Epithelial Tissue Neoplasms 2011-2012

Epithelial Tissue Neoplasms
Neoplasms
Tumor:
It is simply a swelling of tissue and does not denote a neoplatic process.
Neoplasm: Neo =new plasia=growth
Is an abnormal mass of tissue the growth of which exceeds and
uncoordinated with that of normal tissues has the capability of unlimited
proliferation that does not regress after removal of the possible initiating
cause.
Hyperplasia (Reactive lesions):
Hyperplasia is an increase in the size of tissue or organ due to increase in
the number of constituent cells.
Reactive lesions Are these in which the body tissues respond to a certain
stimulus resulting in formation of mass of tissue (hyperplasia) and are
characterized by regression after the removal of the initiating stimulus
(in early lesions). Old lesions sometimes do not regress and may need
surgical treatment.
The main differences between reactive and neoplastic lesions:
Hyperplasia Neoplasia
Etiology
definite etiologic factors:: unknown or
1. Inflammation due to certain causative factors
2. Low grade irritation 1. Ionizing radiation
3. Excessive action of 2. Chemical carcinogen
normal stimulus 3. Oncogenic viruses (e.g.
EBV, HPV)
Rate of growth Related to degree of No relationship between rate
stimulus factor of growth and causative
factors
Persistence Growth persists as long as Once growth start it persists
etiologic factor persist
Progression Lesion regress after removal Progress irreversible whether
of stimulus (reversible) stimulus removed or not
1 Dr. Eman Abdel Aziz
2011-2012
Classification of Neoplasms
A. According to tissue of origin (histogenic)

1. Epithelial
2. Connective tissue
B. According to behavior regarding its biologic effect on the host

1. Benign
2. Malignant
3. Premalignant
The Main differences between benign and malignant neoplasms:
Benign Neoplasms Malignant Neoplasms
1- Clinical and gross appearance:

Growth • Grow by expansion • Grow by infiltration and
• Slow growth rate invasion.
• Lesions tend to stop after • Rapid growth rate
reaching a certain size • It continues to grow until the
patient's death.
General • Well defined masses • Ill -defined masses
clinical • Smooth pushing edges, • irregular infiltrating edges
features • Soft in consistency involving adjacent tissue,
• Not fixed to the Hard
surrounding tissues • often fixed to the underlying
and overlying tissue.
Size • Generally smaller in size • Increase rapidly in size
Ulceration • Intact surface • Frequent surface ulceration
• Ulceration is unusual
except when traumatized
Hemorrhage • Unusual except when • Frequently hemorrhagic
traumatized
Metastasis • Never metastasize • Frequently metastasize
Recurrence • do not recur when properly • Often recur
surgically excised or rare
recurrence

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II- Histologic features:

Differentiation: • well differentiated • range from well
degree of • differentiated to
resemblance of undifferentiated
neoplastic cells
both.
histologically
and
functionally.
Multinucleated • Not found • Common occurrence
giant cells
Capsule • Capsulated, • Not capsulated.
• (with few exceptions as
benign myxoma)
III- Nuclear features:
N/C ratio • Normal ratio • The ratio increases
(nuclear
cytoplasmic
ratio):
Normally =
(1/4)
Chromatin • Normal • Increases
content in the • (normochromatic nuclei), • ( hyperchromatic nuclei)
nucleus
Nuclear • No nuclear pleomorphism • Nuclear pleomorphism
pleomorphism often uniform in size, shape (dyskariosis)
and staining reaction
Mitosis • few normal mitosis • increase in both, normal and
abnormal mitosis

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Benign lesions
 Squamous cell papilloma
 Verruca vulgaris (reactive)
 Keratoacantoma
 Pigmented nevi
Premalignant lesions
 Leukoplakia
 Erythroplasia
 Oral submucous fibrosis
Malignant neoplasms
 Squamous cell carcinoma
 Verrucous carcinoma
 Basal cell carcinoma
 Melanoma

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Squamous Cell Papilloma

Definition:
Squamous papilloma is a benign proliferation of stratified

squamous epithelium, resulting in a papillary or verruciform mass arising
on skin and mucous membrane.
Etiology:
Many oral squamous papillomas have been shown to be associated with

Human papilloma virus (HPV) subtype 6, 11.
 HPV is one of oncogenic virus =tumor producing virus
Clinical Features:
Age: arise at any age.

