MEZINÁRODNÍ CENTRUM KLINICKÉHO VÝZKUMU
„TVOŘÍME BUDOUCNOST MEDICÍNY“
Oncology in ENT I
KOCHHK FNUSA
Ass. Prof. Pavel Smilek, MD, Ph.D.
Clinic of Otorhinolaryngology and Head and Neck Surgery, Masaryk
university, Faculty St. Ann Hospital
Head: Ass. Prof. Gál Břetislav, MD, Ph.D.
Pekařská 53
656 91 Brno, Czech Republic
Incidence
Malignant tumors of head and neck represent in men approx. 6 %,
in women approx. 2 % of all malignant tumors.
In CR incidence of ca orofarynx and oral cavity 12,7/100 000 in man
and 4,6 /100 000 in woman (2012); increasing trend.
Incidence of larynx carcinoma was in CR 9,3/100 000 inhabitants in
men and 1,1/100 000 inhabitants in women (2012).
Incidence partially depends on geographical site (increase from
North to South)
Development of head and neck cancer
incidence in CR
Zdroj: Národní onkologický registr, ÚZIS ČR0
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19771978197919801981198219831984198519861987198819891990199119921993199419951996199719981999200020012002200320042005
Početnovědiagnostikovanýchnádorů
na100000osob
Lip and oral cavity
(C00, C02-C06)
Oropharynx, hypopharynx
(C01, C09-C10, C12-C14)
Epipharynx
(C11)
Salivary glands
(C07-C08)
Larynx
(C32)
Paranasal sinuses (C30-C31)
Lokalizace Smoking Alcohol Viruses Profession Genetics Diet Reflux Sunshine Radiation
Oral cavity + + + + ? + - + +
Oropharynx + + +++ - ? - - - +
Nasopharynx - - +++ - ++ + - - +
Hypopharynx + ++ - - ? + + - +
Larynx + + + +/- ? + + - +
Paranasal sinuses +/- - ? +++ ? + - - +
Skin - - - + + - - +++ +
Salivary glands - - + + ? - - - ++
Risk factors of HNSCC
Therapeutic results of Head and Neck Cancer in relation
to stage
Approximate 5-year survival
I. stage 91 %
II. stage 77 %
III. stage 61 %
IV. a 32 %
IV. b 25 %
IV. c 4 %
The prognosis of patients with the head and neck carcinomas is worsened due to frequent associated diseases.
(hepatic cirrhosis, diseases of circulatory and breathing systems etc.).
Possibility of improvement of therapeutic
results
▪ preventive programs aimed on risk groups (smoking, alcohol, etc.)
▪ earlier detection – increased oncologic „vigilance“ of family
doctors and specialists
▪ new methods of treatment – new chemotherapeutics - new
drugs, new protocols, immunotherapy, gene therapy, irradiation new
regimens, new methods in surgery
▪ suitable individual adaptation of current therapeutical procedures
prognostic factors should be found – for instance evaluation of
proliferation, apoptosis, DNA ploidy
Aim of clinical diagnosis
Determine
• Verification of malignancy; determination of character
(grading) and
• Stage of malignancy – size of primary tumor, Metastatic
aktivity, „staging“. The result is TNM classification.
• Determination of performance status of organism, incl.
psychological and social status.
• Complete history of disease
• Clinical examination - inspection, palpation incl. endoscopy
• Histology of primary tumor, lymphatic drainage (FNAB, FNAC), cytology diagnosis (HPV)
• Diagnostic imaging – CT, MR of the neck, X-ray of chest, better CT, sonography of
abdomen; contrast imaging of esophagus, ev. endoscopy in case of dysphagia; PET-CT,
PET-MR
• Evaluation of general status; Functional examination: swallowing, phonation, breathing,
• Stomatology examination; Nutritive screening
• Exclusion of duplex tumors: prostate in man, gynecology in woman
• Special examination, if necessary: psychologic examination, social status and support,
prevention (smoking)
Clinical diagnosis, assessment of prognosis
History of disease - „Listen to patient, he is saying
diagnosis“
HNSCC tumors (exception of glottic cancer) – some months without specific
symptoms (as civilization disease – chron. pharyngitis, rhinosinusitiss,
laryngitis), later:
• Feeling of foreign body in pharynx, burning, pain, especially one-sided in
swallowing spreading into ears, foetor ex ore
• dysphagia, limited movability of tongue, worse pronunciation – mumbling
due to tongue fixation
• anorexia, cachexia
• bleeding
• trismus
• Impaired nose breathing, epistaxis, external deformities in face
• hoarseness, cough, dyspnea
• tumor on external neck
Remove removable tooth prosthesis, consider pathological changes on
mucous membrane, asymmetry changes in oropharynx
• non healing damage on mucous membrane
• hard tumor covered of mucous membrane, later disintegration into
ulcer.
