Early diagnosis is very important for prompt treatment and better prognosis of oral
Diagnostic aids for oral cancer:
- CT Scan
- Histopathologic Diagnosis
- Brush Biopsy
- Scalpel Biopsy
- Excisional biopsy
- Incisional biopsy
- Needle biopsy
- Exfoliative cytology
- Biomarkers/Tumor Markers
I] Imaging of the Oral Cavity
Unlike many other malignancies, oral cancer can usually be seen with the naked eye.
But as some cancers are located internally in the body, it makes their detection
difficult. Different kinds of scanning options, determining the presence of tumours
or growths detect malignancy, are necessary.
Imaging for oral cancer include:
1. Radiographs:The dentist will take X- rays of
the mouth and teeth to try and determine if anything irregular is visible on these
photos and check for symptoms. Oral cancer tumors develop fairly quickly and can
possibly grow, for example into the jaw bone. X- rays will help a doctor to find
the growth. After that the best method of oral cancer treatment can be picked.
- MRI and CT Scans
X-rays, can assist in determining the potential growth of a tumor into bone. Images
of the chest and lungs can show whether cancer has spread to these areas.
2. MRI and CT Scans: A diagnostic imaging evaluation
consisting of either computer tomography (CT) scanning or magnetic resonance imaging
(MRI) to assesses the extent of local and regional tumor spread, the depth of invasion
and the extent of lymphadenopathy. CT scan is superior in detecting early bone invasion
and lymph node metastasis. MRI assesses the extent of soft tissue involvement and
for providing a three-dimensional display of the tumor. MRI is also the preferred
technique for imaging carcinoma of the nasopharynx or lesions involving paranasal
sinuses or the skull base.
The diagnostic imaging often detects subsurface masses and intra-osseous definite
lesion. Although imaging of pathologic lesions does not produce a diagnosis, it
frequently helps to define the extent of the tumor. Both CT and MRI have its limitations
as well as advantages. This fact frequently makes them complementary rather than
competitive in studies.
3. PET [Positron Emission Tomography]: PET or
Positron Emission Tomography, lets doctors display the body's actual metabolism.
Since cells use a simple sugar- glucose, as a source of energy, PET can track down
how much glucose is being metabolized in different areas of the body. Cancer cells
divide rapidly, they break down glucose much faster than normal cells. The increased
activity will show up on a PET scan to indicate both primary and metastatic tumors.
4. Ultrasound: Ultrasound is a diagnostic technique
which uses high-frequency sound waves to create an image of the internal organs.
Although less frequently used for oral cancer detection, ultrasonography is another
way to produce pictures of an area in the body. This method involves high- frequency
sound waves (ultrasound) bouncing off organs and tissues. The pattern of echoes
produced by these waves creates a picture called a sonogram.
All cases of cancer must be diagnosed by removing a sample of tissue from the patient
and sending it to a pathologist for examination. This procedure is called a biopsy,
a Greek-derived word that may be loosely translated as "view of the living." Any
organ in the body can be biopsied using a variety of techniques. The most common
types include: (a) Excisional biopsy, where an entire lump or suspicious area is
removed; (b) Incisional biopsy, where only a sample of tissue is removed and (c)
Needle biopsy, where a sample of tissue or fluid is removed with a needle. The procedure
is called a core biopsy when a wide needle is used and when a thin needle is used,
the procedure is called a fine-needle aspiration biopsy.
Types of biopsy
a) Excisional biopsy: Here, a whole organ or a
whole lump is removed (excised). This type of biopsy is less common now, since the
development of fine needle aspiration. But, some types of tumours (such as lymphoma,
a cancer of the lymphocyte blood cells) have to be examined whole to allow an accurate
diagnosis. So, enlarged lymph nodes are good candidates for excisional biopsies.
Some surgeons prefer excisional biopsies of most breast lumps to ensure diagnostic
accuracy. Some organs, such as the spleen, are dangerous to cut into without removing
the whole organ, so excisional biopsies are preferred for these.
b) Incisional biopsy: Only a portion of the lump
is removed surgically in this case. This type of biopsy is most commonly used for
tumours of the soft tissues (muscle, fat, connective tissue) to distinguish benign
conditions from malignant soft tissue tumours, called sarcomas.
c) Needle biopsy: Fine Needle Aspiration Biopsy
(FNA biopsy) is an extremely simple technique. A needle no wider than that typically
used to give routine injections (about 22-gauge) is inserted into a lump (tumours)
and a few tens to thousands of cells are drawn up (aspirated) into a syringe. These
are smeared on a slide, stained and examined under a microscope by the pathologist,
who can render a diagnosis in a few minutes. The procedure is called core biopsy
when a wide needle is used.Tumours of deep, hard-to-get-to structures (pancreas,
lung and liver) are especially good candidates for FNA. Otherwise, the only other
way to sample them is with major surgery. Such FNA procedures are typically done
by a radiologist under guidance by ultrasound or computed tomography (CT scan) and
require not even local anasthesia. Thyroid lumps for one, are also excellent candidates
d) Punch biopsy: The punch biopsy technique is
typically used to sample skin tissues and small masses. After a local anesthetic
is injected, a biopsy punch, which is basically a small (3 or 4 mm in diameter)
version of a cookie cutter, is used to carve out a cylindrical piece of skin. The
portion is typically closed with a suture and heals with minimal scarring.
e) Brush biopsy: Please refer "screening" for
Under certain conditions, exfoliative cytology (cell scrapings) serves as an adjunct
to clinical diagnosis, as it enables more extensive screening and provides microscopic
material if there is a delay in or contraindication to biopsy. However, cytologic
smears are used infrequently and patients are not treated on the basis of cytologic
findings alone. Smears are most helpful in differentiating inflammatory conditions,
especially candidiasis, from dysplastic or neoplastic surface lesions. In addition,
cytology may be helpful in detecting field change in oral cancer, especially if
this method is used in conjunction with vital staining. Cytology may also be helpful
when ulcerations following radiation are suspicious and biopsy is delayed.