Sex: men = women.
Site: tongue, lips (vermillion portion of the lip), hard, soft palate and
uvula but any oral surfaces may be affected.
Sign and symptoms:
 Symptom: Asymptomatic
 Shape: Exophytic mass with numerous
finger-like surface projections that give a
''cauliflower'' or wartlike appearance.
 Well circumscribed.
 Color: White, or normal in color depending on the amount of surface
kertinization.
 Consistency: Soft
 Base: Usually pedunculated
 Size: Less than 1 cm in greatest dimension
 Number: Solitary although several lesions may be noted on occasion.
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Histopathologic features:
It consists of:
 Multiple thin long finger-like projections, each made up of continuous
layer of stratified squamous
epithelium.
 The epithelium is hyperplastic
and shows acanthosis (increase in
the number of prickle cell layer)
 The epithelium may show
hyperkeratosis.
 The epithelium covers a thin
branched core of connective tissue that contains blood vessels,
lymphatics and sometimes infiltrated with chronic inflammatory cells.
 Kilocytes, virus-altered epithelial clear cells with small dark
(pyknotic) nuclei, often surrounded by an edematous or typically clear
zone are sometimes seen high in prickle cell layer.
Verruca Vulgaris (Common Wart)

Definition:
 Verruca Vulgaris is a benign, virus- induced, focal hyperplasia of
stratified squamous epithelium.
 Verruca Vulgaris is more common on the hand and fingers skin but
infrequently develops on oral mucosa and considered as analogous to
the oral papilloma.
 It is contagious and can spread to other parts of person's skin or oral
mucous membrane through “autoinoculation” by finger sucking or
fingernail biting.

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Etiology:
 Verruca vulgaris is caused by human papillomavirus (HPV) types 2, 4,
and 40.
Clinical features:
Site: The skin of the hand is usually the site of infection. When the oral
mucosa is involved, the lesions are usually found on
1. Vermillion border,
2. Labial mucosa or
3. Anterior tongue.
 Appear as painless firm, circumscribed,
multiple verrucous papules.
 Most warts regress spontaneous within 2 years.
Histopathology:
 The microscopic picture similar to that of squmnous cell papilloma
Keratoacanthoma
''Self –healing carcinoma''
Definition
 Keratoacanthoma is a self –limiting, epithelial proliferation with a
strong clinical and histopathologic similarity to well –differentiated
squamous cell carcinoma.
 It occurs chiefly on sun exposed skin and far less commonly, at the
mucocutaneous junction.
 The predominance of this lesion on skin because it originates within
the pilosebaceous apparatus (Cells of hair follicle and superficial
epithelium of sebaceous ducts)

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Etiology:
The cause of this lesion is unknown, but some factors have been
proposed.
1. Sun light.
2. Human papilloma virus (HPV), possibly subtype 26, or 37,
3. Chemical carcinogen,
Clinical Features:
Age: elderly, rarely occurs before 45 years
Sex: male > female (ratio 2:1)
Site:
95%  sun–exposed skin: face, neck, dorsum of upper extremities.
5%  lips and vermillion border of both upper and lower lips.
Sign and symptoms:
 The lesion begin as single, firm, round, papule that rapidly progress
to dome shaped (hemispheric) nodule with depressed central core
or plug of keratin surrounded by a concentric collar of raised skin
giving umblicated or ''ceratirfom'' appearance. It resembles a
volcano because of the central crater and sloping sides.
 A peripheral rim of erythema at the lesion's base.
 It is solitary, well -demarcated, 1-1.5 cm
sessile
 Often painful ---V.imp
 Sometimes, regional lymphadenopathy
may occur (reactive). ---V.imp
 Keratoacanthoma develop in 3 stages:
1. First stage rapid enlargement of the lesion to develop to full size

over 4 to 8 weeks-----V.imp
2. Followed by static period for 4 to 8 weeks
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3. Final stage of spontaneous regression for over the next 6-8 weeks.
 The overall duration of this tumor may reach 2 years and
recurrence is rare
 Spontaneous regression occurs by exfoliation of the keratin core
with resorption of the mass, leaving a saucer shaped lesion that
heals with scar formation.
Histopathology:
 The lesion consists of hyperplastic squamous epithelium (acanthosis)

growing into the underlying connective tissue.
 The surface is covered by a
thickened layer of parakeratin or
orthokeratin with a central
keratin plug or core.
 The epithelium at the lateral edge
of the tumor appears with normal
thickness, and then abrupt change to hyperplastic epithelium occurs.
 The cells appear normal, although considerable dyskeratosis
(abnormal or premature keratin production) is typically seen in the
form of deeply located individually cell keratinization and keratin
pearls similar to those found in well differentiated squamous cell
carcinoma.---V.imp
 Marked pseudoepitheliomatous hyperplasia which elicit an intense
chronic inflammatory cell infiltrate.
 Under certain conditions, hyperplastic epithelium (acanthosis)

can cause the rete pegs to assume an irregular and exaggerated
downward growth pattern that resembles squamous cell
carcinoma but cells appear normal. This type of acanthosis is
termed "pseudoepitheliomatous hyperplasia".

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Treatment:
 If no treatment is accomplished, spontaneous involution, often with

scar formation, occurs.
 Surgical excision of large lesions is indicated for optimal aesthetic
appearance because significant scarring may otherwise occur.
 No recurrence is expected
Nevi
Hamartoma is a developmental malformation present as tumor-like

condition, characterized by the presence of normal tissue in normal site,
but in an exaggerating manner.
When hamartomas occur in skin or mucous membrane they are known as

naevi.
Nevi:
They are developmental tumor like malformation of skin or
mucous membrane formed of cells native to the tissue.
Types of nevi that may occur in the oral cavity:
1. Keratotic nevi (white spongy nevus).
2. Vascular naevi:
a. Those occurring in blood vessels are known as haemangiomas.
b. Those occurring in lymphatic vessels are known as
lymphangioma.
3. Pigmented nevi or melanocytic nevi.

