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DR.

SUPRIYA KOKANE PATIL


M.S.(ORL); FELLOW (FACIAL PLASTIC SURGERY)
ASSOCIATE PROFESSOR
• Cancer is the common term for all malignant tumors.

• Cancer (Latin word) : crab (Ancient Greek word)

• Presumably because, a cancer cell adheres to any part that it


seize upon in an obstinate manner like a crab.

• The study of cancer is – “Oncology’’


onco = Greek onkos, meaning bulk, mass, or tumor,
logy = study
• Common terminologies : cancer or tumor

• Literature terminology : neoplasia or neoplasm

• It is a disorder of cell growth, characterized by


uncontrolled, uncoordinated & undesirable cell division.

• There is no exact definition for cancer.


Condition Tissue involved Suffix

Benign Mesenchymal tissue Oma

Benign Epithelial • adenoma


tissue • Papilloma
• Cystadenoma
• Papillary cystadenoma
• polyp
Malignant Mesenchymal tissue Sarcoma

Malignant Epithelial Carcinoma


tissue
• More than 90% of head and neck malignancies are squamous
cell carcinomas.
L. Licitra, E. Felip. Squamous cell carcinoma of the head and neck: ESMO Clinical Recommendations for
diagnosis, treatment and follow-up. Ann Oncol . 2009; 20 (4):iv121-iv122. doi: 10.1093/annonc/mdp149.

• According to Stell & Maran’s Textbook Of Head & Neck


Surgery & Oncology
CANCERS OF HEAD & NECK
Squamous cell carcinoma Non - Squamous cell carcinoma
1. Cancer of oral cavity & 1. Cancer of thyroid
oropharynx 2. Cancer of salivary glands
2. Cancer of larynx & hypophaynx 3. Sarcomas
3. Cancer of nasopharynx - soft tissue
4. Cancer of nasal cavity & paranasal - hard tissue
sinuses
• Cancer is a leading cause of death worldwide, accounting for
7.6 million deaths (around 13% of all deaths) in 2008

• Head and Neck Cancer: Worldwide –


▪ 640,000 cases /year
▪ 356,000 deaths per annum (55% mortality)
▪ 5% incidence of all cancers (excl. skin)
▪ 5% mortality of all cancers

GLOBOCAN 2008 (IARC) Section of Cancer Information (8/12/2013).


- wide variations

✔ France (supraglottic, oral cancers)


✔ Hong Kong (nasopharyngeal cancers)
✔ India (oral cancers)
Region of Contribution
cancer
Oral cavity 41- 43%

Oropharynx 3rd most common

Larynx 30 %

Hypophaynx 10%

Nasopharynx 1-2%

Nasal cavity Rare


Rare
Paranasal
(60-70% in
sinuses
maxillary sinus)
1. Tobacco
2. Alcohol
3. Dental factors
4. Occupational exposures
5. Infections
6. Nutritional factors
7. Inflammatory cause
8. Genetic factors
9. Immunologic factors
10. Endocrinal disturbances
11. Radiation
The areas of oral cavity which is bathed with
saliva, are most common sites to be involved.

Eg. – oropharynx, crypts of


Smoking : tonsil, glossotonsillar sulcus, tongue, soft palate
& posterior pharyngeal wall.
• 90% cases
• Contains 30 known carcinogens : polycyclic aromatic hydrocarbons
: nitrosamines
• Alcohol adds up in pathology
Black / dark Blend & blond
Air cured Flute cured
More carcinogenic
Smokeless :
• Most common in Indian suncontinent

Bidi Chutta

khaini paan
• Synergistic action with tobacco.
• Mostly associated with cancer of - lateral border of tongue
- glossotonsillar sulci
- pharyngoepiglotic fold

7 possible mechanisms –
1. Acts as an solvent
2. Some contents of alcoholic beverages
3. Metabolites like – acetaldehyde
4. Up regulation of enzyme – cyt p450
5. Decreased activity of DNA repair
enzymes
6. Impairment of immunity
7. Decrease resistance to cancer
• Different alcoholic beverages have different carcinogenic
contentes :
- Beer – - Wine –
Nitrosomethylamine tannin

