Published on January 4, 2008
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?