PG

1. Tumours of Nasopharynx
Dr Raju Kafle
3rd year resident
ORL- HNS Dept, NMCTH
1

2. Surgical Anatomy
• Most superior part of the
pharynx , size of around distal
phalynx
• Centre of the head more than 10
cm from the skin surface of the
head in all directions.
2

3. 3

4. 4

5. • Cancers arising from the fossa of Rosenmüller frequently invade the Eustachian
tube -- otological symptoms.
• Thorough clinical examination is difficult.
• Even more difficult to expose the region adequately for surgical resection of
malignant lesions.
• Its vicinity to skull base and cranial nerves further demonstrate its crucial,
functional and structural importance in otorhinolaryngology.
5

6. 6

7. • Lateral walls of the nasopharynx : devoid of bone.
• Immediately lateral to pharyngobasilar fascia : parapharyngeal spaces with
fat pads, muscles of soft palate.
• Just anterior to posterior choana : sphenopalatine foramen
• Ca from lateral wall -- pterygopalatine fossa via sphenopalatine foramen.
• Then Ca from pterygopalatine foramen -- foramen rotundum -- into the
cavernous sinus intracranially (ophthalmoplegia)
7

8. • Floor of sphenoid sinus : thin – spread into sphenoid sinus -- then into orbital
apex (eye symptoms )
• Extensive lymphatic drainage to both sides of the neck from the nasopharynx.
• 1st echelon of lymphatic drainage : retropharyngeal lymph nodes (nodes of
Rouvière).
• Then lymphatic drainage continues to upper jugular nodes (level II) ,the upper
posterior triangle nodes ( level Va) and then further down to the lower neck in
a step-wise fashion – no skip mets
8

9. • The internal carotid artery is located postero-lateral
to the fossa of Rosenmüller and is wrapped by the
carotid sheath.
• The retropharyngeal lymph node closely abuts the
carotid sheath.
• An enlarged retropharyngeal lymph node caused by
cancer metastasis may partially or completely encase
the parapharyngeal internal carotid artery.
• Cancer can also spread along the carotid sheath
superiorly into the foramen lacerum and into the
intracranial cavity
• Figure: Computed Tomography
(axial view)
• Extensve left NPC encasing the
internal carotid artery
9

10. Supraclavicular fossa (or Ho’s
triangle)
Boundaries
• medial (A) and lateral (B) ends of clavicle
• the point (C) where neck meets the shoulder.
• Importance :
• It includes caudal portions of levels IV and V ,
affect staging and prognosis
• If involved by mets : N3b
• If not involved : N1 , N2 and N3a
10

11. CLASSIFICATION OF TUMORS
11

12. 12

13. NASOPHARYNGEAL CARCINOMA
13

14. EPIDEMIOLOGY
• Largest geographical variations among all head and neck cancers, Mongoloid origin
• Incidence in endemic areas (Southern China, Cantonese population of Guangdong
Province) : 50 times higher than low risk areas (Central, East ,North China).
• The incidence in South China is three times higher than the second highest region,
Southwest China.
• Outside China, Southeast Asia (Malaysia and Indonesia) has the highest incidence of
NPC.
• Non endemic areas : bimodal distribution with two maxima, rare below 20 yrs of age
14

15. 15

16. Figure : Age-specific incidence curves showing early plateau for nasopharyngeal carcinoma ( Scott brown 7th edi)
At present : secular trend in past 30 years , due to life style changes and rapid economic development ( up to date 2021)
16

17. AETIOLOGY
Genetic
susceptibility
Confers Increased
Risk
Environmental
factors
Transform to
premalignant stage
EBV
Incorporation and
malignant
transformation
17

18.  Genetic factors
• Basis : Migrants from high-risk populations who settle in low incidence areas, like
Southern Chinese emigrants to North America, have higher incidences than the
native population.
• HLA A2, B14 and B46 : increased risk while HLA A11, B13 and B22 : lower risk
of NPC.
• Current thinking is that individual HLA subtypes associated with NPC may have
impaired immune response to EBV infection and clearance of the virus from the
epithelium.
• Other cancer-associated genes including MDM2 and TP53 and the cell-migration
gene MMP2 have been shown in multiple studies to be associated with NPC
18

