Nasopharyngeal Carcinoma

Nasopharyngeal Nasopharyngeal CarcinomaCarcinoma

IntroductionIntroduction

It is prevalent It is prevalent in Southern China,in Southern China, Southeast Asia, HongKong and Southeast Asia, HongKong and parts of East and North Africa.parts of East and North Africa.

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

AnatomyAnatomy

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 Fossa of Rosenmuller - most common

locationlocation

AnatomyAnatomy

Close association with skull base Close association with skull base foramenforamen

Mucosa Mucosa Epithelium - tissue of origin of NPCEpithelium - tissue of origin of NPC

Stratified squamous epitheliumStratified squamous epithelium Pseudostratified columnar epitheliumPseudostratified columnar epithelium

Salivary, Lymphoid structuresSalivary, Lymphoid structures

EpidemiologyEpidemiology

Chinese native > Chinese immigrant > Chinese native > Chinese immigrant > North American nativeNorth American native Both genetic and environmental factorsBoth genetic and environmental factors

GeneticGenetic HLA histocompatibility loci possible markersHLA histocompatibility loci possible markers

EpidemiologyEpidemiology

EnvironmentalEnvironmental VirusesViruses

EBV- well documented viral “fingerprints” in EBV- well documented viral “fingerprints” in tumor cells and also anti-EBV serologiestumor cells and also anti-EBV serologies

Nitrosamines - salted fishNitrosamines - salted fish Others - polycyclic hydrocarbons, chronic Others - polycyclic hydrocarbons, chronic

nasal infection, poor hygiene, poor nasal infection, poor hygiene, poor ventilationventilation

ClassificationClassification

WHO classesWHO classes Based on light microscopy findingsBased on light microscopy findings

Type I - “SCCA”Type I - “SCCA” 25 % of NPC25 % of NPC moderate to well differentiated cells similar moderate to well differentiated cells similar

to other SCCA ( keratin, intercellular to other SCCA ( keratin, intercellular bridges)bridges)

ClassificationClassification

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

ClassificationClassification

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 cell and Lymphoepitheliomas, spindle cell, clear cell and

anaplastic variantsanaplastic variants

ClassificationClassification

Differences between type I and Differences between type I and types II & IIItypes II & III

5 year survival5 year survival Type I - 10% Types II, III - 50%Type I - 10% Types II, III - 50%

Long-term risk of recurrence for types II & IIILong-term risk of recurrence for types II & III Viral associationsViral associations

Type I - HPVType I - HPV Types II, III - EBVTypes II, III - EBV

Clinical PresentationClinical Presentation

Often subtle initial symptomsOften subtle initial symptoms unilateral hearing loss (SOM)unilateral hearing loss (SOM) painless, slowly enlarging neck masspainless, slowly enlarging neck mass

Larger lesionsLarger lesions nasal obstructionnasal obstruction epistaxisepistaxis cranial nerve involvementcranial nerve involvement

Clinical PresentationClinical Presentation

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 CN’s IX, X, XI, XII - extensive skull base CN’s IX, X, XI, XII - extensive skull base

Clinical PresentationClinical Presentation

Nasopharyngeal examinationNasopharyngeal examination Fossa of Rosenmuller most common locationFossa of Rosenmuller most common location Variable appearance - exophytic, submucosal Variable appearance - exophytic, submucosal

Regional spreadRegional spread Usually ipsilateral first but bilateral not Usually ipsilateral first but bilateral not

uncommonuncommon

Distant spread - rareDistant spread - rare

Diagnose Diagnose

Biopsy under naso-endoscopy Biopsy under naso-endoscopy

— — Gold standardGold standard

— — sometimes repeated biopsy is sometimes repeated biopsy is needed needed

— — additional immunohistochemistryadditional immunohistochemistry

Radiological evaluationRadiological evaluation

Contrast CT with bone and soft tissue Contrast CT with bone and soft tissue windowswindows imaging tool of choice for NPCimaging tool of choice for NPC

MRIMRI soft tissue involvement, recurrencessoft tissue involvement, recurrences

Chest CT, bone scans Chest CT, bone scans

Nasopharyngeal carcinoma. A: Axial contrast-enhanced computed tomography (CECT) demonstrates enhancing lesion (asterisk) involving the pharyngeal mucosa space, retropharyngeal spaces, and prevertebral space. A tumor abuts the skull base. B: Axial CECT image with bone settings at the level of the skull base demonstrates a lytic destructive lesion involving the anteromedial left petrous bone (asterisk), medial portion of greater sphenoid wing (arrowhead),and adjacent clivus (arrow).

Laboratory evaluationLaboratory evaluation

Special diagnostic testsSpecial diagnostic tests IgA antibodies for viral capsid antigen (VCA)IgA antibodies for viral capsid antigen (VCA)

very popular in China very popular in China IgG antibodies for early antigen (EA)IgG antibodies for early antigen (EA)

StagingStaging

Variety of systems usedVariety of systems used Am Jt Comm for Ca StagingAm Jt Comm for Ca Staging International Union Against CaInternational Union Against Ca Ho SystemHo System

Unique NPC prognostic factors often not Unique NPC prognostic factors often not considered and similar prognosis considered and similar prognosis between stagesbetween stages

TreatmentTreatment

External beam radiation: External beam radiation: first choicefirst choice Dose: 6500-7000 cGyDose: 6500-7000 cGy Primary, upper cervical nodes, pos. lower Primary, upper cervical nodes, pos. lower

nodesnodes Consider 5000 cGy prophylactic tx of Consider 5000 cGy prophylactic tx of

clinically negative lower neckclinically negative lower neck

Adjuvant brachytherapyAdjuvant brachytherapy mainly for residual/recurrent diseasemainly for residual/recurrent disease

TreatmentTreatment External beam radiation - complicationsExternal beam radiation - complications

IncludeInclude xerostomia, tooth decayxerostomia, tooth decay ETD - early (SOM), later (patulous ET)ETD - early (SOM), later (patulous ET) Endocrine disorders - hypopituitarism, Endocrine disorders - hypopituitarism,

hypothyroidism, hypothalamic disfunctionhypothyroidism, hypothalamic disfunction Soft tissue fibrosis including trismusSoft tissue fibrosis including trismus Ophthalmologic problemsOphthalmologic problems Skull base necrosisSkull base necrosis

TreatmentTreatment Surgical managementSurgical management

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

TreatmentTreatment Surgical managementSurgical management

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

TreatmentTreatment

ChemotherapyChemotherapy Variety of agentsVariety of agents Chemotherapy + XRT - no proven long Chemotherapy + XRT - no proven long

term benefitterm benefit Mainly for palliation of distant diseaseMainly for palliation of distant disease

ImmunotherapyImmunotherapy Future treatment??Future treatment?? Vaccine??Vaccine??

ConclusionConclusion

Prevalent in Southern China, Southeast Prevalent in Southern China, Southeast Asia, HongKong. And rare in North Asia, HongKong. And rare in North America, and EuropeAmerica, and Europe

Biopsy is the gold standard for Biopsy is the gold standard for diagnosis.diagnosis.

Treatment is primarily Radiation, not Treatment is primarily Radiation, not surgery. surgery.