2015 -1 0 -27 1 D E P A R - PowerPoint Presentation

Slide1

2015

-1

0

-27

1

D

E

P

A

RTMENT OF PEDIATRIC HEMATOLOGY AND ONCOLOGYCOLLEGIUM MEDICUM UMK BYDGOSZCZSOLID TUMORSSEMINAR 5TH YEARPROF. JAN STYCZYŃSKI

ca

t

e

c

h

o

lami

ne

s

c

y

t

o

l

o

g

y

DIFFERENC

E

S

I

N N

E

OPL

A

SMS

B

E

T

W

EEN CH

I

LDREN

A

ND

A

D

U

L

T

S

C

H

IL

DR

E

N

AD

U

L

TS

Primary

o

r

ig

in

t

issue

s

o

rg

a

n

s

H

i

st

o

p

a

t

o

l

o

g

y

n

o

n

-

ep

it

he

lial

>

90

%

:

ep

it

he

lial

80-90%

m

esen

c

h

ymal

a

n

d

e

m

b

r

y

o

n

al

S

t

a

d

i

u

m

80%

d

i

sse

mi

n

a

t

e

d

l

o

c

al a

n

d

r

eg

i

o

n

al

S

c

r

een

i

n

g

neu

r

o

b

la

st

o

m

a

:

mam

mo

g

r

a

p

h

y

,

c

o

l

p

o

s

c

o

p

y

,

R

esp

o

ns

e

t

o

t

he

r

a

p

y

c

he

m

o

- a

n

d

R

T

X

sens

it

i

v

e

l

o

we

r

sens

ivi

t

y

P

r

o

gn

o

s

is

>

60

%

;

+

sp

o

nt

a

ne

o

u

s

r

eg

r

ess

i

o

n

<

50%

-

5-

y

e

ar

su

r

vi

v

al

p

o

ss

i

b

le

Slide2

2015

-1

0

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3

A

GE-DEPEND

ENCE

• 1

y: neuroblastoma, retinoblastoma, hepatoblastoma, Wilms tu• >80% neuroblastoma in first 3 years of life• 80% Wilms tumor in first 5 years of life• 2-5 y: ALL

• 6-10

y: br

ain tumo

rs•

adolescen

ts – H

D, o

steosa

rcoma, E

wing

sarcoma,

STS

• 70%

bone

tum

ors

at ag

e >

15 y

•

Early

childh

ood a

nd 1

5-18

y –

gonadal germinal

tumors in boys

• At

pubert

y –

gon

adal

germi

n

al

tu

mors in girls

SO

L

ID

TUM

O

R

S

IN

CHI

L

D

R

EN

•

B

r

ain

tu

m

o

r

s

•

S

ymp

a

th

e

t

ic

s

ys

t

em

tu

m

o

r

s:

n

e

u

r

o

b

la

s

t

oma

•

N

e

ph

r

o

b

la

s

t

oma

(

Wilms

tu

m

o

r)

•

S

of

t

t

issue

sa

r

c

oma

(

RM

S

-

r

h

a

bd

o

m

y

osa

r

c

oma)

•

B

o

n

e

tu

m

o

r

s

(

o

s

t

e

o

sa

r

c

oma,

E

w

i

n

g

sa

r

c

oma)

•

Ger

m

i

n

al

tu

m

o

r

s

(

g

er

m

i

n

oma)

•

Li

v

er

tu

m

o

r

s

(

h

e

p

a

t

o

b

la

s

t

o

ma,

h

e

p

a

t

o

c

a

r

c

i

n

oma)

•

R

e

t

i

n

o

b

la

s

t

oma

•

H

i

s

t

ioc

yt

osis

•

Ra

r

e

tu

m

o

r

s

Slide3

2015

-1

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-27

g

e

rminal

tumors

)

tumors5CLASSIFICATIONI. NEUROEPITHELIAL TUMORS- gliomas: astrocytoma, oligodendroglioma, ependymoma, GBM- tumors of primary neural cells(neuroblastoma, medulloblastoma/PNET)II. PERIPHERAL NERVES

TUMORS

III. MENINGEAL T

UMORSI

V. L

YMPHOMAS

V. GERM

CELL TU

MORSVI.

