2. INTRODUCTION
ο The origin of the word cancer is credited to the Greek physician
Hippocrates (460-370 B.C.).
ο Hippocrates used the terms carcinos and carcinoma to describe
non-ulcer forming and ulcer-forming tumors.
ο The Roman physician, Celsus (28-50 B.C.) later translated the
Greek term into cancer, the Latin word for crab.
2
3. ο The oral cavity is that part of upper aerodigestive tract
which extends from the mucocutaneous junction at the
vermilion border of the lips to the anterior surface of the
faucial arch.
ο It is lined by squamous epithelium containing
interspersed minor salivary glands and also
dentoalveolar structures which support the upper and
lower dentition.
ο More than 95% of the carcinomas of the oral cavity are
squamous cell type.
3
4. ο Most oral cavity cancers are located in a horseshoe-
shaped area that extends from the anterior floor of the
mouth and includes the tonsillar pillar/ retromolar
trigone complex.
ο The tongue and floor of mouth are the most common
sites of origin for primary squamous cell carcinomas in
the oral cavity.
ο Retromolar trigone and buccal mucosa are the frequently
encountered sites in those parts of the world where
tobacco chewing and chewing of betelnuts are most
prevalent.
4
5. DEFINITIONS
ο Neoplasia literally means βNew Growthβ.
A neoplasm as defined by Willis is- An abnormal mass of
tissues the growth of which exceeds and is un-coordinated
with that of normal tissues and persists in the same
excessive manner after the cessation of the stimuli which
evokes the change.
ο Carcinoma- a malignant growth made up of epithelial
cells that are capable of infiltration and invasion.
5
6. ο Carcinogen is a cancer-causing substance or agent.
ο Co- carcinogen can be defined as a substance or factor that
will not promote cancer by itself but can potentiate cancer
when acting with carcinogenic agents.
6
7. Epidemiology and Incidence
ο Oral Carcinoma is one of the most prevalent cancers in
the world and is one of the 10 most common causes of
death.
ο According to WHO, carcinoma of oral cavity in males
in developing countries, is the sixth commonest
cancer, while in females it is the tenth commonest site
for cancer.
7
8. ο OSCC incidence accounts for up to 40 percent of all
malignancies in India and South βEast Asia.
ο OSCC has been generally associated with old age.
ο But studies by Ribeiro et al and Iamaroon et al suggest
a high increase in oral cancer incidence in young
adults. The reported incidence of oral cancer among
young adults varies between 0.4 to 5.5%.
8
9. ο Overall incidence and mortality due to oral cancer is
increasing, with current estimates of incidence and
mortality of 6.6/ 100,000 and 3.1/ 100,000 in men and
2.9/100,00 and 1.4/ 100,000 in women.
9
11. Tobacco-
ο Oral cancer has been associated with chewing of
tobacco with betel quid in India and other Asian
countries, whereas in western countries smoking and
alcohol consumption are the main causative factors.
11
12. ο Smokeless tobacco contains nitrosamines, at a
concentration 100 times the level permitted in foods as
well as hydrocarbons and polonium-210.
ο The use of smokeless tobacco and snuff is associated
with increase in cancer of the buccal mucosa. The
exposure to snuff results in hyperkeratosis, dysplasia
and squamous cell carcinoma.
12
13. ο The chewing of tobacco with betel quid increases exposure
to carcinogenic tobacco-specific nitrosoamines and to
nitrosoamines released from areca nut alkaloid.
ο Reactive oxygen species are released in the oral cavity
during chewing, which are involved in tumour initiation
process, by inducing mutation or by making the mucosa
susceptible to betel quid ingredients, leading to structural
changes in the oral mucosa.
13
14. ο Betel quid without tobacco has been classified as a
human carcinogen by the International Agency for
Research on Cancer.
ο It elevates the risk of leukoplakia, oral sub mucus
fibrosis, erythroplakia and multiple oral precancers.
ο Increasing frequency and duration of chewing betel
quid without tobacco was associated with increasing
risks of oral precancers.
14
15. There are more than 300 carcinogens identified
in tobacco smoke. The aromatic hydrocarbons
benzypyrene and tobacco- specific nitrosamines
act locally on keratinocyte cells.
