Head and Neck Pathology

Oral Cavity
• Teeth and Supporting
Structures
 Oral Pathology
• Caries ( Tooth Decay) • Gingivitis
• Most common cause of – Dental plaque
tooth loss before age 35 – Calculus
Periodontitis
• an inflammatory process that affects the supporting structures of the teeth
(periodontal ligaments) alveolar bone, and cementum.

• Leads to serious sequelae, including complete destruction of the periodontal

ligament

• Pathogenesis: Poor oral hygiene, with resultant change in oral flora

• facultative gram positive organisms colonize healthy gingival sites

• Adult periodontitis is associated primarily with Aggregatibacter

(Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis, and
Prevotella intermedia.
Aphthous ulcers
• are common, often recurrent, exceedingly painful, superficial oral mucosal
ulcerations of unknown etiology.

• affect up to 40% of the population

• most common in the first 2 decades of life.

• associated with immunologic disorders including celiac disease, inflammatory

bowel disease, and Behçet disease.

• The lesions appear as single or multiple, shallow, hyperemic ulcerations

covered by a thin exudate and rimmed by a narrow zone of erythema

• The lesions typically resolve spontaneously in 7 to 10 days, but may sometimes

persist stubbornly for weeks, particularly in immunocompromised patients.
Aphthous ulcer.
Single ulceration with an erythematous halo surrounding a
yellowish fibrinopurulent membrane.
Hairy leukoplakia

• a distinctive oral lesion on the lateral border of the tongue that is usually seen
in immunocompromised patients and is caused by Epstein-Barr
virus (EBV).

• It can be observed in patients infected with the human immunodeficiency virus

(HIV) and may portend the development of AIDS.

• Can also be found in patients who are immunocompromised for

other reasons including cancer therapy

• Takes the form of white, confluent patches of fluffy (“hairy”), hyperkeratotic

thickenings, almost always situated on the lateral border of the tongue.
• Unlike thrush, the lesion cannot be scraped off.

• distinctive microscopic appearance consists of hyperparakeratosis and

acanthosis with “balloon cells” in the upper spinous layer.
 Precancerous and Cancerous Lesions
Leukoplakia
• defined by the WHO as “a white patch or plaque that cannot be scraped off and
cannot be characterized clinically or pathologically
as any other disease.”
• white patches caused by obvious irritation or entities such as lichen planus and
candidiasis are not considered to be leukoplakias.
• Approximately 3% of the world’s population have leukoplakic lesions;
• 5% to 25% of these lesions are premalignant
• all leukoplakias must be considered precancerous.
Leukoplakia. A, Clinical appearance of leukoplakias is highly variable. In this example, the
lesion is relatively smooth and thin with well-demarcated
borders. B, The histologic appearance of a leukoplakia showing severe dysplasia that is
characterized by nuclear and cellular pleomorphism, numerous mitotic
figures, and a loss of normal maturation.
Erythroplakia
• a red, velvety, possibly eroded area within the oral cavity that usually remains
level with or may be slightly depressed in relation to the surrounding mucosa

• The epithelium in such lesions tends to be markedly atypical

• risk of malignant transformation is much higher than is leukoplakia

Both leukoplakia and erythroplakia may be seen in adults at any age, but they are
usually found in persons aged 40 to 70, with a 2 : 1 male preponderance.

Use of tobacco (cigarettes, pipes, cigars, and certain forms of smokeless

tobacco) is a common antecedent.
 Squamous Cell Carcinoma
• It is an aggressive epithelial malignancy that is
the sixth most common neoplasm in the world
today

• Pathogenesis
– Cigarette smoking and alcohol
– Family History
– HPV
– Betel quid
Squamous Cell Carcinoma

• Approximately 95% of cancers of the head and

neck are squamous cell carcinomas (SCCs), with the
remainder largely consisting of adenocarcinomas of
salivary gland origin.

• the 6th most common neoplasm in the world.

The pathogenesis of squamous cell carcinoma is multifactorial.

