Oral Epithelial Tumors, Melanocytic Nevi, and

Melanoma

LAB 3

Dr. Tahani Abualteen

•Oral Epithelial Tumors may be: Benign tumors Sequamous cell Papilloma Malignant tumors Sequamous cell carcinoma, Basal cell carcinoma & melanoma

•The main tumors derived from oral epithelium are the Sequamous cell Papilloma (benign neoplasm) and Sequamous cell carcinoma (malignant neoplasm)

•Basal cell carcinoma doesn't occur in the oral cavity but may present on the lip and involve the vermilion border

•Melanocytic nevi (hamartoma) and melanoma (malignant neoplasm) are derived from Melanocytes

Human Papilloma Virus (HPV)-DNA virus-More than 75 types-16 types are only isolated from oral lesions-Present in clinically healthy and abnormal epithelia and so its identification doesn’t always mean a causal relationship-Infects keratinocytes resulting in koilocytes

-HPV-associated lesions:Sequamous cell Papilloma neoplasmVerruca vulgaris (common wart) viral infectionCondyloma accuminatum (venereal wart) viral infectionFocal epithelial hyperplasia (heck’s disease) viral infection ** All of these lesions appear clinically as elevated lesions

•40 years old male attended the dental clinic complaining from a warty swelling arising from the vermilion border of the lower lipUpon examination we found the lesion to be solitary and PedunculatedThe histopathological examination is shown below

1- What’s the most likely diagnosis?!

2- Is it considered a tumor or an infection?!

3- What’s the etiology behind this lesion?!

4- What are the usual clinical features?!

5- What determines wither the lesion is pink or white in color?!

6- Describe the histopathological features?!

7- Is it premalignant?!

8- What’s the usual treatment?!

Sequamous cell Papilloma

Characteristic cauliflower appearance

Finger-like epithelial proliferation

Thin fibrovascular cores

Sequamous cell Papilloma

Sequamous cell Papilloma

Management = Excisional biopsy

•12 years old child attended the dental clinic complaining from warty swellings arising from the buccal mucosa anteriorlyUpon examination we found the lesion to be multiple and PedunculatedThe patient stated that similar lesions appeared previously on his fingers which he used to biteThe histopathological examination is shown below

1- What’s the most likely diagnosis?!

2- Is it considered a tumor or an infection?!

3- What’s the etiology behind this lesion?!

4- What are the usual clinical features?!

5- What’s the clinical differential diagnosis for this lesion?!

6- Describe the histopathological features?!

7- Where do lesions start and how they get into the oral cavity?!

8- What’s the usual treatment?!

Verruca vulgaris

Finger-like epithelial proliferation

Thin fibrovascular cores

Verruca vulgaris

Hyperplastic rete ridges around Hyperplastic rete ridges around margins slope inwards towards centermargins slope inwards towards center

Verruca vulgaris

Hyperkeratosis

Verruca vulgaris

Large vacuolated cells (koilocytes) with Large vacuolated cells (koilocytes) with prominent Keratohyaline granulesprominent Keratohyaline granules

•25 years old male attended the dental clinic complaining from flat-toped nodules arising from the ventral tongueUpon examination we found the lesion to be multiple and sessileThe histopathological examination is shown below

1- What’s the most likely diagnosis?!

2- Is it considered a tumor or an infection?!

3- What’s the etiology behind this lesion?!

4- What are the usual clinical features?!

5- Where do these lesions usually occur?!

6- Describe the histopathological features?!

7- It is an oral manifestation of what?!

Keratinization is not a prominent feature

Prominent acanthosis with marked broadening and elongation of rete ridges

Blunted surface projections

Condyloma accuminatum

•33 years old male attended the dental clinic complaining from small elevated lesions arising from the buccal mucosaUpon examination we found the lesion to be multiple and sessileThe histopathological examination is shown below

1- What’s the most likely diagnosis?!

2- Is it considered a tumor or an infection?!

3- What’s the etiology behind this lesion?!

4- What are the usual clinical features?!

5- Where do these lesions usually occur?!

6- Describe the histopathological features?!

