2010 Paediatric Oncology 1

8/12/2019 2010 Paediatric Oncology 1

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Dr. Alex Osei-Akoto

DCH-CHS, KNUST


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Outline

Introduction

Epidemiology

Aetiology

Incidence

Clinical features

Clinical presentation & Staging

Investigation and Diagnosis

Treatment & Prognosis

Complications


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Introduction Burkitt lymphoma (BL)- a highly aggressive B-cell

neoplasm characterized: translocation andderegulation of the c-myc gene on chromosome 8.

Clinical forms: endemic, sporadic, andimmunodeficiency-associated.

histologically identical and have similar clinical

behaviour,differences in epidemiology, clinical presentation, and

genetic features


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Introduction Endemic (African) form: jaw or facial bone tumor that

spreads to extranodal sites including the mesentery,ovary, testis, kidney, breast, bone marrow andmeninges

Nonendemic (Sporadic): usually abdominalpresentation, involving the distal ileum, stomach ,

cecum and/or mesentery, kidney, testis, ovary, breast,bone marrow, or central nervous system.

Immunodeficiency-related: more often involve lymphnodes


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Introduction

Denis Burkitt -1958

Malignancy of B lymphoctes

Commonest childhood malignancy intropical Africa

More than half of all tumours in African

childrenMultiple primary foci

Can present in a variety of ways


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Epidemiology

Burkittslymphoma belt

10-15 north & south of equator

Altitude 26.6 C Annual rainfall >50cm

Coincides with malaria endemic areas

Original Hypothesis Anthropod-borne (possible Mosquito)

Virus


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AetiologyExact cause & mechanisms unknown

Epstein-Barr Virus (EBV): >80% Chn under 5 infected

Immortalized B cell

Falciparum Malaria

B cell proliferation Oncogenes

Activated c-myc oncogene (Chromosome 8)

Chromosomal abnormalities t(8:14) -80%, t(8:22) -15%, t(2:8) -5%

?Immune deficiencyMalnutrition/Poverty


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Incidence

Commonest childhood malignancy in Africa

Accounts >55% of all Paediatric tumours

Over 90% b/n ages 49yrs, peak 4-7(5)yrs

13/100,000 children in Uganda

15/100,000 children(5-9yr) in Nigeria

0-7.6/100,000 pop. in lymphoma. Belt

Commoner in rural areas


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Cancer cases seen in Kumasi in 2008

NUMBER M F

Burkitts

lymphoma

78 (40 abd,30 jaw, 8 abd+

jaw)

50 28

Nephroblastoma(Wilms)

10 3 7

Leukaemia (ALL) 7 5 2

Retinoblastoma 3 2 1

Non-Hodgkinslymphoma (NHL)

2 1 1

Total 100 61 39


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ancer ases seen n umas -

NUMBER M F

Burkitts lymphoma 57 31 26

Nephroblastoma

(Wilms)

14 10 4

Neuroblastoma 5 2 3

Leukaemia (ALL) 5 4 1

Hodgkin'sLymphoma

4 3 1

Retinoblastoma 3 2 1Non-Hodgkinslymphoma (NHL)

2 2 0

Rhabdomyosarcoma 2 2 0

Burkitts leukaemia 1 1 0


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Clinicalfeatures Short Hx b/n S/S onset & presentation

Fastest growing tumour

Doubling time of 24 hrs

2-16 years

Peak 4-7 years

Uncommon < 1 yr Rare below 2yrs (1%) & > 20yrs

15years

Male : Female = 2:1


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Clinicalfeatures

0

1020

30

40

5060

70

80

1 4 7 10 13 16 19 22 25

Age distribution

in 480 BL

patients upto

25yrs (Uganda)


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Age distribution of Burkittscases

2000-2007

16151413121110987654321

Age (years)

20

15

10

5

0

Percent


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Age and Gender distribution

*


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SitesofBurkittsTumour

Usually multifocal, involvement of 1 of thefollowing sites

Facial

Abdominal viscera

CNS

Thyroid, Distal long bones, Skin, Breast,

Kidney, Testes/Ovaries, Parotid glands

Rarely: Bone Marrow, Lymph nodes, lungs,

Mediastenum, Liver, Spleen


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Common sites of primary

tumour Kumasi 2000-2007

Sit f B kitt i


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Sites of Burkitts cases in

Kumasi 2009Site Number

Abdominal 25

Jaw 21

Combined Abdominal +Jaw 5

Testes 2

Armpit 2

Neck 1

Leg 1

Total 57


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Site of primary tumour and Gender


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ClinicalFeatures

Burkitt classically

described:

Large extranodal

tumours affecting

jaw bones (maxilla &

mandible)

and abd. viscera


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ClinicalPresentationOften in good general health

until disease is well advanced

Weight loss

Anorexia Fever

Malaise

Jaw swelling (75%) Abdominal swelling (60%)

CNS involvement (30%)


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Clinicalpresentation Facial Tumours

Younger, peak 5yr

Progressive Painless jaw

swelling ( 1) Maxilla > Mandible

Proptosis 2 orbital

involvement(Maxilla)


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Clinicalpresentation

Facial Tumour

Oral extension

Loose teeth

Misaligned teeth

M ill T ith O bit l


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Maxillary Tumour with Orbital

extension-Proptosis

Before Treatment After Treatment


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Maxillary Tumour with orbital

extensionBefore Treatment After Treatment


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ClinicalpresentationAbd. Tumours

Older children

Peak age -7yr

Progressive abd.swelling

Non-tender, hard,

craggy abd. Mass

Ascites, variable

Any abdominal organ


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Abdominal BurkittsBefore Treatment After Treatment


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Multiple Sites-

Jaw + Abdomen


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CNS

Site of initial

involvement/relapse

Peak age 9yrs

Cranial nerve palsy

Paraplegia(-paresis)

Sphincter dysfunction Pseudo-meningitis/coma

CSF pleocytosis


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Other sites

Testes /Ovaries

Thyroid

Subcutaneous tumour

Cardiac

Breast

Long bones

BM; LN; liver; Spleen


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Investigation 1

Histology

starry sky-immature lymphocytes + macrophage

Cytology

Radiology X-ray (jaw, CXR, others); USG; CT; Radioisotope

Blood

FBC:- may be normal, or Hb; WBC; Plt Renal function

Uric acid, LDH

Na; K; Cl; PO4; Ca


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Investigation 2

Bone marrow aspiration and biopsy R/O

unexpected bone marrow involvement

Lumbar puncture is necessary for evaluation of

CNS involvement.