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Pigmented nevi or melanocytic nevi
• Pigmented Nevi are benign proliferations of nevus cells either in the

epithelium or in the subepithelial connective tissue.
Origin:
• It has neural crest origin.

• It is not yet known whether these cells represent:
1) Altered melanocyte or
2) “First cousins” of melanocyte (i.e. closely related but distinct cell
type).
Types:
1. Junctional nevus
2. Compound nevus
3. Intramucosal nevus (most common)
4. Blue nevus
Clinical features:
Age: Acquired melanocytic nevi begin to develop during childhood, and
the most are present before 35 years of age.
Sex: men = women.
Race: white>black
Size: <6mm
Number: multiple
Site: skin and oral mucosa, the palate is the most common intraoral sites.
May appear on buccal mucosa, labial mucosa, gingiva, alveolar ridge, and
vermillion border.
Most oral lesions present as small (<0.5mm) macule or elevated papules
Some of intra oral nevi (20%) lack clinical pigmentation (accentuation of
normal color).

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Junctional Nevus
 The earliest presentation, infants, children and young adults
 Sharply demarcated macule
 Brown to black
Compound Nevus
 The nevus cells proliferate over a period of years to produce
(compound nevus).
 Macule or slightly elevated soft Papule
 The degree of pigmentation becomes less; most lesions appear brown
Intradermal Nevus; Intramucosal Nevus
 During the later adulthood, the lesion matures into intramucosal nevi.
 Slightly elevated papule may become papillomatous
 Nevus gradually loses its pigmentation appear tan to pigmented
brown.
 Hair may grow from the center
Blue nevus:
 Blue nevus is an uncommon, benign proliferation of nevus cells, deep
in connective tissue.
 The “common blue” nevus is the second most frequent nevus found in
the mouth.
 Children & young adults
 Hand, back, feet and head.
 Orally, most often on the hard palate
 Blue to bluish black in color
 Elevated, smooth-surfaced papules or plaques
 Small, 1-3 cm in diameter
 Usually solitary

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Histopathology of Pigmented nevi:

The acquired nevus is characterized by a benign, un-capsulated
proliferation of “nevus cells”.
 Small
 Round, ovoid to spindle
 Discrete cells
 Uniform nuclei
 Pale esinophilic cytoplasm,
 Distinct cell boundaries.
 May contain granules of melanin pigments
 Arranged into small aggregates or nest (théques).
 Multinucleated giant cells are sometimes seen.
Junctional Nevus
 Nest of nevus cells are found only along the basal cell layer of the
epithelium, especially at the tips of the rete ridges.
 As nevus cells proliferate, groups of cells begin to “drop off” into
the underlying dermis or lamina propria “abtrofung”.
Compound Nevus
 Nevus cells found in the basal region (junctional area) and
underlying connective tissue
Intramucosal Nevus (Intradermal Nevus)

 Nests of nevus cells are found only within the underlying
connective tissue.
 Fibrous connective tissue free of nevus cells separates the nevus
cell nests from the overlying epithelium, Zone of differentiation
often are seen throughout the lesion.
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Blue nevus
Histologically two types of blue nevus are recognized:
1. Cellular blue nevus

2. Common blue nevus
1. The Cellular blue nevus large round or spindle cells with a pale
vaculated cytoplasm arranged in alveolar pattern within the dermis.
2. The Common blue nevus consists of a collection of
a. Elongated, melanocytes with long branching dendritic extension
b. Lies in bundles usually parallel to the surface epithelium.
c. These cells are located deep in middle and lower third within the
dermis
d. The melanocytes are packed with melanin granules and may
obscure the nucleus.

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Premalignant Neoplasms
Premalignant lesion:
 A clinically benign, morphologically altered tissue that has a greater
risk of malignant transformation than normal.
 A lesion that is not yet malignant.
1. A morphologically altered tissue i.e. (dysplasia)
2. Basement membrane intact
3. No invasion to underlying C.T.
4. No metastasis
Epithelial dysplasia
“Epithelial dysplasia” is abnormal and disordered formation of epithelial
tissue
Criteria of Epithelial Dysplasia
A- Cytological (tissue/ cellular) changes (evident at low–power
magnification)
1. Basal cell hyperplasia. The presence of several layers of basal
cells & appearance of crowded cells.
2. Bulbous or teardrop shaped rete ridges  the rete pegs are wide
at their deepest part than they are more superficially.
3. Loss polarity of basal cells. (Lack of progressive maturation
toward the surface).The basal cells have no definite long axis
perpendicular on the basement membrane & directed to the surface
due to loss of hemidesmosome.
4. Loss or reduction of intercellular desmosomal junction  loss

of cellular adhesion (or cohesion).
5. Irregular epithelial stratification or disturbed maturation. The

cells no longer show a proper sequence of morphological and

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maturational changes as they pass from the basal layer to the

surface.
B- Nuclear changes (evident at high–power magnification)

