Nasopharyngeal Carcinoma

Chandraveer suryavanshi

Bombay hospital

Introduction

85% adult nasopharyngeal malignancies are carcinoma.

Nasopharyngeal carcinoma is a non-lymphomatous, squamous-cell Nasopharyngeal carcinoma is a non-lymphomatous, squamous-cell

carcinoma that occurs in the epithelial lining of the nasopharynx. carcinoma that occurs in the epithelial lining of the nasopharynx.

This neoplasm shows varying degrees of differentiation and is This neoplasm shows varying degrees of differentiation and is

frequently seen at the pharyngeal recess (Rosenmüller’s fossa) frequently seen at the pharyngeal recess (Rosenmüller’s fossa)

posteromedial to the medial crura of the eustachian tube opening in posteromedial to the medial crura of the eustachian tube opening in

the nasopharynx.the nasopharynx.

• High index of suspicion required for early High index of suspicion required for early diagnosisdiagnosis

• Nasopharyngeal malignanciesNasopharyngeal malignancies– SCCA (nasopharyngeal carcinoma)SCCA (nasopharyngeal carcinoma)– LymphomaLymphoma

– Salivary gland tumorsSalivary gland tumors– SarcomasSarcomas

Anatomy

• Anteriorly -- nasal cavityAnteriorly -- nasal cavity

• Posteriorly -- skull base and vertebral Posteriorly -- skull base and vertebral bodiesbodies

• Inferiorly -- oropharynx and soft palateInferiorly -- oropharynx and soft palate

• Laterally -- Laterally -- – Eustachian tubes and toriEustachian tubes and tori– Fossa of Rosenmuller - most common locationFossa of Rosenmuller - most common location

• Close association with skull base foramenClose association with skull base foramen

The rigid and tough pharyngobasilar fascia provides structural The rigid and tough pharyngobasilar fascia provides structural support for the nasopharynx. support for the nasopharynx.

The fascia forms a three-sided curtain which opens anteriorly The fascia forms a three-sided curtain which opens anteriorly toward the nasal cavity.toward the nasal cavity.

Superiorly, the fascia is fixed to the skull base from the Superiorly, the fascia is fixed to the skull base from the pterygoid plates to the carotid canal.pterygoid plates to the carotid canal.

Lateraly it is adherent to the cartilaginous portion of the Lateraly it is adherent to the cartilaginous portion of the eustachian tube.eustachian tube.

It forms a closed and resistant barrier It forms a closed and resistant barrier The sinus of Morgagni is the only defect through which the The sinus of Morgagni is the only defect through which the

eustachian tube and the levator veli palatini muscle pass.eustachian tube and the levator veli palatini muscle pass.

Lateral to the pharyngobasilar Lateral to the pharyngobasilar fascia, the nasopharynx is bounded fascia, the nasopharynx is bounded by four spaces which are divided by four spaces which are divided by three layers of deep cervical by three layers of deep cervical fascia.fascia.

These include the masticator These include the masticator (infratemporal fossa), the (infratemporal fossa), the parapharyngeal, the carotid and parapharyngeal, the carotid and the parotid spaces.the parotid spaces.

Lateral deviation and or Lateral deviation and or infiltration of the parapharyngeal infiltration of the parapharyngeal fat are sensitive indicators of the fat are sensitive indicators of the spread of nasopharyngeal diseasespread of nasopharyngeal disease

• Mucosa Mucosa – Epithelium - tissue of Epithelium - tissue of

origin of NPCorigin of NPC• Stratified squamous Stratified squamous

epitheliumepithelium

• Pseudostratified columnar Pseudostratified columnar epitheliumepithelium

– Salivary,Salivary,– Lymphoid structuresLymphoid structures

Race: More in Chinese & North African people

Sex: Male preponderance of 3:1

Age: Small peak: 12-18 yrs;

large peak: 50-60 yrs

Gross: Proliferative,

Ulcerative &

Infiltrative types

Histology: 85% Squamous cell carcinoma

10% Lymphomas,

5% Mixed

Aetiology

1. Genetic: Commonest in Chinese population. HLA-A2

B,C,DR, DQ, DS & HLA-B-Sin 2 histocompatibility

locus

2. Viruses:• EBV- well documented viral “fingerprints” in EBV- well documented viral “fingerprints” in

tumor cells and also anti-EBV serologies with tumor cells and also anti-EBV serologies with WHO type II and III NPCWHO type II and III NPC