TUMORS OF

THE SEL

LAR REGIONV

II. ME

TASTATIC

TU

MORS

Su

prat

ento

ria

l tu

mors

(as

trocy

toma)

Sup

rate

ntorial andc

entral line tumors(p

hary

ngioma

, g

lioma,

I

nfrat

e

nt

o

ri

al(me

dullob

l

as

to

ma

,

e

p

e

n

dymoma)60%LOCALIZATION OF PRIMARY CNS TUMORS IN CHILDREN

BRAIN

TUM

O

RS

Slide4

2015

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6

BRAIN T

UMOR

DIAG

NOSTI

CS• Imaging: CT, MRI, (PET)• Ophthalmological examination• Biopsy and histo-pathological examination• CNS fluid examination• Cancer markers (AFP, HCG)• Endocrinologial examination

• Psy

chological

examina

tion

SYM

PTO

MS A

ND

SIGNS1.

Dysfunc

tion (

related

to loc

alizat

ion of

tum

or)

• sei

zures

, p

aresis

(he

mipa

resis

, facial

par

esis), aphasia, dys

phagia, ataxia, d

izzin

ess;

mot

or /

sensory /

vis

u

al

im

pairment, e

tc2.

Co

n

se

qu

e

n

c

es

of intracranial hypertension• headaches, vomiting (early morning), nausea

,

al

t

e

r

ed

s

t

a

t

e

of

c

o

n

s

c

io

u

s

n

ess

(

som

n

ole

n

c

e,

c

om

a

)

,

a

n

iso

c

ori

a

,

in i

n

f

a

n

t

s: el

e

v

a

t

ed

i

n

t

r

ac

r

a

n

ial

p

r

ess

u

r

e

m

a

y

c

a

u

se

an i

n

c

r

e

a

se

in

th

e

d

iam

et

er

of

th

e

s

k

u

ll

a

n

d

bu

lgi

n

g

of

th

e

f

o

nt

a

n

ell

e

s

Slide5

2015

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8

NEUR

OBLAST

OMA

T

HERAPEUTIC STRATEGYStrategy is dependent on:• Tumor histology• Extent of surgical treatment• Age of patientStrategy of management in MB/PNET:• Diagnostics• Surgery•

Stag

ing

• Post

-opera

tive

chemothe

rapy

• Ra

diother

apy•

Mainten

ance chemother

apy

Slide6

2015

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9

NEUR

O

BL

A

STOMANEUROBLASTOMA• Originates from immature cells of peripheral sympathetic system• 90% diagnosed before age of 5

yrs•

In 9

0% h

ormon

ally

active (

A, N

A, DA,

VMA

)•

Othe

r marker

s: NSE, ferit

in,

LDH

Slide7

2015

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10

NEUR

O

BLA

STOMA

Symptoms and signs related to primary site:ABDOMEN: pain, dyspeptic symptoms, constipation, diarhhoea, swallen belly, ileus, inferior vena cava syndromeCHEST: cough, URTI, chest pain, dyspnea, other br

eathing

proble

ms, H

orner syndrom

e, superio

r ve

na cava syndrome

SPINA

L CORD

: weaknes

s, in

ability

to st

and, crawl,

or

walk; myel

opat

hy, pain

(ra

diculitis- lik

e),

numbness,

pare

sis, sphincte

r dysfun

cti

onsNEUROBLASTOM

A: SYMPTOM

S AND

S

IGN

S

Gene

ral:

