refrat-radio (isa).doc

Retinoblastoma dan Aspek Radiologisnya Isabella (406100133)

RETINA DAN TUMOR INTRAOKULER

RETINA

Retina manusia merupakan suatu struktur yang sangat terorganisir, yang terdiri dari

lapisan-lapisan badan sel dan prosesus sinaptik. Walaupun ukurannya kompak dan tampak

sederhana apabila dibandingkan dengan struktur saraf misalnya korteks serebrum, retina

memiliki daya pengolahan yang sangat canggih. Pengolahan visual retina diuraikan oleh

otak, dan persepsi warna, kontras, kedalaman, dan bentuk berlangsung di korteks.

1. Anatomi Retina :

Retina adalah selembar tipis jaringan saraf yang transparan dan multilapis yang

melapisi bagian dalam dua per tiga posterior dinding bola mata. Retina membentang ke

depan hampir sama jauhnya dengan korpus siliare, dan berakhir di tepi ora serrata. Pada

orang dewasa, ora serrata berada sekitar 6,5mm di belakang garis Schwalbe pada sisi

temporal dan 5,7mm dibelakang garis ini pada sisi nasal. Permukaan luar retina sensorik

bertumpuk dengan lapisan epitel berpigmen retina sehingga juga bertumbuk dengan

membrana Bruch, koroid, dan sklera. Di sebagian besar tempat, retina dan epitelium pigmen

retina mudah terpisah hingga membentuk suatu ruang subretina, seperti yang terjadi pada

ablatio retina. Tetapi pada diskus optikus dan ora serrata, retina dan epitelium pigmen retina

saling melekat kuat, sehingga membatasi perluasan cairan subretina pada ablatio retina. Hal

ini berlawanan dengan ruang subarachnoid yang dapat terbentuk antar koroid dan sklera,

yang meluas ke taji sklera. Dengan demikian ablasi koroid meluas melewati ora serrata, di

bawah pars plana dan pars plikata. Lapisan-lapisan epitel permukaan dalam korpus siliaris

dan permukaan posterior iris merupakan perluasan ke anterior retina dan epitelium pigmen

retina. Permukaan dalam retina menghadap ke vitreous.

Lapisan-lapisan retina, mulai dari sisi dalamnya, adalah sebagai berikut :

(1) membrana limitans interna

(2) lapisan serat saraf, yang mengandung akson-akson sel gangglion yang berjalan

menuju nervus optikus

Kepaniteraan Radiologi 1RS Royal TarumaPeriode 01 November -04 Desember 2010


(3) lapisan sel ganglion

(4) lapisan pleksiformis dalam, yang mengandung sambungan-sambungan sel ganglion

dengan sel amakrin dan sel bipolar

(5) lapisan inti dalam badan sel bipolar, amakrin, dan sel horisontal

(6) lapisan pleksiformis luar, yang mengandung sambungan-sambungan sel bipolar dan

sel horisontal dengan fotoreseptor

(7) lapisan inti luar sel fotoreseptor

(8) membrana limitans eksterna

(9) lapisan fotoreseptor segmen dalam dan luar batang dan kerucut

(10) epitelium pigmen retina

Retina mempunyai tebal 0,1 mm pada ora serrata dan 0,23 mm pada katup posterior.

Di tengah-tengah retina posterior terdapat makula. Secara klinis makla dapat didefenisikan

sebagai daerah pigmentasi kekuningan yang disebabkan oleh pigmen luteal (xantofil), yang

berdiameter 1,5 mm. Defenisi alternatif secara histologis adalah bagian retina yang lapisan

ganglionnya mempunyai lebih dari satu lapis sel. Secara klinis, makula ada;ah daerah yang

dibatasi oleh arkade-arkade pembuluh darah retina temporal. Di tengah makula, sekitar 3,5

mm disebelah lateral diskus optikus, terdapat fovea, yang secara klinis merupakan suatu

cekungan yang memberikan pantulan khusus bila dilihat dengan opthalmoscope. Fovea

merupakan zona avaskular di retina pada angiografi fluoresens. Secara histologis, fovea

ditandai dengan menipisnya lapisan inti luar dan tidak adanya lapisan-lapisan parenkim

karena akson-akson sel fotoreseptor (lapisan serat Henle) berjalan oblique dan pergeseran

secara sentrifugal lapisan retina yang lebih dekat ke permukaan dalam retina. Foveila adalah

bagian paling tengah pada fovea, di sini fotoreseptornya adalah sel kerucut, dan bagian retina

yang paling tipis.

Retina menerima darah dari 2 sumber, yaitu koriokapilarian yang berada di luar

membrana Bruch, yang mendarahi sepertiga luar retina, termasuk lapisan pleksiformis luar

dan lapisan inti luar, fotoreseptor, dan lapisan-lapisan eputel pigmen retina; serta cabang-

cabang dari arteria sentralis retinae, yang mendarahi dua per tiga sevelh dalam. Fovea

sepenuhnya diperdarahi oleh koriokapilaria dan mudah terkena kerusakan yang tak dapat

diperbaiki kalau retina mengalami ablasi. Pembuluh darah retina mempunyai lapisan endotel



yang tidak berlobang, yang membentuk sawar darah-retina. Lapisan endotel pembuluh

koroid dapat ditembus. Sawar darah-retina sebelah luar terletak setinggi lapisan epitel

pigmen retina.

2. Fisiologi Retina :

Retina adalah jaringan paling kompleks di mata. Untuk melihat, mata harus

berfungsi sebagai suatu alat optis, sebagai suatu reseptor kompleks, dan sebagai suatu

tranducer yang efektif. Sel-sel batang dan kerucut di lapisan fotoreseptor mampu mengubah

rangsangan cahaya menjadi suatu impuls saraf yang dihantarkan oleh lapisan serat saraf

retina melalui saraf optikus dan akhirnya ke korteks penglihatan. Makula bertanggung jawab

untuk ketajaman penglihatan yang terbaik dan untuk penglihatan warna, dan sebagian besar

selnya adalah kerucut. Di fovea sentralis, terdapat hubungan hampir 1: 1 antara fotoreseptor

kerucut, sel ganglionnya, dan serat saraf yang keluar, dan hal ini menjamin penglihatan yang

paling tajam. Di retina perifer, banyak fotoresptor dihubungkan ke sel ganglion yang sama ,

dan diperlukan sistem pemancar yang lebih kompleks. Akibat dari susunan seperti itu adalah

bahwa makula terutama digunakan untuk penglihatan sentral dan warna (penglihatan fotopik)

sedangkan bagian retina lainnya, yang sebagian besar terdiri dari fotoreseptor batang,

digunakan terutama untuk penglihatan perifer dan malam (skotopik).

Fotoreseptor kerucut dan batang terletak di lapisan terluar yang avaskular pada

retina sensorik dan merupakan tempat berlangsungnya reaksi kimia yang mencetuskan proses

penglihatan. Setiap sel fotoreseptor kerucut mengandung rodopsin, yang merupakan suatu

pigmen penglihatan fosensitif yang terbentuk sewaktu molekul protein opsin bergabung

dengan 11-sis-retinal. Sewaktu foton cahaya diserap oleh rodopsin, 11-sis-retinal segera

mengalam isomerisasi menjadi bentuk all-trans. Rodopsin adalah suatu glikolipid membran

yang separuh terbenam di dalam lempeng membran lapis ganda pada segmen paling luar

fotoreseptor. Penyerapan cahaya puncak pleh rodopsin terjadi pada panjang gelombang 500

nm, yang terletak di daerah biru-hijau pada spektrum cahaya. Penelitian-penelitian

sensitivitas spektrum fotopigmen kerucut memperlihatkan puncak penyerapan panjang

gelombang di 430, 540, dan 575 nm msding-msding untuk sel kerucut peka biru, hijau, dan

merah. Fotopigmen sel kerucut terdiri dari 11-sis-retinal yang terikat ke berbagai protein

opsin.



Penglihatan skotopik seluruhnya diperantarai oleh fotoreseptor sel batang. Pada

bentuk penglihatan adaptasi gelap ini, terlihat bermacam-macam nuansa abu-abu, tetapi

warna tidak dapat dibedakan. Sewaktu retina telah beradaptasi penuh terhadap cahaya,

sensitivitas spektral retina bergeser dari puncak rodopsin 500 nm ke sekitar 560 nm, dan

muncul sensasi warna. Suatu benda akan berwarna apabila benda tersebut mengandung

fotopigmen yang menyerap panjang-panjang gelombang tertentu di dalam spektrum sinar

tampak (400-700 nm). Penglihatan siang hari terutama diperantarai oelh fotoreseptor kerucut,

senjakala oleh kombinasi sel kerucut dan batang, dan penglihatan malam oleh fotoreseptor

batang.

3. Penyakit pada makula :

Degenerasi makula terkait usia

* Degenerasi makula noneksudatif

* Degenerasi makula eksudatif

Korioretinopati serosa sentralis

Edem makula

Gangguan peradangan yang mengenai makula

* Dugaan sindrom Histoplasmosis Okular

* Epiteliopati Pigmen Plakoid Posterior Multifokal Akut (EPPMA)

* Koroidopati Peripapiler Helikoid Geografik

* Neuroretinopati Makula Akut

* Sindrom Bintik Putih Multipel Evanesen

Angioid Streaks

Degenerasi Makula Miopik

Membran Makula Epiretina

Makula Traumatik

Distrofi Makula

* Etinoskisis Juvenilis Terkait-X

* Distrofi Kerucut-Batang

* Fundus Albipungtatus



* Fundus Flavimakulatus (Penyakit Stargadt)

* Distrofi Viteliformis (Penyakit Best)

4. Penyakit retina perifer :

Ablatio retina

* Ablatio Retina Regmatogenosa

* Ablatio Retina akibat Traksi

* Ablatio Retina Serosa dan Haemoragik

Retinopati Prematuritas

Degenerasi Retina

* Retinitis Pigmentosa

* Amaurosis Kongenital Leber

* Atrofi Girata

* Atrofi Korioretina Perifer

* Degenerasi Lattice

Retinoskisis

5. Penyakit pembuluh retina :

Retinopati Diabetes

* Retinopati Diabetes Nonproliferatif

* Retinopati Diabetes Proliferatif

Sumbatan Arteri Retina Sentralis

Sumbatan Arteri Retina Cabang

Sumbatan Vena retina Sentralis

Sumbatan Vena Retina Cabang

Makroaneurisma Arteriol Retina



TUMOR INTRAOKULAR

Tumor Intraokular Jinak Primer

Angioma Retina

Hamartoma Astrositik (Glial)

Tumor Ganas Primer Pada Struktur Intraokular

Retinoblastoma

RETINOBLASTOMAKepaniteraan Radiologi 6RS Royal TarumaPeriode 01 November -04 Desember 2010


LATAR BELAKANG

Retinoblastoma adalah tumor endo-ocular yamg mengenai syaraf embrionik retina

dan merupakan tumor ganas pada anak serta bersifat fatal bila tidak diobati.

40% penderita retinoblastoma merupakan penyakit herediter. Retinoblastoma

merupakan tumor yang bersifat autosomal dominan dan juga merupakan tumor embrional.

Karena jarangnya kasus ini, sebagian besar dokter anak dan ahli onkologi anak hanya melihat

sedikit kasus, sehingga kadang- kadang diagnosis dan penanganannya masih secara

traditional terbatas pada ahli mata. Dengan demikian banyak petugas kesehatan gagal untuk

mendeteksi secara awal, dan biasanya pertama kali diketahui oleh orangtua. Pada

kenyataannya ahli mata biasanya menentukan diagnosis, memutuskan terapi,dan meonitor

responnya.

Rata-rata usia pasien saat diagnosis adalah 24 bulan pada kasus unilateral, 13 bualn

pada kasus-kasus bilateral. Beberapa kasus bilateral tampak sebagai kasus unilateral, dan

tumor pada bagian mata yang lain terdeteksi pada saat evaluasi. Gambaran ini menunjukkan

betapa pentingnya untuk memeriksa pasien dengan anestesi pada anak-anak dengan

retinoblastoma unilateral,khususnya pada usia dibawah 1 tahun.

Pada saat terakhir ini terlihat kenaikam jumlah anak yang menderita retinoblastoma

di Indonesia. Kenaikan inmsidens tumor ini mungkin sekali akibat meningkatnya penerangan

akan tumnor pada anak, sehingga orang tua penderita lebih cepat memeriksakan mata

anaknya.

Penyakit- penyakit lain termasuk inflamasi dapat menstimulasi tumor ini secara

klinis dan dapat mempersulit diagnosa, jadi radiologi merupakan penunjang yang penting

dalam menentukan diagnosa, dimana pada 75% pemderita retinoblastoma menunjukkan

kelainan pada pemeriksaan radiologisnya.

Aspek radiologis yang lebih sering dipergunakan adalah ultrasonography (USG),

Computerized Tomography Scanning (CT scan), dan Magnetic Resonance Imaging (MRI).

HISTOLOGI



Retinoblastoma adalah tumor yang berasal dari neuroepithelial yang dapat

diklasifikasikan sebagai salah satu dari primitive neuroectodermal tumours anak-anak.

Secara histologi terdiri dari sel-sel yang kecil, undiffrentiated, dan anaplastik dengan

sitoplasma sangat sedikit, nukleus besar dan akan tercat secara jelas dengan hematosiklin,

berasal dari dinding inti. Kalsifikasi terjadi pada daerah nekrotik dan ini adalah gambaran

umum dari tumor yang besar. Yang paling umum adalah tipe highly undifferentiated

retinoblasts ;yang lain berupa sel dengan fotoreseptor yang lebih berdiferensiasi dengan

formasi rosset neuroepithelia. Rosettes Flexner Wintersteiner khas pada retinoblastoma tetapi

dapat juga terlihat pada tumor mata yang lain. Kurang umum adalah bentuk tumor dengan

differensiasi baik, adalah 'bouquet-like' yang disusun oleh sel-sel jinak dengan sitoplasma

yang jelas, nukleus kecil, sitoplasma meluas melewati membran. Retinoblastoma dapat

meluas keluar bola mata, menuju sepanjang nervus optikus dan atau subarachnoid ke

kiasma, otak dan meningen. Metastatik retinoblastoma biasanya mengenai sistem syaraf

pusat berupa massa solid atau lesi multipel atau merata dengan leptomeningeal. Tumor ini

dapat juga meluas ke muka, limfonodi preaurikular dan tulang kepala. Selain itu penyebaran

hematogen termasuk ke tulang, sumsum tulang, dan jarang ke hati, paru-paru, atau beberapa

organ lain.