Focal epithelial hyperplasia

• Little hyperkeratosis

• Rete ridges tend to fuse with each other as we go deeper

• Little papillary surface projections

Focal epithelial hyperplasia

•Clinical presentation of oral Sequamous cell carcinoma can take many forms

•Early diagnosis is the most important factor influencing prognosis

•Clinicians must be suspicious of any lesion for which no cause can be found or which does not respond as expected when possible causes are eliminated

Sequamous cell carcinoma

Sequamous cell carcinomaEarly lesions asymptomatic

Leukoplakia “white patch” Small exophytic mass Small exophytic mass which shows no ulceration or which shows no ulceration or ErythemaErythema

Small indolent ulcer Erythroplakia “Red patch”Erythroplakia “Red patch”

Sequamous cell carcinomaEarly lesions asymptomatic

Carcinoma of vermilion border of lip is clearly visible and may be noticed at an early stage as a slightly raised swelling, or crusty lesion resembling delayed healing of herpes labialis

May be preceded by solar keratosis (actinic cheilitis)

Sequamous cell carcinomaEarly lesions asymptomatic

Sequamous cell carcinoma•Suspicious clinical features for early carcinoma:Persistent ulcerationIndurationFixation to underlying structuresDestruction of underlying bone in alveolar mucosa lesionsEnlarges reactive regional lymph nodes

Sequamous cell carcinomaAdvanced/late lesions asymptomatic

Broad-based exophytic Broad-based exophytic massmass with rough, nodular, with rough, nodular, warty, hemorrhagic, or warty, hemorrhagic, or necrotic surfacenecrotic surface

Sequamous cell carcinomaAdvanced/late lesions asymptomatic

Deeply Deeply destructive, destructive, crater-like ulcercrater-like ulcer with raised, rolled with raised, rolled everted edgeseverted edges

Sequamous cell carcinomaAdvanced/late lesions asymptomatic

Infiltration of musculature

Pain may be a feature

Radiographic evidence of bone destruction

Mobility of teeth

Altered sensation over distribution of mental nerve

Pathologic fracture of mandible

Metastatic spread to regional lymph nodes

Sequamous cell carcinomaAdvanced/late lesions asymptomatic

Size of surface lesion does not indicate extent of underlying invasion

Sequamous cell carcinoma•Considerable variation in the histological appearance of oral Sequamous cell carcinoma

•Cytologically, malignant Sequamous epithelium shows variable degrees of differentiation (e.g. well differentiated, moderately differentiated, and poorly differentiated) and keratinization varies with degree of differentiation

•Invasion and destruction of local tissues accounts for Induration and fixation detected clinically

Well-differentiated tumors:- Obvious Sequamous

differentiation- Masses of prickle cells with

limiting layer of basal cells around them

- Recognizable intercellular bridges

- Central keratin pearl formation

- Nuclear and cellular pleomorphism is not prominent

- Relatively few mitotic figures Keratin pearl

Sequamous cell carcinoma

Well-differentiated OSCCWell-differentiated OSCC

Keratin pearls (arrows)

Moderately differentiated Moderately differentiated tumors:tumors:

- Still readily identified as - Still readily identified as Sequamous typeSequamous type

- Less keratinization- Less keratinization- More pleomorphism of cells - More pleomorphism of cells

and nuclei.and nuclei.- Abundant and atypical - Abundant and atypical

mitotic figuresmitotic figures

Sequamous cell carcinoma

Poorly differentiated tumors:- Cells may be hardly

recognizable as epithelial- Keratinization usually absent- Marked atypical features

Sequamous cell carcinoma

Poorly differentiated OSCC

-We might need immunohistochemistry to identify the type of cells.

- Poorly differentiated SCC may be stained for cytokeratin to identify them, cells stained brown contain cytokeratin

Sequamous cell carcinoma

There's variable lymphocytic and plasma cell infiltration in the stroma supporting a malignant epithelium, this probably represents an immune reaction by host's immune system to tumor antigens as well as a response to tumor necrosis and ulceration

Cohesive invasive front Non-cohesive invasive front

Sequamous cell carcinoma•Pattern of infiltration (invasion) affects prognosis:Cohesive invasive fronts (consists of broad groups or sheets of malignant cells) Better prognosisNon- Cohesive invasive front (consists of separate islands of carcinoma or even individual malignant cells) poorer prognosis

•50 years old male attended the dental clinic concerned about a warty white lesion arising from the lower buccal sulcus and adjacent buccal mucosaPatient stated it is slowly growingPatient admitted snuff dipping habit The histopathological examination is shown below

1- What are the possible differential diagnoses?!