F

at

i

gue, loss o

f appetite,

f

e

v

e

r

,

we

a

kness, bone pain, hypertension, anemiaMetastases: skull bones, bruising and swelling around the eyes or orbi

t

s

,

s

w

a

ll

e

n

bel

l

y

,

b

r

e

at

hi

n

g

pr

o

blems

etc

Slide8

2015

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11

NEUR

OBLASTOMA:

DIA

GN

OSTICS• Imaging (RTG, USG, CT, MRI)• Scintigraphy (local metabolic activity: specific marker MIBG - metyl-jodo-benzyl-guanidine)• Tissue specimen: histopathology,

immuno

histochemis

try,cy

togenet

ics, mol

ecular te

sts

• Ca

techolamine

s (2

4-hour

urinary

output

)•

Biochemic

al

markers: f

erritin,

NS

E, L

DH•

Bone

marrow

bio

psy and

aspir

ation

S

CIN

TIG

RAPH

Y MIBG

•

Diagn

o

s

ti

c

s• Monitor

ing of t

h

e

r

a

p

y

•

Diag

nostics of relapse in neuro-endocrine system

Slide9

2015

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14

WI

LMS

TUMOR

(NEPHR

OBLASTOMA)NEUROBLASTOMA: TREATMENTDIAGNOSTIC AND THERAPEUTIC STRATEGY• Diagnostics - chemotherapy  surgery  chemotherapy stem cell transplantation  radi

other

apy 

immunot

hera

pyAD

VERSE

PROGNOS

TIC FACT

ORS

• Ampl

ificat

ion o

f oncoge

ne N-

MYC

>10 cop

ies

•

Deleti

on 1p,

lac

k of

expr

essio

n CD

44,

TRKA, p75• Age over

1 year• Advance

d st

age

• Bon

e and

bon

e marrow

m

et

as

tases• Incr

eased

values

of

N

S

E,

f

eritin, LDH

Slide10

2015

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15

GE

NET

IC

SYND

ROMES CONCOMITANT WILMS TUMOR7,9% - hamartomas, angiomas, melanocytic naevi4,4% - congenital disorders of urinary tract2,9% - congenital

hemih

yper

trophy

2,9%

- c

ongeni

tal

defe

cts

of bon

es an

d musc

les1

,1%

- c

onge

nita

l a

niridia

WILMS

TUMOR:

C

HARACTERI

STICS

• Orig

inates from low

differentiated re

nal

blast

ema

• P

eak

incide

n

c

e

:

3-4 year of

life•

6%

of

a

l

l

childhood neoplasms• The most frequent kidney tumor in children• Second

m

o

s

t

f

re

qu

e

n

t

r

e

tro

p

e

ri

t

o

n

ea

l

t

u

m

or

i

n c

hild

re

n

•

I

n

1%

-

f

am

il

y

o

c

c

u

re

n

ce

•

P

o

s

s

ibl

e

co

-

e

x

i

st

e

n

ce

wi

th

c

on

g

e

ni

t

a

l

d

e

f

e

c

t

s

Slide11

2015

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16

WIL

MS

TUMOR: DI

AGNO

STICS1. Patient history2. Physical examination3. Urine tests4. Imaging (USG, CT, RTG)5. Biochemical tests6. Cytogenet

ic t

ests (del

11p)

7. Ar

teriog

raph

y of re

nal a

rteri

es (st

adium 5)

8.

Bone sc

int

igr

aph

y

WIL

MS

TUM

OR:

S

YMPT

OMS

AND SIG

NS

1. general symp

toms2. recurren

t urin

ary

tr

act i

nfe

ctio

n

s

3

.

eryth

rocyt

uria

,

h

em

a

t

uri

a

4. hypertension5. abdominal pain6. intestinal s

ym

p

t

oms

(

a

bd

omi

n

a

l

s

we

lling

,

c

on

s

t

i

p

a

t

i

o

n

,

c

r

am

ping

,

d

a

r

k

st

o

ol

s

,

n

a

u

se

a

,

v

omi

tin

g)

7

.