- Dark liquor – - Light liquor –


ester, ester,
acetaldehyde acetaldehyde
• Sharp tooth

• Oral hygiene

• Patients with ill fitting dentures

• Alcohol containing mouth washes (to

mask the smell of tobacco/alcohol)


Cancer Associated factors
Cancer of oral cavity & Wood dust, chemicals, coals
oropharynx
Cancer of larynx & Wood dust, Ni & mustard gas
hypophaynx and asbestos exposure, H2so4 &
HCl
exposure in battery plants
Wood dust, textile & lather dust,
Cancer of nasopharynx
flour, formaldehyde, solvents, Ni
Cancer of nasal cavity & & Cr dust, mustard gas, radium,
isopropyl alcohol.
paranasal sinuses
Cancer of salivary glands Ni alloy dust & si
Sarcomas Urethane, ethylene derivatives,
polycyclic hydrocarbons
30-100% verrucous carcinoma 5% cases of H&E cancers have
50% cases of NPC have HPV HIV inhections (kaposi sarcoma)

Mostly associated with


nasopharyngeal cacinoma

42 % oral cancer & all smokers


with & without cancer,have
higher HSV antibody titre.
Anti-oxydants
Vit A , C,
E
Diet low in iodine : carcinoma of thyroid gland

Carcinogenic nitrosamine
in high salted fish
(NPC)
1. GERD : Risk factor in 36-54 % cases of laryngeal /
pharyngeal cancer.

2. PRECANCEROUS CONDITIONS OR
LESIONS : leukoplakia, erythroplakia
OSMF – in anterior palatoglossal arch
• Li- Fraumeni syndrome : autosomal dominant condition
mutation of p53 gene
• Fanconi’s anemia
• Bloom syndrome Autosomal recessive disorder
with increased chromosomal
• Ataxia fragility are associated with
oral cavity & pharyngeal
• Telegiactasis carcinoma.

• 4-6% of cancer of larynx & hypophaynx have history of


- plummer vinson syndrome
or
- Patterson Brown – Kelly syndrome
• Cancer of nasopharynx has strong predilection for
interaction between genetic & environmental factors.

• Gardener syndrome Increased incidence of thyroid


• Multiple polyposis 25 cancer.
% cases associated with hereditary form
• Cowden disease
• Multiple endocrine neoplasia (autosomal dominant)

• Li- Fraumeni syndrome osteosarcoma


• Children with ratinoblastoma
• Gardener syndrome
• Nevoid basal cell sarcoma
carcinoma syndrome
• Patient suffering from HIV infection.

• Patient on long term immunosupressive medication for organ


transplantations (risk of cancer of skin & oral cavity).

• Compromised general condition


• Early menarchy Increased risk for salivary gland
• Nulliparity carcinomas

• Older age at full term pregnancy Decreased risk for salivary


• Log term Oral contraceptive gland carcinomas
• NPC : Previous history of radiation therapy for cricoid
carcinoma or carcinoma of posterior wall of pharynx.

• Thyroid & salivary gland cancer : history of radiation


therapy, exposure to radiation fallot from nuclear power plant
or nuclear weapon in childhood .
• 4 stages of tumor growth

1. Malignant changes in 1 cell (transformation)


2. Growth of transformed cell
3. Local invasion
4. Distant metastasis
Alteration in 4 normal regulatory genes

I. Growth promoting oncogenes


II. Growth inhibiting tumor suppressor genes
III. Genes that regulate apoptosis
IV. Genes involved in DNA repair
• A proto-oncogene is a normal gene that can become an
oncogene due to mutations or increased expression.
• Proto-oncogenes code for proteins that help to regulate cell
growth and differentiation.

• An oncogene
is a
potential
gene that has
the
cause cancer. In tumor
cells, they are oftento
mutated or expressed at
high levels
• A tumor suppressor gene, or anti-oncogene, is a gene that
protects a cell from the path to cancer.

• Tumor-suppressor genes, or more precisely, the proteins for


which they code, either have a dampening or repressive effect
on the regulation of the cell cycle or promote apoptosis, and
sometimes do both.
• The tumor-suppressor protein p53 accumulates when DNA is damaged due
to a chain of biochemical factors.

