TUMOURS OF NASOPHARYNX

SYNONYMSEpipharynxPost nasal spaceRetro nasal cavity

WHO CLASSIFICATIONEPITHELIAL TUMOURS

› BENIGN MALIGNANTPapilloma NPCPleomorphic Adenoma

AdenocarcinomaOncocytoma Papillary

adenocarcinoma Ectopic pituitary Adenoma Basal Cell Ca Muco-epidermoid

carcinoma Adenoid cystic Ca Polymorphous low grade

Adenocarcinoma

SOFT TISSUE TUMOURSBENIGN MALIGNANT

Angiofibroma FibrosarcomaHaemangioma Rhabdomyosarcoma

Haemangio-pericytoma Angiosarcoma

Neurilemmoma Kaposi Sarcoma

Neurofibroma Malignant Haemangio-pericytoma

Paraganglioma Synovial Sarcoma.

TUMOURS OF BONE AND CARTILAGE

MALIGNANT LYMPHOMASNHLExtra medullary palsmacytomaMidline malignant reticulosisHistocytic lymphomaHodgkin’s disease

MISCELLANEOUS TUMOURBENIGN MALIGNANT

Meningioma Malignant Melanoma Craniopharyngioma Germ Cell Tumour Teratoma Chordoma

SECONDARY TUMOURSUNCLASSIFIED TUMOURSTUMOUR LIKE LEISIONS – cysts /

maningocele / meningoencephalocele / granuloma / amyloid deposits

JUVENILE NASOPHARYNGEAL

ANGIOFIBROMA(NASOPHARYNGEAL FIBROMA)

JUVENILE NASOPHARYNGEAL ANGIOFIBROMA

Commonest of all benign tumours of nasopharynx.

Locally invasive, but histologically benign vascular tumour.

Seen in young adolescent males . It regresses after adolescense.

It is considered as “HAMARTOMA”

PATHOGENESIS Exact etiology is not known. Various theories include: Ringert’s theory. Som & Neffson. Huges-Craniopharyngeal duct. Bensch & Ewing-Embryonic fibrocartilage Brunner. Girgis & Fahmy-Chemodectoma. Osborn. Willis-Inflammatory immune response

Ringertz (1938) – tumor arose from the periosteum of nasopharyngeal vault.

Som and Neffson – inequalities in the growth of bones of skull base results in hypertrophy of underlying periosteum,in response to hormonal influence.

Bensch and Ewing – tumor probably arose from embryonic fibrocartilage between basiocciput and basisphenoid.

Brunner – origin from conjoined pharyngobasilar and buccopharyngeal fascia.

Osborn – possibility of the swelling to be hamartomatous or residues of fetal erectile tissue which were subject to hormonal influences.

Girgis and Fahmy – noted cell nests of undifferentiated epitheloid cells (zellballen) at the growing edge of angiofibromas,likely to that of paragangliomas.

Marten et al – hormonal theory suggesting that these tumors resulted from deficiency of androgen and overactivity of estrogen.

SITE OF ORIGIN AND GROWTH

Posterior part of nasal cavity close to the margin of sphenopalatine foramen.

From here the tumour grows into the nasal cavity, nasopharynx and into the pterygopalatine fossa.

Dumb-bell Shaped.

BLOOD SUPPLY OF THE TUMOUR

Maxillary artery. Ascending pharyngeal artery Un named branches from internal carotid

artery.

SPHENOPALATINE FORAMENIt is formed by:

Orbital & Sphenoidal process of the perpendicular plate of palatine bone.

Horizontal ala of the vomer. Root of the pterygoid process of the sphenoid

bone.

PATHOLOGY

Angiofibroma, as the name implies, is made up of vascular and fibrous tissues

Mostly, the vessels are just endothelium-lined spaces (foetal type of blood vessels) with no muscle coat.

This accounts for the severe bleeding as the vessels lose the ability to contract.

