1. Oral Pathology Exam I Review Slides

2. Premalignant Lesions

3. Items covered: Premalignant Lesions Malignant Epithelial Lesions Oral
Epithelial Dysplasia
Hyperkeratosis
Mild
Moderate
Severe
Carcinoma in-situ
Leukoplakia
Erythroplakia
Proliferative Verrucous Leukoplakia
Oral submucous fibrosis
Skin
Actinic keratosis
Actinic cheilosis
Bowen’s Disease
Arsenical keratoses
Malignant Epithelial Lesions
Squamous Cell Carcinoma (oral/skin)
Lips, tongue, floor of mouth, gingiva/alveolar mucosa, buccal mucosa, palate and skin
Verrucous Carcinoma (oral)
Basal Cell Carcinoma
Nasalpharyngeal Carcinoma
Melanoma (oral/skin)

4. Normal epithelium (skin)

5. Normal Mucosa-lip and oral

6. Epithelial Dysplasia

7. Hyperkeratosis (Atypia)
Hypertrophy exclusively of the stratum corneum is defined as:
Hyperkeratosis (Atypia)

8. Mild dysplasia Atypical changes seen in the lower 1/3 of the epidermis
Hyperchromatic and slightly pleomorphic nuclei are noted in the basal and parabasal cell layers of this stratified squamous epithelium.
Mild dysplasia

9. Moderate dysplasia Atypical changes seen ½ the span of the epidermis
Dysplastic changes extend to the midpoint of the epithelium and are characterized by nuclear hyperchromatism, pleomorphism, and cellular crowding.
Atypical changes seen ½ the span of the epidermis
Begin to see jumbling of cells, rather than lining up at the basal layer
See a fair amount of hyperchromatia, bulbous rete ridges and pleomorphism
Mitotic activity is increased
Moderate dysplasia

10. Cellular crowding and disordered arrangement are noted throughout most of the epithelial thickness, although slight maturation and flattening of the cells appears to be present at the epithelial surface.
Atypical changes similar to moderate dysplasia (jumbling of cells, hyperchromatia, bulbous rete ridges, pleomorphism, increased mitotic activity), but occuring 2/3rds the way up the epidermis
Severe dysplasia

11. Dysplastic changes extend throughout the epithelium.
Epithelium shows dysplasia throughout the epidermis, but has not invaded through the basement membrane
No cell maturation is occuring; no parakeratin production
Carcinoma-In-Situ

12. Architectural changes seen in pre-malignant dysplasia
Tear drop shaped rete ridges
Some evidence of maturation near the surface
No invasion into the basement membrane
Loss of basal polarity: basal cells no longer line up along the basement membrane
Basal layer becomes hyperplastic and crowding of basaloid cells into higher levels

13. Cytologic changes seen in pre-malignant dysplasia
Coarse , dense , dark nuclear chromatin and large nucleoli
Dark nuclei are seen closer to the surface, toward the stratum corneum
Increased nuclear nuclear/cytoplasmic ratio
Pleomorphism
Increased, altered and displaced mitoses (mitoses should be along the basal layer; in dysplasia they are seen closer to the surface)
Dyskeratosis: as cells mature toward the surface, they acquire more cytoplasm containing keratin and will stain very pink. Individual cell keratinization is characteristic of dysplasia

14. Oral Premalignant Lesions

15. This particular type of lesion tends to develop in the high risk sites of the oral cavity
Often appears as a sharply demarcated white plaque with smooth verrucous or micronodular surface
Defined as a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion
Oral Leukoplakia
Note that the term “Leukoplakia” is a clinically descriptive term only. Diagnosis is confirmed by biopsy.

16. (Sorry, couldn’t find a good picture for this one)
Leukoplakia has a tendency to develop in the 5 “high risk” regions-regions that dysplasia is often observed. What are those regions? (Note that regions of leukoplakia may or may not be dysplastic)
5) Tonsillar Pillar
(Sorry, couldn’t find a good picture for this one)
1) Lateroventral tongue
2) Soft palate
3) Floor of the mouth
4) Retromolar Pad

17. Leukoplakia
Histologically, leukoplakia will show some degree of hyperkeratosis as shown above. Note that the underlying dysplasia in the figure is only an estimate, though the potential for more advanced dysplasia is increased as you move to the right.