Once absorbed these compounds
produce DNA adducts that cause
oncogene activation.
15
16. ο Among different smoking habits cigar or
cigarette habit increased the risk by 6 times,
hookah or pipe by 16 times and bidi smoking by
36 times.
ο Garrote et al 2001 have stated that smoking two
cigars a day is equivalent to smoking a pack of
cigarettes daily.
ο Smoking increases the risk for retromolar region,
floor of mouth, lower lip, lower alveolus, tongue
16
17. ο In some parts of the world, cigarettes or cigars are
smoked with the lighted end in the oral cavity (reverse
smoking).
ο In regions of India, reverse smoking is associated with
a high incidence of cancer of the hard palatal mucosa,
a rare site for oral cancer associated with the
traditional form of smoking.
17
18. ο Alcohol consumption is also a strong risk factor for
oral cancer and premalignant lesions. The risk
increases with increased consumption and increased
duration of use.
ο McCoy has stated alcohol may act as a solvent,
enhancing the penetration of oral epithelium by
organic carcinogens present in, tobacco smoke. It also
causes decrease in saliva production. The immediate
metabolite of ethanol is acetaldehyde which damages
the cells.
18
19. ο Alcoholic liver disease is common in heavy drinkers
and this reduces the detoxification of active
carcinogens.
ο Tobacco and alcohol consumption work together
synergistically, increasing the risk of oral cancer to
more than 30 times than that of those who do not
smoke or drink. Pooling in saliva of carcinogens from
both tobacco and alcohol gives rise to cancers in
dependant areas of the mouth.
19
20. Ultraviolet radiation
ο Outdoor workers have an increased risk for cancer of
the lower lip from exposure to ultraviolet radiation.
ο Prolonged exposure to sunlight has been shown to
cause hyperkeratosis and atrophy of fat and glandular
elements within the skin.
20
21. ο The lips are vulnerable to ultraviolet radiation because
they lack a pigmented layer for protection and are
constantly exposed to sunlight.
ο Blacks have some pigment in their lips, which may
explain the fact that cancer of the lip is a rare
occurrence in this population.
21
22. Human Viruses
ο Patients with recurrent herpes stomatitis develop
cancer of the oral cavity even in the absence of other
risk factors.
ο Herpes simplex virus has been shown to act as a
cocarcinogen with tobacco and ultraviolet radiation in
certain animal models, suggesting that prolonged HSV
exposure may sensitize the mucosa to the carcinogens
in tobacco.
22
23. ο Studies by Li and Zhang et al have suggested the role
of HPV in oral cancer.
ο Human papilloma virus (HPV) is a strong risk factor
for oral cancers, especially when the lingual and
palatine tonsils, the soft palate and the base of the
tongue are involved.
ο HPV- 16 and 18 are the most common types associated
with cancer of the oral cavity.
23
24. ο Miller et al 2001 have stated that HPV -16 is twice
likely to be present in precancerous oral mucosa and
five times more likely to be present in cancer of the
oral cavity than in normal mucosa.
24
25. Candida Albicans
ο The leukoplakias with Candida, i.e., candidal
leukoplakias, or speckled leukoplakias, a clinical type
have a relatively high rate of malignant transformation.
ο It is an intracellular parasite and may disrupt the
behavior of keratinocytes.
ο The organism is present in only the superficial
epithelial cells and not in the deeper progenitor cells
where it would have to exert its influence.
25
26. ο Substances produced by Candida may penetrate to the
deeper cells, and some biotypes of Candida are able to
produce nitrosamine at near neutral pH, which have
carcinogenic potential.
26
27. Syphilis
ο The role of syphilis was given recognition in earlier
literature on the basis of positive serological reaction
in oral cancer patients and also on the observation of
cancer development from the syphilitically altered
tongue.
ο Due to advanced treatments tertiary syphilis is
uncommon.
27
28. Dental factors
ο Poor oral and dental hygiene is often associated with
cancer of the oral cavity.
ο The enzymatic conversion of ethanol by oral
microflora can lead to an accumulation of
acetaldehyde, a known carcinogen of the oral cavity.
28
29. ο Poor oral hygiene has been correlated with higher
levels of oral microflora and a two fold increase in
salivary acetaldehyde production.
