eptihelial verbose.txt

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eptihelial verbose.txt
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Epithelial OSD4
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  1. How do you ID HPV
    • in situ hybridization
    • immunohistochemical analysis
    • PCR
    • Not visible w/ routine histopathologic staining
  2. What is the most common soft tissue mass arising from the soft palate?
    Squamous Papilloma
  3. Koilocytes
    virus-altered epithelial clear cells with small dark (pyknotic) nuclei, are sometimes seen high in the prickle cell layer.

    • normal left
    • koilocyte right
  4. Squamous Papilloma
    • • Benign SSE proliferation-> papillary or verruciform mass.
    • • HPV induced (6, 11)
    • • Clinical features
    • o men=women 
    • o any age [dx most often in 30 – 50 yos]
    • o Sites: tongue, lips, and soft palate, but any oral surface may be affected.
    • o Most common soft tissue mass arising from the soft palate.
    • o Soft, painless, pedunculated, exophytic nodule w/ numerous fingerlike surface projections that impart a “cauliflower” or wartlike appearance.
    • • Projections may be pointed or blunted, and the lesion may be white, slightly red, or normal in color, depending on the amount of surface keratinization.
    • o Lesions can be big or small
    • • Histo features
    • o Pedunculated squamous epithelial proliferation.
    • o Multiple papillary projections w/ fibrovascular connective tissue cores.
    • o Keratin layer is thickened in lesions w/ a whiter clinical appearance, and the epithelium typically shows a normal maturation pattern.
    • o Koilocytes – virus-altered epithelial clear cells with small dark (pyknotic) nuclei, are sometimes seen high in the prickle cell layer.
    • • Treatment and prognosis
    • o Conservative surgical excision [w/ base of the lesion] is adequate; recurrence is unlikely.
    • o If left untreated, they rarely transform into malignancy, continuous enlargement, or dissemination to other parts of the oral cavity
  5. What lesions create a cutaneous horn?
    • verruca vulgaris
    • seborrheic keratosis
    • actinic keratosis
    • squamous cell carcinoma.
  6. Verruca Vulgaris [Common Wart]
    • • Benign, virus-induced, focal hyperplasia of stratified squamous epithelium.
    • • HPV types 2, 4, 6, and 40
    • • Contagious,(autoinoculation) 
    • • Infrequently develops on oral mucosa, but is extremely common on the skin.
    • • Clinical Features
    • o Extreme accumulation of compact keratin may result in a hard surface projection several millimeters in height, termed Cutaneous horn/keratin horn.
    • o Other Cutaneous lesions that create a Cutaneous horn: seborrheic keratosis, actinic keratosis, and squamous cell carcinoma.
    • • Histo Features
    • o Numerous papillary projections are covered by hyperkeratotic stratified squamous epithelium.
    • o Elongated rete ridges at the edge of the lesion converge toward the center.
    • o Clear koilocytes in the upper epithelial layers
    • • Treatment and Prognosis
    • o Skin verrucae – topical salicylic acid, topical lactic acid, or liquid nitrogen cyrotherapy.
    • o Surgical excision is indicated only for cases with an atypical clinical presentation in which the dx is uncertain.
    • o Oral lesions – surgical excision, or laser, cryotherapy, or electrosurgery
    • o Recurrence – seen in a small portion of treated cases. w/out treatment, verrucae do NOT transform into malignancy, and 2/3rds will disappear spontaneously w/in 2 years.
  7. Acanthosis
    • diffuse epidermal hyperplasia (thickening of the skin).[1]
    • Implies increased thickness of the Malpighian layer (stratum basale and stratum spinosum).
  8. Condyloma Acuminatum [veneral wart]
    • • Virus-induced proliferation of stratified squamous epithelium of the genitalia, perianal region, mouth, and larynx.
    • • HPV types 6 and 11
    • • STD, w/ lesions developing at a site of sexual contact or trauma.
    • • Represents 20% of all STDs diagnosed in STD clinics and may be an indicator of sexual abuse when diagnosed in young children.
    • • May be passed from mother to child in utero.
    • • Clinical Features
    • o Papillary lesion – occurs in labial mucosa, soft palate, and lingual frenum
    • o All ages affected
    • o Sessile, pink, well-demarcated, nontender exophytic mass w/ short, blunted surface projections.
    • • Histo features
    • o Acanthotic stratified squamous epithelium forming a blunted projection
    • o Koilocytes in the spinous layer [arrows]
    • • Treatment and prognosis
    • o Oral – conservative surgical excision, laser ablation [causes aerosolized microdroplets, leads to airborne spread of HPV].
    • o Anogenital, non-oral lesions - Nonsurgical, patient-applied topical agents – imiquimod or podophyllotoxin
    • • Condyloma infected w/ HPV-16 or HPV-18 are associated w/ an increased risk of malignant transformation to squamous cell carcinoma
    • o Should be removed b/c it is contagious and can spread to other oral surfaces and to other persons through direct (sexual) contact
  9. Multifocal Epithelial Hyperplasia [Heck’s Disease]
    • • Virus-induced, localized proliferation of oral squamous epithelium.
    • • HPV 13 and 32.
    • • genetic susceptibility or HPV transmission b/w family members.
    • o HLA-DR4 allele
    • Risk factors: lower socioeconomic status, crowded living conditions, poor hygiene
    • • Lesions arise more often in people with AIDS
    • Clinical Features
    • o Usually childhood
    • o Slight female predilection or none
    • o sites: labial, buccal, lingual mucosa
    • o alose gingival, palatal, and tonsillar regions
    • o conjunctiva occurs, but is rare
    • Histo features
    • o Prominent aconthosis of the epithelium w/ broad and elongated rete ridges.
    • o Slightly papillary surface alteration may/may not be present
    • o Mitosoid cells contain altered nuclei in otherwise mature and well-differentiated stratified squamous epithelium.
    • • Treatment and Prognosis
    • o Spontaneous regression after months or years->inferred from the rarity of the disease in adults.
  10. Sinonasal Papillomas
    • • Benign, localized proliferations of the respiratory mucosa in the sinonasal region.
    • • Three histomorphologically distinct papillomas:
    • 1. Fungiform
    • 2. Inverted
    • 3. Cylindrical
    • • Keratinizing squamous papilloma, similar to the oral squamous papilloma rarely may occur in the nasal vestibule
    • • 10-25% of all tumors of the nasal and paranasal region.
    • • Half of the sinonasal papillomas arise from the mucosa of the lateral nasal wall; the remainder predominantly involve the maxillary and ethmoid sinuses and the nasal septum.
    • • Causes
    • o Neoplasms
    • o Reactive hyperplasia secondary to environmental stimulants: allergy, chronic bacterial or viral (HPV 11) infection, and tobacco smoking
    • o Inverted papillomas arise from a single progenitor cell, suggesting that these lesions are neoplastic and recurrence may result from growth of residual transformed cells.
  11. Molluscum Contagiosum
    • • Virus-induced epithelial hyperplasia
    • • molluscum contagiosum virus, (DNA poxvirus)
    • • Routes of transmission:
    • o Sexual contact [in adults]
    • o Nonsexual contact [children and teens] – sharing clothing, wrestling, communal bathing, swimming
    • • immunocompromised patients: 5-18% HIV+ prevalence
    • • Clinical Features
    • o children and young adults
    • o Papules are multiple and occur predominantly on the skin of the neck, face, trunk, and genitalia
    • • Histo features
    • o Well-defined epidermal proliferation demonstrating a central craterlike depression filled with virally altered keratinocytes
    • • Treatment and prognosis
    • o Most cases: spontaneous remission: 6-9 months
  12. What other diseases present as white lesions?
    • leukoplakia
    • lichen planus
    • morsicatio
    • frictional keratosis,
    • tobacco pouch keratosis
    • nicotine stomatitis
    • leukoedema
    • white sponge nevus
  13. Proliferative Verrucous Leukoplakia (PVL)
    • high risk form
    • •multiple keratotic plaques w/ roughened surface projections
    • • spread slowly and involve additional oral mucosal sites. 
    • • Gingiva is frequently involved, although other sites may be affected as well. 
    • • Lesions typically begin as simple, flat hyperkeratosis that are indistinguishable from ordinary leukoplakic lesions. 
    • • PVL exhibits persistent growth, eventually becoming exophytic and verrucous innature. As the lesions progress, they may go through a stage indistinguishable from verrucous carcinoma, but they later usually develop dysplastic changes and transform into full-fledged squamous cell carcinoma (w/in 8 years of initial PVL diagnosis). • Strong female predilection, minimal association w/ tobacco use.
  14. acanthosis
  15. What is the significance of Speckled leukoplakia?
    • • Intermixed red and white lesion
    • reveals advanced dysplasia on biopsy.
  16. Describe the histological features of leukoplakia with orthokeratosis.
    epithelium demonstrates a granular cell layer and the nuclei are lost in the keratin layer

