refrat ca ebv
TRANSCRIPT
-
7/29/2019 Refrat CA Ebv
1/27
INFEKSI VIRUS EPSTEIN-BARR
SEBAGAI FAKTOR
ETIOLOGI KARSINOMA
NASOFARING
Oleh
Nur Hidayah J500 050 007
Dian Ardiani Jati 7500 050 008
Pembimbing : dr.Iwan Setiawan, Sp.THT
-
7/29/2019 Refrat CA Ebv
2/27
Pendahuluan
Karsinoma nasofaring (KNF) adalah
keganasan jenis karsinoma yang berasal dari
epitel atau mukosa dan kripta yang melapisi
permukaan nasofaring
kanker yg paling sering di THT.
Nasopharyngeal malignancies
SCCA (nasopharyngeal carcinoma)
Lymphoma
Salivary gland tumors
Sarcomas
-
7/29/2019 Refrat CA Ebv
3/27
Anatomy
Anterior : nasal cavity
Posterior : basis cranii and vertebral
cervicalis 1,2
Inferior : oropharynx and palatum
molle
Lateral :Tuba Eustachius
Fossa Rosenmuller - most common
location
-
7/29/2019 Refrat CA Ebv
4/27
Anatomy
Berhubungan dekat dg Foramen
Basis cranii.
Mucosa
Epithel transisional, peralihan antara :
Epitel squamous kompleks
Epitel pseudokompleks columnar.
Dibawah epitel byk jaringan Lymphoid.
-
7/29/2019 Refrat CA Ebv
5/27
Epidemiology
Chinese native > Chinese immigrant
> North American native
Both genetic and environmental factors
Genetic
HLA histocompatibility loci possible
markers
-
7/29/2019 Refrat CA Ebv
6/27
Epidemiology
Environmental
Viruses
EBV- KNF type II and III
HPV - possible factor pada type I
Nitrosaminesikan asin
Others - polycyclic hydrocarbons, infeksi
hidung kronis, hygiene yg kurang, ventilationyg tidak bagus.
-
7/29/2019 Refrat CA Ebv
7/27
EtiologyVirus Epstein-Barr
Group : Group I (dsDNA)
Family :Herpesviridae
Subfamily: Gammaherpesvirinae
Genus :Lymphocryptovirus
Species : Human herpesvirus 4
(HHV-4)
-
7/29/2019 Refrat CA Ebv
8/27
Patofisiology
EBV merupakan virus DNA mampu
menstimulasi limfosit B dan sel epitel
faring.
Masuk tubuh mll reseptor CR2/CD21
Punya beberapa Ag : VCA, EA,
LMP, nuclear antigen dan Dnase.
Dpt memicu timbulnya respon imun
seluler maupun humoral.
-
7/29/2019 Refrat CA Ebv
9/27
Antibodi spesifik untuk EBV dalam tubuh
IgA-anti VCA,
IgG-anti EBV-EA
sehingga dapat digunakan untukmemantau keberadaan virus EB didalam
tubuh
-
7/29/2019 Refrat CA Ebv
10/27
Bukti kuat yg menunjukkan infeksi
virus EB sebagai salah satu faktor
etiologi utama dari KNF yaituditemukannya
- DNA virus EB di sirkulasi darah
- antigen virus EB (EBNA, LMP,ZEBRA) di dalam sel KNF
- genom virus Epstein Barr dalam
bentuk plasmid di jaringan KNF
- DNA virus EB dan mRNA-EBV
(EBERs) di sel kanker nasofaring.
-
7/29/2019 Refrat CA Ebv
11/27
Classification
WHO classes
Type I - Karsinoma sel skuamosa
dengan berkeratinisasi (25 %)
Type II - Karsinoma sel skuamosa
tanpa keratinisasi (12%)
Type III - Karsinoma tanpa diferensiasi
60 % dari KNF, terbanyak pd usia muda.
-
7/29/2019 Refrat CA Ebv
12/27
Classification
Perbedaan antara type I dan types II & III
5 year survival live
Type I - 10% Types II, III - 50%
Resiko Recurren Jangka panjang, Type II&III
Virus Penyebab :
Type IHPV (Human Papiloma Virus) Types II, IIIEBV (Ebstein-Barr Virus)
-
7/29/2019 Refrat CA Ebv
13/27
Clinical Presentation
Initial symptoms
unilateral HL
Nyeri, pembesaran massa leher secara
pelan2.
Larger lesions
Obstruksi hidung
epistaxis
Keterlibatan Nervi Cranialis.
