PROLIFERATIVE AND 

NEOPLASTIC LESIONS OF THE 
ORAL CAVITY

The majority, greater than 90%, are squamous cell

carcinomas. The remainder are uncommon and comprise
minor salivary gland adenocarcinomas, malignant melanoma,
sarcomas, hematological malignancies, and metastases to the
oral cavity from cancers at other sites.
 Oral squamous cell carcinoma
 
Oral squamous cell
carcinoma is a malignant
epithelial neoplasm that
arises from the lining mucosa
of the oral cavity.
risk factors
 Tobacco
 Betel quid (paan chewing)
 Alcoholic beverage
 HPV-16

Oral cavity of a paan user. Note the

orange discoloration of the buccal
mucosa and the black staining of the
teeth.
HPV-related squamous cell carcinoma. The
malignant cells contain abnormally high levels of p16
protein, which can be detected by
immunohistochemistry (dark brown cells). There is
also evidence of high-risk HPV DNA by in situ
hybridization (blue dots).
 
Signs
 
• Non-healing ulcer (any ulcer that fails to
resolve over a period of 3 weeks)
• Non-homogeneous leukoplakia
• Erythroplakia
• Exophytic growth
• Induration
• Tooth mobility
• Non-healing socket following exodontia
• Pathological fracture
• Cervical lymphadenopathy
Clinical appearance of early stage oral squamous cell carcinomas presenting as
an ulcer (A), an ulcerated nodule (B), a white patch (C), and a red patch (D).
Clinical appearance
of late-stage oral
squamous cell
carcinoma.

An advanced lesion may

present as a broad-
based, exophytic mass
with a rough, nodular,
warty, haemorrhagic, or
necrotic surface, or as a
deeply destructive and
crater-like ulcer with
raised rolled margins
Biopsy from the edge of an oral squamous cell carcinoma.
The cytological features of squamous cell carcinoma.
Broders’ grades of differentiation.
Well-differentiated squamous cell
carcinoma with abundant keratin
formation (A).

Moderately differentiated squamous

cell carcinoma showing focal
keratinization (B).

Poorly differentiated squamous cell

carcinoma with no keratinization (C).
 Uncommon histological
variants of squamous cell
carcinoma.
A spindle-cell carcinoma composed
of sheets of malignant spindle cells
alongside islands of conventional
squamous cell carcinoma (A)

An adenosquamous carcinoma
comprising a mixture of squamous
cell carcinoma and
adenocarcinoma (B; arrow
indicates ductal differentiation).
The invasive front of a squamous cell carcinoma (A) and perineural invasion (B).
 Vascular invasion showing
carcinoma in a lymphatic channel
(A) and a blood vessel (B).

Invasion of the medullary bone

by squamous cell carcinoma.
Neck dissection showing
metastatic carcinoma (white
nodules) invading
parenchymal fat (yellow
tissue), the
sternocleidomastoid muscle
(brown tissue) and
compressing the internal
jugular vein (arrows).
Key points Pathology of oral squamous cell carcinoma
 
• Cytologically malignant squamous epithelium
• Keratinization varies with degree of differentiation
• Local invasion of adjacent tissues
• Vascular invasion
• Neural invasion
• Bone invasion
• Metastasis to cervical lymph nodes
• Extra-nodal extension
• Metastases to distant sites (lungs and bones)
• Second primary tumors
 Oral potentially malignant disorders

Genetic disorders Mucosal atrophy

 • Dyskeratosis congenita  • Oral submucous fibrosis
• Fanconi anaemia • Lichen planus
• Sideropenic dysphagia

Mucocutaneous lesions on the

lip Idiopathic
 • Actinic cheilitis (actinic • Leukoplakia
keratosis) • Erythroplakia
• Discoid lupus erythematosus
 Genetic disorders

Dyskeratosis congenita
 • Skin pigmentation
• Nail dystrophy
• Oral leukoplakia
• Increased risk of oral cancer