• HPV - possible factor in WHO type I lesionsHPV - possible factor in WHO type I lesions

3. Environmental: Exposure to nitrosamines (dry salted fish),

• polycyclic hydrocarbons (smoke from incense & wood),

• smoking,

• chronic nasal infection,

• poor ventilation of nasopharynx

• Poor hygiene of nasopharynx

Classification

• WHO classesWHO classes– Based on light microscopy findingsBased on light microscopy findings– All SCCA by EMAll SCCA by EM

• Type I - “SCCAType I - “SCCA• well differentiated well differentiated • non differentiated non differentiated

– 25 % of NPC25 % of NPC– moderate to well differentiated cells similar to other SCCA ( keratin, moderate to well differentiated cells similar to other SCCA ( keratin,

intercellular bridges)intercellular bridges)

Classification

• Type II - “non-keratinizing” carcinomaType II - “non-keratinizing” carcinoma

– 12 % of NPC12 % of NPC

– variable differentiation of cells ( mature to variable differentiation of cells ( mature to anaplastic)anaplastic)

– minimal if any keratin productionminimal if any keratin production

– may resemble transitional cell carcinoma of may resemble transitional cell carcinoma of the bladderthe bladder

Classification

• Type III - “undifferentiated” carcinomaType III - “undifferentiated” carcinoma

– 60 % of NPC, majority of NPC in young 60 % of NPC, majority of NPC in young patientspatients

– Difficult to differentiate from lymphoma by Difficult to differentiate from lymphoma by light microscopy requiring special stains & light microscopy requiring special stains & markersmarkers

– Diverse groupDiverse group

• Lymphoepitheliomas, spindle cell, clear Lymphoepitheliomas, spindle cell, clear cell and anaplastic variantscell and anaplastic variants

W.H.O. classification

Type 1: keratinizing squamous cell carcinoma

Type 2: non-keratinizing (transitional) carcinoma

• Without lymphoid stroma (intermediate cell)

• With lymphoid stroma (lympho-epithelial)

Type 3: undifferentiated (anaplastic) carcinoma

• Without lymphoid stroma (clear cell)

• With lymphoid stroma (lympho-epithelial)

Clinical Features

• Often subtle initial symptomsOften subtle initial symptoms– unilateral HL (SOM)unilateral HL (SOM)

– painless, slowly enlarging neck masspainless, slowly enlarging neck mass

• Larger lesionsLarger lesions– nasal obstructionnasal obstruction

– epistaxisepistaxis– cranial nerve involvementcranial nerve involvement

Clinical Features

1. Neck swelling (50%): B/L, enlarged upper &

middle deep cervical nodes + posterior

triangle nodes (Rouviere's sign)

2. Nasal (30%): epistaxis, nose block, nasal

discharge ,denasal speech

3. Otologic (20%): Conductive deafness, tinnitus,SOM ,otalgia

Clinical Features• 4. Ophthalmologic (20%): Proptosis (orbit invasion) &

blindness (involvement of CN II)

• Xerophthalmia - greater sup. petrosal nXerophthalmia - greater sup. petrosal n• Facial pain - Trigeminal n.Facial pain - Trigeminal n.• Diplopia - CN VIDiplopia - CN VI• Ophthalmoplegia - CN III, IV, and VIOphthalmoplegia - CN III, IV, and VI

– cavernous sinus or superior orbital fissurecavernous sinus or superior orbital fissure

• Horner’s syndrome - cervical sympatheticsHorner’s syndrome - cervical sympathetics

5. Neurologic (20 %): Jugular foramen syndrome: CN

IX, X, XI involved by lateral retropharyngeal lymph

node

Horner's syndrome: sympathetic chain

involvement( Ptosis +Miosis+Anhidrosis

+Enophthalmos )