s

ym

p

t

oms

of

a

bd

omi

n

a

l

t

u

m

or

Slide12

2015

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17

ST

AGINGStagi

ng –

at

diagnosisSurgery and pathology staging- during surgical operation and after histo-pathological examinationI – Tumor is limited t

o the

kidn

ey an

d is

completel

y ex

cised

II –

Tumor

exte

nds b

eyond

the k

idne

y bu

t i

s comp

lete

ly

exc

ised

III –

Unresec

tab

le

prim

ary tumor / L

ymph node metas

tasi

s /

Tumo

r i

s p

resen

t

at

s

urgical m

argins

/

T

umo

r

s

p

ill

age involving peritoneal surfaces either before orduring su

r

g

e

r

y

IV

–

p

r

ese

nc

e

o

f

h

e

m

at

o

g

e

nou

s

m

et

a

s

t

ases

(

l

ung

,

li

v

e

r

,

bon

e,

o

r

b

r

a

i

n

)

V

–

b

ilateral renal involvementfavorable histology – low grade malignancyintermediate histology – intermediate grade malignancyunfavorable (anaplastic) histology – high grade malignancy

T

R

E

A

T

MENT

S

T

RA

T

EGY

p

re

-

o

pe

r

at

ive

c

hem

ot

he

r

a

py

4

-6 weeks

nephr

e

cto

my

(

d

e

l

a

y

e

d,

e

x

c

e

pt

in

f

ants

a

t

s

t

a

g

e

I

o

r

I

I

)

p

o

s

t

-

o

pe

r

at

ive

c

hem

ot

he

r

a

py

–

wi

t

h

r

e

s

pect

t

o

s

ta

ging

r

a

d

io

t

he

r

a

p

y

(

s

t

a

ge

II

N+

or h

i

gh

e

r)

long-

t

e

r

m

fol

l

o

w-up

Slide13

2015

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19

SOFT

TISSUE SARCOMAS

RHABDOM

YOSARC

OMA

Slide14

2015

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20

E

PIDEMIO

LOG

Y•

6% of all neoplasms in children• In 60% - below 5-6 year of life• Second peak of incidence: 14-18 yrs• In 60-70% - rhabdomyosarcoma

CHARA

CTERIS

TICS

• Tu

mors

origina

ting f

rom pr

imar

y mesenchy

malt

issue

• Tum

ors

of mu

scles

, conne

ctive

ti

ssue

and vessels

•

Growt

h by lo

cal inf

iltr

ation – local recurrences•

Hematogenous metas

tases

Slide15

2015

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21

S

YMPT

OMS AND

SI

GNS: DEPENDENT ON LOCALIZATIONWITH PROGNOSTIC VALUE:1. Head, orbits (perimeningeal localization), neck (40%)2. Urinary bladder (20%)3. Abdomen

: oth

ers (15-

20%)

4. L

imbs (10

%)5.

Oth

ers (10%)

CLINIC

AL

SYM

PTOM

S AND

SIG

NS:

1.

Pre

sence of tu

mor

2.

Com

press

ion t

o o

ther o

rgan

s and tissues

HISTOPATHOL

OGY

Hi

stological

st

ructu

re

d

e

t

erm

ines risk

strat

i

f

ica

t

ion and

se

n

s

itivi

ty to chemotherapy• RMS group (RMS embryonal [favorable], alveolar [unfavorable],

pl

e

o

m

o

r

ph

i

c,

anap

l

a

s

t

ic;

ex

t

r

a

-

b

one

E

wing

s

a

r

co

m

a,

s

a

r

co

m

a

s

y

novial

e

)

•

No

n

-

R

MS g

r

oup

(

l

e

io

m

y

o

s

arcoma, fibrosarcoma, liposarcoma, angiosarcoma, hemangiopericytoma, lymphangiosarcoma)