• exophytic tumors – patient frequently notices itself
• white and red stain persisting on palate, tongue, buccal mucosal
membrane – necessary biopsy and watching.
• neck tumor
Aspection
Palpation (+bimanual palpation)
• form and size in cm, site (localization), topographic description
• consistency - soft, elastic, fluctuant, firm or hard
• mobility - vertically or horizontally, fixed or adherent
• evaluation of borders of tumor
Imaging methods
• CT, MR of the neck, X-ray of chest, better CT, sonography of
abdomen
• PET-CT, PET-MR in advanced stages of pts. with assumption
of curative treatment
• contrast imaging of esophagus, eventually endoscopy in
case of dysphagia
CT vs. MRI
Undesirable side affects – CT: Radiation, MR: Small amount of Gadolinium could be stored in brain
M-classification: M0 no proof for distant. meta,
M1- exist proof for distant metastesis
thyroid gland cancer – metastases in ling M1 (PUL)
Endoscopic evaluation („optic biopsy“)
• Horizontal – NBI, SPIES (Storz Professional Image
Enhancement System – changes of color spectrum of
tissues)
• Vertical - Optical coherence tomography (OKT), - radiation
similar to infrared light penetrating 1-3 mm into depth;
images issues in vertical section
Classification of intraepithelial capillar
vascullar loops - progressive loss of
vascullar microarchitecture (IPCL) - Ni
et al.
The highest changes of vascular
microarchitecture, the most
significant probability of malignancy.
Type of microvasculature Type of pathology
Type I (A1-A3)
Thin, obligue and arborescent
Vocal fold polyp
Type II (B1-B3)
Diameters of oblique and arborescent vessels is enlarged
Chronic laryngitis
Type III (C1-C3)
Intraepithelial papillary capillary loops are obscured by white
mucosa
Light spinocellular hyperplasia
Type IV (D1-D3)
Intraepithelial papillary capillary loops are recognized as a small
dots
Middle degree hyperplasia
Type V (E,F,G)
Va solid or hollow, with a brownish, speckled pattern, various
shapes
Vb irregular, tortuous, line-like shapes
Vc brownish speckles, irregular distribution on the tumor surface
Heavy dysplasia to carcinoma in situ to invasive
spinocellular cancer
Narrow band imaging
Indication
• screening – early diagnosis
• Follow up after oncology treatment
• During evaluation or surgery for aimed biopsy
Limitations
• stagnation of saliva, mucous
• hyperkeratosis
• Influence of age, gender, lifestyle
• False positivity – laryngeal papillomatosis
Quality of life (QOL)
• Endeavor to safe and improve. QOL is possibly limiting factor for oncologic
treatment.
• Measurement of QOL – Karnofski scale, ECOG performance status
• Measurement of QOL after oncologic treatment - psychometric
questionnaires (Quality Of Life Questionnaire), for inst. QLQ-C30, QLQN&N37
a QLQ-H&N35
Karnofski scale
Possibility of improvement of
therapeutical results
• preventive programs aimed on risk groups (smoking, alcohol, etc.)
