This document provides an overview of nasopharyngeal carcinoma. It begins with an introduction defining nasopharyngeal carcinoma as a non-lymphomatous, squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. It then covers the epidemiology, risk factors, clinical presentation, investigations including imaging and biopsy, histopathological classification, staging, and treatment options. The key points are that nasopharyngeal carcinoma most commonly presents with neck swelling, is strongly associated with Epstein-Barr virus, and is classified into three types by the WHO based on differentiation and presence of lymphoid stroma.

1. Nasopharyngeal
Carcinoma
Chandraveer suryavanshi
Bombay hospital

2. Introduction
85% adult nasopharyngeal malignancies are carcinoma.
Nasopharyngeal carcinoma is a non-lymphomatous, squamous-cellNasopharyngeal 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 isThis 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 inposteromedial to the medial crura of the eustachian tube opening in
the nasopharynx.the nasopharynx.

3. • High index of suspicion required for earlyHigh index of suspicion required for early
diagnosisdiagnosis
• Nasopharyngeal malignanciesNasopharyngeal malignancies
– SCCA (nasopharyngeal carcinoma)SCCA (nasopharyngeal carcinoma)
– LymphomaLymphoma
– Salivary gland tumorsSalivary gland tumors
– SarcomasSarcomas

4. Anatomy
• Anteriorly -- nasal cavityAnteriorly -- nasal cavity
• Posteriorly -- skull base and vertebralPosteriorly -- 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

5.  The rigid and tough pharyngobasilar fascia provides structuralThe rigid and tough pharyngobasilar fascia provides structural
support for the nasopharynx.support for the nasopharynx.
 The fascia forms a three-sided curtain which opens anteriorlyThe 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 theSuperiorly, 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 theLateraly it is adherent to the cartilaginous portion of the
eustachian tube.eustachian tube.
 It forms a closed and resistant barrierIt forms a closed and resistant barrier
 The sinus of Morgagni is the only defect through which theThe 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.

6.  Lateral to the pharyngobasilarLateral to the pharyngobasilar
fascia, the nasopharynx is boundedfascia, the nasopharynx is bounded
by four spaces which are dividedby four spaces which are divided
by three layers of deep cervicalby three layers of deep cervical
fascia.fascia.
 These include the masticatorThese include the masticator
(infratemporal fossa), the(infratemporal fossa), the
parapharyngeal, the carotid andparapharyngeal, the carotid and
the parotid spaces.the parotid spaces.
 Lateral deviation and orLateral deviation and or
infiltration of the parapharyngealinfiltration of the parapharyngeal
fat are sensitive indicators of thefat are sensitive indicators of the
spread of nasopharyngeal diseasespread of nasopharyngeal disease

7. • MucosaMucosa
– Epithelium - tissue ofEpithelium - tissue of
origin of NPCorigin of NPC
• Stratified squamousStratified squamous
epitheliumepithelium
• Pseudostratified columnarPseudostratified columnar
epitheliumepithelium
– Salivary,Salivary,
– Lymphoid structuresLymphoid structures

8. Race: More in Chinese & North African people
Sex: Male preponderance of 3:1
Age: Small peak: 12-18 yrs;
large peak: 50-60 yrs

9. Gross: Proliferative,
Ulcerative &
Infiltrative types
Histology: 85% Squamous cell carcinoma
10% Lymphomas,
5% Mixed

10. 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” inEBV- well documented viral “fingerprints” in
tumor cells and also anti-EBV serologies withtumor 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

11. 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

12. 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 differentiatedwell differentiated
• non differentiatednon 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)

13. Classification
• Type II - “non-keratinizing” carcinomaType II - “non-keratinizing” carcinoma
– 12 % of NPC12 % of NPC
– variable differentiation of cells ( mature tovariable differentiation of cells ( mature to
anaplastic)anaplastic)
– minimal if any keratin productionminimal if any keratin production
– may resemble transitional cell carcinoma ofmay resemble transitional cell carcinoma of
the bladderthe bladder

14. Classification
• Type III - “undifferentiated” carcinomaType III - “undifferentiated” carcinoma
– 60 % of NPC, majority of NPC in young60 % of NPC, majority of NPC in young
patientspatients
– Difficult to differentiate from lymphoma byDifficult to differentiate from lymphoma by
light microscopy requiring special stains &light microscopy requiring special stains &
markersmarkers
– Diverse groupDiverse group
• Lymphoepitheliomas, spindle cell, clearLymphoepitheliomas, spindle cell, clear
cell and anaplastic variantscell and anaplastic variants

15. 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)

16. 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

17. 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

18. 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

19. 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 )

20. 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

21. Neck swelling

22. Ptosis & adduction palsy

23. Left proptosis

25. 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 basefor tumor extent, skull base
erosion & cervical lymph node metastasiserosion & cervical lymph node metastasis

26. 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.

27. • 7 Serologic tests: Special diagnostic tests (forSpecial 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

28. Diagnostic Nasal Endoscopy

29. Computerized Tomogram

30. CT scan: retropharyngeal node

31. CT scan: Infratemporal fossa &
orbit involvement

32. Magnetic Resonance Imaging

33. MRI: parapharyngeal mass

34. MRI: neck node metastasis

35. M.R.I.: intracranial extension

36. Endoscopic biopsy

37. CT scan: liver metastasis

38. Whole body bone scan

39. Positron Emission Tomography

40. 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

41. 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

42. Supraclavicular fossa
Synonym: Ho’s triangle
A = medial end of
clavicle
B = Lateral end of
clavicle
C = junction between
neck & shoulder

43. 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

44. 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

45. Cobalt Teletherapy

46. 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

47. 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

48. • osteosarcoma of nose and sinus
• ssc of oral cavity tongue and pharynx
• delayed cranial nerve palsy

49. 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

50. Interstitial Brachytherapy

51. Intracavitary Brachytherapy

52. High Dose Rate Brachytherapy

53. 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

54.  Chua, IJROBP, 2006Chua, IJROBP, 2006
Subgroup analysis of 2 induction studies with cis/epirubicin andSubgroup analysis of 2 induction studies with cis/epirubicin and
cis/bleo/5FUcis/bleo/5FU →→ RTRT vsvs. RT alone. RT alone
Early stage pts (T1-2N0-1, st. IIB) had fewer distant mets with induction andEarly 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 X3Phase II study of gemcitabine/cis X3 →→ cis/accelerated concomitant boostcis/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 X2Phase II study of carbo/paclitaxel X2 →→ cis/RTcis/RT
Overall CR rate=97%Overall CR rate=97%
2Y OS = 92%, 2Y PFS = 79%2Y OS = 92%, 2Y PFS = 79%

55. Surgery
• Primary lesionPrimary lesion
– consider for residual or recurrent diseaseconsider for residual or recurrent disease
– approachesapproaches
• infratemporal fossainfratemporal fossa
• transparotid temporal bone approachtransparotid temporal bone approach
• transmaxillarytransmaxillary
• transmandibulartransmandibular
• transpalataltranspalatal
• Regional diseaseRegional disease
– Neck dissection may offer improved survivalNeck dissection may offer improved survival
compared to repeat radiation of the neckcompared to repeat radiation of the neck

56. 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

57. 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

58. 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 %