Abd. Paracentesis or thoracentesis for

cytogenetic studies if ascites or pleural effusion is

present


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Diagnosis& Investigations

Clinical Presentation

Histology (Hallmark of Diagnosis)

Incisional biopsy

Starry Sky appearance (*Not pathognomic)

Cytology

Quicker and easier

FNA, Ascitic fluid, CSFRadiological investigations

Loss of lamina dura/ Osteolysis/ Malalignment

Blood investigations


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Starry-sky appearance Sheets of uniform monotonous cells

-with round to oval nuclei with multiple nucleoli (2-5)-abundant division figures (frequent mitotic figures)

- cytoplasm is moderate and basophilic, with smallvacuoles

(monomorphic, medium-sized cells with round nuclei,

multiple nucleoli, and basophilic cytoplasm) Diffuse scattering of phagocytic macrophages with

retracted cytoplasm among the tumour cells

Cli i l St i (Zi l & M th


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ClinicalStaging(Ziegler & Magrath

1974)

Stage Criteria

A Solitary extra abdominal site AR Resected ( 90%) intra-abd. tumour

B Multiple extra-abdominal sites

C Intra-abd. tumour facial tumour D Intra-abd. tumour with sites other

than facial


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ClinicalStaging(NCI) Stage Definition

IDx limited to one anatomical area

IIa. Dx limited to two contiguous areas

- b. Dx in 2 or more non-adjacent areas, but

on same side of diaphragm IIIa. Dx involves structures on both sides of

diaphragm

b. Dx involves structures on both sides ofdiaphragm + spread of cells to BM or blood

stream

IV - Dx involves CNS


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DifferentialDiagnosis

BL is greater imitator of other pathology Jaw swelling

Rhabdomyosarcoma

Dental abscess

Dentiginous cyst

Ossifying fibroma

Osteomyelitis

Osteogenic sarcoma Maxilla tumourFibrous dysplasia


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DifferentialDiagnosisOrbital involvement Retinoblastoma / Neuroblastoma

ALL / Rhabdomyosarcoma

Abdominal swelling

Nephroblastoma

Neuroblastoma

Abdominal MTB

Non Burkitt, Non Hodgkins Lymphoma


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Treatment Supportive treatment (very important)

Treat/ Prevent Tumour Lysis Syndrome

Blood and blood products Treat infection vigorously

Symptomatic

Nutritional support Psychological support


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Treatment

Chemotherapy Mainstay of treatment (CTX; VCR; MTX; Pred)

Surgery

Excision biopsy; tumour debulking; laminectomy

Radiation therapy (Not very useful)

Radiosensitive, but rapid growth b/n therapy

Superfractional therapy (days dose 3 @ q4h

Toxicity with BM aplasia Used as last resort e.g. CNS relapse not responsive to

drugs

Immunoaugmentation therapy


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TreatmentHigh relapse rate with single agent (CTX)

COMP

Cyclophosphamide + vincristine (Oncovin) +Methotrexate + Prednisone

CHOP

Cyclophosphamide + vincristine (Oncovin) +Doxorubicin + Prednisone

CHOP plus methotrexate

Cyclophosphamide + vincristine (Oncovin) +Doxorubicin + Prednisone + Methotrexate


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Prognosis

Good Prognosis Isolated jaw mass (i.e. stage A)

90% resected abdominal tumour (i.e. stage AR)

Poor PrognosisCNS involvement

Male sex (sanctuary sitetestis)

Bone Marrow involvement Intra-abd.

Prognosis depends on extent & tumour size atpresentation


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Prognosis

90% response with chemotherapy

80% complete response

10% partial response

50% relapse

Early relapse (3mths respond well, on initial chemo.Up to 30% of CNS cases can be salvaged

Prophylactic IT MTX to prevent CNS relapse


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Complications

Acute Tumour Lysis Syndrome Spinal Cord Compression

Complication of cytotoxic therapy Nausea, anorexia and vomiting

Alopecia, reversible Bone marrow suppression Neutropenic fever / sepsis Haemorrhagic cystitis 2 Cyclophosphamide Azoospermia, testicular atrophy, amennorrhea Extravasation e.g. 2 Vincristine Mucositis
http://c/Documents%20and%20Settings/justice/Desktop/Tumour%20%20Lysis%20Syndrome.ppthttp://c/Users/Justics/Desktop/Spinal_cord.pptxhttp://c/Users/Justics/Desktop/Spinal_cord.pptxhttp://c/Documents%20and%20Settings/justice/Desktop/Tumour%20%20Lysis%20Syndrome.ppt


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Summary

Commonest childhood malignancy in Ghana

Rapid onset (Fast growing tumour)

24hr tumour Doubling time

Multiple primary foci

Facial / Abdominal / CNS etc

DiagnosisHistology or Cytology

Chemotherapy main therapy Combination therapy with CTX

Treat / Prevent Tumour Lysis Syndrome


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Thank you