• earlier detection – increased oncologic „vigilance“ of family doctors
and specialists
• new methods of treatment – new chemotherapeutics - new drugs,
new protocols, immunotherapy, gene therapy, irradiation - new
regimens, new methods in surgery
• suitable individual adaptation of current therapeutical procedures
prognostic factors should be found – for instance evaluation of
proliferation, apoptosis, DNA ploidy
Prognostic factors
▪ In relation to patient ( Age, tobacco use, alcohol abuse, the whole status of
organism, Immunology)
▪ In relation to treatment (tumors responding better to neoadjuvant
treatment have better prognosis and they are suitable for treatment
damaging genome (chemo, radiotherapy)
▪ In relation to disease
Prognostic factors in relation to disease
• primary localization
• TNM stage - TNM classification of malignant tumors, International Union
Against Cancer (UICC)
• serum tumor markers (CEA, SCCA, TPA, CYFRA-21-1)
• Histologic differentiation („grading“ according to Broder)
• Predictive biomarkers
Biomarkers
Help to identify high-risk patients who may benefit from a more aggressive
treatment approach.
Help to identify patients who are resistant to radiotherapy or
chemotherapy, potentially avoiding the morbidity of ineffective
therapies.
May serve as targets for biologic therapies.
Hanahan D, Weinberg RA: The Hallmarks of cancer. Cell 100:57-
70, 2000. (8496 citations)
c-erb-B1 (EGFR)
c-erb-B2 (Her2/neu)
c-erb-B3,4
p53
p21
P16
Cyclin D1
Bcl-2, Bcl-X
BAX
MMP-9
E-cadherin
I-CAM
CD34
VEGF, bFGF
IL-8
Evasion of programmed
cell death
Inhibition of growth
inhibitory signals
Tumor invasion
and metastasis
Angionenesis
Immortalization
Aquisition of autonomous
Proliferative signaling
Telomerasis
Targeted therapy,
Precise therapy
• Higher expression of EGFR in 70-100 % HNSCC
• Blocking of signal pathway
• Activation of ADCC (Antibody-Dependent Cellular Cytotoxicity)
• Activation on complement depended cytotoxicity
• Dependence of outcome on genetic alterations
Precise therapy include mainly genomic aspects in
diagnosis and treatment.
Signal pathway of
EGFR in carcino-
genesis
Mechanism
of efect
inhibitors
EGFR
• More targeted antitumor therapy
and lower undesirable effect than
CHT
• EGFR receptors not present in
hematopoietic tissue, but are
present in skin, liver and GIT.
• Consequence of this are
undesirable effect: diarrhea, rash,
hypomagnesemia
Rash, 14 days after end of therapy (RT+Cetuximab)
Addition of p-16/HPV status to evaluation of existing markers could be
very helpful in prediction of treatment outcome in oropharyngeal cancer.
Prevalence of HPV positivity is given about 60% in Czech population.
Immune-oncology; immune checkpoint inhibitors
(ICIs)
„Inhibitors of check points of immune
reaction“, ICIs: PD-1, PD-L1 (nivolumab,
pembrolizumab) a CTLA-4 inhibitors:
(ipilimumab)
ICI does not act directly cytotoxic on tumor
cells, but the treatment leads to restoration
of tumor-paralyzed immunity of the disease
host.
▪ ICI is the preferred first-line treatment modality for all patients with
recurrent unresectable or metastatic disease without the option of surgical
or radiotherapeutic intervention.
▪ CPS (combined positive score) = number of all positive cells (tumour,
lymphocytes, macrophages) divided by the number of all vital tumour bb
and multiplied by 100.
Recurrent/metastatic squamous cell
carcinoma of the head and neck
Best supportive care
CPS (combined positive score) =
number of all positive cells
(tumour, lymphocytes,
macrophages) divided by the
number of all vital tumour bb and
multiplied by 100.
PS = performance status
Source: Luboš Petruželka, MD, prof., CSc.,
Profi Medicína, 15.1.2024
Independent risk faktor for survival!
Increasing Time to Treatment Initiation
Growth from a tumor of 1 g (the minimum size detectable) to a potentially lethal mass
of 1 kg requires only 10 further doubling of cell number (DeVita: Cancer)
Colin T. Murphy, Thomas J. Galloway, Elizabeth A. Handorf, et al.:
Survival Impact of Increasing Time to Treatment Initiation
for Patients With Head and Neck Cancer in the United States. J Clin Oncol 34:169-178.