Clinical Features

6. Severe Headache (20%): indicates skull base erosion, vth nerve

involment

7. Trotter's triad:

Conductive deafness: Eustachian Tube block

+ I/L temporo-parietal neuralgia: Trigeminal damage

+ I/L palatal paralysis: Vagus damage

8. Distant metastasis: to bone, lung & liver

Neck swelling

Ptosis & adduction palsy

Left proptosis

Investigations

1. Nasopharyngoscopy & Diagnostic Nasal

Endoscopy: Tumor mass seen in nasopharynx

Commonest site is fossa of Rosenmüller

2. Nasopharyngeal tumor biopsy: seen or blind

3. F.N.A.C. of neck node: done in occult primary

4. C.T. scan head & neck:4. C.T. scan head & neck: for tumor extent, skull base for tumor extent, skull base

erosion & cervical lymph node metastasiserosion & cervical lymph node metastasis

Investigations

5. M.R.I. head & neck:

for intracranial and perineural extension.

6. Tests for metastases:

- C.T. chest + abdomen, bone scan,

- P.E.T. scan,

- Liver function tests.

• 7 Serologic tests: Special diagnostic tests (for Special diagnostic tests (for types II & III)types II & III)– IgA antibodies for viral capsid antigen (VCA)IgA antibodies for viral capsid antigen (VCA)– IgG antibodies for early antigen (EA)IgG antibodies for early antigen (EA)

• Special prognostic test (for types II & III)Special prognostic test (for types II & III)– antibody-dependent cellular cytotoxicity (ADCC) antibody-dependent cellular cytotoxicity (ADCC)

assayassay• higher titers indicate a better long-term prognosishigher titers indicate a better long-term prognosis

• CBC, LFT’sCBC, LFT’s

Diagnostic Nasal Endoscopy

Computerized Tomogram

CT scan: retropharyngeal node

CT scan: Infratemporal fossa & orbit involvement

Magnetic Resonance Imaging

MRI: parapharyngeal mass

MRI: neck node metastasis

M.R.I.: intracranial extension

Endoscopic biopsy

CT scan: liver metastasis

Whole body bone scan

Positron Emission Tomography

T.N.M. staging

T1 = confined to nasopharynx

T2 = soft tissue involvement in oropharynx or

nasal cavity or parapharyngeal space

T3 = invasion of bony structures or P.N.S.

T4 = intracranial, involvement of orbit, cranial

nerves, infratemporal fossa, hypopharynx

T.N.M. staging

N0 = no evidence of regional lymph nodes

N1 = unilateral

N2 = bilateral

(Both are above supraclavicular fossa & < 6 cm)

N3 = > 6 cm or in supraclavicular fossa

M0 = no evidence of distant metastasis

M1 = distant metastasis present

Supraclavicular fossa

Synonym: Ho’s triangle

A = medial end of

clavicle

B = Lateral end of

clavicle

C = junction between

neck & shoulder

T.N.M. staging

• Stage I = T1 N0 M0

• Stage II = T2 or N1 M0

• Stage III = T3 or N2 M0

• Stage IV = T4 or N3 or M1

Treatment modalities

1. Teletherapy or External beam radiotherapy

2. Brachytherapy

3. Chemotherapy

4. Surgery

5. Immunotherapy against E.B.V.

6. Vaccination against EBV: experimental

Cobalt Teletherapy

External beam irradiation

2 lateral fields: nasopharynx, skull base & upper

neck; sparing temporal lobe, pituitary & spinal cord.