SPREAD OF TUMOUR Nasal cavity Paranasal sinuses Pterygomaxillary fossa, infratemporal fossa

and cheek Orbits giving rise to proptosis and “frog-

face deformity” through the inferior orbital fissure

Cranial cavity There are two routes of entry:1) By erosion of floor of middle cranial fossa

anterior to foramen lacerum. 2) Through sphenoid sinus

CLINICAL FEATURES

Profuse and recurrent epistaxis. Progressive nasal obstruction. Hyponasal Voice. Conductive hearing loss and serous otitis

media due to obstruction of eustachian tube.

Mass in the nasopharynx Broadening of nasal bridge, Proptosis,

swelling of cheek, Involvement of IInd, IIIrd, IVth, VIth cranial

nerves will depend on the extent of tumour.

Anterior rhinoscopy:-- abundant mucopurulent secretions.-- bowing of the septum to the uninvolved side.

Posterior rhinoscopy:-- pink or red mass filling the nasopharynx.

Gross physical signs are evident when the tumor has involved the infratemporal fossa.

Swelling in the cheek and temple Intraoral palpation in the area between the

ascending ramus of mandible and the side of maxilla – fullness because of tumor that has crept around the back of the antrum

PECULIARITIES More common in young adolescent males. Benign but locally invasive. It has got diffuse attachment and takes blood

supply whereever it goes. No capsule, No pedicle. Recurrences more common.

FISCH CLASSIFICATIONI-confined to Nasopharynx & Nasal

cavity without bone destruction.

II-Pterygopalatine fossa & Sinuses with bone destruction.

III-Infratemporal fossa & Orbit.

IV-Intracranial extension.

FISCH STAGING CLASSIFICATION Done for prognosis and therapeutic approaches

Stage I: Tumor limited to the nasal cavity Stage II: Tumor extension into the pterygopalatine fossa,

or maxillary, sphenoid or ethmoid sinuses. Stage IIIa: Tumor extension into the orbit or

infratemporal fossa without intracranial involvement. Stage IIIb: Stage IIIa with extradural (parasellar)

intracranial involvement Stage IVa: Intradural without cavernous sinus, pituitary,

or optic chiasm involvement Stage IVb: Involvement of the cavernous sinus,

pituitary, or optic chiasm

RADKOWSKI CLASSIFICATION

Stage Ia: limited to the nose and nasopharyngeal area.

Stage Ib: extension into 1 or more sinuses. Stage IIa: minimal extension into

pterygopalatine fossa Stage IIb: occupation of pterygopalatine fossa

without extension to orbit. Stage IIc: infratemporal fossa extension

without cheek or pterygoid plate involvement. Stage IIIa: erosion of skull base(middle cranial

fossa) Stage IIIb: erosion of skull base with

intracranial extension with or without cavernous sinus involvement

DIFFERENTIAL DIAGNOSIS Enlarged Adenoids. Infected AC Polyp. Haemangiomas. Rhinosporidiosis. Inverted Papilloma. Malignancy. Craniopharyngioma.

INVESTIGATIONS

X-ray Soft tissue lateral view of nasopharynx.

X-ray of paranasal sinuses and base of skull.

C.T. Scan - Plain & Contrast to know the Intracranial extension.

Carotid angiography. MR Angiography.

Brown’s Sign CT findings: A Vascular mass located posterior to the

maxillary antrum with anterior displacement of the posterior wall of the maxillary sinus.

X-Ray Findings:Holman Millar Antral Sign – Anterior

bowing of the posterior wall of the Maxillary sinus.

HOLMAN MILLAR SIGN 1) JNA 2) Schwanoma 3) Fibrous dysplasia 4) Nasopharyngeal Carcinoma 5) Tumours of infratemporal fossa.

TRIPLE LINE OF BACLESSE

Submento Vertical View of X-Ray PNS

1) S-Shaped line represents the Posterior wall of the Maxillary sinus. Erosion – into the Subtemporal fossa.

2) Upper curvilinear line represents lateral wall of orbit. Erosion – into the orbit.

3) Lower curvilinear line represents lesser wing of the Sphenoid. Erosion – Skull base.

DIAGNOSIS It is mostly based on clinical picture, Biopsy

is avoided.

EMBOLISATION TREATMENT Surgical excision is now the treatment of

choice1. Wilson’s Transpalatine2. Transpalatine + Sublabial (Sardana’s

approach)3. Extended lateral rhinotomy.4. Midfacial degloving.5. Endoscopic approach.6. Maxillary swing.

