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7/29/2019 Refrat CA Ebv

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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


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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


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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


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Anatomy

Berhubungan dekat dg Foramen

Basis cranii.

Mucosa

Epithel transisional, peralihan antara :

Epitel squamous kompleks

Epitel pseudokompleks columnar.

Dibawah epitel byk jaringan Lymphoid.


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Epidemiology

Chinese native > Chinese immigrant

> North American native

Both genetic and environmental factors

Genetic

HLA histocompatibility loci possible

markers


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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.


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EtiologyVirus Epstein-Barr

Group : Group I (dsDNA)

Family :Herpesviridae

Subfamily: Gammaherpesvirinae

Genus :Lymphocryptovirus

Species : Human herpesvirus 4

(HHV-4)


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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.


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Antibodi spesifik untuk EBV dalam tubuh

IgA-anti VCA,

IgG-anti EBV-EA

sehingga dapat digunakan untukmemantau keberadaan virus EB didalam

tubuh


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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.


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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.


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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)


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Clinical Presentation

Initial symptoms

unilateral HL

Nyeri, pembesaran massa leher secara

pelan2.

Larger lesions

Obstruksi hidung

epistaxis

Keterlibatan Nervi Cranialis.


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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


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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 (


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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


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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

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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


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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


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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


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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


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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


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Treatment

Surgical management

Primary lesion

consider for residual or recurrent

disease

approaches infratemporal fossa

transparotid temporal bone approach

transmaxillary

transmandibular

transpalatal


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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


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Treatment

Chemotherapy

Variety of agents

Chemotherapy + XRT - no proven

long term benefit

Mainly for palliation of distant disease

Immunotherapy

Future treatment??

Vaccine??


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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


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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

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