orbital USG Opthalmology – orbital USG and CTand CT

Treatment – u/l enucleatonTreatment – u/l enucleaton Laser photocoagulation or Laser photocoagulation or

cryotherapycryotherapy B/l B/l enucleation of the more several enucleation of the more several

effected eye.effected eye.

Pediatric cancers that merit genetics evaluation

• Retinoblastoma (RB1)• Bilateral Wilms Tumor (WT1)• Adrenocortical carcinoma (TP53)• Choroid Plexus Tumor (TP53)• Rhabdomyosarcoma < 3 yo

(TP53)• Osteosarcoma < 5-10 yo (TP53)• Medullary thyroid cancer (RET)• Atypical teratoid and malignant

rhabdoid tumor (SMARCB1/INI1/SNF5)

• Hepatoblastoma (APC)• GIST (SDHA,-B,-C,-D)

• Pheochromocytoma / paraganglioma (VHL, NF1, RET, SDHA,-B,-C,-D,-AF2)

• Retinal/cerebellar hemangioblastoma (VHL)

• Endolymphatic sac tumors (VHL)

• Optic pathway tumor (NF1)• Acoustic or vestibular

schwannomas (NF2)• Basal Cell Carcinoma /

Medulloblastoma (PTCH)• Bilateral Neuroblastoma

(ALK, PHOX2B)

Health & Medicine

Paediatric oncology