• Within North America and Europe, oral cavity SCC has classically been a disease of
middle-aged individuals who have been chronic abusers of smoked tobacco and
alcohol.

• In India and Asia, the chewing of betel quid and paan is a major regional
predisposing influence.

• Actinic radiation (sunlight) and, particularly, pipe smoking are known predisposing
influences for cancer of the lower lip.
Molecular Biology of Squamous Cell Carcinoma
• the development of SCC is driven by the accumulation of mutations
and epigenetic changes that alter the expression and function of
oncogenes and tumor suppressor genes, leading to acquisition of
cancer hallmarks such as resistance to cell death, increased
proliferation, induction of angiogenesis, and the ability to invade and
metastasize.
Clinical, histologic, and molecular progression of oral cancer. A, An idealized representation of
the clinical progression of oral cancer. B, The
histologic progression of squamous epithelium from normal, to hyperkeratosis, to
mild/moderate dysplasia, to severe dysplasia, to cancer. C, The sites of the
most common genetic alterations identified as important for cancer development. CIS,
Carcinoma in situ; SCC, squamous cell carcinoma.
• Squamous cell carcinoma may arise anywhere in the head
and neck region that is lined by stratified squamous
epithelium.

• The “classic” oral cavity SCC, the favored locations are the
ventral surface of the tongue, floor of the mouth, lower lip,
soft palate, and gingiva

• As lesions enlarge, they typically create ulcerated and

protruding masses that have irregular and indurated (rolled)
borders.
On histologic examination:
• begin as dysplastic lesions, which may or may not progress to full-thickness
dysplasia (carcinoma in situ) before invading the underlying connective tissue stroma

• Squamous cell carcinomas range from well-differentiated keratinizing neoplasms

to anaplastic, sometimes sarcomatoid, tumors

•
• tend to infiltrate locally before they metastasize to other sites

• most common sites of distant metastasis are mediastinal lymph nodes, lungs, liver, and
bones.
Squamous cell carcinoma.

A, Clinical appearance demonstrating ulceration and induration of the oral mucosa.

B, Histologic appearance demonstrating numerous nests and islands of malignant keratinocytes

invading the underlying connective tissue stroma and skeletal muscle
ODONTOGENIC CYSTS AND
TUMORS
 Dentigerous Cyst
• cyst that originates
around the crown of an
unerupted tooth and is
thought to be the result
of a separation of the
dental follicle
 Radiographic
• unilocular lesions and are
most often associated with
impacted third molar
(wisdom) teeth.

Histologic
•lined by a thin layer of stratified
squamous epithelium
• Often, there is a very dense chronic
inflammatory cell infiltrate in the
connective tissue stroma
 Treatment
• Complete removal of the lesion
• incomplete excision
– may result in recurrence or,
– very rarely, neoplastic transformation
• ameloblastoma or a squamous cell carcinoma.
 Odontogenic Keratocyst (OKC)
• Potential to be
aggressive
• ages 10 to 40
• males
• posterior mandible
 Radiographic
• well-defined
unilocular or
multilocular
radiolucencies
Histologic
•the cyst lining consists of a
thin layer of parakeratinized
stratified squamous
epithelium
•with a prominent basal cell
layer and a corrugated
appearance of the epithelial
surface
 Treatment
• aggressive and complete removal of the
lesion,
– as recurrence rates for inadequately removed
lesions can reach 60%
 Odontogenic tumors
• complex group of lesions with diverse
histology and clinical behavior

• derived from odontogenic epithelium,

ectomesenchyme, or both
• The two most common and clinically
significant tumors are:
• Ameloblastoma
• Odontoma
Ameloblastoma
• arises from odontogenic epithelium and shows no ectomesenchymal
differentiation.
• It is commonly cystic, slow growing, and locally invasive but has an indolent
course in most cases.
• Treatment typically requires wide surgical resection to prevent recurrences.

