Oral Cancer: Oral Cancer Michael E. Mermigas, DDS Assistant Professor of Pharmacology/Toxicology Mylan School of Pharmacy Duquesne University Pittsburgh, PA


Facts: Facts 30,000 Americans will be diagnosed with oral or pharyngeal cancer this year It will cause over 8,000 deaths, killing roughly 1 person per hour, 24 hours per day Of those 30,000 newly diagnosed individuals, only half will be alive in 5 years This is a number which has not significantly improved in decades


Facts: Facts The death rate for oral cancer is higher than that of cervical cancer, Hodgkins disease, cancer of the brain, liver, testes, kidney, or skin cancer (malignant melanoma If you expand the definition of oral cancers to include cancer of the larynx, for which the risk factors are the same, the numbers of diagnosed cases grow to 41,000 individuals, and 12,500 deaths per year in the US alone. Worldwide the problem is much greater, with over 350,000 to 400,000 new cases being found each year


Facts: Facts The death rate associated with this cancer is particularly high due to the cancer being routinely discovered late in its development Often it is only discovered when the cancer has metastasized to another location, most likely the lymph nodes of the neck


Facts: Facts Prognosis at this stage of discovery is significantly worse than when it is caught in a localized area Besides the metastasis, at these later stages, the primary tumor has had time to invade deep into local structures


Facts: Facts Oral cancer is particularly dangerous because it has a high risk of producing second, primary tumors This means that patients who survive a first encounter with the disease, have up to a 20 times higher risk of developing a second cancer


Facts: Facts This heightened risk factor can last for 5 to 10 years after the first occurrence There are several types of oral cancers, but 90% are squamous cell carcinomas


Age, gender, race, and ethnicity : Age, gender, race, and ethnicity The demographics of those who develop this cancer have been consistent for some time While he majority of people are over the age of 40 at the time of discovery, it does occur in those under this age There are links to young men and women who use "smokeless" chewing or spit tobacco


Age, gender, race, and ethnicity: Age, gender, race, and ethnicity Promoted as a safer alternative to smoking, it has in actuality not proven to be any safer to those who use it when referring to oral cancers It is also possible that those in this younger age group have a causal link which is viral based, since the amount of time they have been exposed to other known causative agents such as tobacco is short


Age, gender, race, and ethnicity: Age, gender, race, and ethnicity The human papilloma virus, particularly versions 16 and 18, has now been shown to be sexually transmitted between partners, and is implicated in the increasing incidence of young non-smoking oral cancer patients This is the same virus that is the causative agent in more than 90% of all cervical cancers


Age, gender, race, and ethnicity: Age, gender, race, and ethnicity From a gender perspective, for decades this has been a cancer which affected 6 men for every woman That ratio has now become 2 men to each woman It is a cancer which occurs twice as often in the black population as in whites, and survival statistics for blacks over five years are also poorer at 33%, versus 55% for whites


Age, gender, race, and ethnicity: Age, gender, race, and ethnicity Lifestyle choices still remain the biggest cause


Risk Factors : Risk Factors Age is frequently named as a risk factor for oral cancer, as most of the time it occurs in those over the age of 40 The age of diagnosed patients may indicate a time component in the biochemical or biophysical processes of aging cells that allows malignant transformation, or  perhaps, immune system competence diminishes with age


Risk Factors: Risk Factors It is likely that the accumulative damage from other factors, such as tobacco use, are the real culprits It may take several decades of smoking for instance, to precipitate the development of a cancer


Risk Factors: Risk Factors Tobacco- 75% of all dx tobacco users Alcohol- heavy usage Alcohol + Tobacco- Those who both smoke and drink, have a 15 times greater risk of developing oral cancer than others Considered both chemical and lifestyle factors Ultraviolet radiation- lip and skin cancers Have decreased over the years due to use of sunblocks and education Radiation exposure


Risk Factors: Risk Factors Biologic Factors Virii and fungi HPV is a common, sexually transmitted virus, which infects about 40 million Americans 1% of those infected, have the HPV16 strain which is a causative agent in cervical cancer, and now is linked to oral cancer as well