Grabowski dan Abramson, mengembangkan sistem penderajatan berdasarkan 4 tempat

utama dimana retinoblastoma menyebar sebagai berikut:

- Derajat I Intraokular

a. Tumor retina

b. Penyebaran ke lamina kribosa

c. Penyebaran ke uvea

- Derajat II Orbita

a. Tumor orbita

Sel-sel episklera yang tersebar

Tumor terbukti dengan biopsi

b. Nervus optikus

GENETIK



Retinoblastoma dapat terjadi secara familiar atau sporadik. Hanya 6-10% adalah

familial. Namun demikian dapat juga diklasifikasikam menjadi dua subkelompok yang

berbeda, yaitu bilateral atau unilateral dan diturunkan atau tidak diturunkan. Kasus yang

tidak diturunkan selalu unilateral, sedangkan 90% kasus- kasus-kasus yang diturunkan

adalah bilateral., 10% unilateral. Semua kasus bilateral diturunkan, apakah familial atau

sporadik. Pada tahun 1971, Knudson mengambangkan model matematika untuk

menerangkan penurunan retinoblastoma. Dia menerangkan bahwa dua kejadian benturan 'hit'

harus terjadi pada tingkat gena untuk terjadinya retinoblastoma. Pada kasus-kasus yang

diwariskan, kejadian pertama atau 'hit' adalah mutasi akhir ( germinal muation) artinya akan

diturunkan dan tampak pada semua sel individu yang terkena. Benturan atau 'hit' kedua

kadang-kadang terjadi selama perkembangan sel retina, yang akhirnya menjadi

retinoblastoma. Sebaliknya pada kasus-kasus yang tidak diwariskan, kedua bentura atau 'hit'

tersebut terjadi pada sel-sel retina pada keadaaan karena didapat, dan tidak di deteksi pada

'germ line'. Retinoblastoma yang diwariskan, diwariskan secara trait dominan autosom.

Gen retinoblastoma (RBI) diisolasi dari kromosom 13q 14.Gena ini sangat panjang,

lebih dari 200kb. Gena ini berperan sebagai pengatur pertumbuhan sel pada sel normal.

Mutasi gena RBI ditemukan juga pada tumor lain seperti osteosarkoma, small cell lung

carcinoma, dan kanker payudara. Benturan atau hit pertama biasanya berupa delesi atau

translokasi dari gena retinoblastoma, kejadian ini terjadi baik pada allel pihak ibu atau ayah.

Benturan atau hit kedua sering berupa hilangnya heterosigositas allel sisanya, yang akhirnya

mengalami tranformasi neoplastik. Diagnosis secara molekular memegang peranan penting

pada konseling genetik. Apabila mutasi germ-line ditemukan pada satu keluarga, saudara-

saudara lain dapat di tes, dan funduskopi secara regular (dengan anestesi umum pada anak-

anak yang lebih muda), dapat dihindari dimana tidak ditemukan pembawa gena abnormal.

Diagnosis prenatal juga dimungkinkan, apabial mutasi gen RBI ditemukan pada fetus dari

keluarga yang menderita, persalinan lebih dini dapat dianjurkan, sehingga pengobatan tumor

dapat dilakukan sesegera mungkin.

GAMBARAN KLINIS



Gejala dari retinoblastoma sering diketahui oleh orangtuanya, yang secara umum

konsultasi ke dokter ahli mata karena keluhan seringnya leukocoria, strabismus (mata juling),

mata merah, nyeri mata yang sering disertai dengan glaucoma, dan visus yang menurun.

Gejala yang jarang adalah rubeosis iridis (kemerahan pada iris), sellulitis orbita,

heterochromia iridis (perubahan warna pada tempat yang berbeda pada iris), midriasis

unilateral, hyphaema (perdarahan ke bilik depan, yang akan menghasilkam meniscus yang

akan tampak di belakang iris), nistagmus, pada sebagian kecil anak bisa terjadi gagal tumbuh

dan muka yang tidak normal.

Bukti paling awal dari tumor ini adalah gerakan putih, atau yang dikenal sebagai

gerakan mata kucing (cats-eyes reflex) atau leukocoria. Hal ini menunjukkan adanya tumor

besar yang biasanya tumbuh dari tepi. Cahaya putih yang tampak pada pupil adalah sinar

sementara yang direfleksikan oleh tumor. Hal ini hanya akan nampak apabila anak diperiksa

dari samping atau seandainya pemeriksa ada di sudut miring wajah anak lurus terhadap

kepala. Apabila tumor mencapai bagian macular, refleks ini bisa terlihat meskipun ukuran

tumor cukup kecil. Orang tua mungkin mencatat penampakan kelainan ini saat anakanya di

foto, ada sinar kuat yang melalui pupil dan konjungtiva yang akan menghasilkan gambaran

putih pada foto berwarna.

Gejala kedua yang paling umum adalah strabismus. Tes untuk strabismus dianjurkan

sebagai bagian dari skrinning pemeriksaan visus untuk semua anak. Keadaan ini terjadi

apabila tumor mencapai area macular menyebabkan ketidakmampuan untuk fiksasi dan

akhirnya mata akan mengalami deviasi. Gejala yang tampak lainnya karena lesi sekunder

adalah penurunan ketajaman penglihatan.

Sebagian besar pasien retinoblastoma terlalu kecil untuk mengeluh mengenai

gangguan visual, tetapi mungkin bisa manifestasi awal tumor ini pada anak-anak yang lebih

tua. Gejala manifestasi klinik yang lain adalah mata merah, mata sakit, sering disertai dengan

glaucoma. Kebutaan adalah gejala yang timbulnya akhir dan seandainya terjadi unilateral,

sering tidak diketahui baik oleh orang tua maupun oleh dokter anaknya.

Tumor dengan ukuran sedang akan memberikan gejala hipopion di dalam bilik mata

depan, uveitis, endopthalmitis ataupun suatu panofthalmitis. Tumor dapat menyebar luas di

dalam bola mata sehingga bola mata menjadi besar.



Bila terjadi nekrosis tumor akan terjadi gejala peradangan berat sehingga gambaran

retinoblastoma kabur menjadi seperti selulitis orbita, eksofthalmus, edem kelopak,

konjungtiva kemotik dan uveitis granulomatosa.

Pada retinoblastoma yang besar maka tumor akan mengisi seluruh rongga badan

kaca. Di dalam badan kaca akan terlihat benjolan berwarna putih kekuning-kuningan dengan

pembuluh darah diatasnya. Akibat terdapatnya penimbunan kalsium di dalam tumor maka

untuk diagnosis dapat dilakukan pemeriksaan radiologik.

STAGING RETINOBLASTOMA

Sistem yang digunakan secara luas adalah menurut Reese-Ellsworth, untuk

retinoblastoma intraokular.

Grup Deskripsi

I (a) Tumor solid kurang dari 4 dd (disc diameter), pada atau dibelakang ekuator

(b) Tumor multiple tidak lebih dari 4 dd, semua berada atau dibelakang ekuator

II (a) Tumor solid dengan diameter 4-10 dd, pada atau dibelakang ekuator

(b) Tumor multiple dengan diameter 4-10 dd, pada atau dibelakang ekuator

III (a) Beberapa lesi di depan ekuator

(b) Tumor solid lebih besar dari 10 dd di belakang ekuator

IV (a) Tumor multipel, sebagian besar lebih besar dari 10 dd

(b) Beberapa lesi menyebar ke anterior ke ora serrata

V (a) Tumor masif mengenai lebih dari setengah retina

(b) Penyebaran ke vitreousAda juga pendapat lain yang membagi retinoblastoma dibagi menjadi 3 stadium :

1. Stadium tenang



Pupil lebar, tampak refleks kuning yang disebut 'cat eye phenomena'. Pada funduskopi

tampak bercak kuning yang mengkilap, dapat menonjol ke dalam corpus vitreous. Di

permukaannya ada neovaskularisasi dan hemmoragi. Dapat juga disertai dengan ablatio

retina.

2. Stadium glaukomatous

Oleh karena tumor menjadi besar, menyebabkan tekanan intraokuler meninggi, glaucoma

sekunder, disertai dengan rasa sakit yang sangat. Media menjadi keruh, sehingga pada

funduskopi sukar menentukan besarnya tumor.

3. Stadium ekstraokuler

Tumor menjadi lebih besar, bulbus okuli membesar, menyebabkan exopthalmus, kemudian

dapat pecah ke depam sampai keluar dari rongga orbita disertai nekrosis diatasnya.

Pada stadium ini dapat terjadi metastase tumor.

POLA PERTUMBUHAN DAN PENYEBARAN RETINOBLASTOMA

Pola pertumbuhan retinoblastoma

Retinoblastoma dapat terjadi pada suatu tempat (soliter) atau pada beberapa tempat

(multiple) di retina secara spontan, atau dapat tumbuh pada kedua retina, yaitu pada

retinoblastoma bilateral.

Retinoblastoma dapat tumbuh keluar (eksofilik), kedalam (endofilik), atau difus.

Retinoblastoma eksofilik :

tumor yang tumbuh terutama ke dalam subretina dan pada pertumbuhan selanjutnya

retina akan terdesak dan terlepas dari dasarnya.

Retinoblastoma endofilik :

tumor yang terutama tumbuh ke arah corpus vitreous, pada jenis ini retina tidak lepas

dari dasarnya.

Retinoblastoma difus :

tumor yang tumbuh disepanjang retina, melapisi seperti massa placoid, tidak ditemukan

adanya kalsifikasi

Pola penyebaran retinoblastoma

Penyebaran retinoblastoma terjadi melalui 5 jalur :



a. Cairan serebrospinal => otak dan medula spinalis

b. Aliran darah => melewati jantung => menuju bagian tubuh yang jauh letaknya

c. Dari rongga orbita yang satu ke yang lain

d. Karena pertumbuhan atau bertambah besarnya tumor sendiri => perluasan ke jaringan

sekitar

e. Cairan limfe => kelenjar limfe regional

- Penyebaran ke depan :

Pada penyebaran ke depan akan terjadi penaburan sel ke dalam corpus vitreous,

kemudian juga ke dalam aquos humor, terutama pada jenis retinoblastoma endofilik.

Penaburan sel-sel tumor dalam kamera okuli anterior menimbulkan gejala-gejala yang

menyerupai hipopion.

- Penyebaran ke belakang :

Terutama sel-sel tumor yang tumbuh eksofilik akan masuk ke lapisan koroid dengan

cara implantasi pada permukaan jaringan atau dari tepi nervus optikus pada perbatasan

dengan membran Bruch. Dalam jaringan yang kaya pembuluh darah ini sel tumor

berkembang biak dan sebagai embolus masuk ke dalam vena vortikosa atau pembuluh darah

emisaria yang lain.

Dengan aliran darah melalui jantung, terjadi metastasis ke berbagai alat tubuh yang

jauh letaknya; metastasisi ini dapat pula terjadi melalui vena sentralis retina.

- Penyebaran ke dalam kavum orbita :

Penyebaran ke dalam rongga orbita dapat terjadi melalui beberapa cara, antara lain :

melalui vena emisaria atau karena robeknya bulbus okuli atau tercecernya sel tumor ke

dalam rongga orbita akibat tindakan operasi. Sel tumor yang telah lolos dari bulbus okuli

sesampainya dalam corpus orbita akan berkembang biak, dan kemudian menerobos ke dalam

sinus -sinus dan tulang -tulang di sekitarnya, termasuk mulut dan hidung.

Sel tumor mencapai nervus optikus karena perluasan tumor di papilla nervus optikus

atau menyusupnya tumor di tempat-tempat vasa senralis retina masuk ke dalam nervus

optikus. Dengan cara ini sel tumor mencapai ruang subarachnoid.



- Penyebaran ke dalam rongga tengkorak :

Terutama menyebar ke selaput arachnoid dan subarachnoid. Dalam rongga

tengkorak, sel tumor yang berada dalam ruang subarachnoid sepanjang nervus optikus akan

menempuh 2 jalan, yaitu :

1. Sel tumor akan masuk ke rongga orbita lain, setelah melewati chiasma optikus ,

kemudian tumbuh menjadi besar di belakang bulbus okuli.

2. Sel tumor akan berproliferasi di chiasma optikus dan masuk ke dalam saraf mata

sebelah yang lain atau masuk ke dalam otak.

Jaringan otak sendiri akan terkena karena tumor menjalar dari ruang subarachnoid ke otak

mengikuti pembuluh-pembuluh darah. Ini dapat pula terjadi karena invasi langsung dari

tumor di chiasma optikus atau karena erosi tulang oleh tumor sehingga dapat menembus

duramater, arachnoid, dan piamater.

- Penyebaran ke dalam tulang :

Kalkavarium dan tulang-tulang di sekitar mata terkebna tumor ini karena

penyebarannya yang langsung di mata, sedangkan metastasis ke tulang yang jauh letaknya

terjadi melalui aliran darah. Tulang yang sering terkena adalah tulang rusuk dan tulang

vertebrae. Tulang-tulang tersebut berperan aktif dalam sistem hemopoetik sehingga tumor

dapat tumbuh subur didalamnya.

- Penyebaran ke alat-alat dalam :

Alat-alat dalam yang sering terkena metastasis tumor ini ialah hati, ginjal, dan limpa,

tetapi pada kelainan hati tidak sampai menimbulkan iktherik.

DIAGNOSIS

Diagnosis dari retinoblastoma dibuat dengan melakukan pemeriksaan kedua mata.

Jika bayi yang baru lahir mempunyai riwayat keluarga menderita retinoblastoma, bayi Kepaniteraan Radiologi 14RS Royal TarumaPeriode 01 November -04 Desember 2010


tersebut harus diperiksa segera sesudah kelahiran oleh seorang dokter spesialis kanker mata.

Jika pupil terlihat putih atau strabismus ( mata juling ) ditemukan oleh orangtua pada

anaknya, maka anak sebaiknya dirujuk ke opthalmologist yang familiar dengan

retinoblastoma. Dokter akan melakukan pemeriksaan untuk melihat adakah tumor di retina

atau tidak. Penggunaan anestesi lokal atau umum saat pemeriksaan mata ditentukan

berdasarkan umur anak tersebut. Opthalmologist akan memberikan gambaran tumor pada

mata tersebut untuk menentukan pemeriksaan selanjutnya dan penatalaksanaan yang akan

diberikan, dan mungkin akan memerlukan tes-tes sederhana untuk mendeteksi tumor

tersebut. Tes-tes tersebut diantaranya :

Pencitraan

* USG

USG dapat sangat membantu untuk membuat diagnosis banding dari anak-

anak dengan leukocoria. Pemeriksaan USG mata akan menunjukkan dua kriteria

(khas dan spesifik untuk retinoblastoma), yaitu :

1. Ada massa mengandung deposit kalsium yang tinggi

2. Multifokal echo wave

USG tidak hanya mendeteksi kalsifikasi, tapi juga dapat memperhitungkan ukuran

tumor tersebut.

* CT-scan

CT- scan sangat berguna untuk mengevaluasi nervus optikus, orbital,

keterlibatan sistem saraf pusat dan adanya kalsifikasi intraokular. Pada pasien

retinoblastoma seringkali seperti massa jaringan lunak dengan foci kalsifikasi.

CT-scan dapat mendeteksi kalsifikasi retinoblastoma secara akurat. Ada

korelasi yang jelas antara aslinya dengan derajat kalsifikasi yang terlihat dalam

CT-scan.CT-scan mempunyai sensitivitas yang sama dengan USG dan hasilnya

juga berguna dalam menetapkan penyebaran retrobulbar, metastase intra-kranial

dan tumor-tumor lainnya.