Slide16

2015

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22

S

TA

GING•

I

– localised disease, total resection• II – macroscopic tumor resection, microscopic residual tumor• III – partial tumor resection, macroscopic residual tumor; biopsy only• IV – metastases present at diagnosisDIAGN

OST

ICS

• Pat

ient

histor

y•

Phys

ical

examin

ation

• Imag

ing of prima

ry lo

caliz

atio

n:

CT / MRI

•

RTG

/

scin

tigr

aph

y of b

one

s•

Bone marrow biopsy

• Biochemical

te

st

• Ot

her

–

depe

nd

e

n

t

on localiza

tion

Slide17

2015

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24

TR

EATMENT

1. Induction

chemot

herapy – decreases tumor mass, decreases metastases2. Local therapy (surgery + radiotherapy)3. Adjuvant chemotherapy (supplementary)

Slide18

2015

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25

E

PIDEMI

OLOG

Y

• 5% of all pediatric tumors• Peak incidence: in adolescents (15-19 yrs)• The most frequent: osteosarcoma• Osteosarcoma – localized in long bo

nes

(meta

physes)

• Ewin

g sar

coma

– lo

calized

in

long

bone

s and

flat b

ones

(pelvi

s)

• M

etast

ases

to

lungs,

bon

es, ma

rrow

• I

n 3

0% patients –

metastases are pre

sent

at

diagn

osis

BO

N

E

TUM

O

RS

Slide19

2015

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26

HI

STOPATHO

LOGY

•

Osteosarcoma: originates from bone cells, localized at bone growth centers in long bones (metaphyses)• Ewing Sarcoma: originates from neural cel

ls in

marrow

cavity

– i

n lon

g bo

nes an

d ax

ial s

kele

ton•

Chond

rosarc

oma a

nd fibr

osar

coma

: r

are o

ccur

rence

Slide20

2015

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28

DI

AG

NOST

ICS

• Patient history and patient examination• Imaging: RTG / MRI / CT• Scintigraphy of bones (99TcMDP)• Biochemical tests (alkaline phosphatase

)•

Ches

t CT

• Soft t

issue

invo

lvemen

t• H

isto-pa

thology

– re

sponse

to indu

ction

chem

othe

rap

y

S

YMP

TOMS

AND S

IGNS

•

PAIN

–

worse at night

• TUMOR – grow

ing

rapidl

y,

hard,

no

pai

n

a

t

examinati

on• S

we

lling

,

re

s

t

r

i

c

ted range of locomotion, pathological fracures• Fever• Parap

l

eg

y

•

I

n

4

0

%

of

E

win

g

s

ar

c

o

ma

:

s

u

b

f

e

bril

e

st

a

t

u

s,

a

n

em

i

a

,

s

ym

p

t

oms

of

i

n

f

e

c

ti

on

(i

n

f

e

ction mask)• Injury (in patients history) – indicates disease (sick place)

Slide21

2015

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30

GE

RMINA

L TUMORS

THERA

PEUTIC STRATEGY• Pre-operative multi-agent chemotherapy (aim: decrease of tumor mass, to target micro-metastases, to assess the response

to c

hemothe

rapy)

• Su

rgery

: amput

ation

(endo

prost

hesi

s, bo

ne t

ranspla

nt), th

era

py of m

eta

stases

•

Post-

ope

rat

ive

chem

othe

rapy

• Radiotherapy

– only in Ewing

sarc

oma

Slide22

2015

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31

HIS

TO

PATHOLOGY CLA

SSIFIC

ATION1. TERATOMA – includes structures of 3 germ layers. In 80% - sacro-coccygeal localization, 10% - neck localization.2. GERMINOMA – originates from primary ov

ocyte

(dys

germin

oma) or semi

nal cell

(seminoma).

Localiza

tion:

gonad

s, mediast

inum,

skull.

Rarely in

chil

dren

.3.

CA

RCIN

OMA

EMB

RYON

ALE

4.