© 2015
51,655 pts with HNSCC. Number of days from diagnosis to treatment initiation 61 to 90
days compared with less than 30 days independently increased risk of death (Cox
regress analysis, HR, 1.13; 95% CI, 1.08 to 1.19)
Theory vs.
reality
68 y patient, teacher
1/2018 pain in neck
2/2018 GP gave antibiotics
20/4 2018 evaluated on ENT
Taken sample - cT4 cN3 M0, p16 +
11/6 2018 supposed onset of CHRT
TNM classification
▪ Developed by Pierre Denoix v years 1942-1952; 2017 - 8. edition
▪ Separately assessment of primary tumor (T), local metastasis (N) and distant metastasis (M)
▪ Basic philosophy – more advanced tumor, worse prognosis
Aims:
1. Helps clinician in treatment planning
2. Give information about prognosis
3. Helps in describing treatment outcomes
4. Make easier exchange of information between treatment centers
5. Helps in research HNSCC in man
6. Support activities in fight against malignant tumors
8th edition
of TNM classification
• Published in December 2016, Czech edition 4/2018.
• Main change in comparison with 7. ed. Is separate
classification of p16+ oropharyngeal cancer
HNSCC therapy
▪ Curative – induce permanent remission
▪ Palliative – to stop tumor growth
▪ Symptomatic (Best Supportive Care, BSC) – treat only symptoms (pain food income,
bleeding, breathing)
Localized HNSCC– separate treatment only surgery or radiotherapy (not systemic
treatment as a „definitive“ treatment)
Surgery
• Curative – complete removal of tumor tissue (R0 resection)
• Palliative – to reduce tumor mass and improve usage of other treatment options.
Chemotherapy – only in combination with radiotherapy
Organ saving protocol
• The aim – preservation of the organ and its function
• Surgery is avoided or minimalized
• Organ preservation should not sacrifice length of survival
• Indication: patient with locally advanced but resecable tumor
Criterion for Treatment choice
Overall survival, time to recurrence or progression
versus
QOL, functional status, age of patient and his wish
▪ Patients with tumor penetrating cartilage are usually not suitable for
organ saving protocol
▪ Cost effectiveness
▪ Predictive biomarkers
▪ Neoadjuvant chemotherapy – tumor response to treatment – only in
clinical experiment
Treatment choice
Non surgical treatment (Chemo – radiotherapy)
• higher S-phase fraction (of cell cycle, SPF)
• Lower share of cells with realized proliferation
• Relatively good general condition (KI, BMI, weight loss)
Surgery
• Combination of higher apoptotic threshold (higher expression of p53, bcl-2) and lower share
of cells in SPF and higher share of cells G2M phase
• Advanced tumors (higher tumor volume),
• Lower expression of Ki-67
• lower micro vascular density (hypoxic tumor)
Clinical stage
I a II
Clinical stage
III a IVa,b
Clinical stage
III a IVc (M1) +
recurrences
Surgery Radiotherapy Resectable
disease
Unresectable
disease
Organ saving protocol,
non-surgical treatment
Chemo-radiotherapy
Chemoradiotherapy
or RT + cetuximab or
radiotherapy event.
salvage surgery
Cancer of oral cavity,
oropharynx,
hypopharynx and larynx
Surgery+ RT (CHRT)
Paliative chemotherapy,
Immunotherapy – see
next slide
The treatment strategy is usually is based on international guidelines, such as NCCN.
Nowhere in the whole world doesnt´exist unambiguous consent
regarding choice of the treatment modality. NCCN Guidelines distinguishes various
levels of consensus.
Treatment choice
Recurrent/metastatic squamous cell
carcinoma of the head and neck
Best supportive care
CPS (combined positive score) =
number of all positive cells
(tumour, lymphocytes,
macrophages) divided by the
number of all vital tumour bb and
multiplied by 100.