    hyperparakeratois: no granular cell layer epithelial nuclei are retained in the keratin layer.
  17. Describe the histological features of leukoplakia with hyperparakeratosis.
    no granular cell layer epithelial nuclei are retained in the keratin layer.

    othrokeratosis: epithelium demonstrates a granular cell layer and the nuclei are lost in the keratin layer
  18. Features of leukoplakia dysplasia
  19. • Enlarged nuclei and cells
    • • Large and prominent nucleoli
    • • Increased nuclear-to-cytoplasmic ratio
    • • Hyperchromatic (excessively dark-staining) nuclei
    • • Pleomorphic (abnormally shaped) nuclei and cells
    • • Dyskeratosis (premature keratinization of individual cells)
    • • Increased mitotic activity (excessive numbers of mitoses)
    • • Abnormal mitotic figures (tripolar or star-shaped mitoses or mitotic figures above thebasal layer). 
    • • Bulbous or teardrop-shaped rete ridges
    • • Loss of polarity (lack of progressive maturation toward the surface)
    • • Keratin or epithelial pearls (focal, round collections of concentrically layered keratinized cells)
    • • Loss of typical epithelial cell cohesiveness
  20. Describe the stages of luekoplakia (PVL) lesions
    • • Early – benign hyperkeratosis that is indistinguishable from other simple leukoplakic lesions
    • • Some time later – condition progresses to a papillary exophytic proliferation that is similarto localized lesions of verrucous leukoplakia [verrucous hyperplasia]
    • • Later stages – papillary proliferation exhibits downgrowth of well-differentiated squamous epithelium with broad, blunt rete ridges
    • • Invasion into the underlying lamina propria – indistinguishable from verrucous carcinoma. 
    • • Final stages – invading epithelium becomes less differentiated, transforming into a full-fledged squamous cell carcinoma. • Because of the variable clinical and histopathologic appearance of PVL, careful correlation of the clinical and microscopic findings is required for diagnosis. 
    • o Features of dysplasia
    • • Enlarged nuclei and cells
    • • Large and prominent nucleoli
    • • Increased nuclear-to-cytoplasmic ratio
    • • Hyperchromatic (excessively dark-staining) nuclei
    • • Pleomorphic (abnormally shaped) nuclei and cells
    • • Dyskeratosis (premature keratinization of individual cells)• Increased mitotic activity (excessive numbers of mitoses)
    • • Abnormal mitotic figures (tripolar or star-shaped mitoses or mitotic figures above thebasal layer). 
    • • Bulbous or teardrop-shaped rete ridges
    • • Loss of polarity (lack of progressive maturation toward the surface)
    • • Keratin or epithelial pearls (focal, round collections of concentrically layered keratinized cells)
    • • Loss of typical epithelial cell cohesiveness