ο Oral sores from ill- fitting dentures were associated
with a twofold increase in cancer of the tongue.
29
30. Diet & Nutrition
ο Certain dietary defeciencies such as iron and Vitamins
A, C and E have been associated with oral cancer.
ο Chronic iron deficiency as seen in Plummer Vinson
syndrome is associated with dysphagia, glossitis, and
atrophy of oral and pharyngeal mucosa.
ο The high incidence of cancer of the oral cavity and
pharynx may be due to changes in the mucosa
associated with iron deficiency.
30
31. Normal cell
Acquired
factors
Chemicals
Radiation
Viruses
DNA DAMAGE
Repair
Mutations in
genome of
somatic cells
Genetic factors
Inherited mutations
Alterations of genes
regulating apoptotis
Inactivation of
cancer
suppressor genes
Activation of
growth promoting
oncogenes
Expression of altered gene
products and loss of
regulatory gene products.
MALIGNANT NEOPLASM
31
32. Clinical Presentation
ο Patients with primary malignant tumours in the oral
cavity present with a variety of symptoms according to
the location and extent of the primary tumour.
ο Superficial early stage tumours most often present as
non-healing ulcers with varying degrees of pain and
occasional episodes of bleeding from the lesion.
32
33. ο The clinical characteristics of the primary tumor
arising on the mucosal surface of the oral cavity are
variable.
ο The tumor may be ulcerative, exophytic, endophytic or
a superficial proliferative lesion.
33
34. ο Ulcerative lesions are
usually accompanied by
an irregular edge and
induration of the
underlying soft tissues.
34
35. ο Exophytic lesions may
present as either as a
cauliflower βlike
irregular growth or may
be flat, pink to pinkish-
white proliferative
lesions.
35
36. ο Endophytic lesions have a very small surface
component but have a sustancial amount of soft tissue
involvement beneath the surface.
36
37. ο An ill- fitting denture may be the presenting symptom
in some patients with cancer of the gum or palate.
ο Very advanced lesions cause local pain, referred
otalgia, and restriction in the mobility of tongue.
ο Excessive salivation with reduced mobility of tongue is
an ominous sign and suggests a far advanced
carcinoma of the tongue.
37
38. ο Advanced lesions with invasion of the mandible and
the inferior alveolar nerve may produce anesthesia of
the skin of the chin.
ο Halitosis secondary to a fungating necrotic tumor is
present in some patients with massive lesions.
38
39. ο Progressive trismus is a manifestation of local
progression of tumor in the masticator space and
pterygomaxillary region with invasion of the pterygoid
muscles.
39
40. ο Lymphatic spread of oral carcinoma usually involves
the submandibular nodes, digastrics nodes, the upper
cervical nodes and finally the remaining nodes along
the cervical chain.
ο Lymph nodes associated with cancer become enlarged
and firm to hard in texture.
40
41. ο The nodes are non tender unless associated with
secondary infection or if inflammatory response is
present following biopsy.
ο Fixation of nodes to adjacent tissue due to invasion of
cells through the capsule occurs late.
41
43. Cancer of Lip
ο Epidermoid carcinoma of the lip is a disease that
occurs chiefly in elderly men.
ο Cancer in this location is uncommon in dark or yellow-
skinned people and it is believed that melanin
pigment acts as a protective agent against sunlight.
ο It occurs in men employed in outdoor activities such as
farming and fishing and use of tobacco through pipe
smoking.
43
44. ο The lower lip is affected more than upper lip and the
lateral aspect is involved more than the middle.
ο The common initial signs are ulceration, encrustation,
soreness or a growth.
44
45. ο A small number of lip cancers may initially present as
leukoplakic patches.
ο Carcinoma of lip is slow to metastasize.
45
46. Cancer of Labial Mucosa
ο Labial mucosal involvement is frequently encountered
in population groups who habitually keep a mixture of
tobacco-lime in the labial groove.
ο The lower labial mucosa is more commonly involved
than the upper.
46
47. ο The most initial signs are swelling, soreness and
ulceration.
ο Lymph node involvement is observed in 75% of the
cases, of which 65% had unilateral and 10% had
bilateral involvement (Wahi et al).