19. HLA alleles, haplotype and NPC
• The relative risk of having NPC with particular HLA alleles was calculated as being
1.5 for A2, 1.9 for B46 and 2.1 for B58.
• The highest relative risk of 3.4 was found for the haplotype with A2-Cw1-B46.
• The A2, Cw1, B46 haplotype is associated with an older age ( >30 years old) of onset.
• The A33, Cw3, B58, DR3 haplotype is slightly more common in younger (<30 years
old) patients and is associated with poor survival chances.
19

20.  Environmental factors
• Consumption of salted fish and preserved foods in childhood: increased the incidence of
NPC in early adulthood.
• Nitrosamine content –potent alkylating agent
• Preserved or fermented foods ( meats , fruits , eggs and vegetables): high level of
nitrosamines and bacterial mutagens, direct genotoxins and EBV reacting substances.
• Smoking : more pronounced on well-differentiated type of NPC
• Tunisia, Morocco, Algeria : Consumption of rancid butter, sheep’s fat – by activation of
EBV or promoting effect on EBV transformed cells (upto date 2021)
• Diet deficient in vitamin C
20

21.  EBV
• Central to the pathogenesis of NPC, typically infects B-lymphocytes.
• Found only in the poorly differentiated and undifferentiated form of NPC.
• As evidenced by Nasopharyngeal carcinoma cells express a specific subgroup
of EBV – latent proteins
1. LMP 1
2. LMP2
• The virally infected cells may alter the cytokine environment and assist the
cancer cells to avoid detection by host immune-surveillance
21

22. PATHOLOGY
• Commonest type of malignancy : epithelial origin, immunostain positive for
cytokeratin,
• Histologically, the malignant cells are infiltrated with lymphocytes and plasma
cells, predominately T-cell and are CD8+ ( hence coined as lymphoepithelial
carcinoma )
22

23. • Immunostaining for EBV virus encoded small ribonucleic acid (EBER) is
commonly used to detect the presence of EBV inside the cancer cells.
• In endemic areas like Southern China : non-keratinizing type of NPC constitute
over 95% of the histological subtype of NPC.
• In low incidence populations like Japan or USA, non-keratinizing carcinomas still
are the majority with only 25% of the NPC being the keratinizing subtype.
• Basaloid squamous cell carcinoma is a rare subtype of epithelial cancer seen at
this site.
23

24. • Salivary gland carcinomas : incidence is relatively low, histology and behaviour
similar to other minor salivary gland ca.
• Soft tissue malignancies : including sarcomas, lymphomas and malignant
melanomas.
• Radiation induced : Chondrosarcomas and osteosarcomas in NPC patients treated
with RT.
• For radiation-induced carcinomas: typically well-differentiated squamous cell
carcinoma with EBV absent in cancer cells.
• Hodgkin lymphoma and T-NK lymphoma also harbour EBV in the cancer cells.
(misdiagnosed lymphoma as undifferentiated type of NPC if based only on
presence of EBV in the biopsy )
24

25. Keratinizing SCC (
WHO type 1)
25

26. A. Tumor cells growing in a nested, syncytial pattern with indistinct cell borders, open chromatin,
and prominent nucleoli. (HE stain)
B. Abundant lymphoid infiltrate that obscures nests of tumor cells (arrow) 26

27. Epstein-Barr virus–encoded ribonucleic acid in situ hybridization showing strong nuclear labeling of tumor
for Epstein-Barr virus in nasopharyngeal carcinoma
27

28. MODES OF PRESENTATION
• Generally patients with NPC are younger than patients than other types of head and neck
malignancy with median age of patients with NPC on presentation is 50 years
28

29. Nasal symptoms
• Around 50% of the patients : nasal symptoms at presentation.
• Most common symptoms : blood stained --nasal discharge or post-nasal drip.
• If large tumors: choanal obstruction -- nasal blockage.
• Epistaxis
• Cacosmia (smell of blood )
29