CT-scan merupakan pendiagnosis terpilih pada kasus retinoblastoma dengan

leukocoria, walaupun pemeriksaan ektensif untuk membuktikan tumor

retinoblastoma yang kecil sangat tidak dianjurkan.



* MRI

Pendiagnosaan retinoblastoma pada MRI tidak sespesifik pada CT-scan

karena MRI kurang sensitif untuk mendeteksi kalsifikasi ( kalsifikasi <2mm tidak

terdeteksi oleh MRI ). Tetapi MRI juga dapat berguna untuk mengevaluasi nervus

optikus, orbital, keterlibatan sistem saraf pusat dan adanya kalsifikasi intraokular

sama seperti CT-scan.

MRI spesifik untuk membedakan retinoblastoma dari lesi-lesi yang serupa.

MRI merupakan pendiagnostik terpilih untuk mendeteksi penyebaran dari

retinoblastoma ke subarachnoid. Baik CT-scan maupun MRI dapat mendeteksi

trilateral/tetralateral retinoblastoma sebaik mendeteksi adanya tumor kedua.

* Rontgen

Penemuan dapat berupa “mottled calsification” di nodul tumor kecil yang

telah membentuk degenerasi dan kalsifikasi.

Kalsifikasi dapat metastase ke intraserebral. Dalam penambahan kalsifikasi,

massa jaringan lunak mungkin ada dalam orbitnya. Tumor akan menetap selama

nervus optikus tetap memproduksi pembesaran foramen optic, dimana akan

terlihat pada foto rontgen, dan ketika tumor menyebar diluar nervus optikus, erosi

irreguler dari foramen optic akan berkembang. Pada keadaan dimana pasien

mengeluh nyeri tulang ( kemungkinan metastasis ke tulang ) scan tulang

diindikasikan.

Tes tambahan

* Pemeriksaan darah

Untuk mengevaluasi darah dan mengetahui masalah-masalah yang berhubungan

dengan hati dan ginjal. Dokter juga akan melihat adanya perubahan kromosom 13

melalui pemeriksaan darah.



* Lumbal punksi

Cairan serebrospinal diambil sedikit dengan jarum pada lumbal anak dan

kemudian cairan ini diperiksa dibawah mikroskop untuk melihat ada ato tidak sel

kanker.

* Aspirasi sumsum tulang

Untuk memeriksa apakah ada sel- sel retinoblastoma yang menyebar ke sumsum

tulang. Cairan sumsum tulang yang diambil diperiksa dibawah mikroskop.

* Pemeriksaan Multinucleate Tumor Cells (MNTC)

Merupakan pemeriksaan untuk mengetahui adanya regresi tumor.

* Pemeriksaan Biometric Measurement

Dikerjakan sebagai lanjutan USG dan juga berguna untuk follow-up.

* Pemeriksaan Gen Linkage

Pilihan cara diagnostik berdasarkan deteksi genetik yang menunjukkan

abnormalitas kromosom 13q14. Pemeriksaan ini menggunakan protein esterase-D

yang memiliki lokus gen terdekat dengan gen retinoblastoma. Manifestasi

kliniknya tergantung pada ketiadaan kromosom ke-13.

* Pemeriksaan sitoimunologik

Dikerjakan dengan menggunakan antibodi monoclonal pada S-antigen retinal.

Investigasi ini menggunakan pemeriksaan imunohistopatologik yang sangat

spesifik untuk retinoblastoma dan akan membedakan dari pineoblastoma dalam

kasus trilateral retinoblastoma.



DIAGNOSIS BANDING

Retinoblastoma intraokular Retinoblastoma ekstraokular

Penyakit Coat'sPersistent hyperplastic primary vitreous Retrolental fibroplasiaRetinal hamartomaEndopthalmitis Infeksi toxocaraAstrocytic hamartomasMeduloepiteloima IKatarakUveitis

Sellulitis orbitalNeuroblastoma metastatik Rhabdomiosarcoma orbitalLeukemiaLimfoma

PENATALAKSANAAN

Dua aspek pengobatan retinoblastoma harus diperhatikan, pertama adalah

pengobatan lokal untuk jenis intraokular, dan kedua adalah pengobatan sistemik untuk jenis

ekstraokular, regional, dan metastatik.

Di negara berkembang, kebanyakan pasien memperlihatkan penyakit intraokular,

dan harapan hidupnya sekitar 95%. Pada kasus-kasus ini rencana terapi harus

dipertimbangkan untuk menjaga potensi dan kegunaan visus, meminimalkan komplikasi

jangka panjang. Ukuran, jumlah, dan lokasi tumor dan status mata harus diperhitungkan

untuk memilih terapi. Sebagian besar pasien dengan retinoblastoma bilateral datang dalam

keadaan massa intraokular yang sudah lanjut pada satu mata, sering membutuhkan enukleasi,

sementara pada bagian mata yang lain masih belum lanjut, dan bisa bertahan.

Hanya 17% pasien dengan retinoblastoma bilateral kedua matanya masih terlindungi.

Gambaran seperti ini lebih banyak pada keluarga yang memiliki riwayat keluarga, karena

diagnosis biasanya lebih awal. Sementara 13% pasien dengan retinoblastoma bilateral kedua

matanya terambil atau keluar karena penyakit intraokuler yang sudah lanjut, baik pada waktu

masuk atau setelah gagal pengobatan lokal.



Di negara berkembang, retinoblastoma biasanya didiagnosis setelah menyebar ke

ekstraokuler. Pada kasus seperti ini, tujuan terapi adalah untuk menjaga kehidupan pasien,

karena kematian sangat mungkin terjadi karena metastasis.

Jenis- jenis terapi:

1. Pembedahan

2. Eksternal beam radiotheraphy (EBRT)

3. Radioterapi plaque

4. Cryotherapy dan fotokoagulasi

5. Kemoterapi

Keterangan :

1. Pembedahan

Enukleasi adalah terapi yang paling sederhana dan aman untuk retinoblastoma.

Pemasangan bola mata palsu dilakukan beberapa minggu setelah prosedur ini, untuk

meminimalkan efek kosmetik. Bagaimanapun, apabila enukleasi dilakukan pada dua tahun

pertama kehidupan, asimetri wajah akan terjadi karena hambatan pertumbuhan orbita. Jika

mata kontralateral juga terlibat cukup parah maka pendekatan konservatif mungkin bisa

diambil.

Enukleasi dianjurkan apabila terjadi glaukoma, invasi ke rongga anterior, atau terjadi

rubeosis iridis, dan apabila terapi lokal tidak dapat dievaluasi karena katarak atau gagal untuk

mengikuti pasien secara lengkap atau teratur. Enukleasi dapat ditunda atau ditangguhkan

apabila pada saat diagnosis tumor sudah menyebar ke ekstraokular. Massa orbita biasanya

akan menyusut setelah beberapa siklus kemoterapi, diikuti enukleasi dan eksenterasi orbita

harus dihindari. Pembedahan intraokular seperti vitrektomi adalah kontraindikasi pada pasien

retinoblastoma, karena akan menaikkan relaps orbita.

2. External beam radiotherapy (EBRT)

Retinoblastoma merupakan tumor yang radiosensitif dan radioterapi elektif

lokal untuk kasus ini. EBRT menggunakan akselerator liniar dengan dosis 40-45Gy

dengan pemecahan konvensional yang meliputi seluruh retina. Pada bayi muda harus



dibawah anestesi dan imobilisasi selama prosedur ini, dan harus ada kerjasama yang

erat antara dokter ahli mata dan dokter radioterapi untuk membuat perencanaan.

Keberhasilan EBRT tidak hanya ukuran tumor, tetapi tergantung tehnik dan

lokasi. Gambaran regresi setelah radiasi akan terlihat dengan opthalmoscopy.

Sebagian besar kasus rekurensi setelah radiasi dapat diterapi lagi dengan cryotherapy

atau fotokoagulasi. Efek samping jangka panjang dari radioterapi harus diperhatikan.

Seperti enukleasi, dapat terjadi komplikasi hambatan pertumbuhan tulang orbita,

yang akhirnya akan menyebabkan gangguan kosmetik. Hal yang lebih penting adalah

terjadinya malignansi sekunder.

3. Radioterapi plaque

Radioaktif episkeral plaque menggunakan 60Co, 106Ru, atau 125I sekarang makin

sering digunakan untuk mengobati retinoblastoma. Cara ini biasanya digunakan untuk tumor

yang ukurannya kecil sampai sedang yang tidak setuju dengan cryotherapy atau

fotokoagulasi, pada kasus yang residif setelah EBRT, tetapi akhir-akhir ini juga digunakan

pada terapi awal, khususnya setelah kemoterapi. Belum ada bukti bahwa cara ini akan

menimbulkan malignansi sekunder.

4. Cryotheraphy dan fotokoagulasi

Cara ini digunakan untuk mengobati tumor kecil (kurang dari 5mm) dan dapat

diambil. Cara ini sudah secara luas digunakan dan dapat diulang beberapa kali sampai

kontrol lokal tercapai. Cryotherapy biasanya ditujukan untuk tumor bagian depan dan

dilakukan dengan petanda kecil yang diletakkan di konjungtiva. Sementara fotokoagulasi

secara umum digunakan untuk tumor bagian belakang baik menggunakan laser argon atau

xenon. Fotokoagulasi tidak boleh diberikan pada tumor dekat makula atau diskus optikus,

karena bisa meninggalkan jaringan parut yang nantinya akan menyebabkan ambliopia.

Kedua cara ini tidak akan atau sedikit menyebabkan komnplikasi jangka panjang.

5. Kemoterapi



Pada beberapa tahun terakhir , banyak kelompok yang menggunakan kemoterapi

sebagai terapi awal untuk kasus intraokular, dengan tujuan untuk mengurangi ukuran tumor

dan membuat tumor bisa diterapi secara lokal. Kemoterapi sudah dibuktikan tidak berguna

untuk kasus intraokular, tetapi dengan menggunakan obat yang lebih baru dan lebih bisa

penetrasi kemata, obat ini muncul lagi. Pendekatan ini digunakan pada kasus-kasus yang

tidak dilakukan EBRT atau enukleasi, khususnya kasus yang telah lanjut. Carboplatin baik

sendiri atau dikombinasi dengan vincristine dan VP16 atau VM26 sudah digunakan.

Sekarang kemoreduksi dilakukan sebagai terapi awal kasus retinoblastoma bilateral dan

mengancam fungsi mata.

Penentuan stadium secara histopatologi setelah enukleasi sangat penting untuk

menentukan resiko relaps. Banyak peneliti memberikan kemoterapi adjuvant untuk pasien-

pasien retinoblastoma intraokular dan memiliki faktor resiko potensial seperti nervus optikus

yang pendek (<5mm), tumor undifferentiated, atau invasi ke nervus optikus prelaminar.

Kemoterapi intratekal dan radiasi intrakranial untuk mencegah penyebaran ke otak tidak

dianjurkan.

Apabila penyakitnya sudah menyebar ke ekstraokuler, kemoterapi awal dianjurkan.

Obat yang digunakan adalah corboplatin, etoposid, teniposid, siklofosfamid, ifosfamid,

vinkristin, adriamisin, dan akhir-akhir ini adalah dikombinasi dengan idarubisin. Meskipun

laporan terakhir menemukan bahwa invasi keluar orbita dan limfonodi preauricular

dihubungkan dengan keluaran yang buruk, sebagian besar pasien ini akan mencapai harapan

hidup yang panjang dengan pendekatan kombinasi kemoterapi, pembedahan, dan radiasi.

Meskipun remisi bisa dicapai oleh pasien dengan metastasis, biasanya mempunyai kehidupan

pendek. Hal ini biasanya dikaitkan dengan ekspresi ynag berlebihan p 170 glikoprotein pada

sel retinoblastoma, yang dihubungkan dengan multidrug resistance terhadap kemoterapi.

PROGNOSIS



Tumor mempunyai prognosis baik bila ditemukan dini dan intraokular. Prognosis

sangat buruk bila sudah tersebar ekstraokular pada saat pemeriksaan pertama. Tumor dapat

masuk ke dalam otak melalui syaraf optik yang terkena infiltrasi dari sel tumor.

Dapat terjadi penyebaran melalui kelenjar limfe atau darah. Bila penyebaran melalui

kelenjar limfe selain akan memberikan infiltrasi keluar mata, juga akan mengenai kelenjar

preaurikuler atau submandibula. Penyebaran melalui darah akan mengenai sumsum tulang

dan viscera terutama hati.

KESIMPULAN

Retinoblastoma merupakan tumor ganas fotoreseptor retina pada masa anak-anak

yang jarang terjadi tapi bersifat fatal apabila tidak diobati.

Retinoblastoma biasanya tidak disadari sampai perkembangannya cukup lanjut

sehingga menimbulkan kesulitan melihat, strabismus, leukocoria, peradangan mata atau

proptosis.

Tumor ini bermetastase secara langsung dalam rongga tengkorak dan melalui aliran

darah ke tulang-tulang sketal. Metastasisnya yang pertama ke dalam sumsum tulang dan

rongga medulla dan mengakibatkan perluasan penghancuran tulang spongiosa di dinding

kortikal atas. Kadang-kadang sel neoplasma tumbuh dibawah periosteum dan menyebabkan

pembengkakan sehingga kulit ari dari korteks peripheral dapat terlihat. Dalam fase

selanjutnya sel-sel neoplasma menstimulasi osteoblast untuk memproduksi pertumbuhan

tulang secara berlebih dan menimbulkan reaksi osteoblast. Keduanya mendestruksi dan

menyebabkan timbulnya lesi retinoblastoma di tulang-tulang skeletal.

Sebagian besar penyebaran retinoblastoma bersifat sporadik (tanpa transmisi ke

generasi berikutnya), tetapi sebagian lainnya diturunkan secara autosomal dominan. Pada

anak dari keluarga yang mengidap retinoblastoma familial, perlu dilakukan pemeriksaan gen

linkage.

Bayi dan anak dengan gejala awal strabismus harus diperiksa secara cermat untuk

menyingkirkan retinoblastoma, karena mata yang berdeviasi mungkin merupakan tanda

pertama tumor.



CT-scan dapat mendeteksi kalsifikasi retinoblastoma secara akurat. Ada korelasi

yang jelas antara aslinya dengan derajat kalsifikasi yang terlihgat dalam CT-scan, karenanya

CT-scan sebaiknya dilakukan secara rutin pada pasien yang diduga menderita

retinoblastoma. CT-scan mempunya sensitivitas yang sama dengan USG dan hasilnya juga

berguna dalam menetapkan penyebaran retrobulbar, metastasis imtrakranial dan tumor-tumor

lainnya. CT-scan merurpakan pendiagnosis terpilih pada kasus retinoblastoma dengan

leukocoria, walaupun pemeriksaan ekstensif untuk membuktikan tumor retinoblastoma yang

kecil sangat tidak dianjurkan.