    • oSeverity/intensity of dysplasia
    • • Mild dysplasia– alterations limited principally to the basal and parabasal layers
    • • Moderate –demonstrates involvement from the basal layer to the midportion of the spinous layer
    • • Severe –demonstrates alterations from the basal layer to a level above the midpoint of the epithelium
    • • Sometimes, dysplasia will be seen to extend down the duct of a minor salivary gland,especially in lesions of the floor of the mouth. 
    • o Carcinoma in situ – when the entire thickness of the epithelium is involved. 
    • • Defined asdysplastic epithelial cells that extend from the basal layer to the surface ofthe mucosa. • There may/not be a thin layer of keratin on the surface. • Epithelium may be hyperplastic or atrophic. • No invasion has occurred, despite the fact that the atypical epithelial cells look exactly like those of squamous cell carcinoma• w/out invasion,the most serious aspect of malignant transformation – metastasis – cannotoccur.
  21. Leukoplakia
    • • White patch/plaque cannot be rubbed off and cannot be clinically identified as a
    • specific disease.
    • o Clinical term, no implication of specific histopathologic tissue alteration.
    • • Diagnosis is dependent on exclusion of other entities that appear as oral white plaques
    • [lichen planus, morsicatio, frictional keratosis, tobacco pouch keratosis,
    • nicotine stomatitis, leukoedema, and white sponge nevus]
    • • Clinical white color results from a thickened surface keratin layer, which appears white when wet, or a thickened spinous layer, which masks the normal vascularity (redness) of the underlying connective tissue.
    • Incidence and Prevalence
    • o common
    • o most common indicator of evolving or actual malignancy
    • • Causes
    • o Tobacco
    • o not Alcohol
    • o UV Radiation (lower lip,associated w/ actinic cheilosis)
    • • Immunocompromised patients [transplant] are especially prone to the development of leukoplakia and squamous cell carcinoma of the lower lip vermillion.
    • o Microorganisms
    • • HPV 16 and 18
    • [same HPV subtypes associated w/ uterine cervical carcinoma and a subset of oral SCCs.]
    • could be coincidental
    • • Clinical Features
    • o > 40 yo; prevalence increases rapidly w/ age, especially for males; average age of affected persons (60 yo) is similar to the average age for patients w/ oral cancer
    • o Proliferative Verrucous Leukoplakia (PVL) – special high risk form
    • • Characterized
    • by the development of multiple keratotic plaques w/ roughened surface
    • projections

    • • Multiple PVL plaques tend to spread slowly and involve additional oral mucosal sites.
    • • Gingiva most not all 
    • • Begin simple, flat hyperkeratosis that are indistinguishable from ordinary leukoplakic lesions.
    • • But PVL exhibits persistent growth, eventually becoming exophytic and verrucous in
    • nature. As the lesions progress, they may go through a stage indistinguishable
    • from verrucous carcinoma, but they later usually develop dysplastic changes and
    • transform into full-fledged squamous cell carcinoma (w/in 8 years of initial
    • PVL diagnosis).

    • Strong female predilection, minimal association w/ tobacco use.

    • o Speckled leukoplakia
    • • Intermixed red and white lesion
    • • Represents a pattern of leukoplakia that frequently reveals advanced dysplasia on biopsy.

    • Histo Features
    • o Characterized by thickened surface epithelial keratin layer (hyperkeratosis) with or w/out a thickened spinous layer (acanthosis).
    • o Some leukoplakias demonstrated surface hyperkeratosis but show atrophy or thinning
    • of the underlying epithelium.

    o Frequently, variable numbers of chronic inflammatory cells are noted w/in the subjacent connective tissue.

    • o The keratin layer may consist of parakeratin (Hyperparakeratosis), orthokeratin
    • (hyperorthokeratosis), or a combination of both.
    • • With parakeratin, there is no granular cell layer and the epithelial nuclei are retained in the keratin layer.

    • With orthokeratin, the epithelium demonstrates a granular cell layer and the nuclei are lost in the keratin layer

    • o Stage of lesions:
    • • Early – benign hyperkeratosis that is indistinguishable from other simple leukoplakic lesions
    • • Some time later – condition progresses to a papillary exophytic proliferation that is similar
    • to localized lesions of verrucous leukoplakia [verrucous hyperplasia]
    • • Later stages – papillary proliferation exhibits downgrowth of well-differentiated squamous
    • epithelium with broad, blunt rete ridges

    • • Invasion into the underlying lamina propria – indistinguishable from verrucous carcinoma.
    • • Final stages – invading epithelium becomes less differentiated, transforming into a
    • full-fledged squamous cell carcinoma.
    • • Because of the variable clinical and histopathologic appearance of PVL, careful correlation of the clinical and microscopic findings is required for diagnosis.
    • o Features of dysplasia
    • • Enlarged nuclei and cells
    • • Large and prominent nucleoli
    • • Increased nuclear-to-cytoplasmic ratio
    • • Hyperchromatic (excessively dark-staining) nuclei
    • • Pleomorphic (abnormally shaped) nuclei and cells
    • • Dyskeratosis (premature keratinization of individual cells)
    • • Increased mitotic activity (excessive numbers of mitoses)
    • • Abnormal mitotic figures (tripolar or star-shaped mitoses or mitotic figures above the
    • basal layer).
    • • Bulbous or teardrop-shaped rete ridges
    • • Loss of polarity (lack of progressive maturation toward the surface)
    • • Keratin or epithelial pearls (focal, round collections of concentrically layered keratinized cells)
    • • Loss of typical epithelial cell cohesiveness
    • o
    • Severity/intensity of dysplasia
    • • Mild dysplasia
    • – alterations limited principally to the basal and parabasal layers

    • • Moderate –
    • demonstrates involvement from the basal layer to the midportion of the spinous
    • layer

    • • Severe –
    • demonstrates alterations from the basal layer to a level above the midpoint of
    • the epithelium

    • • Sometimes,
    • dysplasia will be seen to extend down the duct of a minor salivary gland,
    • especially in lesions of the floor of the mouth.