30. Otological
• 30% and 40% of NPC patients
• Eustachian tube dysfunction and OME secondary to tumour bulk and/or invasion.
• Presented with : recent onset of ipsilateral hearing loss, muffled sound, tinnitus and
sensation of ear blockage.
• Trotter's triad of unilateral deafness, neuralgia affecting branches of the
trigeminal nerve, and defective mobility of the soft palate
30

31.  Neck / Cervical
• Up to 70% of patients at presentation, 1/3rd with bilateral
LN involvement.
• The most frequently involved nodes are level II (upper
jugular) and upper level V (apex of posterior triangle).
• Lymphatic spread : orderly fashion from superior to
inferior
• Occasionally, NPC patients can present with metastatic
neck lymph nodes from an unknown primary.
31

32.  Neurological
• Usually signals advanced disease.
• Headache is the most common neurological symptom, in 20% of patients ( vertex
or occiput due to invasion of clivus )
• Facial pain and midface numbness : pterygopalatine fossa and the branches of V2.
• Cranial nerve palsies are caused by extension of the tumour into the skull base or
intracranially.
• Common cranial nerves to be involved at presentation are V2, V3 and VI.
32

33. • Involvement of CNIII, CNIV and CN VI : indicative of cavernous sinus invasion.
• Orbital apex syndrome : Ophthalmoplegia, decreased vision and proptosis : invasion
into orbital apex.
• Trismus -- rare , direct involvement of pterygoid muscles.
• Horner syndrome can occur if the tumour or metastatic lymph node encases the
carotid vessels.
• uncommon mode of presentation as the carotid sheath is tough fascia that
impedes direct tumour invasion.
33

34.  Other symptoms
• Anorexia and weight loss : infrequently seen.
• Symptoms of metastasis : Uncommon
• Usually associated with advanced local or nodal diseases.
• Common sites of distant metastases are liver, lung and bone, with brain (rare)
34

35. Para-neoplastic syndrome
• Around 1% of NPC : dermatomyositis
Others :
• Neutrophilia
• Hypertrophic osteoarthropathy
• Fever of unknown origin
(references : upto date 2021)
35

36. 36

37. DIAGNOSIS
• Thorough history and clinical examination including endoscopy of the nasopharynx.
• Patients with any of four groups of symptoms , and especially if they are from a
high incidence region.
• The ancestry/origin : Of the patient should be sort out
• Family history of NPC : 10% of NPC patients have familial clustering.
37

38. Nasopharyngoscopy
• Fibreoptic flexible endoscope
or rigid endoscopes ( 0,30,70
and 90 degree)
38

39. • In < 5% of patients :
• the nasopharynx may appear normal and other investigations may then be
necessary
39

40. Biopsy of the nasopharynx
• Gold standard in diagnosis of NPC
• In local anesthesia
• Or in general.
By using:
• Flexible endoscopes with a biopsy
channel.
• Biting ethmoid forceps
• Takahashi biting forceps
• Yaunkauers nasopharyngeal speculum
40

41. LABORATORY TESTS
• Aids in monitoring and screening the disease.
• Serology :
• IgA antibodies against viral capsid antigen (VCA—highly sensitive)
• Early antigen (EA—highly specific)
• and EBV nuclear antigen 1 (EBNA1) are commonly used as tumour markers in screening.
• EBV genome -- found in all cancers cells of endemic form of NPC -- EBV DNA will
be shed into the patients blood stream during cell turnover.
• More advanced stage NPC : higher tumour load and larger cancer cell turnover.
• Detection of EBV DNA in the plasma could therefore be used as a tumour marker of
NPC.
41

42. • Brushing : Brushing of the nasopharynx is performed and the cells obtained are
sent for EBV DNA detection with qt-PCR.
• Cytology : FNAC of neck nodes
42

43. Imaging:
a. Computed tomography:
• For tumor extent, skull base erosion and cervical lymph node metastasis.
Fig: An axial CT of the nasopharynx showing a tumour obliterating the right fossa
of Rosenmuller and extending medially to the midline. The contralateral fossa is
normal.
43