YOL

K S

AC T

UMOR – the most

frequent germ cell

tumo

r, r

esemb

les st

ructu

res

of

p

rim

a

ry yolk sack, p

roduces

AF

P

.

5.

CH

O

R

IO

CARCINOMA - rare, malignant, produes -HCG6. POLYEMBRYOMA – very r

a

r

e

7.

G

O

N

A

D

O

B

L

A

S

T

O

M

A

GERMIN

A

L

TUMORS

•

6%

of

all

n

e

op

lasms

in

c

h

il

d

r

en

•

Origi

n

a

t

e

f

r

om

p

rim

a

ry

g

erminal cells• Localization:• Gonadal (1/3)• Extra-gonadal (2/3) – sacro-coccygal region, pineal gland, mediastinum, retroperitoneal space• More frequent: girls• Peak incidence:– I. Age 0-3 yrs (mainly in sacro-coccygal r

egion)–

II. Age

>12 y

rs (mainly

ovarian tu

mors)

Slide23

2015

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32

D

IA

GNOSTI

CS

• Patient history• Patient examination• Biochemical and genetic tests• Neoplastic markers: AFP, beta-HCG• Imaging of primary tumor site

• Imag

ing for

poss

ible me

tasta

ses (bone

s, ch

est)

GE

RMI

NAL

TUMORS:

SYM

PT

OMS A

ND

SIG

NS

•

Abdomina

l t

umo

r, a

bdomin

al

pain

• Tumor in butt

ocks area• Pr

oblem

s wi

th de

fec

ati

on /

c

on

s

t

ipation

• Dysuri

a

/

urin

e

r

e

t

ension• Swelling of testis• Precocious puberty• Secondary amen

o

rrh

e

a

•

H

ea

d

a

c

h

e

s,

v

omi

ting

,

l

o

ca

l

n

e

u

r

o

l

ogi

ca

l

s

ym

p

t

oms

•

P

a

i

n

i

n

t

h

e

c

h

e

s

t, c

ou

g

h

, dyspnea• Leg weakness• Congenital abnormalities

Slide24

2015

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

S

T

AN

DARD RISKsecretingnot obligatory33THERAPEUTIC STRATEGY IN T

HERA

PY

OF MALIG

NANT no

n-

SEMI

NOM

A G

ERMI

NAL

TU

MOR

S (T

GMnS)AF

P <

15 000 n

g/ml

TGMnS

hist

opa

thol

ogy

no

met

aAF

P >

15 000 ng/ml and/or m

eta HIGH RIS

KCa

rci

noma emb

ryo

nale

TGM

n

S

h

istopatho

logy

n

o

n

-

se

c

r

e

t

ing obligatoryTeratoma low-differentiatedTHERAPEUTIC STR

A

TE

G

Y

DEPE

N

DS

O

N:

•

Ini

t

ial

c

li

n

i

c

al

s

t

a

g

e

a

n

d

p

o

s

t

-

o

p

e

r

a

t

i

v

e

s

t

a

g

e

(

T

NM

)

•

Se

c

re

ting character of tumor, histology, initial AFPconcentration (< or > 15 000 mg/ml)Two prognostic groups:- Standard risk- High risk

Slide25

2015

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34

G

ERMINAL TUMO

RS: T

RE

ATMENT• Surgical – solely, only in non-malignant teratoma• Chemotherapy – in most cases (dependent on stage of surgical resection and histology)• Radiothe

rapy:

dysgermi

noma - sens

itiv

e, ov

arian

endoder

mal s

inus tu

mor –

low

sensitivi

ty

Slide26

2015

-1

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35

L

IV

ER TUM

ORS

• hepatoblastoma• hepatocarcinoma• mesenchymoma1% of all neoplasms in childrenPeak incidence: hepatoblastoma - 1 yr; hepatocarcinoma – 12 yrs