47
48. Cancer of Buccal Mucosa
ο In South- East Asia and Central Asia where the habit
of tobacco prevails, buccal involvement has been
reported to be as high as 80% of oral cancers.
ο There is no distinction between commissural and
buccal involvement.
ο A number of buccal cancers actually originate in the
commissural areas and spread posteriorly.
48
49. ο The early lesions are
asymptomatic and may
appear as an
erythematous area or
small ulceration.
ο In many cases buccal
cancers may be
associated with or arise
from leukoplakia or oral
sub mucus fibrosis.
49
50. ο They usually originate from the site of placement of
the quid, such as lower buccal sulcus and posterior
part of the buccal mucosa.
ο The left buccal mucosa is affected more than right
side.
50
51. ο Most of these cancers tend to be ulcerative and
infiltrative and tend to metastatize.
ο The incidence of metastasis is frequently high.
51
52. Cancer of Tongue
ο This type of cancer comprises between 25 to 50 per
cent of all intra-oral cancers.
ο In some areas in India tongue cancer was second most
frequent next to that of buccal mucosa (Wahi et al
1965).
ο It affects men more often than women and almost 80%
of this cancer is located in anterior two- third of the
tongue, more commonly on lateral border and ventral
surface.
52
53. ο In India the habit of chewing tobacco appears to be
related to cancer arising over the anterior two-thirds
and smoking bidis to cancers of the posterior one-
third of tongue.
ο The most common presenting sign is a painless mass
or ulcer.
53
54. ο It begins as a superficial ulcer with raised borders and
may proceed either to produce a fungating exophytic
mass or to infiltrate the deep layers of the tongue.
54
55. ο The cancers located in the anterior two-third of the
tongue are detected in early stages as compared to
those in the posterior one- third.
ο It is believed that tumours in the posterior one- third
are more aggressive and the survival rates of patients
are less, due to the advanced clinical stage of disease at
the time of diagnosis.
55
56. Cancer of Palate
ο Epidermoid carcinoma of palate is not a common
lesion of the oral cavity.
ο The relative frequency of palatal cancer in India has
been reported to vary from 3 to 12 per cent (Wahi et al
1965).
56
57. ο In areas where reverse smoking is practised, palatal
cancer is a common intra-oral cancer comprising 38-
48% of all cancers.
ο Cancer primarily originating in the soft palate is
uncommon.
ο Soft palate cancer constitute 2% of the overall oral
cancers in a reverse smoking area but only 0.4% in a
non- reverse smoking area (Wahi et al 1965).
57
58. ο Palatal cancer usually manifests as a poorly defined,
ulcerated painful lesion on one side of the midline.
ο The tumour on the hard palate may invade into the
bone or nasal cavity while infiltrating lesions of the
soft palate may extend into nasopharynx.
58
59. ο The epidermoid cancer is almost ulcerated lesion,
whereas the tumours of accessory salivary gland origin
(even malignant types) are not ulcerated, but are
covered with an intact mucosa.
59
60. Cancer of Gingiva (upper & lower alveolar ridge)
ο Alveolar ridge squamous cell carcinoma comprises
about 9% of all patients with squamous cell carcinoma
reported by Ildstad et al.
ο About 70% of the carcinomas arise from the
mandibular gingiva and 30% from maxillary gingiva.
60
61. ο The fixed gingiva is more often involved than free
gingiva and edentulous areas more so than areas where
dentition is present.
ο The carcinomas can be insidious in onset and
progression.
61
62. ο Gingival cancers originate in the area of placement of
the tobacco quid.
ο It is initially manifested as an area of ulceration or as
exophytic, granular or verrucous type of growth.
ο Metastasis is a common sequela of gingival
carcinoma. Metastasis to either the sub-mandibular or
cervical lymph nodes occurs in 50% of cases.
62
63. Cancer of Floor of Mouth
ο This represents approximately 15% of all cases of intra-
oral cancer.
ο Floor of the mouth cancer is least common in India,
ranging between 0.2 to 0.6 %.
ο It mostly affects elderly men.
63
64. ο In early stage, it may appear as a reddish area of
thickened mucosa or as a painless nodule and
originate from leukoplakia.