PS = performance status
The methods of surgical treatment
of lymph node metastases
Surgery from external approach – in case of primary surgical treatment,
combined with Radiotherapy/radio chemotherapy
Non surgical treatment – in case of „organ saving protocols“ Radiotherapy/radio
chemotherapy
The methods of treatment
Prescalene node biopsy (Daniels operation)
The radical curative neck dissection (Resectio venae jugularis internae en bloc sec. Crile
1906) - the upper boundary of the operation is the base of the skull and the
lower boundary lies at the level of the clavicle. The sternocledomastoid
muscle, the internal jugular vein are removed.
The goal of neck dissection is complete removal of lymph nodes and vessels
between the superficial and deep cervical fascia.
Functional deck dissection- the sternocleidomastoid muscle, the internal jugular
vein, the accessory nerve are preserved.
An elective neck dissection is a neck dissection carried out in the absence of
palpable lymph nodes for a primary tumor which experience has shown to
have a high metastatic rate - oropharynx, hypopharynx, supraglottic larynx,
the base of the tongue. The purpose of this operation is to deal with micro
metastases.
Types of neck dissections
(classification according to Ferlito)
ND (neck dissection)
L (left,) or R (right,) – side of neck dissection
removed region lymph nodes, described with Roman numeral to VII, in increasing order
removed non lymphatic structures
Examples:
ND (R, I-V, SCM, IJV, CN XI) – Radical neck dissection
ND (L, I-V, SCM, IJV, CN XI, CN XII) - extended Radical neck dissection with removal of n. hypoglossus
ND (I-V, SCM, IJV) – Modified radical dissection with saving n. accessorius (n. XI)
Abbreviations: ND – neck dissection , SCM – m. sternocleidomastoideus, IJV – v. jugularis interna,
CN XII – n. hypoglossus, CN XI, SAN – n. accesorius (spinal accesory nerve), ECA – a. carotis externa, ICA – a.carotis interna, CCA – a. carotis communis, CN VII
– n. facialis,
CN X – n. vagus, SN – neck sympaticus, PN – n. phrenicus, SKN –skin,
PG – glandula parotis, SG – glandula submandinbularis, DCM – deep cervical muscles
Radical neck dissection
ND (R, I-V, SCM, IJV, CN XI) sec. Crile
Modified radical dissection with saving n.
accessorius(I-V, n.XI saved)
Prevention
Therapeutic results of Head and Neck Cancer reveal strong dependency in relation to
stage – therefore prevention!
Primary – to prevent tumor formation by influence risk factors
Secondary – diagnosis of early tumor stages
Tertiary – early detection of local recurrences or distant metastasis or
possibly tumor duplicity
www.makesensecampaign.eu
European campaign focused on secondary
prevention
Schema of preventive evaluations,
tertiary follow-up
•Regular clinical evaluations
1st year : monthly
2nd year : every 2 months
3rd year : every 3-4 months
further years : every 6- 12 months
•Additional evaluations: X-ray examination of lungs/1 year ,
ultrasound of abdominal cavity/1 year, blood account + screening
á 3 month, CT individual. After 3 years the intervals are
protracting.
Tumors of nose and paranasal sinuses
Malignant melanoma of the nose
Carcinoma
maxillae (T4)
Incidence, Symptoms
• Incidence – less than 1% of all malignant tumors
• Usually 6-12 months without clinical symptoms,
• then unilateral nasal obstruction, small bleeding from the
nose, frequently picture of inflammation of maxillary
sinus, discharge, foetid secretion.
• In advanced tumors headache, signs of invasion of
neighboring tissue – eye, cheek, regionally
lymphadenopathy…
Risk factors
• hard wood dust,
• Nickel,
• isopropyl alcohol,
• thorotrast,
• yperit and other
Malignant melanoma of
the nose
Investigation
▪ Rhino - endoscopy biopsy
▪ CT/MR of paranasal sinuses
▪ Investigation for exclusion distant metastasis : X
ray of lungs, Ultrasonography of organs of
stomach cavity, mamma in women and
gynecology, prostate at men, PET.