Pengobatan terpilih untuk hampir semua kasus retinoblastoma unilateral yang luas

adalah enukleasi. Pada kasus bilateral sering digunakan terpai koservatif dengan radioterapi,

baik dengan plaque episklera maupun external beam, dan tehnik-tehnik fotokoagulasi untuk

memperingan keparahan.

DAFTAR PUSTAKA



Sutton, David.1992.A Textbook of Radiology and Imaging fifth edition.Churchill

Livingstone.

Kanski, Jack J. 2000. Clinical Ofthalmology A systemic Approach fourth edition.

Butterworth Heinmann.

Vaughan, Daniel G.,dkk.1996. Ofthalmologi Umum edisi 14.Jakarta: Widya Medika.

Ilyas, Sidarta.2000. Kedaruratan dalam Ilmu Penyakit Mata cetakan kedua.Jakarta:

FK UI.

Permono, H.Bambang, dkk.2010.Buku Ajar Hematologi-Onkologi anak cetakan

ketiga.Jakarta: IDAI.

LAMPIRAN



What Is Retinoblastoma?

Retinoblastoma (reh-tin-oh-blast-oma) is a childhood cancer arising from immature retinal cells in one or both eyes and can strike from the time a child is in the womb up to 5 years of age. This cancer is curable if caught early enough. However, 87% of the children stricken with this disease worldwide die, mostly in developing countries. In developed countries, 97% of those who do live have moderate to severe visual impairment or the child may loose one or both eyes. Retinoblastoma is a relatively uncommon tumor of childhood that accounts for about 3% of the cancers in children under the age of 15. The tumors originate in the retina, the light sensitive layer of the eye, which enables the eye to see. When the tumors are present in one eye, it is referred to as unilateral retinoblastoma, and when it occurs in both eyes it is referred to as bilateral retinoblastoma. 60% of the cases involve only one eye (unilateral); the rest affect both eyes (bilateral). 90% of retinoblastoma patients have no family history of the disease and only 10% of newly diagnosed patients have other family members with retinoblastoma.Early diagnosis and intervention is critical to the successful treatment of this disease.

Common signs of retinoblastoma include:-A white "glow" or "glint" in the pupil of one or both eyes in dim lighting-White pupil in a color photo-Crossed or misaligned eyes

New Brochure Promoting Early Detection

Although it is rare, retinoblastoma can spread or metastasize outside of the eye to the brain, the central nervous system (brain and spinal cord), and the bones. In these cases, chemotherapy is prescribed by a pediatric oncologist and is administered through the peripheral blood vessels or into the brain for months to years after initial diagnosis of metastatic disease.

This photo shows the "white glow" often indicating the presence

of a tumor. If you notice this white glow in any of your children’s

photos, please contact your pediatrician or ophthalmologist

immediately and have their eyes examined. Request pupil dilation

of both eyes. If your physician is unable or unwilling to do the

pupil dilation, please insist on a referral.


http://www.retinoblastoma.net/brochures/RBI_brochure_outside_1009.pdf


Retinoblastoma in children

This information is about retinoblastoma in children. It is helpful to read it alongside

our general information on children's cancer, which contains detailed information

about cancers in children, their diagnosis and treatment, and the support services

available.

Retinoblastoma

About 40 cases of retinoblastoma are diagnosed in the UK each year. Most of these occur in

children under the age of five, although it can affect children of any age.

Retinoblastoma is a tumour that occurs in the retina. This is the light-sensitive lining of the

eye.


http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Childrenscancers/Aboutchildrenscancers/Aboutchildrenscancers.aspx


Structure of the eye

Retinoblastoma can occur in two forms:

-a heritable form where there are often tumours in both eyes (bilateral) or sometimes only

in one eye

-a non-heritable form where there is a tumour in only one eye (unilateral).

Causes of retinoblastoma

The heritable form of retinoblastoma, which accounts for about two in every five cases, is

caused by a genetic abnormality. This means that an abnormal gene allows the tumour to

develop. This abnormal gene may either be inherited from a parent or occur for the first time

at an early stage of development in the womb. People with this gene, known as the Rb gene,

also have an increased risk of developing other types of tumour later in life.

Genetic counselling and support is available for families in which a member has

retinoblastoma. Not all children of an affected parent will inherit this gene. However, all

children born into families with a history of retinoblastoma will be offered blood testing and

will usually be checked (screened) for signs of retinoblastoma so that treatment can be

started early if a tumour does develop.

Screening usually starts shortly after birth and is repeated every few months for five years.

An eye specialist examines the eye, while shining a light into it with an ophthalmoscope.

The cause, or causes, of retinoblastoma remain unknown. However, the genetic abnormality

in the heritable form of the disease is now well understood. The cause of non-heritable

retinoblastoma is unknown.

Signs and symptoms

Some children with retinoblastoma may have no symptoms, but it will be picked up by

screening (in children of families with a history of the condition).

If there is no family history of retinoblastoma, the first sign of the condition is often a white

pupil that does not reflect the light (leucocoria). This may be detected when a picture of your



child is taken using flash photography. The affected eye may look white in the photograph.

Some children may have a squint or, if the tumour is large, they may have a painful red eye.

How it is diagnosed

Tests may involve an examination under anaesthetic (EUA) in which an eye specialist

(ophthalmologist) will examine your child’s eye while they are asleep. Unlike nearly all

other types of cancer, retinoblastomas can be diagnosed just by their appearance, and taking

a tissue sample (biopsy) is not usually necessary. Several more EUAs will be carried out to

check on the progress of treatment.

Once a retinoblastoma is diagnosed, other tests may be done to check the exact position and

size of the tumour, and whether it has begun to spread into surrounding structures. This is

known as staging.

An ultrasound scan may be used, which is a painless scan that uses sound waves to examine

the eye and the surrounding area.

An MRI (magnetic resonance imaging) scan is a series of detailed images that show the

structures of the eye and brain.

A lumbar puncture may be used to examine some of the fluid from around the brain and

spinal cord (cerebrospinal fluid), to see if there are any tumour cells present.

A bone marrow sample may be taken to check if there has been any spread of the cancer to

the bone marrow. Some children may also need a bone scan so that doctors can look more

closely for signs of any spread to the bones.

A blood test may be taken for genetic testing for the Rb gene. Results of this test can take

some months.

Any tests and investigations that your child needs will be explained to you. Our general

information on children’s cancers gives more details of what the tests and scans involve .

Staging


http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Childrenscancers/Symptomsdiagnosis/Tests.aspx

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Lumbarpuncture.aspx


The 'stage' of a cancer is a term used to describe its size and whether it has spread beyond its

original site in the body. Knowing the particular type and the stage of the cancer helps the

doctors to decide on the most appropriate treatment.

A commonly-used staging system for retinoblastoma is described below:

Intraocular retinoblastoma There is cancer in one, or both, eyes but it has not begun to

spread to other parts of the eye or into the tissues surrounding the eye. This stage is

sometimes sub-divided into five grades (A to E) depending upon the size and position of the

tumour, and the extent of any damage to the eye. It gives the doctors more information to

help them plan appropriate treatment.

Intraocular retinoblastoma There is cancer in one, or both, eyes but it has not begun to

spread to other parts of the eye or into the tissues surrounding the eye. This stage is

sometimes sub-divided into five grades depending upon the size and position of the tumour,

and the extent of any damage to the eye. It gives the doctors more information to help them

plan appropriate treatment.

Extraocular retinoblastoma The cancer has spread beyond the eye and into the tissue

surrounding it or to other parts of the body.

If the cancer comes back after initial treatment, it is known as recurrent cancer. It may come

back in the eye, the tissue surrounding the eye, or in other parts of the body.

Treatment

This depends on the number, position and size of the tumours in the eye. The aim of

treatment is firstly to get rid of the cancer and secondly to try to keep the sight in the eye.

Depending on the treatment, some children may lose some of their sight.

Smaller tumours



For smaller tumours, treatment is given to the eye itself (local therapy), by one of the

following methods:

Cryotherapy This is used to freeze the tumours. More than one session may be necessary (in

which case they are usually done at monthly intervals).

Laser therapy A laser is used to heat the tumour. Two or three sessions may be needed at

monthly intervals.

Plaque For slightly larger tumours, and tumours that have not been successfully treated

using other methods, a small radioactive disc can be stitched over the tumour on the

outside of the eye. The disc needs to stay in place for up to four days. The radiation

destroys the cancer cells.

Thermotherapy This process uses heat to destroy the cancer cells and may be combined

with chemotherapy or radiotherapy , as heat can improve the effectiveness of these

treatments. The heat is produced by a laser, which is directed at the tumour.

Larger tumours

These can be treated in a number of ways, including:

Chemotherapy Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer

cells. This may be given before the local treatments mentioned above, to help to

shrink the tumour. This can make the treatment more successful. Chemotherapy can

also be used if the cancer has spread to other parts of the body, or if it is thought that

there is a significant risk that it will do so.

Surgery If the tumour is very large and the vision in the eye is lost, the eye is likely to be

removed. This is called enucleation. An artificial eye (prosthesis) is then fitted.

Radiotherapy External beam radiotherapy can be given to the whole eye. Radiotherapy

treats cancer by using high-energy rays from a machine, to destroy the cancer cells

while doing as little harm as possible to normal cells, although there will be some

effect on the surrounding tissue. Radiotherapy for retinoblastoma is usually used in

situations when other treatments have not been successful.

Side effects of treatment


http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Radiotherapy/Radiotherapy.aspx

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Chemotherapy.aspx

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Radiotherapy/Radiotherapy.aspx

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Chemotherapy.aspx


Treatment for retinoblastoma often causes side effects, some of which can develop many

years later. Your child’s doctor will discuss these with you before treatment starts. Any

possible side effects will depend upon the particular treatment being used.

Clinical trials

Many children have their treatment as part of a clinical research trial . Trials aim to

improve our understanding of the best way to treat an illness (usually by comparing the

standard treatment with a new or modified version of it).

Specialist doctors carry out trials for children's cancer. Your child's medical team will talk to

you about taking part in a clinical trial (if appropriate) and will answer any questions you

may have. Written information is often provided to help explain things.

Taking part in a research trial is completely voluntary, and you'll be given plenty of time to

decide if it is right for your child.

Follow-up

At least 9 out of every 10 children with retinoblastoma are cured. Following treatment, the

eye specialist will frequently examine your child’s eye under anaesthetic to check that the

cancer has not come back. Follow-up is usually in a clinic for childhood cancers (a paediatric

oncology clinic).

If the retinoblastoma is the heritable form, your child will be given genetic counselling when

they are old enough to understand it.

If you have specific concerns about your child’s condition and treatment, it is best to discuss

them with your child’s doctor, who knows the situation in detail.

Your feelings

As a parent, the fact that your child has cancer is one of the worst situations you can be faced

with. You may have many different emotions , such as fear, guilt, sadness, anger and

uncertainty. These are all normal reactions, and are part of the process that many parents go

through at such a difficult time.


http://www.macmillan.org.uk/Resourcessupport/Relationshipscommunication/Emotionaleffects

http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Clinicaltrials/Clinicaltrials.aspx


Your child may have a range of powerful emotions throughout their experience of cancer.

Our booklet, Peppermint Ward is a storybook for 6–9 year-old children with cancer. It

looks at the issues that they and their family may face, and helps them to explore their

feelings.

RetinoblastomaClassification and external resources


http://be.macmillan.org.uk/be/p-301-peppermint-ward.aspx


Retinoblastoma (Rb) is a rapidly developing cancer which develops in the cells of retina,

the light detecting tissue of the eye. In the developed world, Rb has one of the best cure rates

of all childhood cancers (95-98%), with more than nine out of every ten sufferers surviving

into adulthood. Retinoblastoma is a very treatable cancer.

Classification

There are two forms of the disease; a genetic, heritable form and a non-genetic, non-

heritable form. Approximately 55% of children with Rb have the non-genetic form. If there

is no history of the disease within the family, the disease is labelled "sporadic", but this does

not necessarily indicate that it is the non-genetic form.

In about two thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other

third, tumours develop in both eyes (bilateral retinoblastoma). The number and size of

tumours on each eye may vary. In certain cases, the pineal gland is also affected (trilateral

retinoblastoma). The position, size and quantity of tumours are considered when choosing

the type of treatment for the disease.

Signs and symptoms

The most common and obvious sign of retinoblastoma is an abnormal appearance of the

pupil, leukocoria. Other less common and less specific signs and symptoms are:

deterioration of vision, a red and irritated eye, faltering growth or delayed development.

Some children with retinoblastoma can develop a squint, commonly referred to as "cross-

eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in

developing countries and eye enlargement is a common finding.



Depending on the position of the tumors, they may be visible during a simple eye exam using

an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only

with an examination under anesthetic (EUA). A white eye reflection is not always a positive

indication of retinoblastoma and can be caused by light being reflected badly or by other

conditions such as Coats's Disease.

In a photograph, the photographic fault red eye may be a sign of retinoblastoma, if in the

photograph it is in one eye and not in the other eye.

Leukocoria in a child with retinoblastoma Crossed eyes in a child with retinoblastoma

Frequency of retinoblastoma

Retinoblastoma is rare and affects approximately 1 in 15,000 live births.In the UK, around

40 to 50 new cases are diagnosed each year.

Most children are diagnosed before the age of five years old. In the UK, bilateral cases

usually present within the first year with the average age at diagnosis being 9 months.

Diagnosis of unilateral cases peaks between 24 and 30 months.

Cause of retinoblastoma

In children with the heritable genetic form of retinoblastoma there is a mutation on

chromosome 13, called the RB1 gene.The genetic codes found in chromosomes control the

way in which cells grow and develop within the body. If a portion of the code is missing or

altered (mutation) a cancer may develop.

The defective RB1 gene can be inherited from either parent; in some children, however, the

mutation occurs in the early stages of fetal development. It is unknown what causes the gene Kepaniteraan Radiologi 34RS Royal TarumaPeriode 01 November -04 Desember 2010


abnormality; it is most likely to be a random mistake during the copy process which occurs

when a cell divides.

Inherited forms of retinoblastomas are more likely to be bilateral; in addition, they may be

associated with pinealoblastoma (also known as trilateral retinoblastoma) with a dismal

outcome.ef> The genetic codes found in chromosomes control the way in which cells grow

and develop within the body.[5]

Several methods have been developed to detect the RB1 gene mutations and attempts have

been made to correlate gene mutatations to the stage at presentation.

Diagnosis

Screening for retinoblastoma should be part of a "well baby" screening for newborns during

the first three months of life, to include:

The Red reflex: checking for a normal reddish-orange reflection from the eye's retina

with an ophthalmoscope or retinoscope from approximately 30 cm / 1 foot, usually

done in a dimly lit or dark room.

The Corneal light reflex/Hirchberg Test: checking for symmetrical reflection of

beam of light in the same spot on each eye when a light is shined into each cornea, to

help determine whether the eyes are crossed.

Eye examination: checking for any structural abnormalities.

Differential diagnosis

1. Persistent hyperplastic primary vitreous (PHPV): congenital developmental

anomaly of the eye resulting from failure of the embryological, primary vitreous and

hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and

may present with whitening of the pupil.