Fanconi anemia 
• Hematological disorders,
including bone marrow failure and
leukemia
• Oral leukoplakia
• High incidence of oral cancer
and other head and neck
cancers
• Cancer at very young age
• Surveillance for oral cancer is an
important part of multi-
disciplinary care for these patients
 Epithelial dysplasia - ‘abnormal growth’
Architectural features
• Irregular epithelial
stratification
• Loss of polarity of basal cells
• Drop-shaped rete processes
• Increased number of mitotic
figures
• Abnormally superficial
mitotic figures
• Premature keratinization in
single cells (dyskeratosis)
• Keratin pearls within rete
processes
• Loss of epithelial cell
cohesion
Cellular features
 • Abnormal variation in nuclear
size (anisonucleosis)
• Abnormal variation in nuclear
shape (nuclear pleomorphism)
• Abnormal variation in cell size
(anisocytosis)
• Abnormal variation in cell
shape (cellular pleomorphism)
Increased nuclear to cytoplasmic
ratio
• Atypical mitotic figures
• Increased number and size of
nucleoli
• Nuclear hyperchromasia
Grades of epithelial dysplasia: mild (A), moderate (B), and severe (C, D).
 Malignant melanoma

Malignant melanoma of the skin is common and mainly due to excessive UV

exposure. Oral mucosal melanoma is rare, but slightly more common in men
than women, and over 70% of cases involve the posterior maxillary alveolar
ridge and hard palate
Oral manifestations
of leukemia
• Mucosal pallor
• Oral petechiae,
ecchymosis, purpura
• Gingival bleeding
• Gingival swelling
• Loose teeth
• Oral ulceration
• Viral infection
(herpes simplex,
varicella zoster)
• Fungal infection
(candidiasis)
• Lymphadenopathy
• Parotid swelling
Fibroma (fibroepithelial polyp):

Most common
Found in 1.2% of adults and has a 66%
female predilection.
Can occur throughout the oral cavity
Most common along the " bite line."
usually solitary and seldom are larger than
1.5 cm.
Asymptomatic, sessile or pedunculated, firm mass
Microscopically: dense and minimally cellular fascicles
of collagen fibers and have a relatively avascular
appearance.
Treatment -conservative excision, recurrence unlikely,
unless the precipitating trauma is continued or
repeated.
Pyogenic granulomas
12 %
Due to acute or chronic trauma
or infection
Highly vascular lesions similar
to granulation tissue.
raised or pedunculated lesions
that remain less than 2.5 cm
in size.
Histologically , Aggregation of
multinucleated foreign body-
like giant cells separated by
fibroangiomatous stroma.
Treatment - excision and
removal of potential traumatic
or infective factors
Squamous cell papilloma

Associated with HPV-6 and HPV-11 virus

subtypes.
Single, asymptomatic, soft, pedunculated mass
with numerous finger-like projections at the
surface. Histologically, the projections have
fibrovascular cores and demonstrate a
relatively narrow base.
Treatment - surgical excision or ablation with
use of a CO2 laser.
 Granular cell
tumors
Neural in origin.
Usually diagnosed in third decade of life.
Found throughout the body, more than half of all cases
occur in the oral cavity.
Site - dorsum of the tongue , soft palate, uvula, and
labial mucosa
Typically present as firm, painless, relatively immobile,
sessile, nodular-appearing lesions less than 1.5 cm in
greatest dimension.
Histologically – large polygonal, oval, or bipolar cells with
abundant granular eosinophilic cytoplasm. Cells often
appear in a ribbon pattern and extend to the surface
epithelium and demonstrate pseudoepitheliomatous
hyperplasia.
Treatment –Surgical excision. Recurrence is less than
10%, even with a microscopically positive margin
Hemangioma
Hemangioma of the oral cavity represents 14% of all
hemangiomas. Present at birth with a rapid proliferative phase.
May be associated with a number of conditions including Sturge-
Weber- Dimitri syndrome and von Hippel-Lindau syndrome.
Lip is the most frequent site of hemangioma involving the oral cavity.
Present as a soft, painless mass that is red or blue , typically less than
2 cm in greatest dimension
Can become quite extensive to involve significant portions of the
oral cavity and oropharynx to include the tongue. Hemangiomas
tend to spontaneously regress over the years.
Those limit the form and function of the oral cavity and oropharynx
are usually treated with conservative surgical excision.
Intralesional sclerosing agents, interferons, laser treatment, local and
systemic steroids, and radiation have been reported as primary or
adjunctive treatment with varying success.
Cavernous hemangioma