Signs and Symptoms: Signs and Symptoms One of the real dangers of this cancer, is that in its early stages, it can go unnoticed It can be painless, and little in the way of physical changes may be obvious The good news is however, that your dentist or doctor can see or feel the precursor tissue changes, or the actual cancer while it is still very small, or in its earliest stages


Signs and Symptoms: Signs and Symptoms White or red patch in the oral cavity Small indurated ulcer which looks like a common canker sore Many benign tissue changes that occur normally in your mouth, and some things as simple as a bite on the inside of your cheek may mimic the look of a dangerous tissue change, it is important to have any sore or discolored area of your mouth, which does not heal within 14 days, looked at by a professional


Signs and Symptoms: Signs and Symptoms Lump or mass in the mouth or felt in neck Pain or difficulty in swallowing, speaking or chewing Wart like lesion Common areas Lip Tongue Floor of mouth


Slide23: Indurated= hardened lesion


Slide24: Stratum   corneum Cells of the cornified layer are dead, protective keratinized "squames", eventually sloughed off. Stratum granulosum. The presence of this layer is diagnostic for keratinized stratified squamous epithelium. Stratum basale Cells of the basal layer are attached to the basement membrane (dashed line) by hemidesmosomes.  When a basal cell divides, one of the daughters migrates upward to replenish outer layers of cells. Stratum spinosum.  Cells of the "prickle-cell" layer are attached to one another by desmosomes ("spines") and reinforced by tonofilaments.  These cells gradually move outward as new cells are formed from the basal layer


Key Points in Progression of Oral Carcinoma: Key Points in Progression of Oral Carcinoma Hyperkeratosis Dysplasia Erythroplakia Carcinoma in Situ Squamous Cell Carcinoma


Stratified Squamous Epithelium: Stratified Squamous Epithelium


Hyperkeratosis: Hyperkeratosis Excessively thickened layer of the stratum corneum composed of orthokeratin (hyperorthokeratosis) or parakeratin (hyperparakeratosis). Clinical features:  mucosal lesion anywhere in the oral cavity    appears lighter in color than the normal color    flat or raised    may be rough    duration may be weeks to months    cannot be wiped off    usually adult occurance


Hyperkeratosis: Hyperkeratosis Etiology chronic  irritant Thickened keratin layer   Organized connective tissue layer    Possible to have inflammatory reaction in connective tissue due to irritation    Normal maturation of epithelial cells    No evidence of dysplasia 


Histologic Features: Histologic Features hyperkeratosis Stratified squamous epithelium Connective tissue stroma


Hyperkeratosis: Hyperkeratosis


Hyperkeratosis: Hyperkeratosis Main Pathologic Process     benign hyperkeratosis Treatment   removing cause of lesion    may be excised Prognosis good


Dysplasia: Dysplasia A pre-malignant change in epithelium characterized by a combination of individual cell and architectural alterations


Dysplasia: Dysplasia Clinical features white leukoplakic lesion of the oral mucosa    duration varies from months to years


Dysplasia: Dysplasia


Differential Diagnosis: Differential Diagnosis hyperkeratosis    squamous cell carcinoma   epthelial dysplasia    lichen planus


Histologic Features: Histologic Features basal cell proliferation    pleomorphism (cell variation)    mitotic activity, hyperchromatic nuclei    dyskeratosis (abnormal keratosis)    premalignant (cellular change in the epithelium and noinvasion into the connective tissue) 


Slide40: Basal cell proliferation pleomorphism Hyperchromatic nuclei premalignancy


Dysplasia Treatment: Dysplasia Treatment removing the cause    biopsy the lesion to determine severity of dysplasia


Dysplasia Prognosis: Dysplasia Prognosis may regress to normal in early stages    usually considered to be premalignant


Erythroplakia: Erythroplakia A chronic red oral mucosal patch usually not attributed to traumatic, vascular or inflammatory causes but frequently caused by epithelial dysplasia, ca in situ, or squamous cell carcinoma.