    • o Carcinoma in
    • situ – when the entire thickness of the epithelium is involved.

    • • Defined as
    • dysplastic epithelial cells that extend from the basal layer to the surface of
    • the mucosa.

    • • There may/not be a thin layer of keratin on the surface.
    • • Epithelium may be hyperplastic or atrophic.
    • • No invasion has occurred, despite the fact that the atypical epithelial cells look exactly like those of squamous cell carcinoma
    • • w/out invasion,
    • the most serious aspect of malignant transformation – metastasis – cannot
    • occur.

    •  
    • • Treatment and Prognosis
    • o Overall, 4% of oral leukoplakias become squamous cell carcinoma after diagnosis, according to follow-up studies
    • o Erythroleukoplakia carries the most risk [28% transformation potential]
    • o Factors that may increase the risk for cancer in leukoplakic lesions:
    • • Persistence over several years
    • • Occurrence in a female patient
    • • Occurrence in a nonsmoker
    • • Occurrence on the oral floor or ventral tongue
    • o Chromosomal, genetic, and molecular alterations that may aid in predicting the risk of malignant transformation for oral leukoplakia:
    • • Loss of heterozygosity is associated w/ increased risk of malignant transformation.
    • • Microsatellite instability (insertion or deletion of base pairs in repetitive stretches of
    • short DNA sequences)
    • • increased telomerase activity (important for cellular longevity)
    • • changes in expression of various molecular markers
    • o smoking habit cessation is recommended
    • o chemoprevention may be useful, but it remains primarily experimental
  22. Erythroplakia
    • • Red patch that cannot be clinically or pathologically diagnosed as any other condition.
    • • Almost all true erythroplakias demonstrate significant epithelial dysplasia, carcinoma in situ, or invasive squamous cell carcinoma.
    • • May occur in conjunction w/ leukoplakia and has been found concurrently w/ a large proportion of early invasive oral carcinomas.
    • • Less common than leukoplakia, but has a much greater potential to be severely dysplastic at the time of biopsy or to develop invasive malignancy at a later time.
    • • Clinical Features
    • o Altered mucosa appears as a well-demarcated erythematous macule or plaque w/ a soft, velvety texture. It is usually asymptomatic and may be associated w/ an adjacent leukoplakia (erythroleukoplakia).
    • o Conditions that may mimic erythroplakia: nonspecific Mucositis, candidiasis, psoriasis, or vascular lesions.
    • • Histo Features
    • o 90% of erythroplakic lesions histopathologically represent severe epithelial dysplasia, carcinoma in situ, or superficially invasive squamous cell carcinoma.
    • o The epithelium shows a lack of keratin production and often is atrophic, but it may be hyperplastic.
    • o This lack of keratinization, especially when combined with epithelial thinness, allows the underlying microvasculature to show through, thereby explaining the red color.
    • o Underlying connective tissue often demonstrates chronic inflammation.
    • • Treatment and Prognosis
    • o Should be viewed with suspicion, and biopsy should be performed.
    • o Treatment is guided by definitive diagnosis obtained by biopsy.
    • o Lesions exhibiting moderate dysplasia or worse must be removed completely or destroyed by the methods used for leukoplakia.
    • o Best to preserve most of the specimen for microscopic examination because of the possibility that a focal invasive carcinoma might be missed in the initial biopsy material.
    • o Recurrence and multifocal oral mucosal involvement are common w/ erythroplakia, hence long-term follow-up is suggested for treated patients.
  23. Smokeless Tobacco Use
    • • Three main types in the US:
    • o Chewing tobacco
    • o Moist snuff [most commonly used]
    • o Dry snuff
    • • Clinical Features
    • o Variety of local oral alterations are found in chronic users:
    • • Characteristic painless loss of gingival tissues in the area of tobacco contact.
    • • May be accompanied by destruction of the facial surface of the alveolar bone and correlates well with the quantity of daily use and the duration of the smokeless tobacco habit
    • o Dental caries higher in people who use smokeless tobacco – due to high sugar content of some brands.
    • • Long term use may lead to localized or generalized wear of occlusal and Incisal surfaces, especially in those using the product in dusty environments.
    • • A brown-black extrinsic tobacco stain is typically found on the enamel and cementum surfaces of the teeth adjacent to the tobacco.
    • o Halitosis is a frequent finding in chronic users.
    • o Smokeless tobacco keratosis
    • • White plaque, produced on the mucosa in direct contact with snuff or chewing tobacco.
    • • Development of this lesion is most strongly influenced by habit duration and also by the brand of tobacco used, early onset of smokeless tobacco use, total hours of daily use, amount of tobacco consumed daily, and number of sites routinely used for tobacco placement.
    • • Individual lesions begin to develop shortly after heavy tobacco use begins, and new lesions seldom arise in persons w/ a long history of use.
    • • Lesion is confined to areas in direct contact w/ spit tobacco – typically a thin, gray or gray-white, almost translucent plaque w/ a border that blends gradually into the surrounding mucosa; sometimes mild peripheral erythema is present.
    • o Soft, fissured, gray-white lesion of the lower labial mucosa located in the area of chronic snuff placement.
    • • Histo Features
    • o No specific features
    • o Squamous epithelium is hyperkeratinized and acanthotic, w/ or w/out intracellular vacuolization or “edema” of glycogen-rich superficial cells.
    • o Epithelial dysplasia is uncommon in smokeless tobacco keratosis and, when present, is typically mild. Occasionally, however, significant dysplasia or squamous cell carcinoma may be present.
    • • Treatment and Prognosis
    • o Carcinogenic, but the risk is less than that associated w/ cigarette smoking and alcohol abuse.
    • o Clinical appearance of smokeless tobacco keratosis is distinct enough and the malignant transformation potential is low enough so that biopsy is needed for only the more severe lesions [those demonstrating an intense whiteness, a granular or verruciform clinical appearance, ulceration, mass formation, induration, or hemorrhage].
    • o w/out microscopic evidence of dysplasia or malignancy, keratoses are not treated.
    • o SCC related to smokeless tobacco use typically develops after a long latency period of several decades.
    • o Habit cessation leads to a normal mucosal appearance in 98% of smokeless tobacco keratosis lesions that are not intensely white.
    • • A lesion that remains after 6 weeks w/out smokeless tobacco contact should be considered to be a true leukoplakia and should be sampled for biopsy and managed accordingly.
  24. Oral Submucous Fibrosis
    • • Chronic, progressive, scarring, high-risk precancerous condition of the oral mucosa seen primarily in the Indian subcontinent, SE asia, Taiwan, southern China, and Papua New Guinea.
    • • Linked to the chronic placement in the mouth of a betel liquid or paan and is found in India’s Villagers.