ο Advanced cancers may be exophytic or infiltrative.
Patients may complain of speech limitation, excessive
salivation and referred pain in the ears.
ο Metastasis to sub mandibular lymph nodes is
common.
64
66. ο The clinical staging of oral cancer is of paramount
importance as it helps the clinician to plan treatment,
to evaluate various treatment modalities.
ο The tumor-node-metastasis (TNM) staging system
was first reported by Pierre Denoix in the 1940.
ο International Union Against Cancer (UICC) eventually
adapted the system and compiled the first edition of
the TNM staging system in 1968 for 23 body sites.
66
67. ο It is important to realize that the TNM staging system
is simply an anatomic staging system that describes
the anatomic extent of the primary tumor as well as
the involvement of regional lymph nodes and distant
metastasis.
67
68. ο Lingual carcinomas due to extensive local extension
are staged using other systems like :
ο Jakobsonβs malignancy grading system that assesses
tumour cell population and tumour host relationships.
ο Site Tumour Node Metastases Pathology system .
68
69. TNM STAGING
ο Tis Carcinoma in situ
T1 Tumor 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but not more than 4 cm in
greatest dimension
T3 Tumor more than 4 cm in greatest dimension.
T4 Tumor more than 4 cm and invades adjacent structures
(e.g., through cortical bone, into deep [extrinsic] muscle of
tongue, maxillary sinus, skin)
69
70. ο N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or
less in greatest dimension
N2 a Metastasis in a single ipsilateral lymph node, more
than 3 cm but not more than 6 cm in greatest dimension.
N2b Metastasis in multiple ipsilateral lymph nodes, more
than 6 cm in greatest dimension.
N2c Metastasis in bilateral or contralateral lymph nodes,
less than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest
dimension
70
71. ο M0 No distant metastasis
M1 Distant metastasis
71
72. ο Stage 1- The cancer is less than 2 centimeters in size
and has not spread to lymph nodes in the area .
ο Stage 2- The cancer is more than 2 centimeters in size,
but less than 4 centimeters and has not spread to
lymph nodes in the area.
ο Stage 3- The cancer is more than 4 centimeters in size.
The cancer is any size but has spread to only one
lymph node on the same side of the neck as the cancer.
The lymph node that contains cancer measures no
more than 3 centimeters.
72
73. ο Stage 4- The cancer is any size and has spread to more
than one lymph node on the same side of the neck as
the cancer, to lymph nodes on one or both sides of the
neck, or to any lymph node that measures more than 6
centimeters . The cancer has spread to other parts of
the body.
73
74. ο The contribution that site of the lesion and
histological type have on the chance of survival of the
patient is recognized by the STNMP system,
introduced by Rapidis et al (1977).
ο Four stages are recognized by this system ranging from
stage-I, which describes localized disease to stage-IV,
which carries the gravest prognosis.
Cancer 39:204-209, 1977.
74
75. ο S1 β LIP (skin)
ο S2 β LIP( mucus
membrane)
ο S3 β Tongue
ο S4- Cheek
ο S5 β Palate
ο S6 βFloor of mouth
ο S7 β Alveolar process
ο S8- Antrum
ο S9- Central CA of bone
ο T1-Tumor less than 20 mm in
diameter.
ο T2- Tumor between 20 mm
and 40 mm in diameter.
ο T3-Tumor between 40 mm
and 60 mm in diameter
and/or extending beyond the
primary region, and/or
through adjacent
periosteum.
ο T4- Any tumor greater than
60 mm in diameter and/or
extending to involve adjacent
structures.
75
76. ο NO -No palpable nodes.
ο N1- Equivocal node
elargement.
ο N2 -Clinically palpable
homolateral regional
node(s) not fixed.
ο N3 As (N2) but fixed.
ο N4 Clinically palpable
contralateral or bilateral
node not fixed.
N5 As (N4) but fixed.
ο MO- No distant
metastases.
ο M 1 Clinical evidence of
distant metastases
without definite
histological or
radiographic
confirmation.
ο M2 Proven evidence of
metastases beyond the
regional nodes.