Erythroplakia- Clinical Features: Erythroplakia- Clinical Features asymptomatic red macule or patch on a mucosal surface floor of mouth, tongue and palate multiple lesions may be present typical oral lesion is less than 1.5 cm. well-demarcated from the surrounding pink mucosa surface is typically a smooth, soft, velvety texture and regular in coloration predominantly a disease of older men


Erythroplakia- Clinical Features: Erythroplakia- Clinical Features


Differential Diagnosis: Differential Diagnosis atrophic candidiasis erythroplakia focal inflammed mucosa


Erythroplakia- Histologic Features: Erythroplakia- Histologic Features a lack of keratin production in the epithelium thin atrophic epitheliium covering the underlying microvasculature underlying connective tissue often demonstrates chronic inflammation along with increase in size and number of vascular structures


Erythroplakia Treatment: Erythroplakia Treatment biopsy to determine the exact nature of the lesion Prognosis depends on the specific histopathologic diagnosis


Carcinoma in Situ: Carcinoma in Situ White, red, or red/white patch on lining mucosa; may also appear as a small (<1.0 cm) soft ulcer.


Carcinoma In Situ- Histologic Findings: Carcinoma In Situ- Histologic Findings Anaplasia with or without hyperkeratosis; no invasion Anaplasia= cells lack differentiation


Carcinoma In Situ- Histologic Findings: Carcinoma In Situ- Histologic Findings


Squamous Cell Carcinoma: Squamous Cell Carcinoma Malignant neoplasm of stratified squamous epithelium that is capable of locally destructive growth and distant metastasis


Squamous Cell Carcinoma: Squamous Cell Carcinoma   possible sites        lower lip        tongue        floor of the mouth        soft palate        gingival / alveolar ridge        buccal mucosa    more common in adult males    early presentation of leukoplakias and erythroplakias    painless ulcer, tumorous mass, or verrucous (papillary growth)    painless ulcer, tumorous mass, or verrucous (papillary growth)    occasionally loosening or loss of teeth    possible paresthesia of the teeth and lower lip


Differential Diagnosis: Differential Diagnosis squamous cell carcinoma    primary syphilis    tuberculosis    deep fungal infection    traumatic ulcerated granuloma


Histologic Findings: Histologic Findings increased mitotic activity    well differentiated    keratin pearls (abnormal keratinization)    hyperchromatic nuclei    pleomorphism    epithelium islands    connective tissue stroma with chronic inflammation (histiocytes, lymphocytes, etc.)


Slide64: Keratinized Cells Inflamed connective tissue stroma


Squamous Cell Carcinoma: Squamous Cell Carcinoma Treatment:    surgical excision, radiation therapy or both  Prognosis:    left untreated, metastasis via the lymphatic vessels most often to the lungs and liver


Key Points: Key Points Reduce risk factors Regular Screening Early detection Appropriate treatment


Basal Cell Carcinoma: Basal Cell Carcinoma Common, locally destructive, non-metastasizing malignancy of the skin composed of medullary patterns of basaloid cells.


Variants : Variants  Nodular (noduloulcerative) - A pearly, semitransparent papule or nodule often with telangectasia, a central depression and a rolled back waxy border. Ulceration and crusting (rodent ulcer) is not an uncommon finding. Lesions frequently occur on the face.     Superficial - An erythematous, slightly scaling, round, well demarcated, eczematous appearing patch with a pearly rolled border. Lesions often appear atrophic with central erosion and crusting. This type of lesion is most commonly found on the thorax.    


Variants: Variants Scarring (morpheaform) - An atrophic, slightly eroded, crusted plaque that resembles a scar. This is the least common but most aggressive type of BCC.     Pigmented - Shiny, blue-black papules, nodules or plaques. These lesions can also have a pearly, waxy rolled back border and the pigment within lesion may appear uneven or speckled.


