Oral Pathology Exam I Review Slides

Premalignant Lesions

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)

Normal epithelium (skin)

Normal Mucosa-lip and oral

Epithelial Dysplasia

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

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

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

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

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

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

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

Oral Premalignant Lesions

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.

(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

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.

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

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

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

Skin Premalignant Lesions

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

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

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

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

Malignant Epithelial Lesions

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

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

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

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

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

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

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

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

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

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

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.

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.

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.

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.