2. Coat's disease: a typically unilateral disease characterised by abnormal

development of blood vessels behind the retina, leading to blood vessel abnormalities

in the retina and retinal detachment to mimic retinoblastoma.



3. Toxocara canis: an infectious disease of the eye associated with exposure to

infected puppies, which causes a retinal lesion leading to retinal detachment.

4. Retinopathy of prematurity (ROP): associated with low birth weight infants who

receive supplemental oxygen in the period immediately after birth, it involves damage

to the retinal tissue and may lead to retinal detachment.

MRI pattern of retinoblastoma with optic nerve involvement (sagittal enhanced T1-weighted

sequence)

If the eye examination is abnormal, further testing may include imaging studies, such as

Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), and

Ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium

depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow

examination or lumbar puncture may also be done to determine any metastases to bones or

the brain.

Morphology

Gross and microscopic appearances of retinoblastoma are identical in both hereditary and

sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while

zones of necrosis are found in relatively avascular areas. Microscopically, both



undifferentiated and differentiated elements may be present. Undifferentiated elements

appear as collections of small, round cells with hyperchromatic nuclei; differentiated

elements include Flexner-Wintersteiner rosettes and fluerettes from photoreceptor

differentiation.

Treatment

Historical image showing Gordon Isaacs, the first patient treated with the linear accelerator

(external beam radiation therapy) for retinoblastoma in 1957. Gordon's right eye was

removed January 11, 1957 because the cancer had spread. His left eye, however, had only a

localized tumor that prompted Henry Kaplan (doctor) to try to treat it with the electron

beam.

Treatment of retinoblastoma varies from country to country. The first priority is to preserve

the life of the child, then to preserve the vision and thirdly to minimize any complications or

side effects of the treatment. The exact course of treatment will depend on the individual case

and will be decided by the Ophthalmologist in discussion with the Paediatric Oncologist.



Options for treatment include: chemotherapy (which can be administered locally through a

thin catheter that is threaded through the groin through the aorta and the neck into the optic

vessels), cryotherapy, radioactive plaques, laser therapy, external beam radiotherapy and

surgery. Any combinations of these treatments may be adopted.

In recent years, there has been an effort to find alternatives to enucleation and radiation

therapy.

Additional image

Drawing of a large

retinoblastoma

Aspect of trilateral

retinoblastoma on MRI

An ocular ultrasound

of a large

retinoblastoma tumor

within the eye of a

three year old boy

Funduscopic finding

of a retinoblastoma



Ocular fundus aspect of

retinoblastoma

Gross pathology of

retinoblastoma tumor

in enucleated eye of

three year old female

Large exophytic white

tumor with foci of

calcification producing

total exudative retinal

detachment

Flexner-

Wintersteiner

rosettes in

Retinoblatoma

Retinoblastoma, 400 X

magnification

Crystal structure of the

Retinoblastoma tumour

suppressor protein

bound to E2F peptide

Polymer.

Waspadai Kanker Mata Pada AnakKepaniteraan Radiologi 39RS Royal TarumaPeriode 01 November -04 Desember 2010


Kenali gejala awal kanker mata pada buah hati Anda. Sehingga bisa diatasi lebih

cepat.

MINGGU, 15 MARET 2009, 11:31 WIB

Irma Kurniati, Bayu Galih

VIVAnews - Sedikit sekali orang tua yang mengetahui tentang bahaya

retinoblastoma pada anak. Padahal retinoblastoma merupakan kanker mata yang

berisiko diderita bayi dan balita. Tidak hanya menyebabkan kebutaan, kanker mata

ini juga mampu menyebabkan kematian. Namun dengan indikasi sejak dini,

penderitanya memiliki harapan hidup yang tinggi.Ahli mata dari FKUI/RSCM Dr

Rita Sitorus SpM(K) PhD mengatakan retinoblastoma merupakan tumor ganas

primer pada mata yang paling sering dijumpai bayi dan anak-anak. Di RSCM

Retinoblastoma merupakan penyakit kanker kedua terbesar yang diderita anak,

setelah leukemia. “Penyebab penyakit pun belum diketahui secara pasti. Bisa

disebabkan faktor keturunan. Risiko lebih besar apabila dalam keluarga ada yang

menderita Retinoblastoma. Bisa juga disebabkan faktor lingkungan, terutama yang

tidak kondusif dan rentan terhadap persebaran infeksi ,virus, dan bakteri,'' ujar Rita.

Bila ditemukan dan diobati pada stadium dini, angka harapan hidup penderita masih

tinggi, sekitar 80 – 90 persen. Tapi banyak yang tidak menyadari bahaya

Retinoblastoma karena gejala penyakitnya sering dianggap penyakit mata biasa.

“Sebagian besar penderita baru datang ke rumah sakit setelah stadiumlanjut,'' kata

Rita. Karena itu waspadalah apabila anak Anda terlihat mengalami gejala

Retinoblastoma.Apa saja gejala penyakit ini?- Manik mata berwarna putih seperti

mata kucing (cat eye)- Mata merah dan nyeri, dan iris pada kedua mata memiliki

warna berlainan. - Mata juling pun bisa menjadi indikasi, karena juling itu bisa jadi

merupakan tumor yang sudah terdapat di makula mata.

Penanganan“Bila ditemukan dalam stadium dini, mata itu masih bisa diangkat

(operasi bedah mata) dan diganti dengan mata palsu (protesa),” ucap Rita. Dalam



stadium dini, proses pengangkatan juga bisa disertai dengan kemoterapi dan

radioterapi. Tapi apabila dibiarkan hingga stadium lanjut, tumor itu akan

menyebabkan bengkak di bola mata menonjol ke luar. Tidak hanya itu, tumor juga

akan berkembang dan menyebar ke sumsum tulang atau ke otak, sehingga

membahayakan nyawa anak.

Retinoblastoma



The Cancer Center at The Children's Hospital of Philadelphia has a multidisciplinary team of

highly experienced and compassionate professionals who will provide expert management of

your child's retinoblastoma. In addition, Children's Hospital researchers are at the forefront

of researching and developing new therapies to treat retinoblastoma.

What is retinoblastoma?

Retinoblastoma is a rare cancer originating in the part of the eye called the retina. The retina

is a thin layer of nerve tissue that coats the back of the eye and enables the eye to see. Most

cases involve only one eye (unilateral), but both eyes may be involved (bilateral). If

retinoblastoma spreads, it can spread to the lymph nodes, bones or the bone marrow. Rarely,

it can involve the central nervous system (CNS).

Retinoblastoma is a malignant tumor composed of retinoblasts (immature baby cells) in the

retina. These cells form the nerve tissues (rods and cones) at the back of the eye. Their job is

to form images. The images are then transmitted by the optic nerve to the area of the brain

responsible for sight.

Retinoblasts develop from a single cell during the early development of an infant in the

womb. During gestation and early life, these cells are able to divide and multiply. This is the

process that helps make enough cells to populate the retina. As children age, their cells

undergo a process called differentiation and become mature rods and cones. The cells are no

longer able to divide and multiply, which is why retinoblastoma occurs very rarely after the

age of 5 years. Children may be born with retinoblastoma, but the disease is rarely diagnosed

at birth.

We do not know what causes retinoblasts to turn into cancer cells but we do know that it in

order for retinoblastoma to develop there must be a change or mutation in both copies (one

from each parent) of a gene called RB1. What precisely triggers this change or mutation is

not known.


http://www.chop.edu/service/oncology/pediatric-cancer-research.html


Most children who begin treatment before the retinoblastoma has spread beyond the eye are

cured. A major goal of treatment in children with retinoblastoma is preserving vision.

Great strides have been made in treating retinoblastoma in recent years; many children retain

their vision and more than 95 percent of children with retinoblastoma can be cured.

Who is diagnosed with retinoblastoma?

About 300 children are diagnosed with retinoblastoma in the United States each year. The

disease occurs most often in children under 4 years old, and accounts for 2.8 percent of all

cancers in children ages 0 to 14 years old. The average age of children with retinoblastoma is

18 months — and boys and girls are affected equally.

About 60 percent of children with retinoblastoma develop a single tumor in one eye only

(unilateral). There is no increased risk of additional tumors later in life.

When retinoblastoma affects both eyes (bilateral), it is considered a genetic condition.

Rarely, the genetic form occurs only in one eye. The genetic form of the disease occurs in the

youngest children (rarely beyond 1 year old) and increases the childs risk of developing

another cancer later in life. The risk of additional tumors is higher in children who receive

radiation therapy to the orbit (eye socket) to preserve vision or to other parts of the body

where the tumor has spread.

Hereditary retinoblastoma

Some children (40 percent of patients with retinoblastoma) are born with a change in one

copy of the RB1 gene in every cell in the body, including the cells in the retina. If the second

copy of the gene undergoes a change, a retinoblastoma tumor can develop. That's because

every cell already has the first copy of RB1 mutated — making it relatively easy for more

than one cell to undergo a change in the second copy or the gene. These children may have

more than one tumor, and they usually have both eyes affected.

Most children (80 percent) with the genetic form do not have a parent with retinoblastoma.

The change in the gene occurred in either the egg or the sperm of one parent before

conception. Even if your child has the genetic form, if neither parent has the tumor there is

less than a 1% chance that retinoblastoma will occur in another child in your family.



Children with the genetic form may also develop tumors in other parts of their body, such as

the pineal gland in the brain. The pineal gland develops from cells that sense light and are

similar to retinoblasts. As is the case with retinoblastoma, when these cells become mature

and can no longer divide and multiply (sometime around age 5), they are much less likely to

become cancer cells.

Nonhereditary retinoblastoma

Most children with retinoblastoma (60 percent) do not have the genetic form. They are not

born with the RB1 gene mutated in every cell of the body. They develop a tumor in only one

eye because both RB1 genes in a single retinoblast have undergone the mutation. We dont

know how or why this occurs.

If neither parent has had retinoblastoma and the child is over 2 years of age at diagnosis, the

probability of having the genetic form is very small. If eye tumor tissue is available for study,

there is a blood test that can be done to determine whether a child with a unilateral tumor is

one of the 10 percent of children with a tumor in only one eye who has the genetic form.

Your childs oncologist will discuss with you which form of retinoblastoma your child has

and what this means for follow-up for the child and for other members of your family.

What are the signs and symptoms of retinoblastoma?

Sometimes children with retinoblastoma do not show any of the following signs or

symptoms. Often, doctors find retinoblastoma on a routine well-baby examination. Most

often, however, parents notice symptoms such as:

White (leukocoria) or red pupil instead of the normal black

Misaligned eyes (strabismus) looking toward the ear or nose

Reddened, painful eye

Enlarged pupil

Different-colored irises

Poor vision



How do we diagnose retinoblastoma in your child?

The diagnosis of retinoblastoma is made by examining the eyes. If a newborn has a family

history of retinoblastoma, the baby should be examined shortly after birth by an

ophthalmologist (medical eye doctor) who specializes in cancers of the eye.

If a white pupil or strabismus (crossed-eyes) is noticed by a parent or pediatrician, the child

should be referred to an ophthalmologist familiar with the treatment of retinoblastoma. The

doctor will do a thorough examination to check the retina for a tumor. Depending on the age

of the child, either a local or general anesthetic is used during the eye examination. The

ophthalmologist will make a drawing or take a photograph of the tumors in the eyes to

provide a record for future examinations and treatments, and may use additional tests to

confirm or detect tumors. These tests may include:

Imaging tests

Ultrasound. This test looks for tumors in the childs body using sound waves.

Computerized tomography (CT or CAT) scan. A CT scan creates a three-

dimensional picture of the inside of the childs body with an X-ray machine. A

computer then puts these images into a detailed, cross-sectional view that shows any

abnormalities or tumors. Sometimes, a special dye (a contrast medium) is injected

into a vein to provide better detail. A CT scan helps the doctor find cancer outside of

the eye.

Magnetic resonance imaging (MRI). MRI uses electromagnetic waves to create

computer-generated pictures of the brain and spinal column. MRIs may create more

detailed pictures than CT scans and provide the specialist with a picture of the inside

of the eye and the brain.

Additional tests

Children who are diagnosed with retinoblastoma will require a complete physical

examination and, if there are any additional symptoms or abnormal findings, may also

undergo additional tests to determine if the cancer has spread elsewhere in the body. Some of

these tests also will be performed when the child starts therapy.



Blood tests. These tests evaluate the blood and check for problems with the liver and

kidneys. The doctor may also look at the blood for changes in chromosome 13.

Chromosomes are the part of the cell that contains genes. In a few cases of

retinoblastoma, these genes are either missing or nonfunctional.

Lumbar puncture (spinal tap). In this test, a small amount of cerebrospinal fluid is

removed with a needle from the childs back and examined under a microscope to

detect cancer cells.

Bone marrow aspiration. This procedure is performed to determine if any

retinoblastoma cells have spread to the marrow. For this test, a small amount of bone

marrow is removed from the hip with a needle and examined under a microscope.

MRI or CT scan of the brain. This may be recommended to determine if there is an

abnormality of the pineal gland for children with the genetic form of retinoblastoma.

This includes children with bilateral (in both eyes) disease and those with unilateral

with a positive family history. Very young children with a tumor in one eye who do

not have a positive family history may also be at risk, and these studies may be

recommended for them. Scans may also be recommended years after treatment for

children who have received external beam radiation, either as a baseline in the event

that problems arise, or to follow-up on a symptom or sign.

Hearing test. Children with retinoblastoma taking certain chemotherapy drugs may

have their hearing tested (audiology test) to make sure the drugs are not causing

hearing loss.

Staging

After a retinoblastoma has been detected, the doctor will determine the extent of disease in

the eye and if the disease has spread (metasized) outside the eye. This is called staging, and it

helps doctors plan treatment.

Staging categories include:

Intraocular. This means that cancer occurs in one or both eyes, but has not spread into

surrounding tissues or other parts of the body.



Recurrent. The cancer has recurred (come back) in the eye or continued to grow after it has

been treated.

Extraocular. The cancer has spread to tissues around the eye or to other parts of the body.

How do we treat retinoblastoma?

The goal of treatment is to prevent tumor cells from growing and spreading, and to preserve

vision.

Standard treatment for retinoblastoma has changed over the years. A decade ago, treatment

options included enucleation (removal of the involved eye) or radiation. When only one eye

is involved, enucleation is usually the treatment of choice. Children adjust very well to the

loss of one eye, and their vision does not suffer a great deal. However, if a child is very

young, there is a risk that a tumor will develop in the other eye, so the goal in these children

is to remove as much of the tumor as possible while preserving vision.

Small tumors can often be treated successfully using local measures, including:

Cryotherapy: Extreme cold may be used to destroy cancer cells. The procedure is

done in the operating room. The child is discharged the same day after recovering

from anesthesia.

Photocoagulation (laser therapy): Laser light may be used to destroy blood vessels

that supply nutrients to the tumor. The procedure is done in the operating room. The

child is discharged the same day after recovering from anesthesia.