    • • The quid consists typically of a nut from the areca palm tree and slaked lime, usually with tobacco and sometimes with sweeteners and condiments, wrapped in a betel leaf.
    • o The slaked lime acts to release alkaloids from the areca nut, producing a feeling of euphoria and well-being.
    • o Villagers chew them for 16-24 hrs daily.
    • • Characterized by a mucosal rigidity of varied intensity caused by a fibroelastic hyperplasia and modification of the superficial connective tissue.
    • o The submucosal changes may be a response to the areca nut, whereas the epithelial alterations and carcinogenesis may be the result of tobacco contact.
    • o Several studies suggest that even betel quid w/out tobacco may be carcinogenic, albeit probably less so than when combined w/ tobacco.
    • o Nutritional deficiency increases the risk and severity of fibrosis, and some persons seem to have a genetic predisposition to it.
    • • The underlying pathogenic mechanism for oral submucous fibrosis is hypothesized to involve the role of the areca nut in disrupting the homeostatic equilibrium between synthesis and degradation of the extracellular matrix.
    • • Clinical features
    • o First noted in young adult betel quid users, whose chief complaint is an inability to open the mouth [trismus], often accompanied by mucosal pain while eating spicy foods.
    • • An interincisal distance of less than 20 mm is considered severe.
    • • In advanced cases, the jaws may actually be inseparable.
    • • Females are more susceptible to changes than males
    • o First signs and symptoms: vesicles, petichiae, melanosis, xerostomia, and a generalized oral burning sensation [stomatopyrosis].
    • • Histo Features
    • o Mucosa exhibiting hyperparakeratosis, basilar hyperplasia, and fibrosis in the lamina propria.
    • • Treatment and Prognosis
    • o Does NOT regress w/ habit cessation.
    • o Frequent evaluation for development of oral SCC is essential (8% malignant transformation rate).
    • o People who chew this are 19x more likely to develop oral cancer than persons w/out the disease.
  25. Nicotine Stomatitis
    • • White keratotic change associated with tobacco smoking.
    • • Does not appear to have a premalignant nature, because it develops in response to heat rather than the chemicals in tobacco smoke.
    • o Pipe smoking generates more heat on the palate than other forms of smoking, so nicotine stomatitis has been associated most often with this habit.
    • o Similar changes can also be produced by the long-term use of extremely hot beverages.
    • • “reverse smoking” – cigarettes and cigars smoked with lit end held in the mouth.
    • o Produces a pronounced palatal keratosis, which has a significant potential to develop dysplasia or carcinoma.
    • • Clinical Features
    • o Extensive leathery, white change of the hard palate; sprinkled with red papules throughout [represent inflamed salivary duct openings]; gingival mucosa is also keratotic.
    • o There is a white keratotic ring at the lip of many of the inflamed salivary duct openings.
    • • Histo features
    • o Hyperkeratosis and acanthosis of the palatal epithelium. Also squamous metaplasia of the minor salivary gland ducts.
    • • Treatment and Prognosis
    • o Completely reversible, even when it has been present for many decades.
    • o Palate returns to normal within 1-2 weeks of stopping.
    • o Any white lesion of the palatal mucosa that persists after 1 month of habit cessation should be considered a true leukoplakia and managed accordingly.
  26. Actinic Keratosis
    • • Common Cutaneous premalignant lesion that is caused by cumulative UV radiation to sun-exposed skin.
    • • UV light exposure can produce mutations in p53 tumor suppressor gene.
    • • Mutations in the telomerase gene represent another early event in lesion development, resulting in delayed apoptosis and immortalization of cells.
    • • Clinical Features
    • o Usually in persons above 40 yo
    • o Most common sites: face, neck, dorsum of hands, forearms, and scallop of bald-headed men
    • o Individual lesions are irregular scaly plaques, which vary in color from normal to white, gray, or brown, and may be superimposed on an erythematous background.
    • • Keratotic scale peels off.
    • • Palpation reveals a sandpaper roughened texture, and some lesions can be felt more easily than they can be seen.
    • o Occasional lesions produce so much keratin that a horn may be seen arising from the central area.
    • • Histo Features
    • o Extremely excessive amount of parakeratin is noted on the epidermal surface.
    • o Hyperchromatism and pleomorphism of the epidermal cells occurs.
    • • Treatment and Prognosis
    • o Usually recommended that actinic keratosis be destroyed by liquid nitrogen cryotherapy, curettage, eletrodesiccation, or surgical excision.
    • o Recurrence is rare, but additional lesions frequently arise in adjacent sun-damaged skin.
    • o Long-term follow up is recommended.
  27. Actinic Cheilosis
    • • Common premalignant alteration of the lower lip vermilion that results from long term or excessive exposure to UV.
    • • Problem confined predominantly to light-complexioned people with a tendency to sunburn easily.
    • o Outdoor occupation is associated with this problem.
    • o A person with chronic sunlight exposure and compromised immunity [previous transplant recipient] has an elevated risk of developing a cancer of the lower lip vermilion.
    • • Similar to actinic keratosis in its pathophysiologic and biologic behavior.
    • • Clinical Features
    • o Lesion develops so slowly that patients are not aware of a change.
    • o Earliest clinical changes include atrophy of the lower lip vermilion border, characterized by a smooth surface and blotchy pale areas.
    • o Blurring of the margin between the vermilion zone and the Cutaneous portion of the lip is typically seen.
    • o As the lesion progresses, rough, scaly areas develop on the drier portions of the vermilion.
    • o These areas thicken and may appear as leukoplakic lesions, especially when they extend near the wet line of the lip.
    • • Histo
    • o Hyperorthokeratosis and epithelial atrophy.
    • o Underlying solar elastosis.
    • • Treatment and Prognosis
    • o Many of the changes associated with this are probably irreversible, but patients should be encouraged to use lip balms with sunscreens to prevent further damage.
    • o Areas of induration, thickening, ulceration, or leukoplakia should be submitted for biopsy to rule out carcinoma.
  28. Keratoacanthoma
    • • Self-limiting, epithelial proliferation with a strong clinical and histopathologic similarity to well-differentiated SCC.
    • • Some consider it to represent an extremely well-differentiated form of SCC.
    • • Clinical Features
    • o Nontender, well-demarcated nodule of the skin of the nose. Nodule demonstrates a central keratin plug.
    • o Lesion demonstrates a prominent core or plug of keratin.
    • o Evolution:
    • • Growth phase
    • • Rapid enlargement is typical
    • • Helps distinguish it from a more slowly enlarging SCC
    • • Stationary phase
    • • Lesion stabilizes
    • • This phase is of similar duration to growth phase
    • • Involution phase
    • • Most lesions regress spontaneously within 6-12 months of onset, frequently leaving a depressed scar in the area.
  29. squamous cell carcinoma
    • Etiology