▪ stomatology evaluation
Cancer of nose and paranasal sinuses TNM
classification
Öhngren´s plane (UICC)
T1. Tumour limited to the mucosa with no erosion or destruction of bone
T2. Tumour causing bone erosion or destruction, including extension into hard palate and/or …
T3. Tumour invades any of the following: bone of posterior wall of maxillary sinus,
subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses
T4. Tumour invades any of the following: anterior orbital contents, skin of cheek, pterygoid
plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses orbital apex, dura,
brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve V2,
nasopharynx. clivus
Cancer of hard palate
Therapy
Surgical treatment is preferred.
St. I, II – surgery (no risk factors present)
St. III,IV – surgery + radiotherapy (+- adjuvant
chemotherapy).
+ surgery for locoregional lymphnodes – only in their CT or
MR positivity
Surgical approaches
▪ Transfacial Lateral rhinotomy with various modifications
enabling approach to both partial and total maxillectomies.
(Weber-Ferguson)
▪ Endoscopic – benign tumors, inverted papilloma,
carcinomas – CAS (computer assisted surgery)
▪ Sublabial rhinotomy ( „midfacial degloving“) small tumors of anterior wall of
maxillae
▪ Combined craniofacial – intracranial spread of tumor + neurosurgery
bicoronar section
Surgical therapy – external
approach
▪ Maxillary sinus – parcial or total maxilectomy.
▪ Ethmoid sinus - external ethmoidectomy sec.
„Moure“
▪ Frontal sinus classical rhinosurgery - JansenRitter,
Riedel, Killian.
▪ Sphenoid sinus - sphenoidectomy via sublabialis,
transseptalis.
Lateral rhinotomy Weber-Ferguson
Maxillectomy according to Memorial Sloan Kettering
Cancer Center (Spiro 1997)
▪ „limited“ maxillectomy – every maxilectomy with removal only one wall
of antrum Highmori
▪ „subtotal“ maxillectomy – removal of at least two walls of antrum
Highmori
▪ „total“maxillectomy – all maxilla is removed
Midfacial degloving
Cancer of maxillary sinus
▪ Very late diagnosis
▪ Treatment
worsening quality
of life
Surgery of cancer of paranasal
sinuses
Multidisciplinar approach
(otorhinolaryngology, plastic surgeon, neurosurgeon,
stomatosurgeon)
▪ Phase of resection
▪ Phase of reconstruction
Phase of resection
▪ Resection of primary tumor
T1, T2 – limited or partial maxillectomy
T3, T4 - total maxillectomy, extended total maxillectomy,
exenteration of orbitae
▪ Revision of parapharyngeal space (N0), neck dissection
(N>0)
Phase of reconstruction
▪ Microsurgical flaps
(in one surgery)
▪ prosthetic solution
– obturatos and epithesis
– tooth prosthesis
– eye prosthesis
Prosthesis after surgery – covering
defect
Closing the defect - vessel
microsurgery
▪ m. latissimus dorsi, m. serratus
ant. - Muscle – skin flap
▪ China flap - Skin + subcutaneous
flap
▪ Bone-muscle- flap
Ca spinocellulare maxillae l.dx. cT4
Month after surgery
Skin used for
reconstruction of the orbit
Skin used for palate
reconstruction
Reconstruction in one step
+ Enabling sufficient radicality
+ Shorter healing after surgery
+ better cosmetic effect
- difficult possibility of detecting
recurrences in operating cavity
Survival of patients with malignant
tumors of nose and paranasal sinuses
60. year old patient JV
• Nasal polyposis for years
• 9/2009 oedema of right eye, blocked nose, without diplopia
• Tumor adhering to dura mater
• Histology: not differentiated carcinoma karcinom. pT4b N0M0