• Part of this pathway includes alpha-interferon and beta-


interferon, which induce transcription of the p53 gene - p53 protein
level and enhancement of cancer cell-apoptosis.

• P53 -stopping the cell cycle at G1/interphase, to give the cell time to
repair, however it will induce apoptosis if damage is extensive and repair
efforts fail.

• Any disruption to the regulation of the p53 or interferon genes will result in
impaired apoptosis and the possible formation of tumors.
• Self sufficiency in growth signals

• Insensitivity to growth inhibiting signals

• Evasion of apoptosis

• Defects in DNA repair

• Limitless replicative potential

• Sustained angiogenesis

• Ability to invade & metastasize


Acquired / environmental Normal cells
• DNA damaging agents
• chemicals Successful DNA repair
• radiations
• virus DNA
damage Inherited mutations in
• gene affecting DNA
Failure of repairning
DNA • cell growth &
repair apoptosis
Mutation in the genome of somatic cells

Activation of growth Inactivation of tumor Alteration in genes


promoting oncogenes supressor genes regulating the apoptosis

Unregulated
cell
Clonal expansion Decreased apoptosis
proliferation
Angiogenesis &
Additional mutations
Escape from immunity

Tumor progression

Malignant
neoplasm
• Pathway of metastasis

1. Haematogenous spread
2. Lymphatic spread
3. Other routes
- Trancelomic spread
- Spread through the epithelial surface
- Spread through CSF
- Implantation
• Unfortunately patients are most often identified only after
development of symptoms at advanced stages of disease.

• Discomfort is the most common symptom that leads a patient


to seek care & may be present at the time of diagnosis in up
to 85 % of cases.

• As the high risk sites of oral carcinoma are lower lip, anterior
floor of mouth & the lateral border of tongue, the examination
of oral cavity should not be neglected.

• Careful assessment of cervical & submandibular lymph nodes


should be done & followed by examination of oral cavity.
Common signs and symptoms of head and neck cancers include:

• A chronic sore throat


• Hoarseness of voice
• Difficulty in swallowing
• Earache
• Headaches
• Unusual bleeding in the mouth
• A discolouration on the gums, tongue, or lining of the mouth
• Nasal obstruction
• Numbness of the face
• Trouble when breathing or speaking
• Undefined weight loss
1. Red , white or red & white lesions (flat / elevated)

2. Change in surface texture (smooth, granular, rough, crusted)

3. Chronic ulcer , not responding to conservative management

4. Ulcer with irregular edge & induration of underlying soft tissues.

5. Varying degree of pain

6. Occasional episodes of bleeding

7. Exophytic growth may present as a cauliflower like irregular growth / flat

8. Submucosal growth with surrounding indurations (pain in advanced stages )

9. Bleeding & fixity to surrounding structures


10. Buccal mucosa cancers involving the infratemporal fossa may lead to
trismus (D/D OSMF)

11. Hypoglossal palsy & restriction of tongue mobility, progressive difficulty


in mastication & speech, pooling of saliva, friability & surface bleeding.

12. Trismus affects the nutritional status, functional impairment (obstruction


from large mass) – decrease tolerance to CT, RT & surgery.

13. Unexplained loosening of the involved tooth/teeth.


14. Tumor closer to midline & posterior in position in oral cavity/ orophaynx
may involve bilateral lymph nodes.
15. Involved lymph nodes are –

Initially – soft, mobile, non-tender, enlarged

firm to hard in texture, usually non tender,

tender (due to inflammatory response )

Advanced stage (aggressive disease) – fixation of nodes to adjacent tissue


due to invasion of cells through the capsule

16. Fixation of primary tumor to adjacent tissue overlying bone


suggests involvement of periosteum & possible spread to bone.
• Clinical Examination:

– Tumours, when first seen, are almost always confined to the


head and neck with no distant metastasis

– Head and neck tumours are rarely irremovable, all structures


can be removed with the tumour in continuity and repaired
later
• The majority of cases are potentially treatable
• Whether to treat or not depend on:

