Epithelial

malignancies
Squamous cell carcinoma

 In india, it is the most common cancer –

94%
 Risk of oral cancer increases with age
especially for males (3:1)
 Multi-factorial etiology
◼ Both extrinsic and intrinsic factors play a
role – Co-carcinogenesis
Etiology

 Tobacco smoke
 Smokeless tobacco
 Betel quid
 Alcohol
 Radiation
◼ Sunlight – for vermilion cancers
◼ X-radiation
Etiology

 General malnutrition
◼ Iron deficiency anemia
◼ Vitamin A deficiency
 Infections
◼ Syphilis
◼ Candidal infection
◼ Oncogenic viruses

 Immunosuppression
 Oncogenes and tumor suppressor genes
Tobacco Smoking

 2-3 times more risk in smokers than general

population
 Increased risk for second primary carcinoma in
the upper aerodigestive tract
 More in pipe and cigar smokers
 Dose dependent – increased risk with more
cigarrettes and longer duration of the habit.
 Higher risk in reverse smoking
 In non-smokers, SCC occurs in tongue/floor of
mouth, younger females and mutations in tumor
suppressor genes.
Smokeless tobacco

 Four times risk than general population

 50% of cancers occur at the site of
habitual placement
Betel quid

 Slaked lime enhances the absorption of

molecules of other products like areca
nut, betel nuts and tobacco leaf.
 8% is the risk of development
Alcohol

 Synergistic effect with tobacco

 Acts as a potentiator or promoter for
other causative factors
 Risk is dose dependent and time
dependent
 With tobacco, the risk is 15%
 Liver cirrhosis could also be seen.
 With phenols, increased risk for nasal
and nasopharyngeal cancer.
Radiation

 X-radiation during radiotherapy and UV

rays from sunlight
 Risk of development of new primary oral
malignancy
 Effect is dose dependent
 UV rays implicated for lip cancer.
Iron deficiency

 In severe chronic form called Plummer-

vinson syndrome, increased risk for SCC
in posterior mouth, oropharynx and
esophagus.
 Develops in earlier age
 Altered functioning of epithelial cells
leading to atrophy
 Presence of esophageal webs
Vit A deficiency

 Vit A leads to excessive keratinization

and has a protective role
 In deficiency, there is increased risk for
SCC
Syphilis

 Tertiary syphilis strongly associated with

development of SCC in tongue.
 4% is the risk
 This is rare today with the advent of
effective antibiotics.
Candidal infection

 Candida could be superimposed on

existing precancerous lesions
 Could produce nitrosamines that can
promote carcinogenesis.
Oncogenic viruses

 Human papilloma viruses – 16,18,31,33

 Herpes simplex viruses – Type 2
 These agents could integrate into the
host DNA and alter the regular growth
and proliferation and may immortalize
the infected cell.
Immunosuppression

 Lack of immunologic surveillance and

attack
 The malignant cells cannot be
recognized and detected at the early
stage.
 In patients with AIDS, chemotherapy for
malignancy or transplants are at
increased risk for SCC.
Oncogenes and tumor
suppressor genes
 Proto-oncogenes are present in normal
cells and they regulate cell growth
 proto-oncogenes are activated by
viruses, radiation or chemicals and form
Oncogenes which stimulate excessive
production of new genetic material
 Tumor suppressor genes regulate cell
growth and lack of these genes can lead
to malignancy.
Tumor suppressor genes

 Ras,
 myc,
 c-erbB,
 p53,
 pRb,
 E-cadherin
 Multiple mutations affecting inter-related
components leads to malignancy.
Clinical features
 Usually in older men
 Minimal pain during the early phase
 Presents as
◼ Exophytic –
 As a mass – fungating, papillary or verruciform
 Color depends on the amount of keratinization and
vascularity
◼ Endophytic – burrowing – ulcerated
 Depressed, irregular ulcer with rolled out borders
 Induration
◼ Leukoplakic – white patch
◼ Erythroplakic – red patch
◼ Erythro-leukoplakic – combined white and red areas,
Clinical features

 Can involve the

◼ Gingiva, alveolar mucosa and buccal mucosa –
associated with betel quid placement
◼ Tongue – posterior, lateral and ventral surfaces
◼ Floor of the mouth – more among females, younger
age, associated with second primary malignancy
◼ Lips – most cases have actinic cheilosis
◼ Oropharyngeal – most patients are unaware, tumor
size is greater, increased risk for metastasis
Metastasis

 The posterior or inferior location, larger

lesions – increased risk for metastasis.
 Spreads largely through lymphatics to
the ipsilateral cervical lymphnodes
 Metastatic nodes are firm to stony hard
in consistency, non-tender and enlarged,
 In advanced stages, the nodes are fixed
and multiple nodes (contralateral or
bilateral nodes) may be involved.
Metastasis

 Ca of lower lip and oral floor – submental

nodes
 Posterior portions of the mouth –
superior jugular and digastric nodes
 Oropharynx – jugulo-digastric nodes or
retropharyngeal nodes
Staging of disease