76
78. ο The following are the arithmetic values given
to each factor:
ο TI 0 NO 0 MO- 0
ο T2 10 N1 10 M1 - 30
ο T3 20 N2 20 M2- 40
ο T4 35 N3 30
N4 40
N5 40
78
79. ο Squamous cell carcinoma primarily spreads by direct
local extension and regional extension through
lymphatics.
ο Metastasis to distant sites is uncommnon.
ο The most frequently involved sites for distant
metastasis are lung, liver and bones.
79
80. ο Regional spread in the oral mucosa occurs by direct
extension and in some cases by submucosal spread,
which may result in wide areas of involvement.
ο Bone involvement occurs when the periosteal barrier is
violated.
ο Production of type 1 collaginase, proteinases,
prostaglandin E2 and interleukin 1may affect the
extracellular matrix and motility of epithelial cells and
may allow invasion.
80
81. Diagnostic Imaging
ο The goals of imaging in head and neck cancer are to
establish tumor extent and size, to assess nodal
disease, to evaluate for perineural tumor spread, and
to distinguish recurrent tumor from post-treatment
changes.
ο Bone involvement is important in staging, selecting
treatment and determining the prognosis.
81
82. ο Imaging for bone involvement may be done by routine
radiology, CT and bone scanning.
ο Nuclear scintiscanning may provide evidence of bone
involvement by tumour and bony necrosis following
radiation therapy.
ο MRI is of little value in determining bone involvement.
82
83. ο MRI is replacing CT as the imaging technique for the
head & neck.
ο Each MRI image should include T 1 weighted images,
which show the normal anatomy with detail and soft
tissue definition and T2 weighted images demonstrate
the tumour in comparision to adjacent muscle and soft
tissues.
83
84. ο MRI will allow accurate distinctions between tumour
and benign inflammatory disease than CT.
ο CT and MRI aid in determining the status of cervical
lymph nodes.
ο Ultrasonographically guided needle biopsy technique
is useful in the assessment of lymph nodes.
84
85. ο Nuclear medicine or radionuclide imaging procedures
are noninvasive and usually painless. These imaging
scans use radioactive materials called
radiopharmaceuticals or radiotracers.
ο In some centers, nuclear medicine images can be
superimposed with computed tomography (CT) or
magnetic resonance imaging (MRI) to produce special
views, a practice known as image fusion or co-
registration.
85
86. ο The sentinel lymph node is the hypothetical first lymph
node or group of nodes reached by metastasizing cancer
cells from a tumor.
ο Filtered Sulfur Colloid, tagged with the radionuclide
Technetium-99m is injected near the tumour for the
assessment of lymph nodes.
86
87. PET and PET/CT scans are performed to:
ο detect cancer.
ο determine whether a cancer has spread in the body.
ο assess the effectiveness of a treatment plan, such as
cancer therapy.
ο determine if a cancer has recurred after treatment
87
88. ο In the assessment of metastases to lungs,
conventional radiography will detect advanced
involvement, more than 1 cm.
88
89. Histopathology
ο Microscopic examination is required for diagnosis.
ο Histologically squamous cell carcinoma are graded
into well, moderately and poorly differentiated
tumours.
ο The two main features on which grading are based are
proliferation and differentiation.
89
90. ο Rapid abnormal proliferation is characterized by
hyperchromatism, mitotic activity, cellular and nuclear
pleomorphism.
ο Differentiation of the tissue is marked by the presence
of epithelial bridges and the production of keratin.
90
91. ο Mild dysplasia involves
the lower third of
epithelium.
ο There is proliferation of
atypical or immature
basal cells.
91
92. ο Moderate dysplasia
involves the middle third
of epithelium.
ο There is basal cell
hyperplasia, nuclear
atypia, abnormal
maturation with
dyskeartosis.
92
93. ο Severe dysplasia involves
the upper third of
epithelium.
ο It is irreversible and
biologically equivalent to
carcinoma in situ.
ο Abnormal maturation,
numerous mitoses,
keratinized cells at all
levels.
93
94. ο Carcinoma in situ is a lesion in which abnormal cells
involve the entire epithelium without invasion through
the basement membrane and carcinoma is diagnosed
when there is disruption of the basement membrane
and invasion into connective tissue.