-
7/29/2019 Refrat CA Ebv
14/27
Clinical Presentation
Xerophthalmia
Facial painn. Trigeminal
DiplopiaN. VI
OphthalmoplegiaN. III, IV, dan VI
cavernous sinus or superior orbital fissure
CNs IX, X, XI, XII - extensive skull base
-
7/29/2019 Refrat CA Ebv
15/27
Presentasi Klinis
Pemeriksaan Nasopharyng
Fossa of Rosenmuller most common location
Variable appearance - exophytic, submucosal
NP bisa terlihat normal
Regional spread
Biasanya ipsilateral tapi bisa juga bilateral
Distant spread - rare (
-
7/29/2019 Refrat CA Ebv
16/27
Role Of EBV
Infeksi Latent
Bisa terjadi di Awal2 Kehidupan
Definite role in types II & III
Full EBV genome present in all NPC epithelial
cells
Variable role in type I
Associated in endemic regions, but not others
Tobacco, Alcohol & HPV implicated
16
-
7/29/2019 Refrat CA Ebv
17/27
Serological Markers
EBV in epithelial and B Lymphocyte cells
Humoral immune response
multiple anti-EBV serology, includes:
IgG & IgA against VCA & EA
Anti-EBNA IgG
Antibodies against EBV replicator protein
ZEBRA
Circulating EBV DNA (by PCR)
Oncogenes under investigation
17
-
7/29/2019 Refrat CA Ebv
18/27
What is the role of EBV Titres
Potential uses of:
VCA, EA & EBV DNA
Diagnosis
VCA & EA
Diagnosis & Monitoring
EBV DNA
Peter Ross, NasophayrngealCarcinoma
18
-
7/29/2019 Refrat CA Ebv
19/27
Laboratory evaluation
Special diagnostic tests (for types II
& III)
IgA antibodies for viral capsid antigen
(VCA)
IgG antibodies for early antigen (EA)
Special prognostic test (for types II &
III)antibody-dependent cellular cytotoxicity
(ADCC) assay
higher titers indicate a better long-term
prognosis
-
7/29/2019 Refrat CA Ebv
20/27
Treatment
External beam radiation
Dose: 6500-7000 cGy
Primary, upper cervical nodes, pos.
lower nodes
Consider 5000 cGy prophylactic tx of
clinically negative lower neck
Adjuvant brachytherapymainly for residual/recurrent disease
-
7/29/2019 Refrat CA Ebv
21/27
Treatment
External beam radiation - complications
More severe when repeat treatments required
Include
xerostomia, tooth decay
ETD - early (SOM), later (patulous ET)
Endocrine disorders - hypopituitarism,
hypothyroidism, hypothalamic disfunction
Soft tissue fibrosis including trismus
Ophthalmologic problems
Skull base necrosis
-
7/29/2019 Refrat CA Ebv
22/27
Treatment
Surgical management
Mainly diagnostic - Biopsy
consider clinic bx if cooperative patient
must obtain large biopsy
clinically normal NP - OR for panendo
and bx
Surgical treatment
primary lesion
regional failure with local control
ETD
-
7/29/2019 Refrat CA Ebv
23/27
Treatment
Surgical management
Primary lesion
consider for residual or recurrent
disease
approaches infratemporal fossa
transparotid temporal bone approach
transmaxillary
transmandibular
transpalatal
-
7/29/2019 Refrat CA Ebv
24/27
Treatment
Surgical management
Regional disease
Neck dissection may offer improved
survival compared to repeat radiation of
the neck
ETD
BMT if symptomatic prior to XRT
Post XRT observation period if symptoms not severe
amplification may be more appropriate
-
7/29/2019 Refrat CA Ebv
25/27
Treatment
Chemotherapy
Variety of agents
Chemotherapy + XRT - no proven
long term benefit
Mainly for palliation of distant disease
Immunotherapy
Future treatment??
Vaccine??
-
7/29/2019 Refrat CA Ebv
26/27
Conclusion
Rare in North America, more common in
China
40% overall survival at 5 years
Complete H&P, careful otologic,
neurologic, cervical and NP exams
Three WHO types - all from NP epithelium
Types II, III - better prognosis, EBV assoc.
Treatment is primarily XRT
-
7/29/2019 Refrat CA Ebv
27/27
27
Diagnosis - Summary
Serology can provide an adjuvant test
in the diagnosis of NPC
More than one titre is required
Biopsy + viral detection in biopsy is
still the gold standard
There is insufficient evidence for
serological diagnosis or screening alone