2- What’s the most likely diagnosis?!

3- Is it a clinical or a pathological variety?!

4- What are the usual clinical features?!

5- Does this lesion metastasize to regional lymph nodes or distant sites?!

6- Does this lesion invade local structures?! What pattern of invasion does it have?!

7- When will this lesion be able to metastasize?!

8- Describe the histopathological features?!

9- Is it a premalignant lesion?!

Sequamous Cell Carcinoma:Verrucous Carcinoma

Sequamous Cell Carcinoma Vs.

Verrucous Carcinoma

Both of Verrucous carcinoma and SCC arise from Verrucous leukoplakia (Verrucous hyperplasia)

• Heavily keratinized SCC • Very well differentiated,

with little or no cytological atypia

• Mitoses are rare

• Although it is an exophytic tumor, it also has a slowly advancing, pushing, cohesive invasive front causing local destruction

Sequamous Cell Carcinoma:Verrucous Carcinoma

Sequamous Cell Carcinoma:Verrucous Carcinoma

Verrucous carcinoma developed from persistent proliferative Verrucous leukoplakia

Progression of dysplasia

Sequamous Cell Carcinoma:Carcinoma-In-Situ

• A term used to describe severe epithelial dysplasia in which almost the whole thickness of epithelium is involved, but there is no invasion of lamina propria

• In some patients it may progress to invasive carcinoma, but in others it may remain static or even regress

• Usually presents clinically as leukoplakia or Erythroplakia

Sequamous Cell Carcinoma:Carcinoma-In-Situ

Sequamous Cell Carcinoma:Carcinoma-In-Situ

Model for genetic progression based on loss of genetic material from specific locations on chromosomes

{called loss of heterozygosity (LOH)}

Oral Premalignant LesionsOral Premalignant Lesionsa) Leukoplakia

(homogeneous, non-homogeneous, proliferative Verrucous leukoplakia)

b) Erythroplakia

c) Carcinoma in situ

d) Chronic hyperplastic candidosis

Oral Premalignant Conditionsa)a) Oral Submucous fibrosisOral Submucous fibrosisb)b) Lichen planus (atrophic/erosive)Lichen planus (atrophic/erosive)c)c) Actinic Actinic keratosis or cheilitis or cheilitisd)d) Other conditions associated with Other conditions associated with

oral epithelial atrophy, e.g. oral epithelial atrophy, e.g. Sideropenic dysphagiaSideropenic dysphagia

•60 years old male attended the dental clinic concerned about a nodule arising on the skin of facePatient stated it is slowly growingPatient works as a farmer The histopathological examination is shown below

1- What’s the most likely diagnosis?!

2- What areas this condition commonly involve?!

3- What is the etiology behind this condition?!

4- How does this condition clinically present?!

5- If there are multiple lesions of this condition, then what is the most likely diagnosis and what are its features?!

6- Describe the histopathological features?!

Basal Cell Carcinoma (Rodent Ulcer)

-Sun-related skin tumor

- Affects old people

-Typically presents as a slow growing nodule that eventually ulcerates centrally, and may cause extensive damage if not treated

• Malignant basaloid cells Malignant basaloid cells arranged in various arranged in various patterns, invading patterns, invading adjacent tissuesadjacent tissues

Basal Cell Carcinoma (Rodent Ulcer)

Basal Cell Carcinoma (Rodent Ulcer)

• Multiple basal cell Multiple basal cell carcinomas of the skincarcinomas of the skin

• Skeletal abnormalitiesSkeletal abnormalities• Intracranial calcificationsIntracranial calcifications

• Multiple Multiple Odontogenic keratocystOdontogenic keratocyst

Basal cell nevus syndromeBasal cell nevus syndrome( Gorlin-Goltz syndrome)( Gorlin-Goltz syndrome)