Recurrent angiofibroma:

Difficult if it occurs after initial surgical removal Facial disassembly approach. Stereotactic radiosurgery for small intracranial

recurrences. Doxorubicin and decarbazine.

MATERIALS USED FOR EMBOLISATION Autologous substances like fat, blood clot, or

chopped muscle fragments.Artificial materials: Gelfoam, Oxidised cellulose, Tantalum powder, glass beads, polyvinyl alcohol etc.

Embolisation should always be preceded by angiography. 

 Immediate complications of embolisation are pain, embolisation of normal vessels, hypersensitivity. 

Delayed complications include fever, pain and infections.

RADIOTHERAPY Radiotherapy can produce some amount of

tumor regression by radiation vasculitis and occlusion of vessels by perivascular fibrosis. 

Radiotherapy should be reserved for selected patients such as those with inoperable intracranial extensions and recurrent tumors.

External beam radiation is delivered in low dose of 30 – 55 Gy in 15 fractions over 3 wks.

Regression of angiofibromas after radiotherapy is very slow, like 2 to 3 yrs to reduce the tumor size but residual tumor remains.

Disadvantages of radiotherapy:a. If the child is exposed to large doses i.e. above 5000-6000 rads, there may be damage to eyes, spinal cord and brain.

b. Small doses are ineffective in reducing the blood supply or the size of the mass.

c. Radiotherapy may cause fibrosis retardation of facial growth and adhesions of surrounding tissue.  Later surgery upon these patients becomes difficult.

d. Sarcomatous changes can occur in the mass as a result of irradiation.

HORMONAL THERAPYOestrogens - induces shrinkage,collagen

formation,reduces vascularity. Disadvantages – feminizing effects

(breast size)Nonsteroidal androgen receptor blocker,

Flutamide – tumor shrinkage upto 44% was reported.

Disadvantages - breast tenderness, nausea, gynaecomastia.

Hormones by themselves are carcinogens

OTHER BENIGN TUMOURS OF NASOPHARYNX

Teratomas Pleomorphic adenoma Chordoma Hamartoma Choristoma Paraganglioma

NASOPHARYNGEAL CARCINOMA

NASOPHARYNGEAL CANCER

More common among Chinese & South-

east Asians.

Male: Female ratio – 3 : 1

15-19 years of age, 35-65 years of age

PREDISPOSING FACTORS Genetic Factors. Viral – EB Virus. Environmental factors 1) Tobacco Smoking. 2) Salted fish & Preserved Vegetables. 3) Incense Stick Smoke. 4) Household & Industrial fumes. 5) Wood dust.

EPIDEMIOLOGY

Chinese native > Chinese immigrant > North American nativeBoth genetic and environmental factors

GeneticHLA histocompatibility loci possible markers

EnvironmentalViruses

EBV- well documented viral “fingerprints” in tumor cells and also anti-EBV serologies with WHO type II and III NPC

HPV - possible factor in WHO type I lesionsNitrosamines - salted fish ( Cantonese type salted

fish )Vitamin C deficiencyOthers - polycyclic hydrocarbons, chronic nasal

infection, poor hygiene, poor ventilation

ImmunologyIs an epithelial tumour , having antibody

response toViral Capsid Antigen ( VCA )Early Antigen ( EA )Epstein Barr Nuclear Antigen ( EBNA )Antibody dependent Cellular Cytotoxicity ( ADCC )

Genetics ( Related to Oncogens & Tumour supressor genes ) Human Leucocyte Antigen ( HLA ) Chromosomal deletions and translocations

Short arm of chromosome 6 has six lociHLA A , B , C , DR , DQ , DS

HLA AW19 , B17 – Short term survival HLA A2 BW46 – Intermediate term survival HLA A2 without BW46 or B17 – Long term survival

AGE & SEX DISTRIBUTION AGE SEX

Bimodal distribution M : F = 3:1 in chinesePeak age : 4th decade in chinese 2:1 in non-chinese 6th decade in non-chinese

WHO classification and relation to EB virus and radiotherapy.