Slide71: Nodular


Slide72: Superficial


Slide73: Scarring


Slide74: Pigmented


Clinical Features: Clinical Features males are more affected than females   4th decade of life or older    located primarily on sun exposed areas of head and neck with the nose being the most common site    risk factors: childhood sun exposure, blistering sunburns, fair skin, blue eyes, blonde or red hair


Differential Diagnosis: Differential Diagnosis basal cell carcinoma   sebaceous gland hyperplasia    molluscum contagiosum    pigmented nevus    squamous cell carcinoma    malignant melanoma    seborrheic keratosis


Etiology: Etiology ultraviolet (UV) rays from the sun


Tissue of Origin : Tissue of Origin basal cell layer of epithelium


Histologic Features : Histologic Features round to ovoid solid nests of tumor cells showing multiple cystic areas    cells are uniform in size and polygonal in shape with prominent nuclei and scant cytoplasm    invasion into the connective tissue


Treatment : Treatment surgical excision    Mohs´ surgery Mohs surgery is a method where the skin cancer is removed in multiple layers. The tissue is mapped and carefully marked so that its exact location can be pinpointed in the area it was removed. The tissue removed is processed by a specially trained technician into microscope slides. These slides are then examined by your surgeon for evidence of any remaining cancer cells. If any cancer cells are present, your Mohs surgeon is able to go back and remove additional layers in areas only where the cancer is persistent. This process is repeated until no cancer cells are present in the specimen.    electrodessication and curettage    radiation therapy


Prognosis : Prognosis recurrence is uncommon if properly treated    locally destructive and metastases are exceptionally rare


Malignant Melanoma: Malignant Melanoma (Malignant Melanoma, Melanocarcinoma)


Malignant Melanoma: Malignant Melanoma Malignant neoplasm of melanocytes occurring on skin and mucosal surfaces that commonly has a radial and superficial initial growth period before it extends into the deeper underlying tissues and metastasizes


Types: Types Superficial Spreading Melanoma     Lentigo Maligna Melanoma     Acral Lentiginous Melanoma     Nodular Melanoma


Superficial Spreading Melanoma: Superficial Spreading Melanoma Most common form of malignant melanoma, initially appearing as an irregularly shaped brown-black macular area with jagged borders and satellite lesions in which areas of nodular melanoma eventually develop


Clinical Presentation: Clinical Presentation most common in middle aged adults    begins as a small, flat, asymmetrical, unevenly brown-pigmented lesion with various shades of red, white, and blue.    grows outward across the surface of the skin


Differential Diagnosis Superficial Spreading Melanoma: Differential Diagnosis Superficial Spreading Melanoma superficial spreading melanoma    pigmented basal cell carcinoma    seborrheic keratosis    benign nevus    hemangioma


Superficial Spreading Melanoma: Superficial Spreading Melanoma Unknown etiology


Histologic Features: Histologic Features horizontal growth phase:         atypical cells are uniform in shape and size        finely granular cytoplasm and large nuclei with prominent nucleoli    vertical growth phase:         epithelioid cells, spindle cells, nevus-like cells or combinations of each        pigmentation is variable        chronic inflammatory infiltrate is usually present in the subjacent dermis


Superficial Spreading Melanoma: Superficial Spreading Melanoma Treatment:    wide excision Prognosis:    depends on the staging of the lesion


Lentigo Maligna Melanoma: Lentigo Maligna Melanoma (Hutchinson´s Freckle)


Lentigo Maligna Melanoma: Lentigo Maligna Melanoma Slowly evolving melanoma that develops within a pre-existing pigmented macular lesion on the sun-exposed skin of elderly patients


Clinical Presentaion: Clinical Presentaion more common in elderly patients    on skin that is exposed to sun: face, head and upper extremities    flat, mottled, tan-to-brown freckle-like spots with irregular borders    grows outward very slowly gradually forming nodules    flat, mottled, tan-to-brown freckle-like spots with irregular borders


Differential Diagnosis: Differential Diagnosis lentigo maligna melanoma    solar lentigo    pigmented actinic keratosis    seborrheic keratosis    common acquired nevi    dysplastic nevi


Etiology: Etiology unknown


Histologic Features: Histologic Features epidermal atrophy    single dispersed atypical melanocytes along the basal layer of the epidermis    euplastic cells invade the connective tissue    nodule is usually composed of spindle shaped melanocytes    melanin uptake by surrounding melanophages


