nasopharyngeal carcinoma

NASOPHARYNGEAL NASOPHARYNGEAL CARCINOMACARCINOMA

NASOPHARYNGEAL NASOPHARYNGEAL CARCINOMACARCINOMA

Cancer Growing Health ProblemCancer Growing Health Problem

World incidence: 8,068,404 people affected World incidence: 8,068,404 people affected in 1998in 1998 Female: 3,782,881Female: 3,782,881 Male: 4,286,523Male: 4,286,523

MalaysiaMalaysia Female: 10, 680Female: 10, 680 Male: 10,990Male: 10,990

Common sites affectedCommon sites affected

MALE MALE LungLung Colon/RectumColon/Rectum StomachStomach LiverLiver Nasopharynx (885)Nasopharynx (885)

FEMALEFEMALE BreastBreast Colon/RectumColon/Rectum Cervix/UterusCervix/Uterus LungLung OvaryOvary StomachStomach ThyroidThyroid Nasopharynx (370)Nasopharynx (370)

1998

Surgical Anatomy of NasopharynxSurgical Anatomy of Nasopharynx

4cm high, 4cm wide and 3cm in length4cm high, 4cm wide and 3cm in length Anterior Anterior -choanal orifice and posterior -choanal orifice and posterior

margin of nasal septummargin of nasal septum FloorFloor - upper surface of the soft palate - upper surface of the soft palate Roof and posterior wallRoof and posterior wall

Body of the sphenoid, BasiocciputBody of the sphenoid, Basiocciput First two cervical vertebraeFirst two cervical vertebrae

Lateral wallLateral wall Eustachian Tube orificeEustachian Tube orifice Fossa of ROSSENMULLERFossa of ROSSENMULLER

Anatomical relation of FORAnatomical relation of FOR

AnteriorlyAnteriorly Eustachian tube and levator palatiniEustachian tube and levator palatini

PosteriorlyPosteriorly Pharyngeal wall mucosa overlying Pharyngeal wall mucosa overlying

pharyngobasilar fascia & retropharyngeal spacepharyngobasilar fascia & retropharyngeal space MediallyMedially

Nasopharyngeal cavityNasopharyngeal cavity SuperiorlySuperiorly

Foramen lacerum & floor of carotid canalForamen lacerum & floor of carotid canal PosterolateralPosterolateral

Carotid canal & petrous apex, foramen ovale Carotid canal & petrous apex, foramen ovale and spinosumand spinosum

Epidemiology of NPCEpidemiology of NPC

Geography and RaceGeography and Race Distinctive epidemiological patternDistinctive epidemiological pattern IncidenceIncidence

Southern China (Kwantung province)Southern China (Kwantung province) Hong KongHong Kong TaiwanTaiwan South-East Asian races (Malay, Kadazan, Iban, South-East Asian races (Malay, Kadazan, Iban,

Bidayuh, Indonesians and Thais)Bidayuh, Indonesians and Thais) Eskimos, North Africa, TunisiaEskimos, North Africa, Tunisia

Aetiology of NPCAetiology of NPC

Environmental factorsEnvironmental factors Geographical clustering in Southern ChinaGeographical clustering in Southern China Time Trend: High risks among Chinese in Time Trend: High risks among Chinese in

Southern ChinaSouthern China Incidence in Hong Kong, Singapore Incidence in Hong Kong, Singapore

virtually remained unchanged 50 yrsvirtually remained unchanged 50 yrs 2nd and 3rd generation born in USA 2nd and 3rd generation born in USA

shows declineshows decline NPC constitute 16% of all malignant NPC constitute 16% of all malignant

tumors among the chinesetumors among the chinese

Smoking and Alcohol consumptionSmoking and Alcohol consumption OccupationalOccupational

Exposure to nickel, chromiumExposure to nickel, chromium Radioactive metalRadioactive metal Inhalation of chemical fumesInhalation of chemical fumes

IngestionsIngestions Salted fish - NitrosamineSalted fish - Nitrosamine Smoked foodSmoked food