WHO nameWHO name IncludesIncludes EB virus EB virus titretitre

Response to Response to radiationradiation

II Squamous cell Squamous cell carcinomacarcinoma

Well and Well and moderately diff moderately diff sq cell casq cell ca

LowLow poorpoor

IIII Non-Non-Keratinising Keratinising carcinomacarcinoma

Transitonal cell Transitonal cell caca

HighHigh Radio Radio sensitivesensitive

IIIIII UndifferentiatUndifferentiated carcinomaed carcinoma

LymphoepithLymphoepith eliomaelioma

AnaplasticcaAnaplasticcaSpindle cell Spindle cell

cacaClear cell caClear cell ca

HighHigh Radio - Radio - sensitivesensitive

CLASSIFICATION Type I - “SCCA”

25 % of NPCmoderate to well differentiated cells similar to other SCCA

Keratin pearls, intracellular bridges, and increased nuclear-to-cytoplasmic ratios but consistent sizes of the nuclei.

Type II - “non-keratinizing” carcinoma12 % of NPCvariable differentiation of cells ( mature to anaplastic)minimal if any keratin productionmay resemble transitional cell carcinoma of the bladder

Decreased level of differentiation characterized by increased nuclear pleomorphism

Increasing inflammatory infiltrate compared with type I tumors.

Type III - “undifferentiated” carcinoma

60 % of NPC, majority of NPC in young patientsClassic appearance of a lymphoepithelioma with difficult to

distinguish squamous cancer cells in a background of lymphocytes

Diverse group Lymphoepitheliomas, spindle cell, clear cell and anaplastic

variants

Differences between type I and types II & III

5 year survivalType I - 10% Types II, III - 50%

Long-term risk of recurrence for types II & III

Viral associationsType I - HPVTypes II, III - EBV

CLINICAL FEATURES 1)Painless cervical lymphadenopathy 60%

2)Epistaxis

3)Aural symptoms 30%

4)Neurological Symptoms 20%

NPC has a tendency for early lymphatic spread. Retropharyngeal node of Rouviere is the first

echelon node. Commonest first palpable node is the J.D. node

and the apical node under sternomastoid muscle. 46 % - unilateral 22 % - bilateral

AURAL SYMPTOMS

Serous otitis media is commonHearing lossPain in the earAural blockTinnitus

OPHTHALMIC SYMPTOMSPtosisEpiphoraLoss of corneal reflexEOM – impairedEnophthalmosDiplopiaXerophthalmiaRarely optic nerve is involved.

Jacod`s triad Trotter’s triad

Trigeminal neuralgia Trigeminal neuralgia Amaurosis bulbi Palatal Palsy Ophthalmoplegia Conductive HL

PAIN & HEADACHE This is an ominous symptom

Severe pain is hallmark of terminal disease.

Signifies tumour erosion into skull base.

If accompanied by trismus, the disease is very advanced and has extended into pterygopalatine fossa.

SYNDROMES Tapia 9,12 Avellis 9,10 Schmidt 10,11 Vernet 9,10,11 Hughlings Jackson 10,11,12 Collet sicard 9,10,11,12 Villaret 9,10,11,12+ Cervical

Sympathetic Chain Horner’s syndrome , Gradenigo’s Syndrome , Garcin

Syndrome

DISTANT METASTASIS

Incidence is 30%Skeletal metastasis account for more than

one half.Thoraco lumbar spine is the commonest

site followed by the lung and liver.

SPREAD OF TUMOUR

CaNx

Foramen lacerum and Ovale

Eust tube

Nose and Orbit

Distant metastases

Serous O.M

Nasal obst, Epistaxis proptosis

Secondaries Lung, Liver,

bone

Parapharyngeal Space

Retro-pharyngeal

nodesCervical Nodes

Upper jugular & Posterior Δ Nodes enlargement

Cranial nerve palsies IX, X, XI, XII, Horner’s syndrome

Pterygoid muscles Trismus

Neck pain and stiffness

BRODER’S CLASSIFICATION Grade I – 25 % of cells are lacking

differentiation

Grade II – 25 – 50 % of cells are undifferentiated

Grade III – 50 – 75 % of cells are undifferentiated

Grade IV – More than 75 % of cells are undifferentiated

TNM CLASSIFICATION T1- within Nasopharynx

T2-Nasal cavity/oropharynx a)without Parapharyngeal extension b)with Parapharyngeal extension

T3-Invasion of surrounding bony structures & Paranasal Sinuses.