14.10.2009 Exenteratio orbitae l.dx, resectio maxillae partialis
l.dx, resectio baseos fossae cranii anterior, ethmoidectomia l. utr.,
transplantatio durae matris fossae cranii ant. l.dx., recontructio
defectus plastica cum musculus latissimus dorsi
Neurosurgery – resetion of dura
mater, replaced by synthetic
dura
Defect closed with musculocutaneus flap
from m. latissimus dorsi microsurgical
anastomosis on v.a a. facialis
Overall survival – 8
year, good QOL
▪ 2009 – Adjuvant CHRT
▪ Fololow up by NMR/ CT
▪ 11/2012 swelling of head on contralateral side - sinusitis frontalis a
etmoidalis with periorbital swelling
▪ Histology middle turbinate: Chronic inflammatory changesd, withou tumor
▪ Exitus letalis - 11.4.2017 low diff. ductal adenocarcinoma of head of
pancreas
Carcinoma
maxillae (T4)
Ca spino maxillae
pT4 N0 M0
Cancer of pharynx
Cancer of epipharynx(C 11) TNM
classification
T1. Tumour confined to nasopharynx
T2. Tumour extends to soft tissues
T2a. Tumour extends to oropharynx and/or nasal cavity
without parapharyngeal extension*
T2b. Tumour with parapharyngeal extension*
Cancer of epipharynx(C 11) - TNM
classification
T3 Tumour invades bony structures
and/or paranasal sinuses
T4 Tumour with intracranial extension
and/or involvement of cranial
nerves, infratemporal fossa,
hypopharynx, orbit, or masticator
space
N – Regional lymph node
(nasopharynx)
NX Regional lymph nodes cannot be assessed
N0 regional lymph node metastasis
N1 Unilateral metastasis, in lymph node(s), 6 cm or less in greatest
dimension, above the supraclavicular fossa
N2 Bilateral metastasis in lymph node(s), 6 cm or less in greatest
dimension, above the supraclavicular fossa
N3 Metastasis in lymph node(s) greater than 6 cm in dimension or in the
supraclavicular fossa
N3a. greater than 6 cm in dimension
N3b. in the supraclavicular fossa
Note: Midline nodes are considered ipsilateral nodes.
Cancer of epipharynxinvading roof,
extending into torus tubaris – T2
Ca epipharyngis
T4N2c
53 year, random finding, hypacusis
mixta. dx.
Ca epipharyngis
T4N2c
the same patient
Tumors of epipharynx- histologic findings
• Carcinomas (WHO classification) –
• Type 1 – carcinoma spinocellulare with keratinisation
• Type 2 – carcinoma spinocellulare without keratinization
• Type 3 – low differentiated or undifferentiated carcinomas
• Tumors of soft tissue: Juvenile angiofibroma, paraganglioma
(chemodectoma).
• Malignant lymphoma
• Miscellanea: melanoblastomas, chordomas,
craniopharygneomas, neuroblastomas
Lymphoepithelioma of epipharynx
(Schmincke- Regaud)
Nasoharyngeal tumors etiology
Food habits: salt fish (nitrosamins), croton oil –
promotors of some lymphoblastic clons virus Epstein
Barr (EB virus)
Symptoms
▪ Ear – sensation of fullness in ear, worsening of hearing, tinnitus, pain in
the ear
▪ Nose - obstruction, bleeding
▪ Pharyngeal - sensation of foreign body
▪ Eye - diplopy, ophthalmoplegia
▪ Neurologic - trigeminal hypesthesia,
▪ Trotter trias: trigeminal neuralgia, hypacusis conductiva, asymetry of soft
palate from paresis on involved side.
Clinical finding: bumpy, exulcerated, rough, mostly exophytic tissue in
epipharynx
Ca epipharyngis
T4
Therapy
▪ Cancer – current protocol: Curretage of epipharynx +
concomitant chemoradiotherapy. 55 - 70 Gy. Eventually
neck dissection (in case of persistence arter CHRT)
▪ Lymphomas – radiotherapy 40-45 Gy.