Odontoma
• the most common type of odontogenic tumor, arises from epithelium but
shows extensive depositions of enamel and dentin.
• Odontomas are probably hamartomas rather than true neoplasms and are
cured by local excision.
 Ameloblastoma
• arises from odontogenic epithelium
shows no ectomesenchymal
differentiation
• commonly cystic, slow growing, and
locally invasive but has a benign
course in most cases
 Odontoma
• most common type of
odontogenic tumor
• arises from epithelium but
shows extensive depositions
of enamel and dentin
• Tx: local excision
UPPER AIRWAYS: NOSE
 Inflammation
Allergic Rhinitis
• hay fever
• initiated by sensitivity reactions to one of a
large group of allergens, most commonly
the plant pollens, fungi, animal allergens,
and dust mites
• an immunoglobulin E-mediated immune
reaction with an early- and late-phase
response
• characterized by marked mucosal edema,
redness, and mucus secretion, accompanied
by a leukocytic infiltration in which
eosinophils are prominent
Infectious Rhinitis
• "common cold"
• adenoviruses,
echoviruses, and
rhinoviruses
• initial acute stages
– the nasal mucosa is
thickened, edematous, and
red
– nasal cavities are
narrowed;
– turbinates are enlarged
 Nasal Polyps
• Recurrent attacks of
rhinitis eventually lead to
focal protrusions of the
mucosa
• 3 to 4 cm in length

On histologic examination
•consist of edematous mucosa having a loose stroma, often
harboring hyperplastic or cystic mucous glands and infiltrated
with a variety of inflammatory cells
 Pharyngitis and Tonsillitis
• are frequent concomitants of the
usual viral upper respiratory
infections
– rhinoviruses, echoviruses, and
adenoviruses, influenza virus, RSV
• there is reddening and slight edema
of the nasopharyngeal mucosa, with
reactive enlargement of the related
lymphoid structure
• Bacterial infections may be
superimposed, or may be primary
invaders
– β-hemolytic streptococci – most
common
– Staphylococcus aureus
 Nasopharyngeal Angiofibroma
• highly vascular tumor
• exclusively in adolescent males
• Benign nature
• tendency to bleed profusely
during surgery

The dense fibrous quality of the stroma and

numerous thin-walled vessels are characteristic
The cut surface shows the
characteristic spongy appearance
and well-circumscribed outline.
 Sinonasal Papillomas
• benign neoplasms arising from
the sinonasal mucosa
• composed of squamous or
columnar epithelium.
• HPV types 6 and 11
• occur in three forms:
– septal (most common),
– inverted (most important
biologically), and
– cylindrical
• Inverted papillomas

– benign but locally aggressive

– papillomatous proliferation of
squamous epithelium, instead of
producing an exophytic growth (like
the septal and cylindrical
papillomas), extends into the
mucosa, that is, is it inverted

– it has a high rate of recurrence

 Nasopharyngeal Carcinomas
• characterized by a distinctive geographic distribution, a
close anatomic relationship to lymphoid tissue, and an
association with EBV infection
• It takes one of three patterns:
(1) keratinizing squamous cell carcinomas
- least radiosensitive
(2) nonkeratinizing squamous cell carcinomas, and
(3) undifferentiated carcinomas that have an abundant
non-neoplastic, lymphocytic infiltrate
→ lymphoepithelioma
- most radiosensitive
UPPER AIRWAYS: LARYNX
 SQUAMOUS PAPILLOMA
• Benign neoplasms
usually of the true
vocal cords
• Soft, raspberry-like
excrescences rarely
more than 1cm in
diameter
SQUAMOUS PAPILLOMA

• Made up of multiple
slender, finger-like
projections supported by
central fibrovascular
cores
Carcinoma of the larynx

• typically a squamous cell carcinoma seen in male chronic smokers.

Sequence of Hyperplasia-Dysplasia-Carcinoma.