– the age
– the health status of the patient
– advance stage
– local disease

• Full assessment will lead to one of the following


conclusions:
– Patient is potentially curable
– Primary tumour is curable but patient develop another
illness
– Patient is incurable but should be treated
– Patient is incurable and should not be treated
• History:
– Age:
• Patient are generally over 45 years.
• Tumours affecting younger age group are usually
sinister, defective immunological make-up

• Most tumours are of epithelial origin and they require


years of abuse by smoking and tobacco

• Tumours in younger patients, who do not smoke, is


usually very sinister

• Tumours developing in an immuno-compromised


patients do not respond to any treatment modality
• Complaint:
– Vary widely and is often unreliable

– Painless lump which persisted for a varying period of time

– Persistent ulceration

– Difficulty of wearing denture

– Later Symptoms:

• Pain locally or referred to the jaw or ear

• Difficulty with chewing food and swallowing

• Altered speech and respiratory difficulty

– Asymptomatic and noticed during routine dental examination


• Examination:
– Think in term of T Staging, delineate its border by
inspection and palpation

– Record and draw the lesion from different angles using


normal anatomical landmarks

– The status of teeth should be assessed as causative and if


radiotherapy is to considered
CARCINOMA OF LIP
• Age and sex:
– The sixth decade and Male : female ratio is 80:1

• 93% affect the lower lip with squamous cell carcinoma,


exophytic type

• 5% in the upper lip and commonly basal cell carcinoma,


commoner in females
– Solar exposure, more radiation on the lower lip
– Commoner in fair complexion
– Smoker - cigarette, cigar, pipe stem
– In the upper lip, SCC metastasizes earlier than lower lip
– Covered with non-keratinized stratified squamous epithelium which is
transparent, appear red, and contain no hair, sebaceous gland or pigments

– Crusted oozing, non-tender, indurated ulceration of <1 cm


– On the vermilion border it closely cover the orbicularis oris muscle but on
the lingual side mucous gland is present within the muscle and mucosa

– Perineural invasion through mental nerve


– Lymphatic drainage:
• Mucosal and cutaneous systems.
• Lower lip:
– One medial trunk which drain the inner third of the lip into the
submental group
– Two lateral trunk which drain the outer two-third into the
submandibular lymph nodes
– Anastomosis account for bilateral metastases
• Upper lip:
– Drain into the periauricular, parotid, submandibular and
submental lymph nodes
CARCINOMA OF LABIAL MUCOSA

• Lower labial mucosa > upper

• Tobacco pouching

• Exophytic growth , swelling, ulceration

• Unilateral or bilateral lymph nodes may be involved


CARCINOMA OF BUCCAL MUCOSA

Site : along or inferior to a line opposite to occlusion line

(distal to third molars)

Sign : painful lesion

Appearance

Metastasis : The submandibular lymph nodes to the lower deep


cervical chain
CARCINOMA OF TONGUE

• A disease of the middle age and elderly with equal


sex incidence, youngers

• 85% occurs in the lateral border of the anterior 2/3


while tip, dorsum and ventral surface are rarely
involved

• Appearance : painless indurated mass or ulcer


• The lesion may be infiltrative (small on the outside
but palpation shows deep invasion) or exophytic
and usually of the well-differentiated type
– Specialized keratinized epithelium with collection of
minor salivary gland and muscle fibres

– The interlacing muscle fibres form an easy pathway for


cancer spread and the constant movement of the tongue
disseminates the disease widely

• Excision should be wide with 2 cm

safe margin
• Lymph drainage:

– Tip of the tongue:


• To the submental lymph nodes – to the lower
deep cervical chains

– The anterior 2/3:


• the lower deep cervical chains – jugulo-
omohyoid nodes

– The posterior 1/3:


• drain to the upper deep cervical chains

▪ The tip and middle part of the tongue have rich bilateral capillary network
but less in the lateral margins
CARCINOMA OF FLOOR OF THE MOUTH

– Anterior medial part:


• Commoner than the lateral part

• Felame > male


• Spread medially into the ventral
surface of the tongue and laterally

• Deep spread to the base of the


tongue and the hyoglossus and
genioglossus muscles

• Shows bilateral lymphatic spread to


the submandibular and the
submental nodes
– Lateral part:
• Spread medially to the side of the tongue
• May involve sublingual &/or submandibular
glands

• Lateral spread to the alveolar ridge where


presence or absence of the teeth govern the
outcome:

– Teeth act as a barrier against buccal


spread

– In edentulous patient, the alveolar


process has resorbed and cortex is
incomplete, tumour reaches the
cancellous spaces and the canal and
spread through the nerve.
Deeper spread, mylohyoid muscle act as a barrier anteriorly,
posteriorly the floor is close to the skin, appear as a palpable lump in
the submandibular area.