•

Liver m

etast

ases:–

neur

oblast

oma

– Wilms

tumor

– l

ymphom

a–

Langer

hans

ce

ll hi

stio

cyto

sis

(LCH)

•

Non-

malig

nant

tu

mors:

– hamartoma, n

odular hyperplasia, cy

sts

, ad

eno

mas,

et

c

LIVER

TUM

O

RS

Slide27

2015

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36

H

IST

OPATH

OL

OGYHBL• Most often: uni-focal localization in right lobe, with capsula• Morphology:1. Epithelial type (embryonal or germinal cells)2. Mixed type (epithelial o

r mesen

chymal

cells

) (os

teoid)

HCC

• Mu

lti-f

ocal•

Early

metast

ases d

o local

lymp

h n

odes

an

d lun

gs (

rare

ly t

o bo

nes)

PA

T

H

OGENESIS OF LI

VER TUMORSHBL

• G

enetic

fac

tor

s

• c

o

e

xi

s

tance HBL an

d cong

e

n

i

t

al

a

bn

ormaliies

(Beckwith-Wiedeman syndrome, WAGR, neurofibromatosis)• Abnormalities of

c

e

llul

a

r

D

N

A

c

o

n

t

en

t

;

c

h

r

o

m

o

s

o

m

e

11;

tri

s

o

m

y

20

•

E

n

vir

o

nm

e

n

t

al

f

ac

t

o

r

s

•

Us

e

of some drugs (gonadotropins or anticonceptives); exposition to chemicals; alcohol abuseHCC• Hepatitis B infection; coexistance HCC with tyrosinemia; coexistance HCCwith with biliar atresia / fibrosis; drug abuse (anabolics)

Slide28

2015

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37

DI

AG

NOSTICS

•

Blood count• Liver tests (hepatic enzymes, electrolytes, coagulation tests)•  - fetoprotein• Chorionic gonadothropin (-HCG)• Antigen CEA•

Imaging

(rtg,

usg

, CT,

MRI,

angiogra

phy,

scin

tigrap

hy )

• H

BV,

HCV•

Biop

sy

• Sea

rch

for

ext

raliver

foc

i (tho

rax

RTG a

nd

CT,

bone scintigrap

hy, marrow biopsy)

S

Y

MP

TOMS

AND S

IG

NS

•

Loss

of apeti

te, weigh

t loss,

v

omi

t

i

n

g

s

, abdominal tumor, hepatomegaly• Thrombocytosis, cystationuriaRISK GR

OU

PS:

•

Low

ris

k

:

t

u

m

or

w

it

h

in



3

se

c

t

o

r

s

;

li

m

i

t

e

d

t

o

li

v

e

r

(i

n

t

r

a

-

h

e

p

a

ti

c

)

•

High risk: tumor present within all 4 liver sectorsand/or present within abdominal cavity (extra-hepatic)

Slide29

2015

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38

RETINOBLAS

TOM

A

TREA

TMENT• Pre-operative chemotherapy: response to therapy,• Surgery (total surgery possible in 40-50%)• Post-operative surgery (as supplementary therapy)•

Radiother

apy

– limited

value,

as the

rape

utic dose

exce

edest

oleran

t dose

for

liverIn

crea

sed AFP ser

um

conc

ent

ration

ind

icat

es f

or activ

e ne

oplast

ic p

rocess

Slide30

2015

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39

S

YMPT

OMS

AND SIGN

S• Grey / green reflex in pupilla• Leukocoria – white pupillary reflex - evidence of large tumor• Strabismus• Red eye, intraocular pain (secondary infectio

n)