1 anterior field: lower neck; sparing spinal cord & larynx

External beam radiation - complications

– More severe when repeat treatments requiredMore severe when repeat treatments required– IncludeInclude

• xerostomia, tooth decayxerostomia, tooth decay• ETD - early (SOM), otitis externa, later (patulous ET)ETD - early (SOM), otitis externa, later (patulous ET)• Endocrine disorders - hypopituitarism, hypothyroidism, Endocrine disorders - hypopituitarism, hypothyroidism,

hypothalamic disfunctionhypothalamic disfunction• Soft tissue fibrosis including trismusSoft tissue fibrosis including trismus• Ophthalmologic problemsOphthalmologic problems

• Skull base necrosis,temporal lobe necrosisSkull base necrosis,temporal lobe necrosis• nasal crusting,intranasal adhesion ,olfactary dysfunctionnasal crusting,intranasal adhesion ,olfactary dysfunction

• osteosarcoma of nose and sinus

• ssc of oral cavity tongue and pharynx

• delayed cranial nerve palsy

Brachytherapy

• Used for small tumor, residual or recurrent tumor

• Interstitial: Radioactive source (Radium, Iridium, Iodine,

Gold) inserted into tumor tissue

• Intracavitary: Radioactive source placed inside catheter

or moulds & inserted into nasopharynx

• High dose rate (HDR): High intensity radiation delivered

with precision under computer guidance

Interstitial Brachytherapy

Intracavitary Brachytherapy

High Dose Rate Brachytherapy

Chemotherapy

Drugs used:1. Cisplatin

2. 5-Fluorouracil

Role of chemotherapy – radiation sensitization, Role of chemotherapy – radiation sensitization,

locoregional controllocoregional control

Indications: 1. Radiation failure

2. Palliation in distant metastasis

Chua, IJROBP, 2006 Chua, IJROBP, 2006

Subgroup analysis of 2 induction studies with cis/epirubicin and Subgroup analysis of 2 induction studies with cis/epirubicin and cis/bleo/5FU cis/bleo/5FU →→ RT RT vsvs. RT alone. RT alone

Early stage pts (T1-2N0-1, st. IIB) had fewer distant mets with induction and Early stage pts (T1-2N0-1, st. IIB) had fewer distant mets with induction and improved survivalimproved survival

Yau, Head and Neck, 2006Yau, Head and Neck, 2006

Phase II study of gemcitabine/cis X3 Phase II study of gemcitabine/cis X3 →→ cis/accelerated concomitant boost cis/accelerated concomitant boost RTRT

3Y OS = 76%, 3Y PFS = 63%3Y OS = 76%, 3Y PFS = 63%Chan, JCO, 2004Chan, JCO, 2004

Phase II study of carbo/paclitaxel X2 Phase II study of carbo/paclitaxel X2 →→ cis/RT cis/RT

Overall CR rate=97%Overall CR rate=97%

2Y OS = 92%, 2Y PFS = 79%2Y OS = 92%, 2Y PFS = 79%

Surgery

• Primary lesion Primary lesion – consider for residual or recurrent diseaseconsider for residual or recurrent disease– approachesapproaches

• infratemporal fossa infratemporal fossa • transparotid temporal bone approachtransparotid temporal bone approach• transmaxillarytransmaxillary• transmandibulartransmandibular

• transpalataltranspalatal

• Regional diseaseRegional disease– Neck dissection may offer improved survival Neck dissection may offer improved survival

compared to repeat radiation of the neckcompared to repeat radiation of the neck

Surgery

1. Nasopharyngectomy, Cryosurgery:

for residual or recurrent tumor

2. Radical neck dissection:

for radio-resistant lymph node metastasis

3. Palliative debulking: for T4 tumors

4. Myringotomy & grommet insertion:

for persistent otitis media with effusion

Treatment Protocol

T1 = External Radiotherapy (6500 cGy)

T2 = External Radiotherapy (7000 cGy)

T3 & T4 = Radiotherapy + Chemotherapy →

Brachytherapy / Salvage surgery if required

N0 = External Radiotherapy (5000 cGy)

N1, N2, N3 = External Radiotherapy (6000 cGy)

+ Chemotherapy

Prognosis

W.H.O. Type 2 & 3 carcinomas have good

response to radiotherapy & better survival rates.

5 year survival rates for treated patients:

Stage I = 95 – 100 %

Stage II = 60 – 80 %

Stage III = 30 – 60 %

Stage IV = 20 – 30 %