Lymphatic drainage – through submandibular lymph nodes to the


upper deep cervical chains

Sign & symptoms :


• Painful / painless lesion
• Restricted tongue movement
• Slurring of speech
• Excessive salivation
• loosening / exfoliation of teeth
• Root resorption
CARCINOMA OF GINGIVA & ALVEOLOUS
▪ Least associated with tobacco chewing

▪ The lesion is usually painless

▪ Looks like inflammatory or reactive lesion


(eg. Pyogenic granuloma)

▪ Warts around the denture flanges

– Carcinoma of the lower alveolus affects the


antero-lateral part and spread to the floor of
the mouth

– Tongue and floor of the mouth tumours


reach the lower alveolus by marginal spread
in the mucosa and submucosa overlying the
sublingual, submandibular glands and the
mylohyoid muscle. They act as barrier
against deep infiltration.
• Edentulous jaws, mylohyoid line is on the occlusal ridge and the
loss of the cortical bone barrier will allow tumour to spread
downward into the medullary cavity

– The inferior alveolar nerve provide a pathway for perineural spread in a


predominately proximal direction with little involvement of the bone

• Nerve looks clinical normal till late

• Spread is not continuous, multiple pathological samples is required

– Lymphatic spread to the submandibular lymph nodes


CARCINOMA OF PALATE

• Disease of the elderly (60 – 70 years)


• Associated with reverse smoking
• Common location for carcinoma of the minor salivary
gland
• Presented as smooth, rounded, bulging masses
• Squamous cell carcinomas present as ulcerative or
exophytic lesion

• Invade the bone at an early stage

• Involve the tonsillar pillars, soft palate, nasal


cavity, nasopharynx and the antrum
• Metastases to submandibular and upper deep
cervical chains
• Site : soft palate & oropharyngeal mucosa
• Appearance : like other lesions
• Size : greater than that of other sites
• Symptoms : dysphagia (most common)
: pain (dull, sharp, radiating to ear)
• Derived from lining epithelium

of lymphoid tissue.

• Older age & male predilection


SYMPTOMS :
• Initial lesion is small & difficult
• Serious otitis media
to detect.
• Otalgia
SIGN :
• Obstruction of eustachian tube
• First sign is firm to hard
(enlarged) cervical lymph nodes • Hearing loss

• Nasal obstruction
• Neurological symptoms
• Pharyngeal pain
• The sinus is related to the orbit, nose, alveolar process, infratemporal fossa
and nasopharynx.

• It has an outlet to the nose, ethmoid sinuses and the root of the teeth

• Old age & male predilection


SIGN :
SYMPTOMS : • Ulceration or mass on the hard palate
• Pain
• swelling
• Nasal obstruction
• Unilateral nasal stiffness
• Pain / paresthesia of midface
(involvement of maxillary nerve)
• The inferior orbital fissure provide a route for entry of tumours into the
orbit, the periostium offer an excellent resistant barrier to spread into the
orbit.

• The roots of the upper premolars and molars and the alveolus are in
intimate contact to the floor.

• The infratemporal fossa is the space behind the maxillary antrum and it
connects to the para-pharyngyeal space, and the sphenoid bone superiorly
with foramen spinosium and ovale with their emerging nerves.

Lymphatic drainage:
• Drain posteriorly to the retropharyngeal nodes
• Directly to the jugulo-digastric nodes
• If it cross to the nose or the cheek it will drain to submandibular lymph
nodes
Precancerous lesion (precancer/ premalignancy)

A benign, morphologically altered tissue that has a greater than normal risk of
malignant transformation .