1. Increased and abnormal mitoses.
A. Increased mitotic activity (excessive numbers of mitoses)
B. Abnormal location within the epithelium and may appear
at all levels rather than in its usual basal location
C. Abnormal form/figure (tripolar or star shape mitoses).
2. Alteration (increase) in nuclear/cytoplasmic ratio from 1:4 to
1:1 (N=nucleus ≈ 1/6--1/4 of cell).
3. Nuclear hyperchromatism (abnormally excessively dark–
staining nuclei)
5. Prominent and enlarged nucleoli
6. Nuclear pleomorphism. Nuclei and cells are of different size
and shape.
a) Dyskaryosis: nuclear atypism including giant nuclei
b) Piokilokarynosis: division of nuclei without division of
cytoplasm multinucleated giant cell
N.B. Pleomorphism= variation in size and shape
C. Dyskeratosis/abnormal keratinization
• Premature keratinization (maturation) of epithelial cells that
occurring below the normal keratin layer or within the spinous cell
layer either:
1. Individual cell keratinization. premature keratinization of

individual cells within the spinous cell layer

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2. Keratin or epithelial pearls. Disturbed maturation of

intraepithelial group of cells. (Focal, round collections of
concentrically layer of keratinized cells).
Degree/Severity of Epithelial Dysplasia

“Severity" or intensity of dysplasia is classified microscopically
according to amount of involvement of tissue as:
 Mild epithelial dysplasia (focal atypia): alteration limited to basal
and parabasal layers.
 Moderate epithelial dysplasia: demonstrates involvement from basal
layer to mid portion of spinous layer.
 Severe epithelial dysplasia: alterations from basal layer to a level

above the midpoint of epithelium.
• When the entire thickness of epithelium is involved, the term

carcinoma in situ is used.
• Carcinoma in situ is defined as dysplastic epithelial cell that extend

from the basal layer to the surface of mucosa (“top–to–bottom”
change).

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• The important feature of carcinoma in situ is that invasion into

connective tissue has not yet occurred because the basement
membrane is intact thus metastases, cannot occur at this stage.

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Premalignant Neoplasms
1. Leukoplakia
2. Erythroplakia
Leukoplakia
Idiopathic leukoplakia
(leuko= white; plakia= patch)
“A white patch or plaque that cannot be characterized clinically or

pathologically as any other disease”
 The term is a clinical and does not imply a specific histopathologic
tissue alteration.
 Clinical diagnosis of leukoplakia depends on exclusion of other
lesions that appear as oral white plaques.
 As with most oral white lesions, the clinical color results from a
thickened surface keratin layer or a thickened prickle cell layer, this
masks the normal vascularity of the underlying connective tissue.
Etiology:
 The cause of leukoplakia remains unknown, although certain factors
may be considered:
1) Tobacco: Many cases of leukoplakia are related to the use of tobacco
in smoked or smokeless forms and may regress after discontinuation
of tobacco use.
2) Alcohol: have a strong synergistic effect with tobacco relative to oral
cancer production. Alcohol has the ability to:
1) Alcoholic cirrhosis impairs liver function  improper
metabolism of potent carcinogens of tobacco.
2) Irritate mucosa

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3) Act as a solvent for carcinogens especially those in tobacco 

increases the permeability of the oral mucosa,  potentiates the
harmful effect of tobacco on mucosal cells.
3) Ultraviolet radiation is accepted as a causative factor for leukoplakia

of the lower lip vermilion.
4) Microorganisms.
 Candidal leukoplakia /candidal hyperplasia:
 Some of dysplastic lesions disappear or become less extensive,
after antifungal therapy.
 Human papilloma virus (HPV), in particular subtypes 16 and
18, has been identified in some oral leukoplakias.
5) Trauma. Several keratotic lesions are now considered not to be
precancerous.
 Nicotine stomatitis is a generalized white palatal
hyperkeratotic response to the heat generated by tobacco
smoking rather than a response to the carcinogens within the
smoke. Has no malignant transformation potential.
 Frictional keratosis chronic mechanical irritation can produce
a white lesion with a roughened keratotic surface clinically
similar to true leukoplakia, such a lesion is a normal
hyperplastic response. These Keratoses are reversible after
elimination of the trauma. Lesions as linea Alba and cheek
biting have never been documented to have transformed into
malignancy, nor does the presence of dentures or broken and
missing teeth increase the cancer risk.
Clinical features
 Age: middle –aged and older population.

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 Sex: males> women.