    • o Oncogenic
    • Viruses

    • • Viral agents
    • capable of integration into the host’s genetic material may be particularly
    • dangerous and potentially could commandeer the host’s ability to regulate
    • normal growth and proliferation of the infected cell.

    • • Viruses may
    • immortalize the host cell, thereby facilitating malignant transformation.

    • • Retroviruses,
    • adenoviruses, herpes simplex viruses, HPVs have been suggested as playing a
    • role.

    • • HPV is the only
    • one still implicated

    • • HPV 16, 18, 31,
    • and 33 are the strains most closely associated with dysplasia and SCC

    • Mechanism:

    • • E6 – promotes
    • degradation of p53 tumor suppressor gene

    • • E7 – promotes
    • degradation of the pRb tumor suppressor gene

    • o Oncogenes and
    • Tumor Suppressor Genes

    • • Chromosomal
    • components capable of being acted on by a variety of causative agents.

    • • Normal genes
    • [protooncogenes] are transformed into activated oncogenes in certain
    • malignancies through the actions of viruses, irradiation, or chemical
    • carcinogens.

    • • Once oncogenes
    • are activated, they may stimulate the production of an excessive amount of new
    • genetic material through amplification or overexpression of the involved gene.

    • • Oncogenes are
    • involved in the initiation and progression of a wide variety of neoplasms,
    • including oral SCC.

    • Metastasis

    • o Metastatic
    • spread of oral SCC is largely through lymphatics to the ipsilateral [same side]
    • cervical lymph nodes.

    • o A cervical
    • lymph node that contains a metastatic deposit of carcinoma is usually firm to
    • stony hard, nontender, and enlarged.

    • o If the
    • malignant cells have perforated the capsule of the node and invaded into
    • surrounding tissues, then the node will feel “fixed” or not easily movable.

    • o Extracapsular
    • spread (extension of metastatic deposits outside of the lymph node capsule) is
    • a microscopic feature associated with poor prognosis, including increased risk
    • of locoregional recurrence, distant metastasis, and lower survival rates.

    • o Occasionally,
    • contralateral or bilateral metastatic deposits are seen, and some patients have
    • distant [below the clavicle] metastasis at diagnosis.

    • • Most common
    • sites of distant metastasis: lungs, liver, bones.

    • • Any part of the
    • body may be affected

    • o Carcinoma of
    • the lower lip and oral floor tends to travel to the submental nodes.

    • o Tumors from the
    • posterior portions of the mouth travel to the superior jugular and digastric
    • nodes.

    • o Lymphatic
    • drainage from the oropharynx leads to the jugulodigastric chain of lymph nodes
    • or to the retropharyngeal nodes, and metastatic deposits from oropharyngeal
    • carcinoma are usually found here.

