tumours of nasopharynx (2) itp class dr.davis - 03.06.16
TRANSCRIPT
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
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