Melanocytes-Melanocytes are present in the basal layer

-Produce melanin

-They are widely distributed and present in large numbers in oral mucosa of clinically pigmented and non-pigmented races, the difference being of activity and not number

1) Melanotic macule → Overproduction of melanin

2) Melanotic nevi → Hamartoma or benign proliferation of Melanocytes with variable melanin pigment production

• May be junctional, compound or intra-dermal (intra-mucosal)

• Commonly form during early childhood • Commonly found in the head and neck area• Genetic and environmental (e.g. sun exposure) factors• Malignant change can rarely occur in nevi

2) Melanoma→ Malignant proliferations of Melanocytes

Acquired Melanocytic NeviAcquired Melanocytic Nevi

Rarely, present intraorally (palate & buccal mucosa)

Common on skin (face)

Natural history of nevi

Nevus cells = mature Melanocytes

Acquired Melanocytic Nevi:Acquired Melanocytic Nevi:Junctional nevusJunctional nevus

Acquired Melanocytic Nevi:Acquired Melanocytic Nevi:Compound nevusCompound nevus

Acquired Melanocytic Nevi:Acquired Melanocytic Nevi:Intra-mucosal nevusIntra-mucosal nevus

The most common intra-orally

Malignant Melanoma• ABCD Clinical Features:ABCD Clinical Features:1.1. AAsymmetry (uncontrolled symmetry (uncontrolled

growth pattern)        growth pattern)        2.2. BBorder irregularity order irregularity (uneven

edges)                      3.3. ColourColour variation variation (2 or more

shades)                     4.4. DDiameter greater than 6 mm iameter greater than 6 mm

(greater than 1/4 inch)

•Excessive exposure to UV light is the most important predisposing factor for malignant melanoma of the skin

•Many melanomas arise in head and neck area

•Skin lesions may present as pigmented plaques or nodular lesions and may be preceded by melanoma in situ characterized by horizontal spread within epithelium

•Vertical spread into dermis characterizes invasive melanoma

Malignant Melanoma

Malignant Melanoma

• Highly Pleomorphic neoplasmsHighly Pleomorphic neoplasms

• Variable melanin production Variable melanin production

• Melanin may be absent Melanin may be absent (amelanotic melanoma)(amelanotic melanoma)

• Immunohistochemical Immunohistochemical studies studies using specific markers using specific markers for malignant Melanocytes for malignant Melanocytes ((S-100S-100 and HMB-45) are and HMB-45) are usefuluseful

• Ultra-structural examination Ultra-structural examination to identify immature to identify immature melanosomes can be usedmelanosomes can be used

Malignant Melanoma

Amelanotic melanoma

Oral Malignant Melanoma

Oral Malignant Melanoma

•Rare

•Slightly more common in males than females

•> 70% involve posterior maxillary alveolar ridge and hard palate

•Oral melanomas present as dark brown or bluish black slightly raised lesions with an uneven nodular or papillary surface

•Some lesions don’t produce melanin “a-melanotic lesions” and these tend to appear reddish

•Growth may be rapid with extensive destruction of bone and loosening of teeth

•Most are advanced & extensively invasive at presentation, with both regional lymph node and blood-borne metastases common

•Prognosis is very poor in most of the cases

Oral Malignant Melanoma

Case report • A 46-year-old man • Chief complaint : pigmented lesions of the

internal face of the lower lip and the cheek• History: alcohol consumption for 5 years and

smoking (1 to 1.5 packages per day ) for 10 years. He had 3 asymptomatic progressively enlarging pigmented macules. According to the patient, the lesions were roughly of 4 months duration and did not significantly change in color and in size over time, but after another month the patient had noticed the appearance of a nodule in median lesion of lower lip

• Clinical findings: Diffuse lesions, irregularly pigmented

approximately 10-15 mm in diameter with a nodule of 0.5 cm

Case report

Clinical Picture

Histopathological Picture

• Final diagnosis → Malignant melanoma• In searching for distant metastasis, a

nodule was found in the spleen!• Recall the poor prognosis!

Definitive diagnosis