 Site: the buccal mucosa, mandibular mucosa and lip vermilion,
account for almost half of the leukoplakias. Followed by The floor
of the mouth and retromolar sites lip vermillion, tongue and
gingiva.
Individual lesions may have a varied clinical appearance and tend to
change overtime:
 Mild or thin leukoplakia Early and mild lesions appear as slightly
elevated gray or grayish white plaques, which may appear somewhat
translucent, and are typically soft and flat. They usually have sharply
demarcated borders but occasionally blend into normal mucosa.
 Seldom shows dysplasia on biopsy may disappear or continue

unchanged.
 Homogeneous or thick leukoplakiafor tobacco smokers who do

not reduce their habit, lesions slowly extends laterally, become
thicker, and attains white appearance. The affected mucosa may
become leathery to palpation, and fissures may deepen and become
more numerous.
 Most thick, smooth lesions remain indefinitely at this stage. Some,

perhaps as many as one third, regress or disappear; a few become
even more severe
 Granular or nodular leukoplakia the lesions develop increased

surface irregularities. Some lesions demonstrate sharp or blunt
projections and have been called verrucous or verruciform
leukoplakia.

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 Leukoplakia may become dysplastic, even invasive, with no change

in its clinical appearance. However, some lesions eventually
demonstrate scattered patches of redness, called erythroplakia. Such
areas usually represent sites in which epithelial cells are so immature
or atropic that they can no longer produce keratin.
 This intermixed red-and white lesion, called erythroleukoplakia or
speckled leukoplakia, represents a pattern of leukoplakia that
frequently reveals advanced dysplasia upon biopsy.
Histopathology:
 Microscopically, leukoplakia is characterized by a thickened keratin

layer (hyperkeratosis), with or without thickened spinous layer
(acanthosis).
 Some leukoplakias demonstrate surface hyperkeratosis but show
atrophy or thinning of the underlying epithelium.
 The keratin layer may consist of parakeratin (hyperparakeratosis),
orthokeratin (hyperorthokeratosis), or a combination of both.
o With parakeratin, there is no granular cell layer and the
epithelial nuclei are retained in keratin layer.
o With orthokeratin, the epithelium demonstrates a granular
cell layer and nuclei are lost in keratin layer.
 Most leukoplakic lesions demonstrate no dysplasia on biopsy.
 Evidence of epithelial dysplasia is found in only 5% to 25% of cases.
 When present dysplasia range from mild, moderate to severe form.
When the entire thickness of epithelium is involved, the term
carcinoma in situ is used.
 Frequently, variable numbers of chronic inflammatory cells are noted
within the subjacent connective tissue.

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Erythroplakia
 Erythroplakia is a clinical term defined as a red patch on oral mucous

membrane that cannot be clinically or pathologically diagnosed as any
other condition.
 Erythroplakia is less commonly than its white counterpart, i.e.;
leukoplakia. But, it is a more serious because of the significantly
higher percentage of malignancies associated with it.
 It does not indicate a particular microscopic diagnosis; almost all true
erythroplakias demonstrate significant epithelial dysplasia, carcinoma
in situ, or invasive squamous cell carcinoma.
Etiology
 The causes of this lesion are believed to be similar to those

responsible for oral cancer
Clinical Features
 Age: older men (65 to 75 y).

 Site: The floor of the mouth,
tongue and the soft palate
 The altered mucosa appears as a
well- demarcated red patch with a
soft, velvety texture.
 It is usually asymptomatic
 May be associated with an adjacent area of leukoplakia
(erythroleukoplakia).

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Histopathology
 90% of erythroplakic lesions represent either severe epithelial

dysplasia, carcinoma in situ, or superficially invasive squamous cell
carcinoma
 The epithelium shows a lack of keratin production and often is
atrophic. This lack of kertinization especially when combined with
epithelial thinness and a relative increase in vascularity allows the
underlying microvasculature to show through thereby account for the
color of these lesions explaining the clinical red color
 The underlying connective tissue often demonstrates chronic
inflammation.

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Malignant Epithelial Neoplasms

1. Squamous cell carcinoma
2. Verrucous carcinoma
Squamous cell carcinoma

Definition: A malignant neoplasm of squamous epithelial origin.
Squamous cell carcinoma represents more than 90% of all head and neck
cancers.
Etiology
The cause of oral squamous cell carcinoma is multifactorial. No sing le
causative agent or factor (carcinogen)
1. Extrinsic factors carcinogen
a. Tobacco (smoked or smokeless)
b. Alcohol
c. Microorganisms
i. Candida albicans
ii. Syphilis
iii. Oncogenic viruses
1. Human Papilloma virus
2. Herpes simplex virus
3. Epstein –Barr virus
d. Ultraviolet light (for vermilion cancers only), X-irradiation
2. Intrinsic factors  co-carcinogen
a. Hereditary factor
b. Nutritional factor
1. Iron deficiency Plummer-Vinson syndrome
2. Vitamin A &B deficiency
c. Immunosnppression.
3. Pre-existing benign or pre-malignant lesions or conditions
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Clinical features
Age: older over 50 years
Sex: men >women
 Early lesions are usually asymptomatic, pain may be a prominent
complaint when deep invasion occur.
 Destruction of underlying bone, when present, may be painful or
completely painless, and it appears on radiography as "moth –eaten"
radiolucency with ill defined margins.
Site: Behavior of squamous cell cancer depends on its site of origin. Each
anatomic site has its own particular spread pattern and prognosis.
1. Carcinoma of the lip

