KARSINOMA

NASOFARING
Referat

Presentan : dr.F ITRIA SHOLIHAH

Pembimbing : dr. HASRAYATI AGUSTINA, SpPA(K)., Mkes.
Opponent : dr. SRI SURYANTI MS., SpPA(K)
 PENDAHULUAN
• Karsinoma nasofaring merupakan neoplasma
yang paling sering didapatkan pada
nasofaring.
• Merupakan salah satu jenis yang memiliki
prognosis buruk.
• Pada referat ini akan dibahas tentang
epidemiologi, etiologi, patogenesis, klasifikasi,
patologi, diagnosis banding, terapi dan
prognosis.
 ANATOMI

Sumber : Van de Graaf

 HISTOLOGI

Mukosa dilapisi epitel

pseudostratified bersilia

Membrana basalis tidak

mencolok

Terdapat komponen limfoid

• Sumber : Wenig BM : Atlas of Head and Neck Pathology 3rd ed.

DEFINISI DAN EPIDEMIOLOGI
Definisi :
karsinoma yang muncul di mukosa nasofaring
yang memperlihatkan struktur diferensiasi
skuamosa

Epidemiologi :
jarang pada etnis Kaukasia, lebih banyak pada
etnis Cina, Afrika Utara, dan Inuilt di Alaska.
 INSIDENSI
• Amerika Utara 0,3 – 0,7 kasus / 100.000
penduduk
• Hongkong, Cina 12,5 kasus /100.000 penduduk
laki-laki ; 4,1 kasus / 100.000 penduduk
perempuan
• Cina Utara 15 – 40 kasus / 100.000
• Laki-laki : perempuan = 2 – 3 : 1
• Muncul pada usia 30 tahun, puncaknya 40 – 60
tahun
 ETIOLOGI
• Genetik
terutama pada etnis Cina
• Epstein Barr Virus (EBV)
terutama sangat berkaitan erat dengan
undifferentiated non-keratinizing
nasopharyngeal squamuous cell carcinoma
• Pengaruh Lingkungan
ikan yang diawetkan (nitrosamine), paparan
terhadap uap formaldehyde, debu kayu,
rokok, uap kimia lain
LOKASI
 WHO-Hystological Classification of Head
and Neck Tumours 2017

Nasopharingeal carcinoma :

• Keratinizing squamous cell carcinoma

• Non-keratinizing squamous cell carcinoma
• Basaloid squamous cell carcinoma
 MAKROSKOPIS
• Tonjolan yang halus pada mukosa

• Nodul dapat berkembang dengan atau tanpa

ulserasi

• Sebagai masa infiltratif yang jelas terlihat

• Terkadang tidak terdapat lesi gross yang terlihat

• Blind biopsy dari area nasofaring harus

dilakukan ketika ada kecurigaan
 MIKROSKOPIS
• Keratinizing squamuous cell carsinoma - well
differentiated

- Differensiasi squamosa dengan pembentukan keratinisasi

• Sumber : Wenig BM : Atlas of Head and Neck Pathology 3rd ed.

 MIKROSKOPIS
Keratinizing squamuous cell carsinoma - moderatelly
differentiated

• Sumber : Wenig BM : Atlas of Head and Neck Pathology 3rd ed.

 MIKROSKOPIS
• Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC)

- Papillary architecture WHO Classification of Head and

- Membentuk papil-pail exophytic dengan fibrovascular core Neck Tumour, 2017
 MIKROSKOPIS
• Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - differentiated

- Interconnecting cords/trabeculae dari permukaan epitel

- Intercelullar bridges yang bervariasi
- Absence of keratinization
- Peningkatan aktifitas mitotic
• Sumber : Wenig BM : Atlas of Head and
Neck Pathology 3rd ed.
 Non-keratinizing Squamuous Cell Carcinoma (NK-
NPC) - differentiated

- Masih memperlihatkan stratifikasi seluller

- N : C ratio lebih rendah dibandingkan type undiff
- Nuclei lebih hyperchromatis
- Nucleloli kurang menonjol Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
 MIKROSKOPIS
• Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - undifferentiated

- - Regaud pattern-
- Sarang-sarang tumor berbentuk bulat/oval
berinfiltrasi Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
- Proliferasi lymfoid (non neoplastik)
 • Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - undifferentiated

- Syncitial neoplastic nest : sel dengan inti yang bulat dan

membesar , khromatin yang vesiculer, prominent eosinofilic
nucleoli, sitoplasma pucat.
Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
 MIKROSKOPIS
• Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - undifferentiated

-Scmincke pattern-
Diffuse, Non cohesive celluler infiltrat, terdiri dari sel-sel dengan inti yang bulat dan membesar, anak
inti eosinofilik dan menonjol, sitoplasma pucat, batas sel tidak jelas

Scmincke pattern Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
 • Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - undifferentiated

Terdiri dari sel-sel dengan inti yang bulat dan membesar, anak inti eosinofilik dan menonjol, sitoplasma
pucat
Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
• Non-keratinizing Squamuous Cell Carcinoma
(NK-NPC) - undifferentiated

fascicular growth composed of spindle-shaped cells;