 Based on
◼ the tumor size and
◼ the extent of metastatic spread,
 Used to assess the prognosis and
clinical outcome.
 TNM staging is widely used
◼ T- Primary tumor size
◼ N – Regional lymph node involvement
◼ M – Involvement by distant metastasis
 (TNM)- Primary tumor size
Tx No available information on primary tumor

T0 No evidence of primary tumor

T1s Only carcinoma in situ at primary site
T1 Tumor is less than 2cm in greatest diameter
T2 Tumor is 2 - 4cm in greatest diameter

T3 Tumor is greater than 4cm in greatest diameter

T4 Massive tumor greater than 4cm in diameter, with

involvement of antrum, ptergygoid muscles, base of
tongue or skin.
 (TNM)- Regional LN inv
Nx Nodes could not be or were not assessed
N0 No clinically positive nodes

N1 Single, clinically positive, homolateral node, less than

3cm in diameter.
N2a Single, clinically positive, homolateral node, 3 - 6cm in
diameter.
T2b Multiple, clinically positive, homolateral nodes, none more
than 6 cm in diameter
N3a Clinically positive, homolateral node or nodes, one more
than 6 cm in diameter
N3b Bilateral, clinically positive nodes
N3c Contralateral, clinically positive node or nodes.
(TNM)- Distant metastasis

Mx Distant metastasis was not

assessed
M0 No evidence of distant
metastasis
M1 Distant metastasis is present.
 TNM clinical staging
Stage TNM classification 5 year survival
rate
Stage I T1 N0 M0 85%

Stage II T2 N0 M0 66%

Stage III T3 N0 M0 41%

T1,T2, T3 with N1 M0
Stage IV Any T4 lesion 9%
Any N2 or N3 lesion
Any M1 lesion
Histopathology

 Grading of tumors is done to assess the

degree of resemblance to parent tissue
and production of their normal product –
epithelium and keratin
 Can be grouped into
◼ Low grade / Well differentiated
◼ High grade/ Anaplastic / Poorly
differentiated
◼ Intermediate grade / Moderately
differentiated
Histopathology

 Shows dysplastic epithelium with

malignant cells in the connective tissue
stroma in the forms of sheets, islands or
cords
 Angiogenesis and inflammatory
response
 Hyperchromatic nuclei with keratin pearl
formation, individual cell keratinization,
Well differentiated Moderately differentiated

Poorly differentiated
Epithelial islands

Epithelial cords
Keratin pearls
Individual cell keratinization
Inflammatory cells
Vascularity & haemorrhage
Invasion
Treatment and prognosis

 Surgery
 Chemotherapy
 Radiation therapy
 Based on clinical staging – prognosis
assessment
Recurrences

 Improper management
 Recur at the same site
 Occur at different sites other than the
primary
 Occur at distant site
Multiple carcinomas

 Synchronous tumors – additional concurrent

tumors
 Metachronous tumors – additonal tumors at a
later time
 Involvement of esophagus, upper aerodigestive
tract, stomach, lungs and other sites
 Highest incidence in patients who continue
smoking and alcohol abuse after therapy.
Field cancerization

 Diffuse exposure to local carcinogens,

increases the malignant transformation
potential of all exposed epithelial cells
 Genetic alterations could be detected.
 Additional tumors are not clones of
original – they have not migrated from
the original tumor cells.
Variants of SCC

 Verrucous carcinoma – low grade

 Spindle cell carcinoma – high grade
 Adenosquamous carcinoma – high
grade
 Basaloid squamous cell carcinoma –
high grade
Verrucous carcinoma

 Also called snuff dippers cancer,

Ackerman’s tumor
 Low grade variant of SCC
 First reported by Ackerman in 1948 is
association with tobacco usage
 Also occurs in larynx, vagina, rectum,
breast, axilla, ear canal and soles of feet.
 HPV 16 & 18 can be seen in these
lesions.
Clinical features

 In men older than 55 yrs

 In mandibular vestibule, buccal mucosa and
hard palate
 Often corresponds to the site of chronic tobacco
placement
 Diffuse, well demarcated, painless, thick plaque
with papillary or verruciform surface projections
 Typically white
 It can develop as a component of proliferative
verrucous leukoplakia
Histopathology

 Benign microscopic appearance

 Wide, elongated rete ridges which push
into the underlying connective tissue
 Show abundant keratin production
 Parakeratin plugs – keratin filling the
numerous clefts and crypts
 Lesional cells show normal maturation
 Intense chronic inflammatory infiltrate
 SCC could be seen in association.
Treatment and prognosis

 Surgical excision without radical neck

dissection
 Metastasis is extremely rare
 Carcinoma of maxillary sinus

 Uncommon malignancy
 Weak association with tobacco use
 Strong relationship – wood & leather
dust exposure
 3% of H & N carcinomas
 Remains asymptomatic or mimic
sinusitis for long periods and fills up the
sinus
 Usually squamous cell carcinoma
 Disease of elderly person & male
predilection
 80% cases are in advanced stage (stage
3 & 4 ) at time of diagnosis.
 Nasal stiffness or an ulcer or mass of the
hard palate or alveolar bone
 Intense pain or paraesthesia mimicking
toothache
 Loose teeth
 “Moth eaten” appearance & cloudy sinus
appearance (CT & MRI)
 Cervical & submandibular lymph node
metastasis
 H / P – squamous cell carcinoma (
moderately or poorly differentiated )
 Treatment & Prognosis
◼ Radical surgery & radiotherapy
Nasopharyngeal carcinoma