Etiology
 Ultraviolet radiation of sun light
 Pipe smoking due to heat, trauma and combustion end products of
tobacco
Clinically
 Most of lesions are located on the lower lip on vermillion lateral to the
midline.
 The typical carcinoma appear as:
1) Slow growth rate

2) Chronic non-healing crusted, oozing, non tender indurated
ulceration, or
3) Thickened area or exophytic proliferative mass;
4) Metastasis is late usually to submental lymph node and is more
likely with large more poorly differentiated lesions.
5) Being visible, it is of recognized at a very early stage and so has
very favorable prognosis than intraoral carcinoma.

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2. Carcinoma of the tongue

 Carcinoma of the tongue account for more than 50% of all intraoral
carcinomas.
Clinically
Site: about 2/3 of lingual carcinomas are found on middle and posterior
lateral border of the tongue, some occur on anterior lateral and ventral
surface and rarely on the dorsal surface.
 Lingual carcinomas appear as indurated fixed exophytic
fungating masses or malignant ulcers (non healing, crater like
ulcer with raised, rolled everted edge indurated base and necrotic
friable easily bleeding floor).
 Advanced lesions produce extensive induration of the surrounding
tissue, often resulting in immobility, altered speech and difficulty
in swallowing (dysphagia).
 Metastasis commonly occurs early in the course of the disease and
extends to the submandibular and deep cervical lymph nodes.
 Prognosis: The common occurrence of tongue cancers occur in
posterior one third or base of the tongue are dangerous because of
their silent progression in an area that is difficult to visualized and
rich lymphatic channels in the base of the tongue. So, these
lesions are more often advanced or have metastasized regionally by
the time they are discovered, reflecting a significantly poorer
prognosis.
3. Carcinoma of the floor of the mouth

 Carcinoma of the floor of the mouth is the second most common
intraoral location of squamous cell carcinoma accounting for 35% of
all intraoral cancer.
 It is most likely to arise from preexisting leukoplakia or erythroplakia.
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Clinically:
 Site: midline near the frenum.

 It appears as non-healing, indurated ulcer or as a white or red
patch.
 In advanced cases, lesions infiltrate widely the soft tissues of the floor
of the mouth, causing fixation and decreased mobility of the tongue
and extension onto the gingiva.
 Metastasize relatively early to the submandibular and cervical
lymphnode upper jugular chain lymph nodes.
4. Carcinoma of the gingiva
Clinically
 Site: painless and most frequently arise from keratinized mucosa in a
posterior mandibular site.
 If the tumor is adjacent to a tooth, it may mimic periodontal disease or
reactive lesions such as "pyogenic granuloma" of the gingiva.
 When the cancer develops in an edentulous area, it may give rise to a
mass that "wraps around" a denture flange resembles inflammatory
fibrous hyperplasia (epulis ftssuratum) and leading to ill-fitting
denture.
 Tumors of maxillary alveolar ridge may extend onto the hard palate
and may invade the maxillary sinus
 Gingival carcinoma often destroys the underlying bone, causing tooth
mobility.
 Metastasis is usually to the submandibular and cervical lymph nodes.

2011-2012
5. Carcinoma of the palate
Clinically
 Palatal carcinomas are commonly encountered in countries such as
India, where reverse smoking is common.
 May appear as red or white plaques that may ulcerate
 Soft palate and oropharyngeal mucosa > hard palate
 In this posterior location the patient often is unaware of its presence
and the diagnosis may be delayed.
 The initial symptoms are usually pain or difficulty in swallowing
(dysphagia). The pain may be dull or sharp and frequently is referred
to the ear.
 Metastasize to the cervical and jugular lymph nodes also distant
metastasis at diagnosis is higher
6. Carcinoma of Maxillary sinus
 The cause is unknown, although squamous metaplasia of sinus

epithelium (respiratory epithelium) may be associated with chronic
sinusitis or oral antral fistulas.
Clinically
 The clinical manifestation depends on the extent of the disease to the

various walls of the antrum.
A- When the neoplasm originate in the sinus floor
1. Tooth ache neoplastic involvement of superior alveolar nerve
2. Vertical mobility of teeth (teeth undermined by neoplasm).
3. Malocclusion and displacement of teeth
4. Loosening or elongation of maxillary molars
5. Failure of a socket to heal