A spectrum
of epithelial alterations is seen in the larynx. They
range from hyperplasia, atypical hyperplasia, dysplasia, and
carcinoma in situ to invasive carcinoma. Grossly, the epithelial
changes vary from smooth, white or reddened focal
thickenings, sometimes roughened by keratosis, to irregular
verrucous or ulcerated white-pink lesions
 SQUAMOUS CELL CARCINOMA

• 95% of laryngeal
carcinomas are typical
squamous cell tumors
• The tumor usually develops
directly on the vocal cords
SQUAMOUS CELL CARCINOMA, WELL
DIFFERENTIATED
• The normal respiratory
tract pseudostratified
columnar epithelium has
been replaced by the
metaplastic squamous
epithelium
• Arising at the center is a
well-differentiated
squamous cell carcinoma
that infiltrates downward
into the stroma.
SQUAMOUS CELL CARCINOMA,
MODERATELY DIFFERENTIATED

• Tumor cells show

greater pleomorphism
and nuclear
hyperchromasia
SQUAMOUS CELL CARCINOMA,
POORLY DIFFRENTIATED

• Mitosis is evident
and numerous
EARS
 Epidermal inclusion cyst
• Appear as firm, round,
mobile, flesh-colored to
yellow or white
subcutaneous nodules of
variable size
• Thick cheesy material
can sometimes be
expressed, usually
through a punctum
 Epidermal inclusion cyst

Gross
• Fluctuant round to
ovoid tissue
• Cut section: cystic
structure filled with
gray, flaky material,
usually foul smelling
Microscopic
• Cystic tissue
• Lined with stratified
squamous epithelium
• Filled with keratinous
material that is often in
a laminated
arrangement
Cholesteatoma
• Lesions lined by
keratinizing squamous
epithelium (similar to
epidermal inclusion
cyst) and filled with
amorphous debris
(derived largely from
desquamated
epithelium)
PATHOLOGY OF THE NECK

DELBRYNTH P. MITCHAO
Postgraduate Intern
May 24, 2011
BRANCHIAL CYST
• Lymphoepithelial cyst
• Benign
• Usually appears on the
anterolateral aspect of
the neck
• Circumscribed, 2-5 cm
in diameter
• Enlarge slowly over time
 BRANCHIAL CYST

• Stratified squamous to
pseudostratified
columnar epithelium
• Cystic contents: watery to
mucinous or may contain
desquamated granular
cellular debris
• Often surrounded by
lymphoid tissue
At LPO
CAROTID BODY TUMOR

• Paraganglia – clusters of
neuroendocrine cells
connected with the
sympathetic or
parasympathetic nervous
system.
• Parasympathetic ganglioma
• Painless mass
• Cranial nerve palsies – vagus
and hypoglossal
CAROTID BODY TUMOR

• Rarely exceeds 6 cm
• Arises close to or envelops
the bifurcation of the
common carotid artery.
• Red-pink to brown
• Rare
• Arise in the 6th decade of life
• May recur
• Many metastasize to local
and distant sites
CAROTID BODY TUMOR

• Composed of nests
(zellballen) of polygonal
chief cells enclosed by
trabeculae of fibrous and
sustentacular elongated
cells
• Abundant, clear or
granular, eosinophilic
cytoplasm and uniform,
round to ovoid.
 TRANSITIONAL PAGE

PATHOLOGY OF
THE SALIVARY
GLANDS
 SALIVARY GLANDS

• Major
1. Parotid
2. Submandibular
3. Sublingual
• Innumerable minor salivary
glands distributed throughout
the mucosa of the oral cavity
SALIVARY GLANDS

Submandibular Gland
 MUCOCELE
• most common lesion
of the salivary glands
• most often found on
the lower lip
• Mucous retention cyst
• Most common lesion
of salivary gland
• Resulted from
blockage or rupture or
salivary gland duct
• Secondary to trauma
 MUCOCELE

• Obstruction of the duct of

the gland
• Expansion of the gland with
secretions to form the small,
smooth-surfaced mass
• Can rupture and produce a
foreign body granulomatous
response with pain and
Mucocele Involving a Minor Salivary enlargement.
Gland
MUCOCELE