44. Fig: A coronal CT of the nasopharynx showing a
right-sided tumour with extensive skull base erosion.
Fig: Computed tomography showing a
metastatic cervical lymph node with central
necrosis (arrow).
44

45. Magnetic Resonance Imaging
• MRI is the preferred imaging modality for NPC staging and treatment because
of its superior soft tissue resolution.
• For assessment of tumour extent, MRI can better delineate parapharyngeal
extension of tumour, spread and marrow infiltration of clivus .
• Precontrast : grayish mass
• Post contrast T1 or T2 sequences : hyperintense
45

46. Fig: MRI (axial view) showing
nasopharyngeal carcinoma (C)
Fig: Sagittal MRI of the nasopharynx
showing a
Tumour (Gray) with erosion through the
clivus and extensive infiltration of its
marrow space ( bright) 46

47. Fig: T2-weighted MRI of the nasopharynx showing a nasopharyngeal tumour extending from the
nasopharynx to the right nasal fossa with secondary maxillary sinusitis.
47

48. 48

49. Positron Emission Tomography
• detecting residual or recurrent disease following radiation or
chemoradiation.
Fig: PET showing residual tumour in the nasopharynx after chemoradiation
(arrows). 49

50. Figure 188.10 Approach to patients with suspected nasopharyngeal carcinoma, ref:
stell maran 5th edition
50

51. 51

52. 52

53. Treatment
RADIOTHERAPY
• Is primary treatment modality for locoregionally confined
nasopharyngeal carcinoma (from stage I to IVB diseases).
• Early stage ( stage I and low-risk stage II ): radical radiotherapy
alone.
• Stage II disease with higher tumour load and stage III, IV :
combination chemotherapy and radiotherapy.
53

54. Conventional 2D Radiotherapy
• Employing high megavoltage radiation, a dose
of 65–70 Gy is normally given to the primary
tumour, 65–70 Gy to the involved neck nodes,
and 50–60 Gy to the nodenegative neck.
• Conventional two-dimensional treatment
planning and radiotherapy use two or three
large fields to cover the primary upper neck
and one or two fields to cover the lower neck
54

55. • Intensity-modulated radiotherapy (IMRT) is the
standard of care for radiation treatment of NPC.
• Radiotherapy planning
with individualized immobilization device
thermoplastic cast for the head and neck
• The required doses to targets and the dose constraints to
normal tissues are input into the computer planning
system.
• In turn it will generate the optimal radiation plan that
concentrates the radiation dose in targets while
minimizing the dose to normal tissues
55

56. • Gross tumour volume (GTV) -- both for the primary in NP and for
involved neck nodes.
• Clinical target volume (CTV) -- GTV plus covering for subclinical
disease spread around NP and neck.
• Planning target volume (PTV) -- CTV plus a margin to allow for
possible errors in daily positioning and treatment of patient during
radiotherapy).
56

57. • GTVs will include the tumour in NP and any enlarged (> 6 mm) retropharyngeal and
neck nodes or lymph nodes with necrotic centres.
• CTV1 includes the GTVs with margin and requires radiation dose of around 70 Gy.
• CTV 2 requires at least 60 Gy, include CTV1 with margin plus areas at risk of
microscopic involvement, including the entire NP, retropharyngeal nodal regions,
skull base, clivus, pterygoid fossae, parapharyngeal space, sphenoid sinus, and the
posterior part of the nasal cavity/maxillary sinuses that includes the pterygopalatine
fossae.
• A lower dose, 54–60 Gy, may be given for prophylactic irradiation of uninvolved
nodal regions.
57

58. • IMRT has ‘dose-painting’ capacity : allows
different dose levels to different regions to be
applied in the same treatment.
• With IMRT, local control rates of over 90%
have been reported.
• The complications from conventional two-
dimensional radiotherapy such as hearing
loss, xerostomia, temporal lobe neuropathy,
trismus and neck brosis, are reduced.
58