2011-2012
6. Intense pain or paresthesia of the mid face or maxilla  second

division of the trigeminal nerve
7. Palatal ulcer and mass or bulging of maxillary alveolar ridge and
mucobuccal fold.
8. Loosening or inability to tolerate the maxillary dentures
9. X-ray "moth eaten" destruction of lamina dura and surrounding
bone
B- When the neoplasm originate in the lateral wall of the sinus 

unilateral facial swelling and bulging of cheek
C- When the neoplasm originate in the sinus medial wall  unilateral

chronic unilateral nasal stiffness, obstruction, discharge or hemorrhage
D- When the neoplasm originate superiorly  displacement or
protrusion of eye ball.
Prognosis: Carcinoma of maxillary sinus is very dangerous, due to delay

in seeking treatment, as the tumor is asymptomatic for long periods & the
diagnosis may not be made until the lesion grows to fill the sinus and
perforated through the surrounding bone.
Death usually occurs from local destruction and inability to control
primary disease.
Metastasis of oral carcinoma
 The metastatic spread of oral squamous cell carcinoma is largely

through the lymphatics to the ipsilateral cervical lymph nodes.
Occasionally, contralateral or bilateral metastatic deposits are seen.
 Lymph node that contains a metastatic deposit of carcinoma is usually

firm to stony hard, nontender, and enlarged. If the malignant cells

2011-2012
have perforated the capsule of the node and invaded into surrounding
tissues the node will feel "fixed" or not easily movable.
 Distant metastasis (below the clavicles) may occur at diagnosis. The
most common sites are the lungs, liver, and bones, but any part of the
body may be affected.
 Clinical Staging (TNM system) of oral squamous cell

carcinoma
T - Size of primary tumor in cm

 T 1  Tumor size, 2cm or less.
 T2  2 to 4cm.
 T3  Greater than 4cm.
N- Involvement of local (Regional) lymph nodes
 N0  Absence of involved nodes.
 N1  Palpable homolateral node less than 3 cm in diameter.
 N2  Palpable single or multiple homolateral node 3 to 6 cm in
diameter
 N3  Massive homolateral node or nodes, bilateral nodes or
controlateral node or nodes or >6 and Fixed nodes.
M - Distant Metastasis
 MO  No distant metastasis.
 Ml  Presence of distant metastasis.
Scores are combined to designate the stage as follows:

 Stage 1 T1N0M0
 Stage 2 T2N0M0, or any T and N1M0
 Stage 3 T3N0M0
 Stage 4  any T4 anyN2orN3 any Ml

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Histopathologic Features of squamous cell carcinoma

 Squamous cell carcinoma arises from dysplastic surface
epithelium and is characterized histopathologically by invasive
islands and cords of malignant squamous epithelial cells.
 There is often a strong inflammatory or immune cell response to

invading epithelium, and focal areas of necrosis may be present.
 The lesional epithelium is capable of inducing the formation of

new small blood vessels (angiogensis) and, occasionally, dense
fibrosis (desmoplasia).
 Histopathologic grading (Broder’s classification)

 The grading is evaluation of the level of differentiation of the
tumor cells: Degree to which the tumor cells
a) Resemble their parent tissue (squamous epithelium).
b) Produce their normal product (keratin).
 According to percentage (%) of differentiated tumor cells
present: Lesions are graded on three-point (grades I to III) or a
four-point (grades I to IV) scale. The less differentiated tumors
receive the high numerals.
1. Grade I (Well differentiated) >75%
2. Grade II (Moderately diff.) 75%-50%
3. Grade III (Poorly diff.) 50%-25%
4. Grade IV (Undifferentiated, Anaplastic) <25%
 Most oral squamous cell carcinomas are moderately or well-
differentiated lesions
 The histopathologic grade of a tumor is related to its biologic
behavior. Neoplasms with less differentiation are more aggressive,
growing, invading, and metastasizing more quickly
2011-2012
 Considerable variation between tumors is seen relative to numbers of

mitoses, nuclear pleomorphism, and the amount of keratinization.
 Low grade, grade I, or well-differentiated squamous cell

carcinoma: a tumor that is mature enough to closely resemble its
tissue of origin produce their normal product (keratin) seems to
grow at a slower rate and to metastasize later in its course.
 High grade, grade II/IV, poorly differentiated, or anaplastic: a

tumor with much cellular and nuclear pleomorphism and with little
or no keratin production may be so immature that it becomes
difficult to identify the tissue of origin. Such a tumor often enlarges
rapidly, metastasizes early in its course.
 "Moderately differentiated" carcinoma. A tumor with a

microscopic appearance somewhere between these two extremes.
 Rarely, an oral squamous cell carcinoma appears as a proliferation

of spindle cells that may be mistaken for a sarcoma.
 This type of tumor, known as spindle cell carcinoma or sarcomatoid

carcinoma, arises from surface epithelium, usually of lips and
occasionally of the tongue. Immunohistochemical staining can be
used to identify keratin antigens in this lesion