Lentigo Maligna Melanoma: Lentigo Maligna Melanoma Treatment:    wide excision Prognosis:    depends on the staging of the lesion


Acral Lentiginous Melanoma : Acral Lentiginous Melanoma Mucosal Lentiginous Melanoma


Acral Lentiginous Melanoma: Acral Lentiginous Melanoma A melanoma that is a brown, irregularly shaped macular lesion of the unexposed skin of the hands and feet that undergoes progression to nodular melanoma


Clinical Features: Clinical Features patients older than 60 years    most common in Africans and Asians    occurs on non-hair-bearing sites: soles, the palms, the digits, subungual and periungual areas, and mucosal surfaces    dark patch


Differential Diagnosis: Differential Diagnosis acral lentiginous melanoma   benign nevus    benign pigmented streak in nails    hematoma 


Acral Lentiginous Melanoma: Acral Lentiginous Melanoma Unknown etiology


Histologic Features: Histologic Features proliferation of individual large atypical melanocytes at the basal region of the epithelium    single melanocytes and clusters of melanocytes are dispersed through the full thickness of the epidermis.    predominantly spindle-shaped neoplastic melanocytes extend into the connective tissue


Acral Lentiginous Melanoma: Acral Lentiginous Melanoma Treatment Wide excision Prognosis    depends on the staging of the lesion    seldom metastasizes


Nodular Melanoma : Nodular Melanoma A form of melanoma of the skin and occasionally the mucosa that arises as a raised mass with a limited macular radial-growth phase, quickly invades and metastasizes and consists of a wide variety of cell shapes and sizes


Clinical Presentation: Clinical Presentation 10-15% of melanomas    small, smooth, firm, blue-black or dark gray, papules or nodules   typically has a raised "blueberry" appearance    considered to be the most aggressive form of the cancer    usually found on the legs in women and the trunk in men


Differential Diagnosis: Differential Diagnosis nodular melanoma    basal cell carcinoma    squamous cell carcinoma    merkel cell tumor    atypical fibroxanthoma    early dermatofibroma    inflamed intradermal nevus


Etiology: Etiology unknown, possibly ultraviolet (UV) rays from the sun


Histology: Histology malignant melanocytes and melanin production    dermal component is usually composed of epithelioid type of cells    epidermal invasion


Nodular Melanoma: Nodular Melanoma Treatment:    surgical excision  Prognosis:    poor, metastasis to lymph nodes


Malignant Melanoma: Malignant Melanoma Oral Course


Clinical Features: Clinical Features males more often than females    usually palate or maxillary gingiva    5th decade or older    ABCD Clinical Features         Asymmetry (uncontrolled growth pattern)         Border irregularity         Color variation        Diameter greater than 6 mm


Differential Diagnosis: Differential Diagnosis nevi    melanotic macules    amalgan tattoo    Kaposi´s sarcoma    melanoma    physiologic pigmentation


Malignant Melanoma: Malignant Melanoma Etiology    unknown but possibly UV radiation induced DNA damage


Histology: Histology lentiginous (spindle-shaped) or epithelioid hyperplasia of melanocytes    random cytological atypia with enlarged hyperchromatic melanocytic nuclei    nests of melanocytes bridging or adjacent to rete ridges    lamellar and concentric dermal fibroplasia    patchy or diffuse superficial dermal lymphocytic infiltrate   elongation of rete ridges   radial growth phase - neoplastic cells spread laterally in all directions remaining in the surface epithelium    vertical growth phase - neoplastic cells invade the connective tissue


Melanoma Staging: Melanoma Staging The Clark system of measurement assigns a "level" to the lesion that depends on the deepest anatomic cutaneous region that has been invaded by tumor cells. The Breslow classification is based on the actual measurement of the distance from the top of the granular cell layer to the deepest identifiable point of tumor invasion.


Malignant Melanoma: Malignant Melanoma Treatment:    complete surgical excision   chemotherapy   radiation  Prognosis:    depends on the staging of the lesion   metastasis occurs frequently to the lungs and lymph nodes


Questions?: Questions?