    • o Metastasis is
    • not an early event for carcinoma of the oral cavity proper.

    • Staging

    • o
    • Tumor-Node-Metastasis System

    • • T – size of the
    • primary tumor, in centimeters

    • • N – involvement
    • of local lymph nodes

    • • M – distant
    • metastasis

    • Histo

    • o Islands of
    • malignant squamous epithelium invading into the lamina propria.

    • o Dysplastic
    • epithelial cells with keratin pearl formation.

    • o Numerous
    • pleomorphic cells within the lamina propria – represent anaplastic carcinoma

    • • Treatment and
    • Prognosis

    • o Squamous cell
    • carcinomas of the upper lip vermilion appear to have a different biologic
    • behavior than do those of the lower lip.

    • o Clinical stage
    • of the disease guides the tx of intraoral SCC

    • • Wide (radical)
    • surgical excision, radiation therapy, or a combo of surgery and radiation
    • therapy.

    • o Tumor’s
    • location may influence the tx plan

    • • Oropharyngeal
    • lesions usually receive radiation therapy.

    • o Although
    • chemotherapeutic agents may reduce the size of a tumor mass temporarily, none
    • has improved survival rates significantly.

    • o For the small
    • intraoral carcinoma, a single treatment modality is usually chosen.

    • • Patients w/
    • larger lesions or lesions w/ clinically palpable lymph nodes typically require
    • combined therapy.

    • o Radical neck
    • dissection is essentially an en bloc removal of all fibrofatty tissues of the
    • lateral triangle of the neck, including the superior, middle, and inferior
    • jugular nodes, the supraclavicular group of nodes, and variable portions of the
    • surrounding musculature.

    • o The use of
    • sentinel-node biopsy to identify patients with occult neck metastasis has shown
    • promise but remains investigational for patients with oral cancer.

    • o Prognosis for
    • survival from oral cancer depends on tumor stage.

    • • 5 year survival
    • for small cancers is 60%.

    • • Most deaths
    • occur within 5 years.

    • o 5 year survival
    • rate for intraoral carcinoma in whites in the US and Europe has increased from
    • 40% to 59%, whereas the rate for black Americans has increased from 36% to 39%.


    • • Probably due to
    • differences in access to health care services.

    • o Despite
    • advances in tx and in the understanding of the underlying molecular
    • pathogenesis of oral cancer, survival rates over the last several decades have
    • not improved significantly and have remained in 50-59%.

    • • Early diagnosis
    • is essential for improving patient outcomes.

    • • Multiple
    • Carcinomas

    • o Pts w/ 1
    • carcinoma are at n increased risk for additional concurrent [synchronous] or
    • later [metachronous] primary surface epithelial malignancies of the upper
    • aerodigestive tract, the esophagus, the stomach, the lungs, and other sites.

    • • Highest risk is
    • in male patients who continue to smoke and drink after therapy.

    • o In pts w/ more
    • than 1 malignancy, some of the tumors arise simultaneously. Of the rest, the
    • 2nd lesion usually develops within 3 years after the initial cancer.

    • • This is called
    • field cancerization – may reflect diffuse exposure to local carcinogens, a
    • process that increases the malignant transformation potential of all exposed
    • epithelial cells.

    • o There are genetic
    • alterations shared between tumor tissue and adjacent clinically normal
    • appearing tissue in 1/3 to ½ of cases