94
96. ο Precancerous lesions, conditions and early stage oral
cancers cannot be adequately identified by visual
inspection alone and may be easily overlooked.
ο Advancements in the adjunctive techniques have led to the
development of diagnostic tools at both the clinical and
molecular level for the early detection of oral mucosal lesions
in the oral cavity which remains the best way to ensure patient
survival and quality of life.
96
97. Vital tissue staining
ο§ Toluidine blue- (tolonium chloride) is an acidophilic
metachromatic dye of the thiazine group which stains
acidophilic tissue components like DNA and RNA.
ο§ It may bind preferentially to tissues undergoing rapid cell
division (such as inflammatory, regenerative and neoplastic
tissue), to sites of DNA change associated with oral
premalignant lesions or both.
ο§ The binding results in the staining of abnormal tissue in
contrast to adjacent normal mucosa.
97
98. ο TB staining may appear as a Dark Royal Blue or a Pale Royal
Blue colour.
ο This test appears to be highly sensitive (97.8β93.5%)
but less specific (92.9β73.3%), mainly because of
false positive results.
Toluidine blue uptake in potentially malignant oral lesions in vivo: Clinical
and histological assessment. Oral Oncology (2006) 42, 89β95.
98
100. ο Lugolβs Iodine- normal tissue stains brown but
proliferating epithelium is unstained or poorly stained.
ο It produces a brown- black stain by reaction of the iodine
with glycogen.
ο Glycogen content is inversely related with degree of
keratosis.
100
101. Visualization Adjuncts
ο These are intended for use as adjuncts to the standard
visual and tactile oral examination under incandescent
light.
ο They function under the assumption that mucosal tissues
undergoing abnormal metabolic or structural changes have
different absorbance and reflectance profiles when exposed
to various forms of light or energy.
JADA 2008;139 (7)
101
102. ο The term ββchemiluminescenceββ was first coined by Eilhardt
Weidemann in 1888.
ο The term βChemiluminescenceβ refers to the emission of light
from a chemical reaction.
Chemiluminescence as a diagnostic aid in the detection of oral
cancer and potentially malignant epithelial lesions
Int. J. Oral Maxillofac. Surg. 2005; 34: 521β527.
102
103. ο Vizilite is a recently introduced (commercially available)
diagnostic tool devised for the early detection of oral cancer
and is based on the principle of chemiluminescence.
ο It is an easy, safe and non-invasive technique capable of
detecting early asymptomatic precancerous and cancerous
lesions.
ο It has the advantage in that it is capable of delineating the
sharp borders between normal and abnormal oral mucosa.
103
104. ο Vizilite kit consists of a Vizilite 1% acetic acid solution, a
capsule or a lightstick.
ο Vizilite passes over oral tissue that has been treated with the
rinse solution, normal healthy tissue will absorb the light and
appear dark, abnormal tissue will appear white.
104
105. ο As a cell becomes dysplastic the nucleus becomes
larger compared to the rest of the cell.
ο The enlarged nucleus reflects light and appears white.
105
106. ο The VELscope system is a multiuse device with a
handheld scope through which the clinician can scan the
mucosa visually for changes in tissue fluorescence.
ο The proposed mechanism of tissue fluorescence is that
mucosal tissues have a reflective and absorptive pattern
based on naturally occurring fluorophores in the tissue.
106
107. ο§ These include fluorophores from tissue matrix molecules and
intracellular molecules like collagen, elastin, keratin, and
NADH.
ο§ The presence of disease changes the concentration of these
fluorophores as well as the light scattering and absorption
properties of the tissue, due to changes in a.o. blood
concentration, nuclear size distribution, epithelial thickness,
and collagen content.
Journal of Biomedical Optics 9(5), 940β950 (September/October
2004)
107
108. ο It emits a safe blue light
which excites the tissue
from the surface of the
epithelium through to the
basement membrane and
into the stroma.
ο Abnormal tissue typically
appears as an irregular, dark
area that stands out against
the otherwise normal, green
fluorescence pattern of
surrounding healthy tissue.
Normal tissue produces
fluorescence & appears
as an apple green glow
Abnormal
epithelial cells
Abnormal epithelial tissue
causes loss of fluorescence &
thus appears dark
108
110. Exfoliative cytology
ο It is the microscopic examination of shed cells from an
epithelial surface.