18. Velvety red, well demarcated patch, usually affecting the lateral tongue, floor of the mouth or soft palate (high risk sites)
A red patch that cannot be clinically diagnosed as any other condition
Note the white associated with this lesion-this would be described as a erythroleukoplakia
Erythroplakia

19. Proliferative Verrucous Leukoplakia
This lesion has a uncommon, high risk presentation
Demonstrates extensive, and often multiple keratotic plaques in older adults
Female prediliction (4:1)
Lesions develop on the gingiva
Hyperkeratosis/hyperplasia with variable dysplasia
70% will develop SCC within a mean follow-up of 8 years
Malignant transformation is a frequent complication
Proliferative Verrucous Leukoplakia

20. Oral Submucous Fibrosis
Related to pre-malignant changes
Chronic progressive scarring disease, primarily in india/southeast asia
Formation of fibrous bands affecting oral mucosa
Causes gradually increasing trismus
Leukoplakic lesions develop which tend to become malignant
Hyperkeratosis with epithelial atropy and atypia
Pronouced collagen deposition is noted in the submucosal connective tissue, and is much denser than normal
Teeth become stained, tissues look hyperkeratotic, loss of vestibular depth, pallor of palate
Associated with betel nut chewing
Oral Submucous Fibrosis

21. Skin Premalignant Lesions

22. Actinic Keratosis Classic premalignant sun-induced skin lesion
Common on facial skin and vermillion zone of the lips in fair skinned persons over 40 years old
Scaly plaque with sandpaper texture
White hyperkeratotic, often has a red base
Microscopy: Hyperkeratosis (usually parakaratin, contrasts orthokeratin in leukoplakia)
Bulbous rete ridges
Some degree of epithelial dysplasia
Associated with solar elastosis:-a UV induced degeneration of connective tissue which assumes a light bluc color instead of pink
Actinic Keratosis

23. Actinic keratosis involving the vermillion zone of the lower lip
Chronic scaling, crusting, ulceration and/or fissuring of the lip may be seen
White plaque lesions
Hyperorthokeratosis and epithelial atrophy are seen histologically
Solar elastosis is observed
Actinic Cheilosis

24. Bowen’s Disease Skin equivalent of carcinoma-in-situ
Erythematous and scaly, well defined, irregular plaque on keratinized skin
Not necessarily associated with sun exposure (differentiating point from actinic keratosis)
Bowen’s Disease

25. Arsenical Keratosis Condition is related to xposure to arsenic
Keratosis of palms and soles-may possibly become malignant
Darkened skin pigmentation
Skin tumors (Bowen’s disease, BCC, SCC)
Increased risk of internal malignancy associated with this
Arsenical Keratosis

26. Malignant Epithelial Lesions

27. Squamous Cell Carcinoma
(75-80%) Associated with cigarette smoking, with or without alcohol
Irregular shape, mixture of red and white
Often ulcerated with “rolled border” and asymmetric
Exophytic or endophytic growth pattern, or a combination of both
Epithelial extentions are seen in the connective tissue
Often much firmer than surrounding tissues
Typically will affect the lower lip more commonly than the upper lip due to sun exposure
Arises in the setting of actinic cheilitis
Lateroventral tongue most commonly affected in the oral cavity
Common to see leukoplakia with associated with this
Slow growing usually well differentiated lesions
Relatively good prognosis
Squamous Cell Carcinoma

28. Histologic appearance of Squamous Cell Carcinoma
Lose rete ridges where invasion occurs
Microscopically, invasive cords and nests of malignant squamous epithelial cells arising from dysplastic surface epithelium…lots of keratin which stains pink
Tumor cells show an increased nuclear/cytoplasmic ratio, cellular and nuclear pleomorphism, and mitotic activity
Varying degrees of keratin production may be seen (well vs. poorly differentiated-will not see any keratin production in poorly differentiated cells)
Normal epithelium looks very organized, SCC will be very disorderly
Always look for variation/pleomorphism
Histologic appearance of Squamous Cell Carcinoma

29. Radiographic Appearance of SCC
Due to direct invasion of bone-usually a late phenomenon
Ragged, “moth-eaten” radiolucency (chewed away at the borders of the radiolucency-note that this occurs with osteomyelitis as well)
Ill defined borders
History is important in the diagnosis of this lesion
Pathologic fracture is possible
Very rare to have SCC exclusively in bone, more likely to be periodontal disease
Perio disease will show vertical defects
In SCC, horizontal bone loss occurs in a very short period of time
Radiographic Appearance of SCC

30. Less aggressive, relatively uncommon, form of SCC, but is NOT SCC
Elderly male predilection
Smokeless tobacco is often mentioned as a contributing factor, particularly in some southern states
Proliferative verrucous leukoplakia may give rise to this
Clinically presents as a diffuse white or mixed red and white plaque
Does not infiltrate like SCC
Alveolar mucosa, hard palate and buccal mucosa are most frequent sites (Note that these are low risk sites for SCC)
Tends to grow laterally, invades with a “pushing margin” but doesn’t infiltrate
Only grows exophytically along surface
Verrucous Carcinoma

31. Verrucous Carcinoma Microscopically appears very bland
Does not appear like most cancers-lacks pleomorphism, no mitotic activity, no bulbous rete ridges, no hyperchromaticism
Does not appear dysplastic when viewed at high power
Diagnosis is based on the overall architecture (low power, far away view) of the tumor, rather than on the appearance of individual cells
Papillary surface folds
Parakeratin plugs (clefting)
Wide, elongated rete ridges (instead of tear-dropped) that invade by pushing into connective tissue
Normal maturation, little atypia
Often intense chronic inflammatory infiltrate (lymphocytic response)
Overall, looks very different than SCC
Verrucous Carcinoma

