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 doesnt always mean a causal relationship -Infects keratinocytes resulting in koilocytes -HPV-associated lesions: Sequamous cell Papilloma neoplasm Verruca vulgaris (common wart) viral infection Condyloma accuminatum (venereal wart) viral infection Focal epithelial hyperplasia (hecks 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 lip Upon examination we found the lesion to be solitary and Pedunculated The histopathological examination is shown below 1- Whats the most likely diagnosis?! 2- Is it considered a tumor or an infection?! 3- Whats 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- Whats the usual treatment?!

Sequamous cell Papilloma

Characteristic cauliflower appearance

Sequamous cell Papilloma

Finger-like epithelial proliferation Thin fibrovascular cores

Sequamous cell Papilloma

Management = Excisional biopsy

12 years old child attended the dental clinic complaining from warty swellings arising from the buccal mucosa anteriorly Upon examination we found the lesion to be multiple and Pedunculated The patient stated that similar lesions appeared previously on his fingers which he used to bite The histopathological examination is shown below 1- Whats the most likely diagnosis?! 2- Is it considered a tumor or an infection?! 3- Whats the etiology behind this lesion?! 4- What are the usual clinical features?! 5- Whats 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- Whats the usual treatment?!

Verruca vulgaris

Verruca vulgaris

Finger-like epithelial proliferation Thin fibrovascular cores

Verruca vulgaris
Hyperkeratosis

Hyperplastic rete ridges around margins slope inwards towards center

Verruca vulgaris

Large vacuolated cells (koilocytes) with prominent Keratohyaline granules

25 years old male attended the dental clinic complaining from flat-toped nodules arising from the ventral tongue Upon examination we found the lesion to be multiple and sessile The histopathological examination is shown below 1- Whats the most likely diagnosis?! 2- Is it considered a tumor or an infection?! 3- Whats 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?!

Condyloma accuminatum
Keratinization is not a prominent feature
Prominent acanthosis with marked broadening and elongation of rete ridges

Blunted surface projections

33 years old male attended the dental clinic complaining from small elevated lesions arising from the buccal mucosa Upon examination we found the lesion to be multiple and sessile The histopathological examination is shown below

1- Whats the most likely diagnosis?!

2- Is it considered a tumor or an infection?! 3- Whats 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

Focal epithelial hyperplasia

Little hyperkeratosis Rete ridges tend to fuse with each other as we go deeper Little papillary surface projections

Sequamous cell carcinoma

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

Early lesions asymptomatic

Leukoplakia white patch

Small exophytic mass which shows no ulceration or Erythema

Sequamous cell carcinoma

Early lesions asymptomatic

Small indolent ulcer

Erythroplakia Red patch

Sequamous cell carcinoma

Early 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 carcinoma

Suspicious clinical features for early carcinoma: Persistent ulceration Induration Fixation to underlying structures Destruction of underlying bone in alveolar mucosa lesions Enlarges reactive regional lymph nodes

Sequamous cell carcinoma

Advanced/late lesions asymptomatic

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

Sequamous cell carcinoma

Advanced/late lesions asymptomatic

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

Sequamous cell carcinoma

Advanced/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

Sequamous cell carcinoma

Advanced/late lesions asymptomatic Metastatic spread to regional lymph nodes

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

Sequamous cell carcinoma

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

Well-differentiated OSCC

Keratin pearls (arrows)

Sequamous cell carcinoma

Moderately differentiated tumors: - Still readily identified as Sequamous type - Less keratinization - More pleomorphism of cells and nuclei. - Abundant and atypical mitotic figures

Sequamous cell carcinoma

Poorly differentiated tumors: - Cells may be hardly recognizable as epithelial - Keratinization usually absent - Marked atypical features

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

Sequamous cell carcinoma

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

Cohesive invasive front

Non-cohesive invasive front

50 years old male attended the dental clinic concerned about a warty white lesion arising from the lower buccal sulcus and adjacent buccal mucosa Patient stated it is slowly growing Patient admitted snuff dipping habit The histopathological examination is shown below 1- What are the possible differential diagnoses?! 2- Whats 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)

Sequamous Cell Carcinoma: Verrucous Carcinoma

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

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

Sequamous Cell Carcinoma: Carcinoma-In-Situ

Usually presents clinically as leukoplakia or Erythroplakia

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 Lesions

a) Leukoplakia (homogeneous, nonhomogeneous, proliferative Verrucous leukoplakia) b) Erythroplakia c) Carcinoma in situ d) Chronic hyperplastic candidosis

Oral Premalignant Conditions

a) b) c) d) Oral Submucous fibrosis Lichen planus (atrophic/erosive) Actinic keratosis or cheilitis Other conditions associated with oral epithelial atrophy, e.g. Sideropenic dysphagia

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

1- Whats 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

Basal Cell Carcinoma (Rodent Ulcer)

Malignant basaloid cells arranged in various patterns, invading adjacent tissues

Basal Cell Carcinoma (Rodent Ulcer)

Basal cell nevus syndrome ( Gorlin-Goltz syndrome)

Multiple basal cell carcinomas of the skin Skeletal abnormalities Intracranial calcifications Multiple Odontogenic keratocyst

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 (intramucosal) 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 Nevi

Common on skin (face)

Rarely, present intraorally (palate & buccal mucosa)

Natural history of nevi

Nevus cells = mature Melanocytes

Acquired Melanocytic Nevi: Junctional nevus

Acquired Melanocytic Nevi: Compound nevus

Acquired Melanocytic Nevi: Intra-mucosal nevus

The most common intra-orally

Malignant Melanoma
1. 2. 3. ABCD Clinical Features: Asymmetry (uncontrolled growth pattern) Border irregularity (uneven edges) Colour variation (2 or more shades) Diameter greater than 6 mm (greater than 1/4 inch)

4.

Malignant Melanoma
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 neoplasms Variable melanin production Melanin may be absent (amelanotic melanoma) Immunohistochemical studies using specific markers for malignant Melanocytes (S-100 and HMB-45) are useful Ultra-structural examination to identify immature melanosomes can be used

Amelanotic melanoma

Oral Malignant Melanoma

Oral Malignant Melanoma

Rare

Oral Malignant Melanoma

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 dont 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

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

Case report
Clinical findings: Diffuse lesions, irregularly pigmented approximately 10-15 mm in diameter with a nodule of 0.5 cm

Clinical Picture

Histopathological Picture

Definitive diagnosis
Final diagnosis Malignant melanoma In searching for distant metastasis, a nodule was found in the spleen! Recall the poor prognosis!