Thompson LDR : Head and Neck Pathology. 2nd ed

• Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
 MIKROSKOPIS
• Basaloid squamuous cell carcinoma

• Tumor ini secara morfologis identik terhadap tumor analog yang muncul di area lain pada
kepala dan leher, dan sangat jarang dilaporkan sebagai tumor primer dari nasofaring.
• Festooning growth pattern, diselingi sel-sel tumor dengan differensiasi skuamosa.
WHO Classification of Head and Neck Tumours, 2017
 GEJALA
KLINIS

• Biasanya tidak
spesifik dan tidak
jelas, sehingga
menyebabkan
keterlambatan
dalam diagnosis.
 DIAGNOSIS
• Ditegakkan melalui pendekatan klinis,
pemeriksaan fisik
• Pemeriksaan penunjang :
radiologi, MRI, PET-CT, serologis, PCR
• Patologi Anatomik :
 Gross/Makroskopis
 Histopatologi/Mikroskopis
 Immunohistokimia
DIFFERENTIAL
DIAGNOSIS

Sumber : Wenig BM : Atlas of Head and Neck Pathology 3rd ed.

 IMMUNOHISTOKIMIA

• EBER Nuclear Positive Cytokeratin positif

Gold standar
Strong and diffuse
nuclear staining
TNM STAGING
• Sumber : Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
 THERAPY
• Pilihan terapi untuk karsinoma nasofaring
adalah radioterapi, dan juga kombinasi
dengan kemoterapi.
• Pada lebih dari 5000 kasus di Hongkong,
83% penderita mengalami remisi
sempurna dengan 10 year survival rate
adalah 43%.
 PROGNOSIS
5 Year Survival Rate

Stadium
I
• 98% Umur

Stadium
II
• 95% Type
Histol Stadium
ogi

Stadium
III
• 86% Regio
Volume
Metas tumor
tasis
Stadium
IVA - B
• 73%
 PEMBAHASAN
• Karsinoma nasofaring merupakan
keganasan yang biasanya terjadi pada
orang dewasa pada usia 40 – 60
tahun,walaupun tumor ini bisa muncul
pada anak-anak.
Perbedan Klasifikasi WHO
WHO Classification of Head and
Neck Tumour, 2017
 Perbedan Klasifikasi WHO
• Non-keratinizing carcinoma merupakan
NPC klasik. Terdapat dua tipe yaitu :
differentiated dan undifferentiated.
• Untuk membedakan klasifikasi non-
keratinizing menjadi tipe differentiated dan
undifferentiated merupakan hal yang
cukup sulit dan tidak signifikan baik secara
klinis maupun prognosis.
 Differensial Diagnosa
NK-NPC, Undifferentiation Oropharymgeal NK SCC

- Interconnecting cords/trabeculae dari permukaan epitel

- Batas sel jelas, intercelullar bridges yang bervariasi
Terdapat foci clasic dari NK-Carcinoma,
- Absence of keratinization Mature squamuous differentiation
- Peningkatan aktifitas mitotic
NK-NPC, Undifferentiation Oropharymgeal NK SCC

(+) EBER (+) p16

 NK-NPC Undiff. Type Schmincke

• Sumber : Rosai, Surgical Pathology 11th ed.

 SNUC

Cells with clear cell

cytoplasm

* (+) pada IHK CK7, CK8, CK9

• Sumber : Pathology Outlines (-) pada CK 4. CK5/6, CK14
(+/-) p63
 Diffuse Large B Cell Lymphoma

CD 45 (+)

• Sumber : Pathology Outlines CD 20 (+)

NK-NPC, Undifferentiation Mucosal Malignant Melanoma
• EBV biasanya didapatkan pada tipe non-
keratinizing dibandingkan tipe keratinizing.
• Hibridisasi insitu atau PCR (polymerase chain
reaction) biasanya diperlukan untuk
memperlihatkan adanya EBV. Walaupun
demikian EBV encoded early RNA (EBER)
merupakan pemeriksaan yang paling sensitif
dan spesifik yang ada pada saat ini untuk
mendeteksi adanya EBV pada karsinoma
nasofaring.
• Pada EBER positif, potensi residual / reccurent
tumor lebih besar.
 SIMPULAN
• Karsinoma nasofaring merupakan keganasan yang paling sering terjadi
pada nasofaring
• Karsinoma nasofaring jarang dijumpai pada ras kaukasia, tetapi umum
terjadi pada ras Cina terutama Cina Selatan dan Afrika Selatan, hali ini
dicurigia erat hubungannya dengan faktor genetik dan juga kebiasaaan
mengkonsumsi ikan yang diasinkan yang mengandung kadar nitrosamine
yang tinggi.
• Undifferentiated non keratinizing squamuous cell carcinoma merupakan
type yang tersering diantara semua klasifikasi carcinoma nasofaring,
sedangkan type keratinizing squamuous cell carcinoma mempunyai
prognosis lebih buruk dibandingkan type non keratinizing squamuous cell
carcinoma.
DD/ Undiff Non Kerat dg
Limfoma
Waldeyer’s Rings
 Waldeyer’s Rings
Pharyngeal Tonsil
Tubal Tonsil

Palatine Tonsils Lingual Tonsil

 NK-NPC, differentiated.