32. Nasopharyngeal Carcinoma
Uncommon neoplasm in much of the world
Arises from Waldeyer’s ring (nasopharynx, palatine tonsil, base of tongue)
Primary tumor is generally very small and metastasizes very easily
Associated with Eppstein Barr infection, though etiology is likely multifactorial
Bimodal age distribution
Teenagers and most commonly in middle aged adults
Male predilection (3:1)
Metastasis to cervical nodes is first sign in over half of patients
Epistaxis or obstruction (often unilateral) are common presenting symptoms
Non-tender cervical nodes
Nasopharyngeal Carcinoma

33. Basal Cell Carcinoma Looks like a Werther’s original candy
Nodulo-ulcerative type with the most common clinical presentation
Umbilicated (central depression, edges are curved) papule or nodule that may show central ulceration
Rolled pearly whiteish/yellow border (border is elevated, pearly white color)
Telactangic vessels along border, causing occasional spontaneous bleeding
Central ulceration
Lack of adnexal skin structures (hair), whereas a nevus would have hair growing from it
May be referred to as a “rodent ulcer”-Can look like a rodent has been chewing on it
Basal Cell Carcinoma

34. Basaloid cells that appear to “drop off” of the basal cell layer of the epidermis into the connective tissue
Nodulo-ulcerative: large lobules of tumor cells are characteristic of this
May show some similarity to ameloblastoma
Basal Cell Carcinoma

35. Early lesions appear as brown/blue/black macules with irregular borders. A minority are colorless
With time, lesion becomes nodular and may ulcerate
80% found on hard palate, maxillary alveolus as a blue/brown spot
Bone involvement shows a ragged radiolucency
Risk factors include: History of blistering sunburn early in life, indoor occupation, outdoor recreation, Family/personal history of this condition
Invasive cells (melanocytes) are spindle-shaped or epithelioid and are pleomorphic
Epitheloid cells contain a lot of cytoplasm and produce a lot of pigment
Invasion of blood vessels and lymphatics is more common in oral lesions than cutaneous lesions
Acral letiginous is the most common variant
Oral Melanoma

36. Melanoma ABCDE’S Melanoma-ABCDE’s (KNOW THESE WELL) Asymmetry
Border irregularity
Color variation
Diameter greater than 6 mm (size of pencil eraser)
Evolving-lesions that have changed over time

37. Atypical melanocytes are initially seen at the epithelial and connective tissue junction. From here, they have the potential to proliferate throughout the epithelium, laterally along the basal cell layer and downward into the connective tissue.
In the early stages of the neoplasm, atypical melanocytes are seen either scattered singly among the basal epithelial
cells or as nests within the basal cell layer. The atypical melanocytes are usually larger than normal melanocytes,
and have varying degrees of nuclear pleomorphism and hyperchromatism.
Melanoma
Acral lentiginous melanoma. This palatal melanoma
demonstrates numerous atypical melanocytes in the basilar
portion of the epithelium with invasion into the superficial lamina propria. This represents the biopsy specimen from the image on top.

38. When malignant melanocytes are observed invading
the connective tissue, the vertical growth phase has taken
place. In this neoplasm, this vertical growth phase
occurs early In the course of the tumor. No radial growth
of cells can be observed in the overlying epithelium
beyond the edge of the invasive tumor. The invasive melanocytes usually appear either spindle-shaped or epithelioid and Infiltrate the connective tissue as loosely aggregated cords or sheets of pleomorphic cells. Oral lesions tend to show invasion of lymphatic and blood vessels more readily than skin lesions.
Nodular melanoma
A nodular mass of spindle shaped malignant melanocytes is seen invading into the dermis. Note the lack of radial growth in the adjacent overlying epidermis. The inset shows the tumor at higher power.

39. Superficial spreading melanoma
With this neoplasm, pagetoid spread often is seen. Large melanoma cells infiltrate the surface epithelium singly or in nests. The resulting
microscopic pattern is called pagetoid because it resembles an intraepithelial adenocarcinoma known as Pagers disease of skin.
The spreading of the lesional cells along the basal layer constitutes the radial growth phase of the neoplasm.
Such lateral spread of cells within the epithelium, which occurs before invasion into the underlying connective tissue, is characteristically seen in superficial spreading melanoma, lentigo maligna melanoma, and acral lentiginous melanoma.
Superficial spreading melanoma
The radial growth phase is characterized by the spread of atypical melanocytes along the basilar portion of the epidermis. Also note the presence of individual melanocytes invading the higher levels of the epithelium.

40. Melanoma Histology
I didn’t see a lot of histologic material on melanoma in Shumway’s notes, all the info in this section is from the book.