59. Chemotherapy:
• Acts as a radiosensitizer and reduces distance mets.
• Indications
• Advanced Stage
• Radiation Failure
• Palliation
59

60. 60

61. 61

62. Adjuvant capecitabine for locally advanced
NPC ( August 2021, upto date )
• Before this , platinum based agents ( cisplatin and carboplatin was
used ) as adjuvant to CCRT
• In 400 patients of locoregionally advanced NPC , the addition of 1
year adjuvant therapy with Capecitabine to CCRT improved overall
survival rate to 93% and was well tolerated with high rates of
treatment compliances
62

63. 63

64. Monitoring and follow up plan
• Endoscopy and biopsy of the nasopharynx: To confirm disease resolution after the
completion of RT.
• This should not be performed too early after radiotherapy
• as tumour cells continue to undergo apoptosis weeks after completion of
radiotherapy
• Persistent disease : disease should only be considered persistent if biopsy is
positive at 12 weeks after radiotherapy
• Most failures occurs within 2 years of treatment ( small percentage : > 10 years )
64

65. • Distant failure can occur several years after treatment
• Long term complications of radiotherapy may not be seen until 5 years after
treatment.
• There is no consensus on the optimal follow up schedule.
Currently used schedule:
• Regular 2–3monthly follow-up in the first 2 years
• Increased to 3–4 times per year in the third to fifth years
• Followed by 6-monthly or yearly
65

66. Salvage treatment
Stereotactic radiosurgery
• This technique involves the localization of a
small target which is irradiated by multiple
convergent beams providing a large single
dose of radiation (via nylon tubes)
• Is to deliver a boost dose after a second course
of radiotherapy or as a salvage treatment for
local recurrence.
• Stereotactic radiosurgery alone can achieve
local control rates of 53–86 per cent for locally
recurrent nasopharyngeal carcinoma.
Clinical photograph showing the placement of
hollow nylon tube (arrow) over the tumour bed
after radical neck dissection
66

67. Brachytherapy : continious low dose radiation
• The radiation dosage is highest at the source
and decreases rapidly towards the periphery.
• This enables a high dose of irradiation to be
delivered to the residual or recurrent tumour
while surrounding tissue receives a much
smaller dose.
• Intracavitary brachytherapy
• The main radioactive sources used are
iridium-192 (Ir192) and gold 198 grains
(Au198).
• Both isotopes emit gamma radiation.
• Both techniques are only suitable for small
tumours less than 2cm in maximal
dimension.
67

68. Radiotherapy for local failures : Sterotactic radiosurgery,
IMRT and Brachytherapy
• Traditionally: external beam RT
• With the development of 3D radiotherapy
techniques --3D stereotactic radiotherapy
and IMRT, it is possible to reduce the dose
or radiation to the vital organs
Fig-- Isodose distribution of target covered by
radiosurgery with single isocentre with a dose of 12.5 Gy
to target periphery.
68

69. Radiotherapy for nodal failures : Brachytherapy
• In the era of concurrent chemoradiation, isolated nodal failure is an uncommon
event.
• Only 5% of patients may suffer from isolated nodal failures.
• Persistent nodal disease : Patients who have persistently enlarged neck lymph
nodes 3 months after completion of radiotherapy should be considered to have
persistent nodal diseases and offered salvage treatment
• Additional radiotherapy also increases the radiation damage to the soft tissues in
the neck; therefore, re-irradiation treatment for salvaging nodal failure is not
recommended.
• Due to the limited penetration of brachytherapy techniques, they can be used for
treatment of nodal failure in conjunction with surgical resection of the nodal
metastasis
69

70. Surgery : as salvage procedure /nasopharyngectomy
Approach
Anterior approach
Lateral rhinotomy
Transnasal transmaxillary
Midfacial degloving
Le forte osteotomy
Maxillary swing
Inferior approach
Transpalatal
Mandibular swing
Lateral skull base
approach
70

71. Inferior approach : Transpalatal
• Advantages :
• minimal bone removal and no facial
incision
• Disadvantages :
• limited lateral access to the parapharyngeal
space
• and risk of palatal fistula
71