DrugsDrugs Chinese herbal medicineChinese herbal medicine

Cooking habitsCooking habits Household smoke and fumesHousehold smoke and fumes

Religious practiceReligious practice Incense and joss stick smokeIncense and joss stick smoke

Socioeconomic statusSocioeconomic status Nutritional deficiencies eg. Vitamin A & CNutritional deficiencies eg. Vitamin A & C

Aetiological role of Epstein-Barr virus in NPCAetiological role of Epstein-Barr virus in NPC

More than 90% of patients having elevated More than 90% of patients having elevated antibody titres to Epstein-Barr virus are antibody titres to Epstein-Barr virus are those who have NPC of the those who have NPC of the undifferentiated / poorly differentiated undifferentiated / poorly differentiated formsforms

Moderate to well differentiated NPC are Moderate to well differentiated NPC are devoid of Epstein-Barr virus antigendevoid of Epstein-Barr virus antigen

Thus the role of virus in NPC is still Thus the role of virus in NPC is still controversialcontroversial

Immunogenetics of NPCImmunogenetics of NPC

Prominent genetic susceptibilityProminent genetic susceptibility High risk among southern Chinese populationHigh risk among southern Chinese population Differential high risk in emigrant Chinese Differential high risk in emigrant Chinese

compared to indigenous populationcompared to indigenous population Family clustering of NPC in ChineseFamily clustering of NPC in Chinese Elevated risk in people having genetic Elevated risk in people having genetic

admixture with Chineseadmixture with Chinese Low risk in other racial groups despite living in Low risk in other racial groups despite living in

high-risk countries eg. Indians in high-risk countries eg. Indians in Malaysia/SingaporeMalaysia/Singapore

Histocompatibility Locus Antigen (HLA)Histocompatibility Locus Antigen (HLA)

HLA patternHLA pattern

AW 19-B17AW 19-B17

A2-BW 46A2-BW 46

A2 without B17 or B46A2 without B17 or B46

Clinical behavior & Clinical behavior & survivalsurvival

Short term survivalShort term survival Age<30 yearsAge<30 years Died<2yrsDied<2yrs

Intermediate term survivalIntermediate term survival Age>30 yrs.Age>30 yrs.

Long term survivalLong term survival 5years survival:40%5years survival:40%

Clinical FeaturesClinical Features

Mostly seen in 5th to 7th decades Mostly seen in 5th to 7th decades but not uncommon to see in the but not uncommon to see in the twenties and thirtiestwenties and thirties

Males - 3 times more prone that Males - 3 times more prone that femalesfemales

Symptoms and SignsSymptoms and Signs

Bewildering array of symptoms and signsBewildering array of symptoms and signs

““ALWAYS a challenging problem, both from ALWAYS a challenging problem, both from diagnostic and therapeutic standpoint, diagnostic and therapeutic standpoint, malignant lesions of the nasopharynx are malignant lesions of the nasopharynx are perhaps most commonly misdiagnosed, perhaps most commonly misdiagnosed, most poorly understood, and most most poorly understood, and most pessimistically regarded of all tumors of pessimistically regarded of all tumors of the upper part of the respiratory tract”the upper part of the respiratory tract”

That statement is still true.That statement is still true.

Neck lump - 60%Neck lump - 60% Block sensation of ear - 41%Block sensation of ear - 41% Hearing loss - 37%Hearing loss - 37% Nasal bleeding - 30%Nasal bleeding - 30% Nasal obstruction - 29%Nasal obstruction - 29% Headache - 16%Headache - 16% Ear pain - 14%Ear pain - 14% Neck pain -13%Neck pain -13% Weight loss 10%Weight loss 10% Diplopia - 10%Diplopia - 10%

Cervical Lymphadenopathy (60%)Cervical Lymphadenopathy (60%)

NPC - commonest mode of presentation is NPC - commonest mode of presentation is neck swellingneck swelling Tendency for Early Lymphatic SpreadTendency for Early Lymphatic Spread Retropharyngeal group of L.N. (Rouviere) Retropharyngeal group of L.N. (Rouviere)