Thermotherapy: Heat may be used to destroy cancer cells. Radioactive plaques,

sewn into the back of the eye and removed after the required dose of radiation is

delivered, are also successful.

Plaque radiotherapy: A radioactive device is implanted in the affected eye with a

specific dose of radiation directly applied to the tumor. The procedure is performed

in the operating room. The child will have to stay in the hospital for a few days while

the implanted radiation plaque delivers the planned dose to the tumor.



Radiation therapy

The goal in treating children with tumors in both eyes is to save the child's life and preserve

vision with a minimum of side effects. Radiation therapy has been the treatment of choice for

children with bilateral disease. However, radiation may produce damage to the retina many

years after it has been given. That damage can result in loss of vision.

Radiation when given to very young children also results in decreased growth of the bone

surrounding the orbit. It can also increase the risk of second non-retinoblastoma cancers from

10 to 50 years after treatment.

Chemotherapy

Chemotherapy is medication used to destroy cancer cells. When tumors are too large to apply

local measures, we may recommend chemotherapy to shrink the tumors so that local therapy

can be used successfully.

Because chemotherapy can also affect normal cells along with cancer cells, certain side

effects can occur. Any plan of chemotherapy will include a discussion of the potential side

effects, the ways in which they can be prevented, and what tests we may need to do to look

for them.

All of the chemotherapy medications given for retinoblastoma are given via an intravenous

(IV) catheter placed in the arm or foot. Some children may require a semi-permanent type of

IV catheter, called a central venous catheter, that is placed under the skin in the chest.

Each child is affected differently by chemotherapy. Before each cycle of chemotherapy, a

pediatric oncologist will examine your child.

As with any cancer, the prognosis and long-term survival can vary greatly from child to

child. Prompt medical attention and aggressive therapy are important for the best prognosis.

Great strides have been made in treating Retinoblastoma in recent years. More than 95

percent of children with retinoblastoma can be cured. Many children with tumors in both

eyes can retain vision.



Retinoblastoma and Your Child's Eyes

Retinoblastoma is a malignant tumor on the retina, the light-sensing part of the eye, and is

highly curable if treated early. This type of cancer can be present in one or both eyes.

What Causes Retinoblastoma?

Our eyes begin to develop very early in the womb. Rapidly growing cells in the eye, called

retinoblasts, will eventually mature and form the retina, the light-sensing part of the eye that

is located in the back of the eye. Sometimes, these specialized cells do not stop reproducing

and form a tumor on the retina. These tumors may continue to grow, filling almost the entire

vitreous humor (the jellylike substances the fills the eyeball). These tumors can also break

off and spread to other parts of the eye, and eventually outside to lymph nodes and other

organs.

Who Gets Retinoblastoma?

Retinoblastoma occurs most often in children 5 years and under. It rarely occurs in adults.

Between 200 and 300 children are diagnosed with retinoblastoma each year, affecting one in

every 20,000. About 40% of all cases of retinoblastoma are inherited, meaning the cancer is

passed on from parent to child. Retinoblastoma occurs about 75% of the time in one eye, and

25% of the time in both eyes.

What Are the Symptoms of Retinoblastoma?

Symptoms of retinoblastoma include:

A pupil that appears white when light is shone into it, called leucocoria, may mean

that a retinal tumor is present. Blood vessels in the back of the eye will normally

reflect red.

The eyes may not move or focus in the same direction.



Eye pain.

The pupil is constantly dilated.

Red eye(s).

How Is Retinoblastoma Diagnosed?

An eye exam and imaging test given by an eye doctor can diagnose retinoblastoma.

If retinoblastoma is suspected, an ophthalmologist will need to examine the eye using special

equipment to see the retina. Other tests may be conducted to determine the stage of the

retinoblastoma, or how far it has spread. These tests include ultrasound, MRI scans, CT

scans, bone scans, spinal tap, and bone marrow tests.

What Are the Stages of Retinoblastoma?

Stages of retinoblastoma include:

Intraocular retinoblastoma. The earliest stage of retinoblastoma, found in one or both eyes.

It has not yet spread to tissue outside of the eye.

Extraocular retinoblastoma. This type of cancer has either spread outside of the eye or to

other parts of the body.

Recurrent retinoblastoma. The cancer has come back or spread in the eye or to other parts

of the body after being treated.

How Is Retinoblastoma Treated?

Because it is usually found before it spreads outside of the sclera (white of the eye),

retinoblastoma is highly curable. There are also many types of treatment that can save sight

in the eye affected by retinoblastoma. Treatments are selected based on the stage of cancer at

the time of diagnosis. Options include:


http://www.webmd.com/content/article/63/71990.htm


Photocoagulation. A laser is used to kill blood vessels that feed the tumor.

Cryotherapy. Extremely low temperatures are used to kill cancer cells.

Chemotherapy. Chemotherapy is a treatment given intravenously (injected into the

vein), orally, or is injected into the fluid that surrounds the brain and spinal cord,

called intrathecal chemotherapy. These powerful doses of cancer-killing drugs help

kill or slow the growth of multiplying cancerous cells.

Radiation therapy. Radiation may be given externally or internally. External-beam

radiation therapy uses X-rays to kill cancer cells. Internal, or local radiation therapy,

involves placing small amounts of radioactive material inside of or near the tumor to

kill cancer cells.

Enucleation. Surgery to remove the eye

What Does the Future Hold for People With Retinoblastoma?

Over 90% of children will survive more than five years after being diagnosed with

retinoblastoma. The degree of vision retained depends on the extent of the disease, as well as

the treatment chosen.

Hereditary forms of retinoblastoma are more likely to reoccur years after treatment;

therefore, close follow-up after treatment is important for these patients.

Is Retinoblastoma Preventable?

Because heredity and age play such large roles in retinoblastoma, the best prevention is

through early detection. All babies should have a general eye exam at birth and then again

during the first year of life (these are usually included during the "well-child" visits

scheduled at 2, 4, 6, 9, and 12 months of age). Your child should also have regular exams

scheduled for 15, 18, and 24 months of age and every year after that. At these regularly

scheduled visits, a doctor can detect any serious congenital problems or the appearance of

retinal tumors. Newborns with a family history of retinoblastoma should have a more

thorough eye exam at birth, again at several weeks of age and then once every few months as

directed by your child's doctor.Kepaniteraan Radiologi 51RS Royal TarumaPeriode 01 November -04 Desember 2010


Note: If you notice something unusual about your child's eyes in between the regularly

scheduled visits, contact your doctor for an appointment immediately.

In some cases of retinoblastoma, there is a genetic mutation responsible for the disease. A

blood DNA test can be used in select cases to screen for this mutation. For those with a

family history of retinoblastoma, this test may be recommended.

For adults, prevention means getting a thorough regular eye exam at least once a year and

more often, as recommended by your ophthalmologist, if you have a personal or family

history of eye disorders or diabetes.

Retinoblastoma



Author: Marichelle Aventura Isidro, MD, Consulting Staff, Department of Ophthalmology, Santo Tomas University Hospital of Manila, Philippine Heart CenterCoauthor(s): Manolette R Roque, MD, MBA, President and CEO, Service Chief of Ocular Immunology and Uveitis, Refractive Surgery, EYE REPUBLIC Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines; Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, St Luke's Medical Center Global City; Senior Eye Surgeon, The LASIK Surgery Clinic; Senior Eye Surgeon, Precise Eye Laser Center; Thomas M Aaberg, Jr, MD, Clinical Assistant Professor, Department of Surgery, Michigan State University College of Human Medicine; Consulting Staff, Department of Ophthalmology, Associated Retinal Consultants; Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co; Ophthalmology Consultant, Eye Republic Ophthalmology Clinic; Visiting Ophthalmologist, QC Eye Center and Asian Hospital and Medical Center

Contributor Information and DisclosuresUpdated: Sep 21, 2010

Introduction

Background

Retinoblastoma is the most common primary ocular malignancy (eye cancer) of childhood.

Peter Pawius of Amsterdam provided the first description of a tumor resembling

retinoblastoma. He wrote of a malignancy invading the orbit, the temporal region, and the

cranium, a picture now strongly suggestive of untreated retinoblastoma. The tumor was

described as filled with a "substance similar to brain tissue mixed with thick blood and like

crushed stone."

In 1805, William Hey coined the term fungus haematodes, which he used to describe a

fungating mass affecting the globe of the eye and destroying its internal organization.

In 1809, the Scottish surgeon James Wardrop pieced together the random isolated facts and

observations of previous authors. Despite not having a microscope at his disposal, his

meticulous dissection and astute interpretations of some of these eyes led him to conclude

that in most instances, the tumor arose from the retina. Wardrop documented the extension of

the tumor to the optic nerve and brain. Later, he described metastasis to different parts of the

body.

In 1836, Langenbech, Robin, and Nystin of Paris confirmed by microscopic studies that the

tumor definitely arose from the retina.

In 1864, Virchow named the tumor a glioma of the retina, supporting glial cells as the cell of

origin of the tumor.

In 1891, Flexner of Johns Hopkins was first to notice rosettes within the tumor (shown in the

image below).A few years later in 1897, Wintersteiner concurred with Flexner and proposed



the name neuroepithelioma noting its resemblance to rods and cones and traced one tumor to

the photoreceptor cell layer. Presently, their names are attached to these rosettes.

Most cells comprising the tumor histologically resemble the cells of an undifferentiated

retina of the embryo called retinoblasts. This resemblance prompted Verhoeff to coin the

term retinoblastoma, which later was adopted by the American Ophthalmological Society in

1926 as a general term for this entity.

In 1970, Tso and colleagues established that the tumor arises from photoreceptor precursors.

In October of 2007, a team of investigators at St. Jude Children's Research Hospital

(Memphis, Tenn) claimed to have identified the specific cell that gives rise to

retinoblastoma.The major importance of this discovery is the idea that retinoblastoma can

arise from fully matured nerves in the retina called horizontal interneurons, disproving the

long-held scientific principle that fully formed, mature nerves cannot multiply like young

immature cells.

Pathophysiology

The most widely held concept of histogenesis of retinoblastoma holds that it generally arises

from a multipotential precursor cell (mutation in the long arm of chromosome 13 band

13q14) that could develop into almost any type of inner or outer retinal cell. Intraocularly, it

exhibits a variety of growth patterns, which have been described as outlined below.

Endophytic growth

Endophytic growth occurs when the tumor breaks through the internal limiting membrane

and has an ophthalmic appearance of a white-to-cream mass showing either no surface

vessels or small irregular tumor vessels. This growth pattern is typically associated with

vitreous seeding, wherein small fragments of tissue become separated from the main tumor.

In some instances, vitreous seeding may be extensive and allow tumor cells to be visible as

spheroid masses floating in the vitreous and anterior chamber, simulating endophthalmitis or

iridocyclitis, and obscuring the primary mass. Secondary deposits or seeding of tumor cells

into other areas of the retina may be confused with multicentric tumors.



Exophytic growth

Exophytic growth occurs in the subretinal space. This growth pattern is often associated with

subretinal fluid accumulation and retinal detachment. The tumor cells may infiltrate through

the Bruch membrane into the choroid and then invade either blood vessels or ciliary nerves

or vessels. Retinal vessels are noted to increase in caliber and tortuosity as they overlie the

mass.

Diffuse infiltrating growth

This is a rare subtype comprising 1.5% of all retinoblastomas. It is characterized by a

relatively flat infiltration of the retina by tumor cells but without a discrete tumor mass. The

obvious white mass seen in typical retinoblastoma rarely occurs. It grows slowly compared

with typical retinoblastoma.

Frequency

United States

An estimated 250-500 new cases of retinoblastoma occur in the United States yearly.

International

Worldwide, the incidence of retinoblastoma is recorded to be about 11 cases per million

children younger than 5 years. A more commonly used estimate is 1 case of retinoblastoma

per 18,000-30,000 live births, depending on the country.

In the Philippines, unpublished reports have estimated the incidence to be more than 1 case

of retinoblastoma per 18,000 live births.

Mortality/Morbidity

Survival rates for patients with retinoblastoma range from a reported 86-92%. However,

these figures must be kept in the context of the retinoblastoma cancers. In actuality, the

survival rate drops with each decade of life for patients with the genomic mutation.

The genomic mutation is a gene mutation within every cell of the individual's body. These

patients typically present with either bilateral disease or unilateral-multifocal (one eye with Kepaniteraan Radiologi 55RS Royal TarumaPeriode 01 November -04 Desember 2010


multiple distinctly separate tumor foci) disease. These individuals have a predisposition for

developing second cancers later in life.

Mortality in these individuals is consequently much higher than rates for those with somatic

mutations (ie, affecting one retinal cell only and unilateral-unifocal disease). The greatest

predictor of death is extraocular extension, either directly through the sclera or via extension

along the optic nerve.

Race

No racial predilection appears to exist for retinoblastoma.

No difference in incidence exists among blacks and whites.

Sex

Studies show no significant difference in the incidence of retinoblastoma by sex for

children aged 0-14 years.

The estimated boy-to-girl ratio is reportedly 1.12:1.

Age

Retinoblastoma is diagnosed in patients at an average of 18 months, with 90% of

cases diagnosed in patients younger than 5 years.

Children who are affected bilaterally are diagnosed at an average age of 13 months,

while patients with unilateral retinoblastoma are diagnosed at an average age of 24

months.

When a known family history of retinoblastoma exists, patients with bilateral

retinoblastoma are diagnosed at an average age of 11 months.

A few cases of retinoblastoma in adults (aged 20 y and older) have been reported in

the literature. Some theorize that these lesions arise from a previously existing

retinocytoma that underwent malignant transformation.

Clinical



History

At the time of initial examination, obtain a careful family history.

Specifically ask parents about the occurrence of retinoblastoma in the family.

Elicit a history of eye tumors, previous enucleation, or any malignancy in childhood

in any of the family members.

Only about 5% of patients who develop this disease have a positive family history.

A large number of patients with retinoblastoma (95%) have no previous family

history, including those who have the bilateral hereditary form of the disease.

Physical

The clinical findings in all the stages of retinoblastoma are numerous and varied. The image

below presents an overview of the presenting signs in retinoblastoma.

Leukocoria (white pupillary reflex or cat's eye reflex) is the most common presenting

sign, accounting for about 56.1% of cases. Leukocoria is shown in the image below.

Strabismus, which occurs as a result of visual loss, is the second most common mode

of presentation. Thus, funduscopic examination through a well-dilated pupil must be

performed in all cases of childhood strabismus.

Retinoblastoma can cause secondary changes in the eye, including glaucoma, retinal

detachment, and inflammation secondary to tumor necrosis.

Pseudouveitis, with a red eye and pain and associated hypopyon and hyphema, is a

rare presentation. It is characteristic of an infiltrating type of retinoblastoma in which

the tumor cells invade the retina diffusely without forming a discrete tumor mass.

Orbital inflammation mimicking orbital cellulitis may occur in eyes with necrotic

tumors and does not necessarily imply extraocular extension.

Proptosis is a more common presenting symptom in most underdeveloped countries.

Causes



Retinoblastoma is caused by the so-called retinoblastoma gene, which is a mutation in the

long arm of chromosome 13.