T4-Intracranial extension.

Regional lymph nodes Nx and No

N1- Unilateral 6cm or less above supra clavicular fossa

N2- bilateral 6cm or less above supra clavicular fossa

N3a - >6cm above supra clavicular fossa

N3b – extends into supra clavicular fossa

Neel and Taylor System› Extensive primary tumor +0.5

› Sx’s present < 2 months before dx - 0.5

› Seven or more sx’s +1.0

› WHO type I +1.0

› Lower cervical node dx +1.0

Neel and Taylor System

Stage A = < 0

Stage B = 0 to 0.99

Stage C = 1 to 1.99

Stage D = > 2

Grossly the tumour presents in three forms.

ProliferativeUlcerativeInfiltrative

The commonest site of origin is fossa of Rosenmuller in the lateral wall of nasopharynx.

INVESTIGATIONS 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

CBC, ESR, chemistry profile, LFT’s Audiological Tests , Field test & other

Ophthalmic tests

AngiographyContrast CT with bone and soft tissue windows

imaging tool of choice for NPC ( Erosion of med.pterygoid plate , lateral extension into ITF , invasion of the middle fossa, by orbit / Sup.orbit fissure )

Involvement of sphenoid sinus (70%) , ITF (60%) , Orbit (30%) , MCF (20%)

MRI - soft tissue involvement, recurrencesX rays, Skeletal Scintigraphy , CXR , USG - AbdomenChest CT, bone scans

TREATMENTRadiotherapy is the definitive

treatment.Chemotherapy is used to supplement

R.T. in advanced cases with cervical metastasis

Role of surgery is only to take biopsy or to deal with cervical metastasis after the primary has been sterilized.

Mega Voltage External Radio-theraphyTwo lateral opposing and one anterior field Dose: 6500-7000 cGy , Consider 5000 cGy prophylactic tx

of clinically negative lower neck Five / six daily sessions per week for a total of six

weeks. Early disease ( stage I / II ) – conventional

radiotheraphy alone Locally advanced non-metastatic disease ( stage III /

IVB ) – Chemotheraphy + CRT

Adjuvant brachytherapymainly for residual/recurrent disease

COMPLICATIONS OF RT Mucositis Xerostomia Dental caries Radiation myelitis Optic atrophy Early intranasl

adhesions Otitis externa with

osteoradionecrosis

ETD - early (SOM), later (patulous ET)

Endocrine disorders - hypopituitarism, hypothyroidism, hypothalamic disfunction

Soft tissue fibrosis including trismus

Temporal lobe necrosis Hypoglossal nerve palsies

Chemotherapy ( Neoadjuvant / Concurrent / Adjuvant )Variety of agents - Bleomycin / Methotrexate /

Hydroxyurea / 5-Fluorouracil / CisplatinChemotherapy + XRT - no proven long term benefitMainly for palliation of distant disease

ImmunotherapyFuture treatment ??Vaccine ?? Use of EBV structural antigens / Cytotoxic T –

Lymphocytes epitopes.

SURGICAL APPROACHES

Anterior approaches Inferior approachesLateral rhinotomy

Transpalatal Transnasal transmaxillary

Mandibular swingMidfacial deglovingLe fort 1 osteotomyMaxillary swing

PHOTODYNAMIC THERAPY Salvage for recurrent / residual NPC Tumouricidal effect – laser activation of

photosensitizer – selectively taken up and retained by the tumour

1st gen PDT – combination of HPD (Hemato-porphyrin derivatives) & laser light of 630mm red light from a gold vapour / pumped dye laser.

2nd gen PDT - combination of m-THPC (m-tetrahydroxyphenylchlorin ) &activated by 652mm red light from diode laser

PROGNOSIS

5 - Year survival rateStage I – 90%Stage II – 70%Stage III – 60%Stage IV – 40% without metastasis 0% with metastasis

THANK YOU