72. Inferolateral approach : transcervico- mandibulo-palatal
approach
• Improves the exposure of a transpalatal approach by the addition of the lip-splitting
mandibulotomy – then mandible is swung laterally -- floor of mouth incision is
extended superiorly along anterior pillar of the tonsil – division the soft palate
from the hard palate and nasopharynx visualize inferolaterally
• Advantages : a wider view and can offer access to the ipsilateral
parapharyngeal space
• Disadvantages : owing to disruption of large amounts of normal anatomy,
signicant long-term morbidities are associated with this technique
• palatal defect, trismus; dysphagia and malunion of the mandible.
72

73. Anterior approach : Midfacial degloving approach
• To increase the exposure of the nasopharynx and room for instrument
manipulation, bilateral medial maxillectomies and posterior nasal septectomy
should be performed.
• Advantages : are the lack of facial scar and avoiding the risk of a palatal fistula.
• Disadvantages :
1. Exposure can be poor
2. limited lateral access with this approach
73

74. Anterolateral approach : maxillary swing approach
• This approach provides wide exposure of the
nasopharynx and parapharyngeal space.
• In addition, the surgeon can localize the
parapharyngeal internal carotid artery by palpation
during dissection in the parapharyngeal space
• Disadvantages:
1. Facial scar,
2. Risk of trismus and
3. Palatal fistula formation
74

75. Lateral approach : lateral skull base approach
• Via an extended post-auricular incision
• In this approach : The tissue inparapharyngeal space including the cartilaginous
Eustachian tube can be resected en bloc with the tumour in the nasopharynx.
Advantages : Early identication and protection of the internal carotid artery.
Disadvantages
1. More extent of mobilization of normal tissues -- subsequent morbidity.
2. The visualization of the midline of the nasopharynx and access to resect lesions
extending anteriorly to the nasal cavity and paranasal sinuses is poor
75

76. ENDOSCOPIC APPROACH
• Endoscopic endonasal approach : now an
established surgical approach to resect tumours in
the nasal cavities, paranasal sinuses and anterior
skull base.
• Endoscopic approach causes no damage to normal
structures of the facial skeleton and minimal loss
of function.
• An extension of the endoscopic approach is the
application of the da Vinci surgical robot to assist
the minimally invasive nasopharyngectomy.
• Advantages of the surgical robot includes
• 3D optics, superior manipulation of surgical
instruments in tight space, motion scaling and
tremor ltration
76

77. Others methods
• Immunotherapy :
 EBV structural ag
 Cytotoxic T-lymphocyte epitopes from latent EBV ag as immunogen.
 Vaccines against EBV in endemic areas : under trial , not recommended yet
77

78. Complications of radiotherapy:
• Acute complications:
Xerostomia: after first few dose of RT.
Oropharyngeal mucositis, altered taste sensation
Dermatitis, alopecia.
picture of the mouth and
oropharynx
showing marked mucositis in
the early phase of radiothera py.
Note the diffuse i nfla mmation
and excoriation of the m ucosa.
78

79. • Subacute complications: 25-30%
• AOM, OME and OE.
• Olfactory dysfunction, nasal crusting, rhinosinusitis and
intranasal adhesions.
Fig: adhesions around the posterior ends of the middle and inferior turbinates
and the nasal septum.
79

80. • Late complications: 30%
• Trismus and neck stiffness.
• Osteoradionecrosis of the anterior and lateral skull base.
• Hypothalamic-pituitary dysfunction.
• Temporal lobe necrosis (> 10 years)
• Radiation-induced malignancy (>10 years) after completion of radiotherapy.
• Osteosarcoma of the nose and sinuses
• Squamous cell carcinoma of the oral cavity, tongue and pharynx.
80

81. …..Thank you
81
References :
1. Scott brown 7th and 8th edition
2. Stell and maran’s head and neck oncology 5th edition
3. Jatin shah head and neck oncology 5th edition
4. Grays anatomy student version, 2nd edition
5. NCCN guidelines for head and neck cancers
6. Upto date 2021
7. Various internet sources