This gene name is actually a misnomer because the gene does not actively lead to

retinoblastoma. The unaffected gene actually suppresses the development of

retinoblastoma.

When both homologous loci of the suppressor gene become nonfunctional by either

deletion error or by mutation, retinoblastoma develops.

A positive family history is present in 5-10% of children who develop this disease.

Laboratory Studies

Blood counts and electrolyte determination as well as urinalysis and liver function

tests are useful in excluding other conditions confused with retinoblastoma.

Blood specimens should be taken not only from the patient but also from the parents

and any siblings for DNA analysis, which could aid in genetic counseling.

There are direct and indirect methods in the analysis of the retinoblastoma

gene. The direct method aims to find the initial mutation that precipitated the

development of the tumor; then, it is determined whether that mutation is in

the germline of the affected patient. Indirect methods can be used in cases

where the initial mutation cannot be located or it is uncertain whether it

exists.

Sources of DNA to be evaluated directly are either from tumor cells or

leukocytes.

Deletions or rearrangements of the retinoblastoma gene can be detected by

either karyotyping or Southern blotting techniques.

Point mutations in the retinoblastoma gene can be detected by the following

techniques: ribonuclease protection, denaturing gradient gel electrophoresis,

single-strand conformation polymorphism, or direct DNA sequencing

amplified by the polymerase chain reaction.

Retinoblastomas also may arise by hypermethylation of the promoter region

of the retinoblastoma gene, which deactivates this gene but does not alter the

DNA sequence. This also can be detected by Southern blot analysis.



Indirect methods of analysis of the retinoblastoma gene rely on DNA

polymorphisms within this gene.

Assays of aqueous humor enzyme levels could offer useful information to patients

with suspected retinoblastoma. Lactate dehydrogenase (LDH) is a glycolytic enzyme

that uses glucose as an energy source. It is present in high concentrations within

metabolically active cells. Normally, its concentration in serum and aqueous humor

is low and the ratio of aqueous humor to serum LDH is less than 1.0 in patients with

ocular disease other than retinoblastoma. However, aqueous humor for eyes with

retinoblastoma exhibits increased LDH activity expressed as an aqueous humor/LDH

ratio of greater than 1.0.

Imaging Studies

Cranial and orbital computerized tomography provides a sensitive method for

diagnosis and detecting intraocular calcification and shows intraocular extent of the

tumor even in the absence of calcification (examples shown below). This

neuroimaging technique is also invaluable in assessing the CNS anatomy, including

the optic nerve, for possible extension of retinoblastoma.

Ultrasonography is useful in distinguishing retinoblastomas from non-neoplastic

conditions. It is also useful in detecting calcifications.

MRI

MRI may be beneficial in estimating the degree of differentiation of retinoblastomas

but is not as specific as computerized tomography because of its lack of sensitivity in

detecting calcium.

Studies show that on T1-weighted images, the tumors usually have a low intensity

and are usually difficult to distinguish from surrounding vitreous, but, on T2-

weighted images, retinoblastoma tumors demonstrate very low intensity compared to

vitreous. Calcification is more pronounced on T2 sequences.

MRI also is useful in identifying any associated hemorrhagic or exudative retinal

detachment. This is seen as a localized subretinal area of higher signal intensity

compared to vitreous on both T1- and T2-weighted sequences.



X-ray

In areas of the world where ultrasonography and computerized tomography are not

available, x-ray studies may be the only means of identifying intraocular calcium in

patients with opaque media.

Other Tests

Immunohistopathologic staining

The aim of immunohistochemical studies is to decide whether

retinoblastomas come from a common progenitor cell capable of

differentiation into either glial or neuronal cells or from neuron-committed

cells.

Numerous variables alter the results in these studies. These variables include

tissue fixation, staining procedures, specific areas taken into consideration,

tumor cell differentiation, antigen expressivity, and age of tumor.

Caution is required when interpreting most immunohistochemical results

because of the related controversies associated with these tests. An

experienced immunopathologist is required to provide worthwhile results.

Immunohistochemical and biochemical studies show an S-antigen detected

in well-differentiated retinoblastomas using immunoperoxidase staining of

paraffin sections. Felberg and Donoso have performed several related

studies.

Bridges and colleagues performed biochemical assays and showed

interphotoreceptor retinoid-binding protein (IRBP) in retinoblastoma. These

findings suggested an embryonic origin of the cells.

Numerous contradictory studies providing evidence for a neuronal nature and

differentiation exist.

Transmission electron microscopy

Ultrastructural investigations have paved the way for more definitive

descriptions of retinoblastoma. Research using this technology provided



evidence of the presence of photoreceptor cell elements in retinoblastoma,

and a strong evidence of retinoblastoma to human fetal retina has been

demonstrated.

The ultrastructural findings of retinoblastoma investigations have been

described previously.

Procedures

Patients noted to have presenting signs of retinoblastoma should undergo prompt

office examination.

Complete eye examination should be performed including an estimation of the

patient's visual acuity for both eyes.

A dilated fundus examination with indirect ophthalmoscopy should be completed

since ancillary diagnostic studies play only a secondary role when the fundus can be

visualized clearly.

Bone marrow aspiration and biopsy

A bone marrow aspiration and biopsy could be performed as well as lumbar puncture

with cytocentrifuge examination for tumor cells. These may prove useful in the early

diagnosis of distant spread since the primary mode of spread of retinoblastoma is

hematogenous to the bone marrow and back through the optic nerve into the

cerebrospinal fluid (CSF).

Results of a study by Moscinski et al recommends performing bone marrow and CSF

evaluations only in patients with clinical, histologic, or radiologic evidence of local

or systemic extension or in patients presenting with 1 R-E group V eye with

retrolaminar or extrascleral extension of their tumor. They also recommend limiting

follow-up bone marrow and CSF determinations to those patients who develop

objective signs and symptoms of metastasis or recurrence.

Histologic Findings


http://emedicine.medscape.com/article/207575-overview


The classic histologic findings of retinoblastoma are Flexner-Wintersteiner rosettes and less

commonly fleurettes. A Homer-Wright rosette can be encountered, but they are also seen in

other neuroblastic tumors.

Considerable variability exists in the histologic features. Some neoplasms display marked

necrosis and prominent foci of calcification. Few show areas of glial differentiation.

Note: In an enucleated eye that is being prepared for gross examination and fixation for

histopathologic examination, it is essential that adequate fixation is attained (fixation is

usually complete within 48 h). Thorough fixation is especially important for eyes removed

for retinoblastoma because the tumor is friable and may be spilled into the uvea or outside of

the eye when the eye is sectioned, thereby confusing the assessment of the confinement of

tumor to the interior of the eye (a feature that is important for the assessment of survival).

Treatment

Medical Care

Medical therapy should be directed toward complete control of the tumor and the

preservation of as much useful vision as possible. Treatment is usually individualized to the

specific patient.

External beam radiation therapy

Incidence of local control is high and retinal late effects are minimal with radiation

doses of 4000-4500 cGy used with 200 cGy fractions. However, morbidity and

mortality associated with external beam radiation therapy (EBRT) are significant.

EBRT results in cessation of bone growth. Therefore, children with retinoblastoma

who are treated with EBRT have significant midface hypoplasia. (The younger the

child is when EBRT is instituted, the more dramatic the outcome.) More importantly,

EBRT has been shown to increase the risk of developing second cancers almost 6-

fold during the lifetime of these patients. Today, neoadjuvant chemotherapy

(chemoreduction) has superseded EBRT in order to (hopefully) circumvent these

terrible adverse effects of EBRT. Nevertheless, EBRT is still indicated in selected

circumstances, as follows:



For eyes with significant vitreous seeding

For children who have progression of disease while undergoing chemoreduction

For tumors extending up to or beyond the cut margin of the optic nerve of an

enucleated eye (The best method of treatment is being debated in such a case.)

Radioactive isotope plaques

Use of radioactive 60 Co (cobalt); radioactive 125 I (iodine), which is presently the

most used; radioactive 192 Ir (iridium); or radioactive 106 Ru (ruthenium)

Radioactive 125 I plaque treatment is recommended for treatment of one larger

tumor or a limited number of moderately sized tumors (<3) present in noncritical

areas.

Advantage - Locally directed treatment to the tumor, minimizing radiation to the normal

tissue

Disadvantage - Incomplete treatment, high dose to local sclera, significantly less irradiation

for anterior lesions, and difficulty placing posterior plaques

Chemotherapy

Primary neoadjuvant chemotherapy or chemoreduction has been the most significant

recent advance in the treatment of retinoblastoma. This is typically the principle

mode of treatment for eyes in intraocular groups C and D. However, our

understanding of dose, duration, and end points are still evolving with this relatively

new treatment modality.

Prophylactic chemotherapy is recommended if a tumor is in the optic nerve past the lamina

cribrosa because these cases have a poor survival prognosis.

Use of neoadjuvant chemotherapy has the advantage of limiting the necessity for EBRT and

reducing the possibility of EBRT-related complications.

Chemotherapy also may be used prior to EBRT, as completed by Kingston and associates in

an attempt to improve local control and visual outcome in children with group V tumors,

using carboplatin, etoposide, and vincristine, followed by 40-44 Gy of EBRT.



Shields and associates used carboplatin, etoposide, and vincristine chemotherapy, followed

by cryotherapy, photocoagulation, and 125 I plaque treatment in an attempt to improve

outcome for eyes with more advanced retinoblastoma commonly treated with enucleation.

Current studies completed by the Retinoblastoma Study Group show the promising use of

chemotherapy (carboplatin, vincristine sulfate, and etoposide phosphate) as a primary mode

of treatment in reducing tumor bulk, followed by various forms of local approaches

(radiotherapy [external beam or plaque], cryotherapy, thermotherapy, and photocoagulation)

that can be used for final tumor control.

Some reports suggest the addition of cyclosporine in combination with the chemotherapy

regimen of carboplatin, etoposide, and vincristine. These reports showed that this addition

enhances the efficacy of chemotherapy and eliminates the need for radiation.

Abramson and colleagues have demonstrated successful salvage of eyes typically enucleated

for advanced disease.15 Intra-arterial chemotherapy for advanced retinoblastoma offers

another weapon in the arsenal of therapies for retinoblastoma. However, there are still

potential complications to consider, and, consequently, this procedure should be performed at

tertiary care institutions that specialize in the care of patients with retinoblastoma.

Surgical Care

Surgical removal of the tumor has been the standard management of very unfavorable

retinoblastoma cases.

Enucleation

Enucleation is performed when there is no chance of preserving useful vision

in an eye.

Patients generally requiring enucleation are those who present with total

retinal detachments and/or the posterior segment is full of the tumor, in

which case it is clear the patient cannot retain any form of useful vision.

Cryotherapy



Cryotherapy can be used primarily for small anteriorly located tumors,

remote from the disc and macula but also may be indicated for

recurrence after radiation therapy.

Cryotherapy is performed transsclerally. Under direct visualization,

freezing is carried out until the ice ball incorporates the entire tumor. A

refreeze-thaw cycle is repeated 3-4 times.

Complete disappearance of the tumor with a flat pigmented scar is the

sign of successful treatment. This can be repeated if the tumor does not

respond initially.

Photocoagulation

Photocoagulation can be used as primary therapy for small posteriorly

located tumors.

There is a danger of producing large field defects near the disc and

decreased vision resulting from macular pucker by photocoagulation

near the macula.

The technique is performed by placing a double row of confluent burns

around each tumor using a photocoagulator.

It is important not to do direct treatment on the tumor itself because the

light color of the tumor generally precludes absorption of sufficient

energy and there is a danger of exploding the tumor with spread of

viable tumor debris into the vitreous and other parts of the retina.

Successful treatment with photocoagulation takes weeks to evolve and

consists of complete disappearance of the tumor, which is replaced with

a flat area.

Photocoagulation can also be used for tumor recurrences after EBRT.

Exenteration is still performed, especially in most underdeveloped

countries, when extension of the tumor into the surrounding areas is

considerable.

Consultations



Patients with retinoblastoma should be evaluated and treated by a team of medical

professionals, including an ophthalmologist (preferably an ocular oncologist), pediatrician,

oncologist, radiologist, and pathologist. Given that this is a relatively uncommon disease,

patients should try to seek attention from physicians with subspecialty training and

experience in retinoblastoma, and who are actively participating in organizations that explore

up-to-date treatments for retinoblastoma.

The pathologist plays a special role in the treatment of a patient with retinoblastoma.

The surgical specimens should be evaluated with care to guide the clinicians with the

appropriate postsurgical management.

Appropriate consultations are needed to provide much needed information to each

other. In some instances, frozen sections are requested after enucleation or

exenteration.

Medication

Use of chemotherapeutic drugs should be limited to specific group of patients for whom the

benefits outweigh the potential disadvantages.

Anticancer drugs

Used for management of metastasis but also used as adjuvant therapy for patients with high-

risk retinoblastoma.

Vincristine (Vincasar, Oncovin PFS)

Cycle-specific and phase-specific, which blocks mitosis in metaphase. Binds to microtubular

protein, tubulin, GTP dependent. Blocks ability of tubulin to polymerize to form

microtubules, which leads to rapid cytotoxic effects and cell destruction.

Dosing :



Adult

2 mg IV push

Pediatric

1.5 mg/m2 (0.05 mg/kg for children < 36 mo; not to exceed 2 mg/dose) IV q2wk for 9 cycles

Interaction :

Neurotoxicity may be additive with drugs acting on the peripheral nervous system;

allopurinol may increase incidence of cytotoxic-induced bone marrow depression

Contraindications :

Documented hypersensitivity to vinca alkaloids

Precautions :

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Caution in patients with impaired hepatic function or biliary obstruction

Carboplatin (Paraplatin)

Inhibits both DNA and RNA synthesis. Binds to protein and other compounds containing SH

group. Cytotoxicity can occur at any stage of the cell cycle, but cell is most vulnerable to

action of these drugs in G1 and S phase.

Dosing :

Adult

360 mg/m2 IV q3wk as monotherapy or 300 mg/m2 q4wk as combination therapy

Pediatric

For retinoblastoma: 560 mg/m2 (18.6 mg/kg for children < 36 mo) IV q3wk for 9 cycles

Interaction :Kepaniteraan Radiologi 67RS Royal TarumaPeriode 01 November -04 Desember 2010


Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs

Contraindications :

Documented hypersensitivity; preexisting severe renal impairment and myelosuppression;

severe allergy to platinum components

Precautions :

Pregnancy


Caution in pregnancy and breastfeeding; peripheral blood counts and neurologic and renal

functions to be monitored closely

Etoposide (Toposar, VePesid)

Blocks cells in the late S-G2 phase of the cell cycle. Binding of drugs to enzyme-DNA

complex results in persistence of transient cleavable form of complex and, thus, renders it

susceptible to irreversible double strand breaks.