1st lymphatic filter not palpable1st lymphatic filter not palpable Commonest palpable node - Commonest palpable node -

jugulodiagastric, L2/L3/L5 leveljugulodiagastric, L2/L3/L5 level Contralateral lymph nodes metastasis Contralateral lymph nodes metastasis

(nasopharynx is midline structure)(nasopharynx is midline structure)

Aural SymptomsAural Symptoms

NPC leads to eustachian tube occlusion Sensation of a blocked earSensation of a blocked ear Impaired hearingImpaired hearing TinnitusTinnitus Serous Otitis MediaSerous Otitis Media

““Adult Chinese patients with unresolving Adult Chinese patients with unresolving unilateral serous otitis media have to be unilateral serous otitis media have to be presumed to have nasopharyngeal presumed to have nasopharyngeal carcinoma until proven otherwise”carcinoma until proven otherwise”

Epistaxis and Nasorespiratory SymptomsEpistaxis and Nasorespiratory Symptoms

Blood stained nasal dischargeBlood stained nasal discharge Blood stained saliva on hawkingBlood stained saliva on hawking Profuse epistaxisProfuse epistaxis Nasal obstructionNasal obstruction Ozanea due to tumor necrosisOzanea due to tumor necrosis

Neurological PalsiesNeurological Palsies

Most frequently involved are:Most frequently involved are: VI - Lateral rectus palsy - Diplopia & squintVI - Lateral rectus palsy - Diplopia & squint III, IV, VI - are commonly affected together III, IV, VI - are commonly affected together

(opthalmoplegia)(opthalmoplegia) V - High neck & pacial pain & paraesthesiaV - High neck & pacial pain & paraesthesia IX, X & XI - Jugular Foramen SyndromeIX, X & XI - Jugular Foramen Syndrome

Isolated single C.N. palsy common with Isolated single C.N. palsy common with nerves V & VInerves V & VI

Pain and HeadachePain and Headache

Hallmark of terminal diseaseHallmark of terminal disease Erosion of skull base (intracranial Erosion of skull base (intracranial

extension)extension) Sepsis - sphenoidal sinusitisSepsis - sphenoidal sinusitis

TrismusTrismus Inviltration of pterygoid musclesInviltration of pterygoid muscles

Diagnostic EvaluationDiagnostic Evaluation

Anterior Rhinoscopy ExaminationAnterior Rhinoscopy Examination Difficult to assess NP spaceDifficult to assess NP space Blood stain nasal discharged Blood stain nasal discharged Tumour extending into nasal cavityTumour extending into nasal cavity


Post-Nasal ExaminationPost-Nasal Examination Post nasal mirror - can assess NP space and Post nasal mirror - can assess NP space and

tumourtumour Difficult to perform in sensitive patientsDifficult to perform in sensitive patients


Head and Neck ExaminationHead and Neck Examination Lymph node Lymph node

L2, L3, L5 levelL2, L3, L5 level Progressively enlarging, hard, fixed, Progressively enlarging, hard, fixed,

painless swellingpainless swelling


Aural ExaminationAural Examination OtoscopyOtoscopy Examination under microscopeExamination under microscope

Retracted tympanic membraneRetracted tympanic membrane Fluid in the middle earFluid in the middle ear


Cranial Nerve ExaminationCranial Nerve Examination


Diagnostic Nasal EndoscopyDiagnostic Nasal Endoscopy Rigid Nasal EndoscopeRigid Nasal Endoscope

Inspection of the nasopharynx spaceInspection of the nasopharynx space Localisation and extent of tumourLocalisation and extent of tumour Biopsy under visionBiopsy under vision

PathologyPathology

Grossly the tumour presents in 3 forms:Grossly the tumour presents in 3 forms: Proliferative growth causing nasal Proliferative growth causing nasal

obstructionobstruction Ulcerative causing epistaxisUlcerative causing epistaxis Infiltrative which causes cranial nerve Infiltrative which causes cranial nerve

involvementinvolvement


Diagnostic Nasal EndoscopyDiagnostic Nasal Endoscopy Flexible Nasal EndoscopeFlexible Nasal Endoscope