This remains the most acceptable method for the definitive diagnosis. But it is
invasive and cannot be used in high risk surgical patients. Studies have proved
that any surgical invasiveness for oral cancer, including incisional biopsy, causes
dissemination of cancer cells into circulation, resulting in increase risk of metastasis.
There in lies the importance of tumor markers in the early detection of cancer since
biochemical studies of serum is a non- invasive procedure, rapid and easy to perform.
Tumour markers are biological products synthesized or released by cancer cells or
produced by host cells under the influence of tumour cells. An ideal tumour marker
should differentiate cancer not only from healthy state (control) but also from
benign/non-malignant and precancerous lesions and conditions.
A major goal in oral pathology has been the search for such markers of potential
malignancy. There is a need to identify those potentially malignant lesions that
will truly progress to malignancy from the majority that will not.
a) Carbohydrates: Cell surface carbohydrates,
recently, have attracted much interest because essentially all human cancer show
changes in the synthesis of many of these structures. In a recent study of the occurrence
of a carbohydrate, blood group antigen H, there was a loss of expression of H antigen
on cells at both invasive margins of the tumors with the presence of metastasis
and with poor prognosis.
b) Histocompatibility antigens: A small molecular
protein, beta 2 microglobulin which is a component of histocompatibility antigens
has been seen to be elevated in patients with oral squamous cell carcinoma, oral
keratosis and dysplasia.
c) Other squamous cell antigen: The detection
of Ca-1-antibody and Ca antigen, a glycoprotein with high carbohydrate content on
cell membranes of a variety of malignant cells, seemed to be a breakthrough for
the immunohistochemical detection of cancer.
d) Growth factors and receptors: Epidermal growth
factors (EGF), a polypeptide is found in small amount in oral mucosa, mainly in
the lamina propria close to the epithelium. Increased amounts of EGF at this site
are seen in dysplastic and malignant oral epithelial lesions. Two forms of transforming
growth factors (TGF) are not expressed in normal epithelium but are expressed in
oral squamous cell carcinoma.
e) Intracellular markers: Cytokeratins can be
used as epithelial differentiation markers in oral malignant lesions and epithelial
tumours has rapidly become a diagnostic routine method. Involucrin a precursor of
the envelop protein present in the stratum corneum is useful as a specific marker
for squamous differentiation e.g. in spindle cell carcinoma. The increased concentration
of microfilament action in cells during locomotion and in invasive malignant cells
has been known for sometime and could be demonstrated by immunohistochemistry and
by electron microscopy. Using commercial antibodies, the occurrence of carcinoembryonic
antigen (CEA) has been demonstrated. e.g. tumors of the salivary glands and the
f) Nuclear analysis: The number of mitotic figures
as well as the expression of proliferation- associated antigens like the Ki-67 antigen
or the S- phase correlated antigen proliferating cell nuclear antigen (PCNA) are
increased indicating of high cell turnover in oral dysplasia.
g) Silver binding nuclear organizer regions: Silver
binding nuclear organizer regions (AgNORs) are loops of ribosomal DNA that can transcribe
for ribosomal RNA. In a cancer cell chromosome disarray with multiple nucleoli appears
to result in an increase in AgNORs and higher AgNORs count indicates poor prognosis
for oral cancer.
h) Oncogenes: In the deregulation and differentiation
of cell growth that can lead to cancer, genetic disorders are observed. Oncogenes
may well play a role in carcinogenesis and there have now been several studies of
them in oral cancers.
i) Tumour suppressor genes: Oncosuppressor gene
p53 appear to be one of the commonest genetic changes in human cancer. Mutations
can result in increased expression of p53 and this now has been demonstrated in
head, neck and oral carcinomas as well as in premalignant lesions. There is also
a clear correlation reported between p53 expression and heavy smoking and alcohol
j) Arachidonic acid products: Lipoxygenase metabolites
including prostaglandin E2, 5, 12 and 15 hydroxyeicosatetraenoic acids and leukotriene
B4 are increased in oral squamous cell carcinoma.
k) Enzymes: Gamma glutamyl transpeptidase (GGT)
is a membrane associated enzyme involved in transport of aminoacids. GGT is expressed
in dysplasias and carcinomas of the oral, pharyngeal and laryngeal mucosa. High
activity of lactate dehydrogenase and changes in isoenzyme pattern have been demonstrated
in oral carcinoma cells but not in adjacent normal oral epithelium. In oral squamous
cell carcinoma, guanidinobenzoatase can be demonstrated in area of invasion and
it has therefore been advocated as a marker of tumor cells.
Most of these cell products are glycoprotein in nature. The cell surface membrane
is chiefly composed of glycoproteins and lipids. Any intracellular change may lead
to alteration in the surface membranes constituents, releasing certain molecules
in the blood of such patients.