    • o Lots of 2nd
    • primary tumors develop from the same preneoplastic precursor lesion or field,
    • with the remaining cases representing tumors that develop independently.
    • Researchers have proposed that patches of clonal cells can progress to develop
    • additional mutations and give rise to sub clones in a process known as clonal
    • divergence, which would account for the genetic heterogeneity typically seen
    • among these tumors.
  30. Verrucous Carcinoma
    • • Low-grade variant of oral SCC.
    • • If oral lesions, then probably associated with tobacco.
    • • HPV 16 and 18 are found in a minority of oral verrucous carcinomas.
    • • Some arise from the oral mucosa in people who chronically use chewing tobacco or snuff, typically in the area where the tobacco is habitually placed.
    • • Cases also occur in nonusers, but the exact figure is difficult to assess b/c patients will often deny the tobacco habit.
    • o If smokeless tobacco is used, SCC is more likely than VC.
    • • Clinical Features
    • o Extensive papillary white lesion of the maxillary vestibule
    • o Large, exophytic papillary mass of the maxillary alveolar ridge
    • • Histo
    • o Deceptively benign microscopic appearance.
    • • Characterized by wide and elongated rete ridges that appear to push into the underlying CT.
    • o Lesions usually show abundant keratin (parakeratin) production and a papillary or verruciform surface.
    • o Parakeratin typically fills the numerous clefts or crypts (parakeratin plugs) between the surface projections. Projections may be long and pointed or short and blunted.
    • o Lesional epithelial cells show normal maturation pattern w/ no significant degree of cellular atypia. There is frequently an intense infiltrate of chronic inflammatory cells in the subjacent connective tissue.
    • o Histo dx requires an incisional biopsy.
    • o 20% of these lesions have routine SCC developing concurrently w/in the verrucous carcinoma.
    • o Marked epithelial hyperplasia w/ a rough, papillary surface and keratin plugging.
    • o Bulbous rete ridges w/out significant dysplasia.
    • • Treatment and Prognosis
    • o Metastasis is extremely rare in VC, so tx of choice is surgical excision w/out radical neck dissection.
    • • 90% of pts are disease free after 5 years, although some qill require at least 1 additional surgical procedure during that time.
    • o Tx failures usually occur in pts with the most extensive involvement or in those unable to tolerate extensive surgery b/c of unrelated systemic diseases.
    • o Additional cause of tx failure is the initial inability to ID a focal squamous cell carcinoma arising concurrently w/in the less aggressive lesion.
    • o VC w/ SCC should be treated as SCC.
    • o Alternative primary tx: radiotherapy
    • • Provides poorer local control and is less effective than surgery.
    • • Also, poorly differentiated or anaplastic carcinoma has been shown to develop within the lesion after tx.
    • o Chemo may temporarily reduce the size of VC and may be an option for inoperable cases, but it is not considered a definitive, stand-alone tx.
    • o In a limited # of cases, tumor regression after radiochemotherapy or photodynamic therapy has been reported, although these tx alternatives require further study.
  31. Spindle Cell Carcinoma
    • Rare variant of SCC characterized by dysplastic surface squamous epithelium in conjunction w/ an invasive spindle cell element. May be indistinguishable from CT sarcomas or other spindle cell malignancies at the level of the light microscope.
  32. Nasopharyngeal Carcinoma
    • • Group of malignancies that arise from the lining epithelium of the lymphoid tissue-rich nasopharynx; similar tumors are found in the palatine tonsil and base of tongue.
    • o Waldeyer’s Ring
    • • Rare in most areas of the world. Could be environmental causative agent.
    • • Other factors: infection w/ EBV, diets deficient in vitamin C, consumption of salt fish that contains carcinogenic N-nitrosamines, tobacco
    • • Treatment and Prognosis
    • o Radiation and Chemotherapy
    • o Nasopharynx is relative inaccessible, and there is a high frequency of metastasis at diagnosis.
  33. Basal Cell Carcinoma
    • • Most common skin cancer (most common of all cancers) is locally invasive, slowly spreading, primary epithelial malignancy that arises from the basal cell layer of the skin and its appendages.
    • • Incidence increases with age, but there is a disproportionate increase among young adults (women).
    • • Mainly results from chronic exposure to UV radiation. Frequent sunburns, and tendency for freckling are associated w/ an increased risk.
    • • Less risk factors: exposure to significant ionizing radiation, ingestion of arsenic, immunosuppressive therapy, psoralen and UV A treatment (used for psoriasis). Associated w/ Gorlin syndrome.
    • • Dysregulation of the hedgehog signaling pathway is a critical early event in the development of basal cell carcinoma.
    • • Mutations in p53 are found in many sporadic BCC. May represent tumor development later on.
    • • Clinical Features
    • o Disease of adult whites, especially those with fair complexions.
    • o Most pts are 40+ yo at time of dx, but lesions may be detected early.
    • o Most lesions occur on the head and neck.
    • o Most common form: nodular basal cell carcinoma
    • • Begins as a firm, painless papule that slowly enlarges and gradually develops a central depression and an umbilicated appearance.
    • o Blood vessels are usually seen coursing over the rolled border surrounding the central depression. Expanding ulceration often develops in the central depressed area, and the patient may give a history of intermittent bleeding followed by healing.
    • • Untreated lesions continue to enlarge slowly over months and years, with ulceration and destruction of underlying structures, hence their historical name – rodent ulcer.
    • o Destruction of underlying bone or cartilage may occur, but metastasis is extremely rare.
    • o Some lesions can be pigmented [brown color]
    • • Histo
    • o Ulceration of the epidermal surface associated w/ an invading tumor of hyperchromatic epithelial cells.
    • o Islands of basophilic epithelium w/ peripheral palisading.
    • • Tx and Prognosis
    • o Depends on the size and site of the lesion.
    • • Small lesions – surgical excision, laser ablation, electrodesiccation and curettage
    • • Results in 95-98% cure rate
    • • Larger lesions – radical surgical excision and radiation therapy.
    • o Mohs micrographic surgery – used for slcerosing lesions, recurrent lesions, or those near embryonic planes of fusion
    • • Uses frozen section evaluation of specifically mapped and marked surgical specimens to determine whether tumor tissue has been left behind.
    • • If such tissue has been left behind, then the surgeon can return immediately to that particular area and remove more tissue, repeating the process until the patient is free of disease.
    • o Recurrence is uncommon, and metastasis is really rare.
    • o In pts w/ uncontrollable disease, death is usually the result of local invasion into vital structures.
    • o Pts who have had 1 are at risk for more, and also have increased risk of SCC.
  34. Sebaceous
    • • Characterized by a localize proliferation of sebaceous glands of the skin.
    • • Can be associated w/ cyclosporine, systemic corticosteroids, hemodialysis, and Muir-Torre syndrome (a rare autosomal dominant disorder characterized by visceral malignancies, sebaceous adenomas and carcinomas, and keratoacanthomas).
    • • Clinical features
    • o Lesions are usually umbilicated, with a small central depression, representing the area where the ducts of the involved sebaceous lobules terminate.
    • o Compression of the lesion usually causes sebum [thick yellow-white product of the sebaceous gland] to be expressed in the central depressed area.
    • • Helps distinguish sebaceous hyperplasia from basal cell carcinoma.
    • • Oral counterpart appears as a white to yellow papule or nodular mass w/ a cauliflower appearance, usually of the buccal mucosa.
    • o Multiple soft papules of the midface are umbilicated and small. Sebum can be expressed from the central depressed area.
    • • Histo
    • o Glands are enlarged and more numerous than normal, but they demonstrate no other changes.
    • • Tx and Prognosis
    • o None necessary except for aesthetic reasons or unless basal cell carcinoma cannot be eliminated from the clinical differential dx of Cutaneous lesions.
    • o Excisional biopsy is curative.
    • o Cryosurgery, electrodessication, laser therapYy, and photodynamic therapy are other methods.

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