CH

ARACTERIS

TICS

• 2% of

all

neopla

sms in

children

• The

mos

t frequ

ent in

tra

ocula

r ne

opla

sm i

n child

ren

• H

ighl

y mali

gna

nt

• Ori

ginates from low

-differentiated

re

tina

l cel

ls

• Ma

inly

i

n

c

hildren 1-3 year

s• Un

i

-

or

bil

a

t

e

r

al, uni- or multifocal stage,• 2/3 one eye-ball, 1/3 both eye-balls (usu

a

ll

y

n

ot s

i

m

ul

t

a

n

o

u

s

l

y

),

Slide31

2015

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42

T

RE

ATMENT

•

Dependent on clinical stage, presence of metastases and other symptoms.• Therapy of intraocular disease include:1. surgery2. radiotherapy3. cryotherapy

Exam

ples:

teler

adioth

erapy

, br

achyt

hera

py, ph

otoc

oagulat

ion, c

ryother

apy

, la

ser

D

IA

GNO

STIC

S

• Op

htha

lmo

scop

y

• Ocular utrasoun

d• CT of orbits• H

ead /

bra

in

NMR

• Bo

ne

ma

r

r

ow

biopsy•

Biochem

i

c

a

l

t

e

s

ts

(ferritin, NSE, CEA, AFP)

Slide32

2015

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43

CHEM

OTHE

RAPY

•

Improves results of therapy inpatients with extraocular RET• Not obligatory in intraocular stage, but it decreases tumor massand possible met

astases

• Obli

gator

y in

relap

se af

ter e

nucle

ation

• In

pat

ients

with CNS

invo

lveme

nt: cr

anial

ra

dioth

erap

y +

in

trat

hec

al

chem

otherapy

SURGICAL TREATME

NTE

ye-

bal

l enuc

lea

tionI

nd

i

c

a

tions:1. Un

ilater

al

t

um

o

r

,

i

nvolving whole eye-ball, with loss of retinal integrityand disa

b

li

n

g

vi

s

i

o

n

p

r

ese

r

v

a

tio

n

.

2.

T

umo

r

w

i

th

e

x

t

e

n

s

i

o

n

t

o

a

n

t

e

r

i

o

r

ch

a

mb

er

3.

G

l

a

ucoma with intensive pain, loss of vision due to iritis.4. Tumor not responding to local therapy5. Persistent loss of sight with intraocular tumor6. Bilateral stage with complete loss of vision

Slide33

2015

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44

RARE

TUMO

RS

RE

SULTS OF THERAPY• 5-year survival in 80-90% patients in unilateral, 65-70% in bilateral disease• Prognosis – depends on clinical stage, loca

lizat

ion an

d histo

logy

• In

30-

50% p

atie

nts visi

on is

preser

ved

• Over

all

su

rviva

l 8

0%

in e

xtr

aocul

ar R

ET

Slide34

2015

-1

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45

THY

ROID

TUMOR

S

• Possible correlation with RTX of neck• MEN syndromeHEAD AND NECK CANCERS• Nose and pharynx cancer• Esthesioneuroblastoma (olfactory neuroblastoma)• Thy

roid

tumo

rs•

Oral

cance

r• P

arotid

cancer

s•

Laryng

eal tum

ors

Slide35

2015

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46

B

RE

AST C

ANCER

• Non-malignant in most cases• Incidence: both boys and girls– Increased risk in girls after HD with RTX– Carcinoma > sarcoma– Mammography to be performed from age of 25 yr

s

THOR

ACIC

TUMORS

• B

reast

canc

er•

Bronchial

carcinoi

d•

Pleur

al carcion

ama

• Oesophage

al c

arcinoma

• T

hym

oma an

d t

hymus

ca

ncer

•

Car

diac tumors• Mesot

helioma

Slide36

2015

-1

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47

O

THER R

ARE TUMO

RS

IN CHILDREN• Multiple endocrinal neoplasms• Skin neoplasms:– Melanoma– Basal cell cancer– Squamous cell cancerABDOMINAL TUMORS• Adrenal cortex tumors• Renal tumor•

Stoma

ch c

ancer•

Panc

reatic

tumor

• Larg

e int

estine

cancer

• Car

cinoid•

Vesical c

arc

inoma•

Ovar

ian

tumor