2011-2012
Verrucous carcinoma
Snuff dipper's cancer
 It is a low grade variant of squamous cell carcinoma
 It is diffuse, verruciform, superficial spreading, non-metastasizing
form of well-differentiated squamous cell carcinoma
It differs from the usual SCC in:
 Always exophytic, verrucous, (wart like) mass.
 Caused by use of smokeless tobacco (snuff dipping).
 Superficially invasive and laterally spreading.
 Slow growing.
 Slow metastatic potential.
 Very well differentiated epithelial cells.
 Treated by simple local excision
 Very favorable prognosis.
Etiology
 Chronic use of smokeless tobacco, chewing tobacco or snuff dipping;
arise typically in the area where the tobacco is habitually placed.
Clinical features
Age: over 50 years of age.
Sex: male > female
Site: often correspond to the site of chronic tobacco placement.
 It may arise at any intra-oral site, but
most cases involve mandibular
vestibule, the buccal mucosa and
gingiva, palate and tongue may be
involved.
 Verrucous Carcinoma is usually
extensive by the time of diagnosis
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 Lesion appear as:

 Painless
 Diffuse, broad-based, exophytic, indurated lesion
 Pebbly or corrugated surface projections, or verruciform
 Whitish surface (due to extensive surface keratinizing)
 Gingival lesion  fixed to the underlying periosteum with gradual
invasion and destruction of the bone.
 Regional lymph node involvement is usually inflammatory
Histopathology
 Verrucous carcinoma has a misleadingly benign microscopic

appearance and the absence of significant cellular atypia.
 Marked epithelial proliferation (acanthosis) characterized by wide
bulbous, blunt-ended and elongated rete ridges that appear to "push"
into the underlying connective tissue rather than invading it.
 The basement membrane is well defined.
 Abundant keratin (usually parakeratin) production and a papillary or
verruciform surface.
 Parakeratin typically fills the numerous
clefts or crypts (parakeratin plugs)
between the surface projections
{hallmark}.
 The epithelial cells are well-
differentiated no significant degree of
cellular atypia.
 There is frequently an intense infiltrate of chronic inflammatory cells
in the subjacent connective tissue.

2011-2012

Epithelial Tissue Neoplasms 2011-2012

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Epithelial Tissue Neoplasms 2011-2012

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Epithelial Tissue Neoplasms

A. According to tissue of origin (histogenic)

B. According to behavior regarding its biologic effect on the host

The Main differences between benign and malignant neoplasms:

Benign Neoplasms Malignant Neoplasms

1- Clinical and gross appearance:

2 Dr. Eman Abdel Aziz

II- Histologic features:

3 Dr. Eman Abdel Aziz

Epithelial Tissue Neoplasms

 Squamous cell papilloma

 Verruca vulgaris (reactive)

 Oral submucous fibrosis

 Squamous cell carcinoma

 Basal cell carcinoma

4 Dr. Eman Abdel Aziz

Squamous Cell Papilloma

Squamous papilloma is a benign proliferation of stratified

Many oral squamous papillomas have been shown to be associated with

 HPV is one of oncogenic virus =tumor producing virus

Age: arise at any age.

Verruca Vulgaris (Common Wart)

6 Dr. Eman Abdel Aziz

 The microscopic picture similar to that of squmnous cell papilloma

7 Dr. Eman Abdel Aziz

 Keratoacanthoma develop in 3 stages:

1. First stage rapid enlargement of the lesion to develop to full size

 The lesion consists of hyperplastic squamous epithelium (acanthosis)

 Under certain conditions, hyperplastic epithelium (acanthosis)

 If no treatment is accomplished, spontaneous involution, often with

Hamartoma is a developmental malformation present as tumor-like

When hamartomas occur in skin or mucous membrane they are known as

10 Dr. Eman Abdel Aziz

Pigmented nevi or melanocytic nevi

• Pigmented Nevi are benign proliferations of nevus cells either in the

• It has neural crest origin.

11 Dr. Eman Abdel Aziz

12 Dr. Eman Abdel Aziz

Histopathology of Pigmented nevi:

Intramucosal Nevus (Intradermal Nevus)

Histologically two types of blue nevus are recognized:

1. Cellular blue nevus

14 Dr. Eman Abdel Aziz

4. Loss or reduction of intercellular desmosomal junction  loss

5. Irregular epithelial stratification or disturbed maturation. The

15 Dr. Eman Abdel Aziz

maturational changes as they pass from the basal layer to the

B- Nuclear changes (evident at high–power magnification)

1. Individual cell keratinization. premature keratinization of

16 Dr. Eman Abdel Aziz

2. Keratin or epithelial pearls. Disturbed maturation of

Degree/Severity of Epithelial Dysplasia

 Severe epithelial dysplasia: alterations from basal layer to a level

• When the entire thickness of epithelium is involved, the term

• Carcinoma in situ is defined as dysplastic epithelial cell that extend

17 Dr. Eman Abdel Aziz

• The important feature of carcinoma in situ is that invasion into

18 Dr. Eman Abdel Aziz

“A white patch or plaque that cannot be characterized clinically or

19 Dr. Eman Abdel Aziz

3) Act as a solvent for carcinogens especially those in tobacco 

3) Ultraviolet radiation is accepted as a causative factor for leukoplakia