“sheets of tumour separated by dense

infiltrat of lymphoscytes and plasma cells”
“tumour islands in lymphoid cell rich stroma”
Lymphosit dapat terlihat dengan tumor

WHO Classification of Head and Neck Tumour, 2017

MMM
• Wenig BM : Atlas of Head and Neck Pathology 3rd ed.
• NPC frequently metastasizes to
regional lymph nodes and the
presence of lymph node
metastasis decreases survival by
approximately 10% to 20%.
• • A large percentage of NPC,
particularly of the undifferentiated
type, metastasize to sites below
the clavicle, including the lungs,
bone (ribs and spine), and liver.
• • Patterns of spread include
invasion into adjacent soft tissues,
sinonasal tract, paranasal sinuses,
posteriorly to the carotid sheath
with involvement of cranial nerves
IX, X, or XI, and skull base as well
as spreading intracranially
 Symptoms
• A lump in the neck: One of the most common ways a nasopharyngeal cancer is detected is after it has spread to
the lymph nodes in the neck. Up to 80 percent of people with NPC first come to their doctor with a lump in the
neck.14
• A blocked-up nose: Difficulty breathing from one or both sides of the nose (obstruction) can be caused by a large
tumor blocking the nasal breathing passage.
• Bleeding from the nose or mouth: This can be caused by a tumor in the back of the nose.
• Ear problems: Ear-related problems, such as hearing loss on one side, ringing in the ear on one side, an ear
infection in an adult or fluid behind the eardrum can be caused by a tumor mass blocking the Eustachian tube.
• Cranial nerve (CN) problems: A problem with the cranial nerves can be caused by a tumor extending into the
skull or along the skull base where the nerves exit. A tumor growing into one of these nerves can cause a variety
of problems, depending on which nerve is affected:
– Slurred speech: CN XII is called the hypoglossal nerve, and it controls the muscles of the tongue.
– Double vision: CN III, IV and VI are three different oculomotor nerves, and they control the muscles that
move the eye.
– Loss of feeling in part of the face: CN VIII is the third division of the trigeminal nerve, and it sends sensation
signals from the lower part of the face to the brain.
– Difficulty with shoulder movement: CN XI is called the spinal accessory nerve, and it controls movement of
some of the shoulder and neck muscles.
– Change in voice and swallowing: CN IX and X are called the glossopharyngeal nerve and vagus nerve, and
have a number of different functions, some of which include controlling muscles of the voice and swallowing.
• Headache: A bad headache can be caused by a tumor growing into the skull.
• Difficulty with mouth opening (trismus): This can happen when the tumor invades into muscles that move the
jaw.
 T stage: the main tumor

T1 The tumor is just within the nasopharynx, or it has grown into the oropharynx and/or
nasal cavity, but there is no extension into the parapharyngeal space (soft tissue
space behind and to the side of the pharynx).
T2 The tumor extends into the parapharyngeal space (soft tissue space next to the
pharynx).
T3 The tumor has grown into the bone of the head, including the skull base and/or the
sinuses.
T4 The tumor has grown into the skull and/or involves the cranial nerves, hypopharynx,
or eye socket (orbit). Or it has extended to the infratemporal fossa or masticator
space.
 N stage: spread of cancer to the lymph nodes in the neck

M stage: spread of cancer outside the head and neck

N0 There is no evidence of cancerous spread to lymph nodes in the neck or retropharyngeal space.
N1 There are cancerous lymph nodes on just one side of the neck, where the largest is 6 centimeters or less, and
all the lymph nodes are above the supraclavicular fossa. Also, the cancer is at this stage if the lymph nodes
are found in the retropharyngeal space (6 centimeters or less in size, one side or both).
N2 There are lymph nodes with cancer on both sides of the neck (where the biggest lymph node is 6 centimeters
or less in size, and all the lymph nodes are above the supraclavicular fossa).
N3a There is a lymph node with cancer that is bigger than 6 centimeters.
N3b There is a cancerous lymph node of any size that is far down in the neck, just above the clavicles
(supraclavicular fossa).
 M stage: spread of cancer outside the head and neck

M0 No evidence of distant (outside the head and neck) spread.

M1 There is evidence of spread outside of the head and neck (i.e., in the lungs, bone,
brain, etc.).
Stage 0 Tis N0 M0
Stage 1 T1 N0 M0
Stage 2 T1 N1 M0
T2 N0 M0
T2 N1 M0
Stage 3 T1 N2 M0
T2 N2 M0
T3 N0 M0
T3 N1 M0
T3 N2 M0
Stage 4a T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage 4b Any T N3 M0
Stage 4c Any T Any N M1