 Arise from lining epithelium of lymphoid

tissue-rich nasopharynx
 Involves the lateral pharyngeal wall and
shows cervical lymph node enlargement
 Aggressive tumor with three variants,
◼ Keratinizing squamous cell carcinoma
◼ Non-keratinizing squamous cell carcinoma
◼ Undifferentiated non-keratinizing
carcinoma
Basal cell carcinoma

 Also called rodent ulcer

 Most common skin cancer
 Locally invasive, slowly spreading primary
epithelial malignancy
 Arises from basal cell layer of skin and its
appendages.
 85% in the skin of head and neck – result of
chronic exposure to UV light
 Treated by surgery
Clinical features

 In adult whites
 Five clinical forms,
◼ Nodular – nodule with central umbilication,
telangiectatic vessels on the border
◼ Pigmented – uneven melanin
◼ Sclerosing – resembles a scar
◼ Superficial – multiple lesions
◼ Association with Nevoid basal cell
carcinoma syndrome
Histopathology

 Uniform ovoid, dark staining basaloid

cells with moderate sized nuclei and little
cytoplasm
 Well demarcated islands and strands
invading into the connective tissue
 Palisading of peripheral cells surrounded
by a clear zone
 Malignant melanoma

 Melanocarcinoma
 Melanocytic origin that arises from a
◼ Benign melanocytic lesion
◼ Denovo from melanocytes of normal skin / mucosa
 Most occur on the skin, caused by UV radiation
 MORE INCEDENCE – Light comlexioned people
as they approach equator
 Acute sun exposure than chronic – greater
importance
 Oral lesions – no relation to sun exposure
 3rd most common skin cancer with high
mortality rate
 Mucosal melanomas are common in H/N
area, followed by urogenital & rectal
 Mucosal melanomas aggressive than
cutaneous
 Genetic alterations – BRAF protein kinase
Clinical features

 In white adults, 50-55 yrs

 ABCDE – clinical features
◼ A – asymmetry
◼ B – border irregularity
◼ C – color variegation (brown, black, white, red,
blue)
◼ D – diameter greater than 6mm (pencil eraser)
◼ E - evolving ( change wrt size, shape, color,
surface or symptoms over time)
Growth phases

 Radial growth phase – malignant

melanocytes spread horizontally through
the basal layer of the epithelium
 Vertical growth phase – malignant
melanocytes invading the underlying
connective tissue
Clinical features

 In white adults
 Four types
◼ Superficial spreading – interscapular area, satellite
macules or nodules of malignant cells around the
primary lesion.
◼ Nodular – in head and neck region, more
aggressive and short radial phase, deeply
pigmented lesion
◼ Lentigo maligna M – long radial phase arising from
precursor LM
◼ Acral lentiginous M – in blacks, most common oral
melanoma, in palms and soles,
Oral findings
 Often nodular
 In 6th – 7th decades, male predominance
 Hard palate and maxillary alveolus
 Brown to black macule with irregular
borders and a lobular exophytic mass
develops with the vertical growth phase
 Soft on palpation
 “Moth-eaten destruction”
Histopathology

 Atypical melanocytes at the epithelial and

connective tissue junction
 These cells are larger than normal melanocytes
with varying degrees of pleomorphism and
hyperchromatism
 Pagetoid spread is seen in superficial spreading
melanomas.
 The invasive melanoma cells appear spindle
shaped or epitheloid and arranged in cords and
sheets.
 Invasion into blood vessels and lymphatics
 Few oral melanomas – Bone & Cartilage –
misdiagnosed as Pl. Adenoma, ost.
Sarcoma & mes. Chondrosarcoma
 Some cases do not express melanin within
the melanocytes – Amelanotic melanoma
 IHC for S-100 protein, MART-1 and HMB-45
to confirm the diagnosis
 Treatment and prognosis
 Clinical staging is based on TNM
 Histopathological grading is based on two systems,
◼ Clark system - assigns a level based on the deepest
anatomic tissue invaded by the tumor cells
◼ Breslow system - measures the distance form the top of
granular cell layer to the deepest identifiable point of
tumor invasion
 Surgery with radical neck dissection
 Prognosis is extremely poor and most patients
usually die due to distant metastasis
 Treatment and prognosis
Clark’s defintion Clark’s Breslow’s depth of
classification invasion (mm)2
Cells confined to Level I N/A
epithelium
Cells penetrating Level II 0.00 to 0.75mm
papillary dermis
Cells filling papillary Level III 0.76 to 1.69mm
dermis
Cells extending into Level IV 1.70mm to 3.59mm
reticular dermis
Cells invading Level V >3.6mm
subcutaneous fat