ο Application of exfoliative cytology as a diagnostic
technique in the management of oral malignant and
premalignant lesions has been limited due to the
occurrence of false negative results.
110
111. Indications:
ο Periodic reviews of high risk patients, oral
premalignant lesions and oral cancer patients.
ο Determination of a suitable biopsy site.
ο Unavailability of embedding and sectioning
technology.
ο Population screening for oral cancer.
111
112. ο§ Oral brush biopsy is a recent development that is been heavily
marketed to dentists and was introduced in 1999.
ο§ Oral brush cytology uses a special brush to collect the
epithelial cells.
112
113. ο This consists of a neural network based, image-
processing system, specifically designed to detect oral
epithelial precancerous and cancerous cells.
ο The brush is placed in contact with oral epithelium and
rotated with firm pressure 5 to 10 times.
113
114. Properly performed, the
brush collects cells from
all three layers of the
epithelium.
It is based on the principle
that the dysplastic cells
have few desmosomal
attachments to
neighbouring normal cells,
so they can be easily
scraped off.
114
115. The pathologists classifies the oral brush cytology
specimen into one of three categories:
ο§ Negative β no epithelial abnormality is detected.
ο§ Positive - definitive cellular evidence of epithelial
dysplasia or carcinoma is present
ο§ Atypical - abnormal epithelial changes are present.
115
116. Biopsy
ο It is a controlled and deliberate removal of tissue from
a living organism for the purpose of microscopic
examination.
ο It is considered to be confirmative for evaluating the
cancerous or precancerous nature of a lesion.
ο The techniques used to perform a biopsy are incision,
excision and punch biopsy.
116
117. Immunohistochemistry
ο The application of immunologic research methods to
histopathology has resulted in marked improvement
in the microscopic diagnosis of neoplasms.
ο Distinguishing between undifferentiated neoplasms of
different origins is achieved through the detection of
tumor antigens by using known antibodies.
117
118. ο The selection of antibodies for immunohistochemical
testing is made on the basis of their tumor specificity
and the likelihood that they will react with the tumor
under evaluation.
ο It is a very sensitive system that can detect antigens
expressed at relatively low levels, and if carefully
selected, antibody-antigen binding can be very
specific.
118
119. TUMIOUR IMMUNOSTAIN
ο Carcinomas
ο Sarcomas
ο Pankeratin, Epithelial
membrane antigen,
Carcinoembryonic
antigen, Neuron specific
enolase.
ο Vimentin, Desmin,
Muscle specific actin,
Myoglobin, Factor VIII.
119
120. ο Helps in diagnosis of tumours of uncertain origin, primary
as well as metastatic from an unknown primary tumour.
ο Helps to predict the prognosis by identification of
enzymes, oncogenes, tumour- specific antigens, tumour
suppressor genes.
120
121. ο Matrix metalloproteinases 1, 2, 3, 9, and 13 have also
been demonstrated in invasive carcinomas and are
believed to play a significant role in matrix
degradation. In particular, matrix metalloproteinases
3 and 13 are associated with advanced head and neck
carcinomas.
ο Most head and neck carcinomas have telomerase
activity through neoexpression of this enzyme, giving
the neoplastic cell extended life.
121
123. Quantification of nuclear DNA content
ο Atkin and Richards have established that the
quantitative analysis of DNA content reflects the total
chromosomal content which can be used to
distinguish between malignant and normal cells.
123
124. ο The flowcytometer is an objective measuring device of
cellular DNA content and cell cycle analysis.
ο It can detect DNA aneuploid (abnormal number of
chromosomes) populations in mild, moderate and
severe dysplasias of premalignant oral lesions.
124
126. ο Most field changes appear to be induced by smoking,
which implies carcinogen-induced field cancerization
rather than field cancerization due to migrated
transformed cells.
ο Multiple tumors seem to develop independently as a result
of the continuous carcinogenetic influence of alcohol
and/or tobacco.
Oral Field Cancerization: Carcinogen-induced Independent Events or
Micrometastatic Deposits? Cancer Epidemiology, Biomarkers &
Prevention March 1, 2000 9, 249 .
126