Dosing :

Adult

100 mg/m2 IV days 1-5

Pediatric

For retinoblastoma: 150 mg/m2 (5 mg/kg for children <36 mo) IV q3wk for 9 cycles

Interactions :

May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine

and etoposide have additive effects in the cytotoxicity of tumor cells



Contraindications :

Documented hypersensitivity; myelosuppression; liver impairment; IT administration may

cause death

Precautions :

Pregnancy


Bleeding and severe myelosuppression may occur immunosuppressants

The addition of cyclosporine in combination with chemotherapy regimen of carboplatin,

etoposide, and vincristine reportedly have showed enhanced efficacy of chemotherapy.

Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-

mediated immune reactions such as delayed hypersensitivity, allograft rejection,

experimental allergic encephalomyelitis, and graft-vs-host disease for a variety of organs.

For children and adults, base dosing on ideal body weight.

Dosis :

Initial PO dose: 14-18 mg/kg/d PO 4-12 h

Maintenance PO dose: 5-15 mg/kg/d PO qd or divided bid

Initial IV dose: 5-6 mg/kg IV qd 4-12 h

Maintenance IV dose: 2-10 mg/kg/d IV divided q8-12h

Interactions :

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease

cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole,

fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides,

acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute



renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with

lovastatin

Contraindications :

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer

concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer

Precautions :

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans;

may use if benefits outweigh risk to fetus

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum

bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use

only for those who cannot take PO

Follow-up

Further Inpatient Care

Inpatient care is mostly supportive during the period of recuperation after surgery or

during chemotherapy.

Daily attention to the cleansing and dressing of a postenucleated eye or

postexenterated orbit is necessary.

Further Outpatient Care

Patients with treated retinoblastoma as well as siblings who are at risk of inheriting

the tumor need to be monitored indefinitely.

Patients and siblings of patients in whom the risk of retinoblastoma cannot be ruled

out by genetic studies should be monitored with examination under anesthesia every

3-4 months until age 3-4 years, after which they are examined under anesthesia every

6 months until age 5-6 years and then annually thereafter. At about age 8 years, most

patients are able to tolerate a dilated fundus examination in the office without

anesthesia and can be examined annually in the office thereafter.



Visual acuity, alignment, and general ocular health should be should be periodically

examined in office. The patient and parents should be questioned about and warned

about signs of secondary nonocular tumors during these examinations.

Formal examination under general anesthesia is completed 6 months after

completion of radiation therapy.

As long as the tumor is not enlarging, it can be considered to be locally controlled by

radiation therapy.

Inpatient & Outpatient Medications

Only supportive medications during chemotherapy or after surgery are needed. These

include antinausea agents, broad-spectrum antibiotics, and painkillers.

Deterrence/Prevention

Frequent ophthalmologic examination is indicated for children at elevated risk.

Estimation of risk can be completed using molecular genetics.

DNA testing can be a cost-effective component of the care of patients with

retinoblastoma and their relatives.

Diagnosing the tumor as early as possible is important to prevent progression leading

to metastasis and ultimately death.

Complications

Secondary nonocular tumors can develop in survivors of retinoblastoma. In order of

decreasing frequency, they are as follows: osteosarcoma, various soft tissue

sarcomas, malignant melanoma, various carcinomas, leukemia and lymphoma, and

various brain tumors. (See Special Concerns.)

Cataract formation: Radiation doses of 800 cGy to the lens using dose rates of 150-

300 cGy/min usually lead to cataract formation in 18 months to 3+ years.

Vascular complications: Retinal vascular damage and hemorrhage may be seen after

external beam radiation using 70-75 Gy with 200-350 cGy per fraction.


http://emedicine.medscape.com/article/1222849-followup#MiscellaneousSpecialConcerns


Bone, dental, and soft tissue effects: Hypoplasia of bone and soft tissue structures

after treatment with radiation doses exceeding 3500 cGy may occur. The maxillary

molar tooth buds located high in the maxilla just inferior to the posterior apex of the

orbit may become irradiated with treatment. Numerous reports of failure of tooth

eruption have been noted in patients with retinoblastoma treated with irradiation.

Prognosis

The prognosis in retinoblastoma is good where prompt medical care is available. The

overall survival rate of retinoblastoma in the United States and Great Britain is

presently greater than 85%.

The cure rate is almost 90% if the optic nerve is not involved and enucleation is

performed before the tumor passes through the lamina cribrosa.

Survival rates decrease to 60% if the tumor extends beyond the lamina cribrosa even

if the cut end of the nerve is free of tumor cells.

Survival rates decrease to less than 20% if the tumor cells are found at the surgical

transection sight.

Death occurs secondary to intracranial extension. Treatment with EBRT results in an

85% cure rate.

Visual preservation occurs in 90% of children with group I and II disease (Reese-

Ellsworth classification); 30-40% for group IV and 10-15% for patients with

advanced group V disease.

Of patients previously treated with EBRT, 60% require further therapy with

cryotherapy or photocoagulation.

Of patients requiring treatment with EBRT, 20% eventually require enucleation.



Patient Education

Genetic counseling for retinoblastoma

In 1979, Vogel published his review on the genetics of retinoblastoma in the Journal

of Human Genetics. He reviewed the likelihood for the recurrence of retinoblastoma

in close relatives of a patient with the disease, based on clinical criteria, as shown

below. It is the physician's responsibility to inform the patient's family that

retinoblastoma can be hereditary. The methods for screening and estimation of risks

are highly improved with use of molecular genetics techniques, although this

sometimes can prove to be very expensive.

Normal individuals have 2 copies of the retinoblastoma gene, 1 coming from each

parent. However, in patients with retinoblastoma, one copy of the gene is inactivated

by an initial mutation.

When the initial mutation arises from a somatic cell (retinal), the patient has the

nonhereditary type of retinoblastoma and the relatives have a low risk for the disease.

These individuals have 1 abnormal gene in all their cells, and the mutation in the

other gene (in the retinal cell) allows the expression of the tumor.

When the initial mutation arises from the germline, the patient has the hereditary

type of retinoblastoma and the relatives of the patient have a significant risk for

retinoblastoma. In these individuals, both mutations occur only in the retinal cell that

has become malignant.

Miscellaneous

Medicolegal Pitfalls

Retinoblastoma is a rare but extremely important disease to the ophthalmologist

since its misdiagnosis is one of the few errors in the practice of ophthalmology that

can lead to the death of a child.

Special Concerns

Adult retinoblastoma has been reported several times in the literature. Identifying

this subgroup of patients with retinoblastoma is important. Clinicians should include



retinoblastoma in the differential diagnosis of intraocular tumors occurring in older

individuals.

Parents and siblings of patients with retinoblastoma should be evaluated for

untreated retinoblastoma or retinoma.

Some recent reports have suggested that patients with retinoblastoma without

neurologic abnormalities or evidence of extraocular extension do not require

systemic metastatic evaluation (bone marrow and lumbar puncture).

Concerns related to retinoblastoma in the developing world

It is unfortunate that in a time when more than 90% of patients with

retinoblastoma are able to survive with appropriate treatment, neglected

cases of highly advanced retinoblastoma are still seen in developing

countries, particularly the Philippines.

Factors such as poverty, illiteracy, cultural beliefs, health-seeking behavior,

politics, and public health information affect the patient's time of

presentation to a health institution or a clinician.

In the Philippine General Hospital (PGH), the largest tertiary hospital in the

Philippines, 1-3 new advanced cases of retinoblastoma are seen each month.

Steps for globe preservation are attempted, but, in most instances wherein

tumor growth and extension are extensive, surgical debulking combined with

radiotherapy and chemotherapy is the only logical route.

A retinoblastoma clinic has been set up at the PGH Department of

Ophthalmology and Visual Sciences (1998) in an attempt to address the

continuing needs of patients with retinoblastoma. In its initial year of

operation, a total of 39 new retinoblastoma cases were seen. Linear follow-

up care has improved, but the specialty clinic continues to experience

funding and staffing problems.

Retinocytoma

Retinocytomas are rare tumors that are composed entirely of benign-

appearing cells with numerous fleurettes and show no evidence of necrosis or

mitotic activity.



Some studies suggest that these lesions can reactivate and undergo malignant

transformation.

Genetic implications of retinocytoma are the same as that of retinoblastoma.

Examine family members of patients with retinoblastoma closely for

retinocytoma and if positive, follow up periodically throughout their lives.

Even patients without a family history of retinoblastoma but with a retinal

lesion suggestive of retinocytoma should be monitored carefully.

Trilateral retinoblastoma

These are cases of bilateral retinoblastoma associated with an ectopic

intracranial retinoblastoma usually involving the pineal gland or the

parasellar region.

Trilateral retinoblastomas contribute significantly to the overall mortality in

patients with hereditary retinoblastoma in the first decade of life accounting

for approximately 50% of deaths.

Screening efforts for patients with trilateral retinoblastoma should be

directed to those at risk, namely those patients with bilateral or multifocal

disease and those with a positive family history.

Current recommendations in screening for trilateral disease uses gadolinium-

enhanced MRI or computed tomography with contrast every 6 months up to

age 5 years in patients with hereditary cases of retinoblastoma.

Secondary malignancies

Studies show that up to 50% of patients who survive bilateral retinoblastoma

develop secondary nonocular tumors during their lifetime.

Patients treated with EBRT appear to be at a much greater risk of developing

second tumors. Dunkel et al demonstrated that by age 40 years, 6% of those

patients who did not receive EBRT had developed second primary malignant

neoplasms as compared to 35% for those who did receive EBRT.16

Patients and their siblings should be assessed periodically for any signs of

developing tumors other than retinoblastoma.



Status post (S/P) enucleation for retinoblastoma, right eye retinoblastoma, recurrence, right

eye. History: IJ, 3-year-old male with chief complaint of right orbital mass. At age

2 months, opacity in right eye is noted. Five months prior to admission (PTA),

consultation with an ophthalmologist for proptosis, right eye. Four months PTA,

the patient underwent enucleation, right eye, with no alleged tumor involvement of

the tumor resection margins on histopathology. One month PTA, gradually

enlarging orbital mass, right side, was noted. Examination: Visual acuity right eye,

not applicable (S/P enucleation); visual acuity left eye, at least 6/12 (20/40). No

masses are seen in left eye on indirect ophthalmoscopy. Diagnostics: Skeletal

survey showed lytic lesions on the humerus, femur, and pubic bones.

LEUKOKORIA



Leukokoria due to advanced intraocular retinoblastoma of right eye



Strabismus as presenting manifestation of retinoblastoma. Left esotropia plus enlarged

corneal diameter, corneal clouding, and loss of red reflex in left eye (top). Left exotropia,

plus slightly enlarged corneal diameter and loss of red reflex in left eye (bottom)

Endophytic and exophytic forms of retinoblastoma. Advanced endophytic

retinoblastoma appears as avascular white mass inferiorly associated with prominent

intravitreal tumor seeds (top). Advanced exophytic retinoblastoma appears as ill-

defined yellow-white vascularized fundus mass superiorly associated with total

bullous retinal detachment (bottom)



Vitreous seeding (intraocular retinoblastoma)

An endophytic retinoblastoma. The tumour grows

into the vitreal cavity. (In exophytic type, the

tumour grows into the subretinal space)



Optic nerve (O) invaded by retinoblastoma (R)

Optic nerve (left) infiltrated by retinoblastoma (right). Note the

presence of retinoblastoma (dark blue) in the optic nerve substance.

Eye with retinoblastoma showing implantation tumors on iris



Flexner Wintersteiner rosettes: clusters of cuboidal or short columnar cells

arranged around a central lumen. The nuclei are displaced away from lumen.

Histopathology of retinoblastoma. Low-power photomicrograph (left) and higher-power

photomicrograph (right) showing cellular necrosis (pale, nonstaining areas) and intralesional

calcification (intense reddish-purple foci) surrounding areas of viable retinoblastoma.



Tissue and cellular differentiation in retinoblastoma. Left: Flexner-Wintersteiner

rosettes. Center: Homer-Wright rosettes.Right: Fleurette.

Macular retinoblastoma



Small intraretinal retinoblastoma. White tumor is fed and drained by slightly dilated, mildly

tortuous retinal blood vessels

Slightly larger intraretinal retinoblastoma with prominent feeding and draining retinal blood

vessels



Prominent vitreous seeds of retinoblastoma overlying large intraretinal vascularized white

retinal tumor

Retinoma. This spontaneously arrested retinoblastoma appears as a calcific tumor residue

centrally surrounded by chorioretinal atrophy.



Fundus retinoblastoma



Retinoblastoma treated by chemotherapy only with carboplatin, etoposide, and vincristine.

Regressed macular tumor appears as well-defined clump of calcific tissue surrounded by foci

of chorioretinal atrophy

Retinoblastoma treated by chemotherapy plus laser therapy and cryotherapy. Superior tumor

residue is completely calcific and partly surrounded by chorioretinal atrophy following laser

therapy. The inferonasal lesion (also treated by laser) is completely atrophic, as is the inferior

peripheral lesion (treated by cryotherapy)



Retinoblastoma treated by plaque radiotherapy.Left:Tumor prior to

treatment. Right: Regressed lesion 3 months following I-125 plaque radiotherapy. Lesion is

markedly shrunken and exhibits foci of calcification

Retinoblastoma treated by external beam radiation therapy. Left: Multiple tumors prior to

treatment. Right: Same tumors 6 months following irradiation (45 Gy over 5 weeks).

Superior tumor has almost completely disappeared, and inferior tumor has regressed to a

shrunken, calcific nodule



Patient with retinoblastoma, glaucomatous stage. Intracranial extension on CT

scan.

Patient with retinoblastoma, glaucomatous stage. Another CT scan slice, showing

the intracranial extension of the tumor.


Media file 8: Retinoblastoma, intraocular stage (CT scan

findings). History: 5-month-old female with chief complaint of

"cat's eye reflex." Two months prior to admission (PTA), cat's

eye reflex noted with outward deviation of left eye. The

patient's 29-year-old mother had bilateral retinoblastoma and

underwent enucleation, left eye, at age 2 years. Examination:

Regressed type stage III, left eye visual acuity (+) dazzle right

eye; indirect ophthalmoscopy (+) mass nasal retina with

seeding, multiple tumors in peripheral retina, left eye. E/N

Retina: Right eye. Management: The patient underwent

enucleation, left eye. Examination under anesthesia of right

eye: E/N. Histopathology: Retinoblastoma, intraocular stage,

well-differentiated left eye.


Ectopic intracranial retinoblastoma in child with bilateral retinoblastoma (trilateral

retinoblastoma). Computed tomography scan of brain reveals prominent suprasellar

mass that exhibits contrast enhancement



B-scan ultrasonography of retinoblastoma. Image of tumor obtained at

typical gain setting (76 dB) for diagnostic examination of eye (left). Tumor

appears generally but nonuniformly bright (hyperreflective). Same tumor at

reduced gain setting (60 dB) is ill defined but exhibits multiple persistent

strong particulate intralesional echoes (foci of calcification) (right)



Computed tomography scan of bilateral retinoblastoma (without contrast

enhancement). Intraocular tumors appear bright because of intralesional

calcification.

MRI pattern of retinoblastoma with optic nerve involvement (sagittal

enhanced T1-weighted sequence)


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