• cystlike space that is

lined by inflammatory
granulation tissue
• cystic spaces are filled
with mucin as well as
inflammatory cells,
particularly
macrophage
PLEOMORPHIC ADENOMA

• Also called mixed tumors

• Most common salivary gland tumor
• Represent about 60% of tumors in the
parotid
• Less common in the submandibular
glands
• Benign
• Radiation exposure increases the risk
PLEOMORPHIC ADENOMA
• Derived from a mixture of ductal
(epithelial) and myoepithelial cells
• Show both epithelial and mesenchymal
differentiation.
• Rounded, well-demarcated masses
• Rarely exceeding 6 cm in greatest
dimension
• Encapsulated
• Painless, slow-growing, mobile, discrete
• Cut surface is gray-white
 PLEOMORPHIC
ADENOMA
• Epithelial elements
resembling ductal cells or
myoepithelial cells are
disposed in duct formations,
acini, irregular tubules,
strands, or sheets of cells.
• No epithelial dysplasia or
evident mitotic activity
At LPO
 PLEOMORPHIC
ADENOMA

At HPO. Mixed proliferation of both ductal epithelium and

a chondroid/myxomatous stroma
 WARTHIN’S TUMOR
• Second most common salivary
gland neoplasm
• Almost always in the parotid
gland (the only tumor virtually
restricted to the parotid)
• Males > females
• Fifth to seventh decades of life
• 10% are multifocal & 10%
bilateral
Parotid Gland • Smokers have eight times the
risk of nonsmokers
 WARTHIN’S TUMOR
• Round to oval
• Encapsulated masses
• 2 to 5 cm in diameter
• Arising in most cases in the
superficial parotid gland
• A pale gray surface punctuated
by narrow cystic or cleft-like
spaces filled with a mucinous or
serous secretion.
Parotid Gland
 WARTHIN’S TUMOR

At LPO. A rim of compressed normal parenchyma is seen at the left.

spaces are lined by a double layer of epithelial cells resting on a
dense lymphoid stroma sometimes bearing germinal centers.
 WARTHIN’S TUMOR
• Cystic to cleft-like spaces filled
with pale pink mucinous to
serous secretions.
• Lined by a double layer of pink
(oncocytic) cuboidal to
columnar epithelial cells over
papillary fronds.
• Fronds beneath the
epithelium are filled with
lymphocytes, sometimes with
germinal centers.
At HPO.
MUCOEPIDERMOID
CARCINOMA
• Most common form of malignant
tumor primary in the salivary
glands
• Most common radiation-induced
neoplasm
• 15% of all salivary gland tumors
• 60% to 70% in the parotids
• Accounts a large fraction of
salivary gland neoplasms in the
minor salivary glands
MUCOEPIDERMOID
CARCINOMA
• Range up to 8 cm in diameter
• Circumscribed
• Lack well-defined capsules and are
often infiltrative at the margins.
• Pale gray-white on transection
• Low-grade type:
• Relatively well-circumscribed mass
• Cystic areas containing mucinous material
• High-grade type
• More solid
• More infiltrative pattern of growth
 MUCOEPIDERMOID
CARCINOMA
• Basic histologic pattern is
that of cords, sheets, or
cystic configurations of
squamous, mucous, or
intermediate cells
• Low-grade lesions:
mucus-secreting cells,
often forming glandular
spaces.
• High-grade tumors:
Mucous, squamous, and squamous cells with only a
intermediate cells can be scattering of
seen. mucus-secreting cells.
ADENOID CYSTIC CARCINOMA
• Relatively uncommon in the
parotids
• Most common neoplasm in the
other salivary glands
• Typically cribriform pattern of
cells:
• Small having dark, compact
nuclei and scant cytoplasm
• bland appearance
• in nests and columns
LPO • arranged concentrically
around glandlike spaces
(‘pseudocysts')
 ADENOID CYSTIC CARCINOMA

At HPO. Numerous ‘cylinders’ containing a homogeneous acidophilic

material can be seen.