Eg : leukoplakia
erythroplakia
mucosal changes associated with smoking habits
carcinoma insitu
Bowen disease
Actinic keratosis, cheilitis & elastosis
Malignant potential : 0.3 – 10 %
Mild / thin leukoplakia Nodular/ speckled leukoplakia

Homogenous / thick leukoplakia

Erythroleukoplakia

Verrucous leukoplakia

Ulcerated leukoplakia
Homogenous & smooth Erythroplakia Granular Erythroplakia

Erythroleokoplakia
Stomatitis nicotina Snuff dipper's lesion

Cigarette smoker’s lip lesion


-Mostly involve skin
- but sometime also may involve mucosa
- SCC in situ is termed as – Bowen Disease
• A cutaneous premalignant lesion

• Gives – SAND PAPER APPEARANCE

• KERATIN HORN may present


Precancerous condition

It is a disease or patient’s habit that doesn’t necessarily alter the clinical


appearance of the local tissue but it is associated with a greater than normal
risk of precancerous lesion / cancer development in the tissue.

Eg : OSMF
syphilis
sideropenic dysphagia
OLP
Diskeratosis congenita
Lupus Erythmatosis
Malignant potential : 0.2 – 0.5 % in INDIA
Malignant potential : 0.4 – 12.3 %

Wickham’
s striae are
diagnostic
It presents a chronic multiple oral mucosal
ulcers, which occurs when there is extreme Malignant potential : 1 – 15 %
degeneration of basal cell layer of
epithelium.
Staging is the process subdivision of cases of cancer into same
groups in which behavior will be similar.
• Over the last decade the 2 principle staging classification system of head &
neck cancer, those of AJCC & UICC have undergone a convergent
evolution & are now to all interest & purposes identical.

• Classification by anatomical extent of disease is determined clinically &


histopathologicalyl is the one that the TNM system primarily uses:

T : enlargement of & invasion by primary tumor

N : spread to regional lymph nodes

M : spread to different metastatic sites


4 classifications –
1. Clinical classification / pretreatment Clinical classification (cTNM)
2. Pathological classification / postsurgical H/P classification (pTNM)
Gx : Grade Of Differentiation Can Not Be
Assessed G1 : Well Differentiated

G2 : Moderately Differentiated
G3 : Poorly Differentiated
G4 : Undifferentiated

3. Retreatment classification (rTNM)


Rx : Grade Of Differentiation Can Not Be Assessed
R0 : No residual tumor is present
R1 : microscopic residual tumor
R2 : macroscopic residual tumor

4. Autopsy classification (aTNM)

Other descriptors
i. “m” suffix (> 1 primary at single site)
ii. “y” prefix : ycTNM, ypTNM
T. Primary Tumor
TX. Primary tumor cannot be assessed
T0. No evidence of primary tumor
Tis. Carcinoma in situ
T1, T2, T3, T4. Increasing size and/or local extent of the primary tumor

N. Regional Lymph Nodes


NX. Regional lymph nodes cannot be assessed
N0. No regional lymph node metastasis
N1, N2, N3. Increasing involvement of regional lymph nodes

Mx : Metastasis cannot be assessed


M0 : No evidence of metastasis
M1 : Presence of metastasis
Classification schemes that histologically categorize precursor and
related lesions
Squamous
Ljubljana
intraepithelial
Definition WHO 2005 neoplasia classification
(SIN) system
An increase in the number of cells, but Squamous Squamous cell
with no cellular atypia cell (simple)
hyperplasia hyperplasia
Changes are confined to the lower third Mild SIN 1 Basal/parabasal
of epithelium dysplasia cell hyperplasia
Changes extend to the middle third of Moderate SIN 2 Atypical
the epithelium. Cytological changes can dysplasia hyperplasia
be more marked
Changes involve at least 2/3rd of the Severe SIN 3 Atypical
epithelium & atypia is more marked. Dysplasia hyperplasia
Changes involve the full thickness of Carcinoma SIN 4 Carcinoma in situ
epithelium, but no invasion of in situ
basement membrane
1. Barnes L, Eveson JW, Reichart PA, Sidransky D. World Health Organization classification of tumours. Pathology
and genetics. Head and neck tumours. World Health Organization; 2005.

1. Isaäc van der Waal. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification
and present concepts of management. 2009; 45(4-5):317–323

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