Oral cavity anatomic sublocalisations
▪ Lips
▪ Mucosa membrane of lips and cheek
▪ Retro molar region
▪ Bucoalveolar sulcus
▪ Superior alveolus and gingiva
▪ Inferior alveolus and gingiva
▪ Hard palate
▪ Tongue before papillae circumvallate
▪ Base of oral cavity
TNM classification
▪ TNM – borders 2cm -4 cm, infiltration of corticalis ane deep muscles of
tongue
▪ Important – thickness of tumor– even in clinically negat. neck in tumor
more than 5mm thick neck dissection necessary
▪ Infiltration of bone - T4
▪ Reconstruction with help of tongue or cheek flaps or soft palate or
microsurgery flaps
Laser surgery of
tongue
Cancer of oropharynx
what we knew
Cancer of pharynx and larynx were considered to
have the same cause - smoking…
what we have learnt
Many of epidemiologic studies of molecular
pathology document, that human papillomavirus
(HPV), especially type 16 is etiologically connected
with oropharyngeal cancer
▪ Gillison 2009
HPV and prognosis of OSCC
Prognosis of HPV related cancer is better than tobacco
related cancer.
Expression of p16 in HNSCC marked group of HPV induced
tumors with good prognosis
Treatment of HPV positive OSCC
✓Organ saving strategy should be more successful.
✓Better response on induction chemo and chemoRT
Fakhry J Nat Inst 2008: 100, 261
HPV+ HPV Incidence
↑ ↓
Age <50 50-70
Risk factors oral sex smoking, alcohol
Histology
low differentiated, nonkeratinizing,
bazaloid
middle to good differentiated,
keratinizing
Markers p16 p53
TNM klassification Lower T N++ higher T N+
Metastasis in
lymphnodes cystic more homogenous
Chemoradiosenzitivity high lower
Prognosis good worse
OS (5 year) >80% < 40-50%
Comparison of HPV+ a
HPV- tumors
Tumors of oropharynx symptoms
At least half year without clinical symptoms:
▪ Painful dysphagia
▪ Pain in the ear
▪ Feeling of foreign body in the pharynx
▪ bleeding
▪ trismus
Clinical finding: hard knot covered with mucose membrane
(induration of the tonsil), later ulceration, oral fetor.
Important – unilateral changes, palpation !
Ca spino palati mollis cT2-3 cN2b M0 st. IVa
histology: low
diferentiated
nonkeratinising
squamocelular
cancer
p16 negative
MKN: C051
MKN-O:
M-8070/3 3
Retromolar trigonum cancer T2
Ca spino palati molle T1
Left tonsil cancer
Cancer of oropharynx – soft palate IV.
stage
Cancer of the base of the tongue
Tumors of oropharynx TNM
classification
T1. Tumour 2 cm or less in greatest dimension
T2. Tumour more than 2 cm but not more than
4 cm in greatest dimension
T3. Tumor more than 4 cm in greatest dimension
T4a. Tumor invades any of the following: larynx
deep/ extrinsic muscle of tongue (genioglossus,
hyoglossus, palatoglossus, and styloglossus),
medial pterygoid, hard palate, and mandible
T4b. Tumor invades any of the following: lateral
pterygoid muscle, pterygoid plates, lateral
nasopharynx, skull base; or encases the carotid
artery
Therapy of oropharyngeal cancer
Radically resecable tumors
Radical surgery (safe margins, R0) + neck dissection+ actinotherapy vs. Primary
nonsurgical treatment Actinotherapy LD 55-60 Gy + boost 10-15 Gy +
chemotherapy in risk factors, always prophylactic lymph node actinotherapy.
Lymphomas 40-45 Gy.
Advanced not radically resecable tumors
Palliative radiotherapy or chemo-radiotherapy with attempt of curative
treatment or only BSC
Routes of access for tumors of the mouth and pharynx
Transoral(1)
• Limited indications – small accessible tumors
External approaches saving mandible (3-5)
• Lateral pharyngotomy
• Suprahyoid median pharyngotomy
External approaches with mandibulotomy (-ectomy)
(2)
• Lateral pharyngotomy with removal of mandibular angle
• Trans mandibular buco-pharyngectomy (BPTM)
• BPTM with resection o lateral mandible segment
Ca spino gingivae of mandibulae left –pT2N2bM0. Partial
mandibulectomy without discontinuance
Bucopharyngectomy