Fine Needle Aspiration Cytology of the Fine Needle Aspiration Cytology of the neck lymph nodeneck lymph node


CT ScanCT Scan Extent of tumorExtent of tumor Neck node involvementNeck node involvement

Bone ScanBone Scan Skeletal metastasis- thoracolumbar regionSkeletal metastasis- thoracolumbar region

MRIMRI

Distant MetastasisDistant Metastasis

Incidence rate is about 30%Incidence rate is about 30% Sites commonly involved:Sites commonly involved:

Skeletal - Thoracolumbar spine > 50%Skeletal - Thoracolumbar spine > 50% Lung metastasisLung metastasis Liver metastasisLiver metastasis

90% of patients die within the 1st year of 90% of patients die within the 1st year of diagnosis of the first metastasisdiagnosis of the first metastasis

Staging of NPC- TNM ClassificationStaging of NPC- TNM Classification

Primary TumourPrimary Tumour T1 - tumour confined to one site of T1 - tumour confined to one site of

nasopharynx or positive biopsy onlynasopharynx or positive biopsy only T2 - tumour involving two sitesT2 - tumour involving two sites T3 - tmour extending into nasal cavity or T3 - tmour extending into nasal cavity or

oropharynxoropharynx T4 - tumour invasion of skull or cranial T4 - tumour invasion of skull or cranial

nerve involvement or bothnerve involvement or both


N - Cervical Lymph NodesN - Cervical Lymph Nodes N0 - no clinically positive nodeN0 - no clinically positive node N1 - single clinically positive homolateral N1 - single clinically positive homolateral

node 3cm or less in diameternode 3cm or less in diameter N2 - single clinically positive homalateral N2 - single clinically positive homalateral

node > 3cm but < 6cm or multiple clinically node > 3cm but < 6cm or multiple clinically positive homolateral nodes > 6cm in positive homolateral nodes > 6cm in diameterdiameter

N3 - massive homolateral node(s), bilateral N3 - massive homolateral node(s), bilateral nodes or contralateral node(s)nodes or contralateral node(s)


M - Distant MetastasisM - Distant Metastasis MX - not assessedMX - not assessed M0 - no (known) distant metastasisM0 - no (known) distant metastasis M1 - distant metastasis presentM1 - distant metastasis present


I T1 N0 M0II T2 N0 M0III T3 N0 M0

T1-3 N1 M0IV T4 N0-1 M0

T1-4 N2-3 M0T1-4 N0-3 M1

Stage GroupingStage Grouping

Treatment PolicyTreatment Policy

Chemo-RadiotherapyChemo-Radiotherapy Primary modality of treatmentPrimary modality of treatment

Radiotherapy- 6000 radsRadiotherapy- 6000 rads.. ChemotherapyChemotherapy

Cisplatin and 5-flurouracilCisplatin and 5-flurouracil SurgerySurgery - limited role - limited role

Biopsy of the nasopharyngeal mucosaBiopsy of the nasopharyngeal mucosa Radical neck dissection for radioresistant Radical neck dissection for radioresistant

lymph nodeslymph nodes

Recurrent NPCRecurrent NPC

BrachytherapyBrachytherapy 22ndnd course of radiation course of radiation

Chemotherapy Chemotherapy For distant metastasisFor distant metastasis Failed radiationFailed radiation

ConclusionConclusion

Early diagnosis of NPC (stage I)Early diagnosis of NPC (stage I) Early treatmentEarly treatment Good prognosis (>5years)Good prognosis (>5years) Patients should be followed up regularlyPatients should be followed up regularly

1st year: once a month1st year: once a month 22ndnd year: every 2 year: every 2ndnd month month 33rdrd year: every 3 months year: every 3 months 44thth year: every 6 months year: every 6 months >5years: Once a year>5years: Once a year

THANK YOU

THANK YOU

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nasopharyngeal carcinoma