E2 Study Guide Combined PDF

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Pink = high yield Yellow = tutor Yellow Star = test question Bold/Blue = lecture emphasis Purple = professor/D4 Green = quiz EXAM MATERIAL Ana Goldstein L11-12: VIRAL INFECTIONS PATHOLOGY DEFINITION CAUSE/EFFECT (SYMPTOMS) FUN FACTZ HERPES VIRUS -Human herpesvirus (HHV) -All 8 types cause and primary infection and remain latent for -Humans are the only natural reservoir for these officially known as life. With reactivation, they can cause recurrent infections viruses Herpetoviridae -Shed in saliva or genital secretions Herpes Simplex -DNA virus (stable) Diseases/Infections related to HSV: -Testing HSV: Antibody titers useful Virus -Includes HHV 1 and HHV 2 -Erythema multiforme: more than 15% of cases of this are -Dx à cytologic smear and tissue biopsy -HHV 1 à Affects pharynx, preceded by a symptomatic recurrence of HSV 3-10 days -Asymptomatic oral HSV shedding in up to 10% of intraoral sites, lips, eyes, and earlier. Frequent EM warrants antiviral prophylaxis the general population. During periods of stress, viral skin above waist. Spread through -Herpetic whitlow (herpetic paronchia): infections of thumbs shedding rises to 1/3 of people previously exposed infected saliva or active perioral or fingers. Self-inoculated in children. -HSV is leading infectious cause of blindness in the lesions -Herpes gladiatorum (scrumpox): wrestlers and rugby players, US Autoinoculation of eyes -HHV 2 à Typically involves areas of abrasion -Acyclovir suspension for children (15 mg/kg or up to genitalia and skin below the -Herpes barbae: on bearded region, related by daily shaving adult dose of 200 mg) waist. Spread through sexual -Penciclovir cream (Denavir) started at prodrome contact Histopathologic features: -Systemic medications include acyclovir, famciclovir, -Infected epithelial cells exhibit Tzanck cells (acantholytic valacyclovir. Latter 2 are better and more epithelial cells), nuclear clearing, and nuclear enlargement convenient. (ballooning degeneration) -For patients (dental) 2g Valtrex (Valacyclovir) bid on -Acantholysis: loss cellular cohesion, nuclear clearing, and day of procedure and 1g taken bid the next day enlargements. Termed ballooning degeneration. Tzanck cells -Prophylaxis à acyclovir (400 mg bid), Valacyclovir (1 g daily), famciclovir (250 mg bid) -Primary Herpes -Occurs after initial exposure -Often asymptomatic -Typically, young age HHV 1 without antibodies to the virus -Symptoms in young patient à gingivostomatitis -Virus is taken up by sensory ganglia -HSV does not survive long in the -Symptoms in adults à pharyngotonsillitis -After primary exposure, most frequent site of external environment, and latency is the trigeminal ganglion almost all primary infections -Travels along the axons of the sensory neurons to occur from contact with an travel back and forth to the peripheral skin or infected person who is releasing mucosa the virus -Very rare to see in the mouth -Acute -Most common pattern of -Onset abrupt and often accompanied by anterior cervical -Mostly age 6 months to 5 years herpetic symptomatic primary HSV lymphadenopathy, chills, fever, nausea, anorexia, irritability, -Peak prevalence age 3 gingivostomatitis -Percentage of primary care and oral ulcers -Kids are likely to self-inoculate and spread the infections may be higher than -Can range from mild to severely debilitating lesions to and from the fingers, eyes, and genitals reported -Small vesicles form which rapidly collapse to form numerous -Mild cases last 7 days -Mostly affects gingiva red lesions then ulcerate -Severe cases last 14 days -Both movable and attached mucosa affected -In all cases, gingiva is enlarged, painful, and extremely erythematous -Distinctive punched out erosions – free gingiva -Perioral skin commonly affected -Primary -Primary herpes symptoms in -Initial Sx includes sore throat, fever, and malaise -Affects young adults – higher socioeconomic groups Herpes adults -Numerous small vesicles in the tonsils and pharynx -Most frequent site of latency is the trigeminal Pharyngotonsilitis -Mostly affects back of mouth -Diffuse, gray yellow exudate over the ulcers ganglion -Travels along the axons of the sensory neurons to travel back and forth to the peripheral skin or mucosa -Secondary or -Symptomatic recurrences are -Prodromal signs: symptoms that occur 6-24 hours before -HSV can be reactivated by old age, UV, Recurrent Herpes common lesions develop include pain, burning, itching, tingling, physical/emotional stress, fatigue, heat/cold, -Affect epithelium supplied by localized warmth, and redness/erythema of the involved pregnancy, dental trauma, respiratory illness, fever, HHV 2 sensory ganglion epithelium menstruation, systemic diseases, and malignancy -Occur on surface epithelium -Almost always limited to keratinized mucosa such as -Healing within 7-10 days supplied by the involved attached gingiva, hard palate. Likely won’t see these lesions -About 2 recurrences per year is normal but may ganglion on the inner lips, floor of mouth, cheeks, or under the tongue. occur more frequently -Most common site: vermillion -Begin as 1-3 mm vesicles -Crusted lesions indicate that the virus is no longer border and adjacent skin of lips -Rapidly collapse to form a cluster of erythematous macules shedding herpes labialis (cold sore or -Coalesce or slightly enlarge fever blister) – 30% US -Yellowish area of ulceration develops population -Symptoms most severe in first 8 hours -Mostly hard palate, lip, and -Rupture of vesicles may release virus-filled fluid which can attached gingiva spread lesions HHV 3 -Varicella Zoster Virus (VZV) -VZV Vaccine is 98% effective and extensively used in -Primary infection is chicken pox Japan -Secondary infection is Zoster -Chicken Pox -Primary infection HHV 3 -Malaise, pharyngitis, rhinitis -Contagious from 2 days before until all lesions crust -Characteristic intensely itchy rash -More severe in adults -Each lesion rapidly progresses through stages of erythema à vesicle à pustule à hardened crust -Successive crops over 3-4 days -Oral lesions are fairly common. Tend to be painless Resemble HHV1 without pain -Gingival lesions resemble primary herpes  -Zoster/Shingle -Secondary infection HHV 3 -Predisposing factors: immunosuppression, cytotoxic drugs, -10-20% of individuals -After initial infection, VZV is radiation, malignancies, old age, alcohol abuse, and dental -Prevalence increases with age transported up sensory nerves manipulation -Single occurrence more common than multiple and establish latency in dorsal -Begins with pain in the area. Prodromal pain present 1-4 days recurrences spinal ganglia before -Eye involvement of Herpes Zoster can cause -Typically, one dermatome affected (Geometric) blindness or death -Vesicles become pustular à ulcerate à crusts after 7-10 days -Tx: supportive, topical analgesics, steroids to -Scarring not unusual minimize associated neuralgia -Lesions follow path of nerve and terminate at midline -Resolves within 2-3 weeks -Pain lasting > 1 month = postherpetic neuralgia (severe, shooting pain due to damaged or irritated nerve) -Tip of nose affected à nasociliary branch of 5th nerve A suggests possible ocular infection. Huge red flag for potential blindness! Hutchinson Sign -Oral lesions: movable or bound mucosa, often extends to midline -Ramsay hunt syndrome: 7th/8th nerve involvement (facial and HHV 4 -Epstein Barr Virus A auditory nerves). Cutaneous lesions of external auditory meatus. Facial paralysis, hearing deficits, vertigo -Fever, pharyngitis, tonsillitis -Symptomatic infections in young adults -Infectious mononucleosis -Prominent lymphadenopathy (>90%): typically enlarged, -Asymptomatic in children -Glandular Fever or Kissing symmetric, tender, frequently posterior/anterior cervical -Dx: increased WBC and presence of Paul-Bunnell Disease chains. heterophil antibody (monospot, mono-test) -Occurs by intimate contact, >80% tonsillar enlargement with abscess -Resolves within 4-6 weeks direct salivary transfer such as -Classic oral sign = petechiae on palate in about 25% shared straws or kissing -ANUG is fairly common & HHV 5 -Cytomegalovirus -Almost 90% asymptomatic -Most clinically evident disease found in neonates or -Can reside latently in salivary -Infants: encephalitis leads to mental and motor retardation immunosuppressed glands, endothelium, -Acute adult infection similar to infectious mono -Preemie babies macrophages, and lymphocytes ENTEROVIRUS -More than 30 exist, +ssRNA -Herpangina -Caused by coxsackie virus A -Acute onset sore throat, dysphagia, and fever -Very similar to herpes -Oral lesions (2-6) around the soft palate or tonsillar pillars. Looks like mono -Almost always affects soft Begin as red macules à vesicles à rapidly rupture palate or tonsillar pillars -Usually less severe infection. Less fever, and lymphadenopathy -Hand food -Caused by coxsackie virus A16 -Oral lesions almost always present, numerous (1-30) -Very common in daycares and swimming pools mouth disease -Most well-known enterovirus -Sore throat, mild fever infection -Skin: 1-100 red lesions on palms and soles and the ventral surfaces/sides of fingers and toes Rubeola -Measles -Incubation (10-12 days) -Vaccine since 1963 is 95% effective -Paramyxovirus -Begins with prodromal symptoms of fever, malaise, runny -In immunocompromised, high risk of complications -Spread via respiratory droplets nose, conjunctivitis, and cough and death -Exanthematous rash follows and lasts 4-7 days -Fatality rate of measles in patients with a -Distinct oral manifestation = Koplik spots à multiple areas of malignancy is more than 50% erythema on buccal and labial mucosa, with areas of numerous small bluish-white macules Rubella -German Measles -Congenital rubella syndrome: risk correlates with time of -Greatest importance = teratogenic (affects the -Mild illness produced by a infection. Frequency of transmission from an infected mother growing fetus) togavirus is more than 80%. Classic triad = deafness, heart disease, and -Transmitted to nearly 100% of individuals in close -Spread via respiratory droplets cataracts living conditions -Effective vaccine since 1969 -Vaccination of post pubertal females must be stressed Mumps -Epidemic parotitis -About 30% of infections are subclinical -Incidence decreased by 98% -Paramyxovirus -Parotid gland involved most frequently -Primarily affects salivary glands -Discomfort, swelling surrounding lower half of external ear -Spread via urine, saliva, or and extending down along the posterior inferior border of respiratory droplets adjacent mandible -Peaks within 2-3 days – pain most intense HIV/AIDS -HIV recovered from serum, -Normal response to pathogen diminishes -Most common CNS-AIDS-Dementia complex blood, saliva, semen, tears, -Primary target is CD4+ helper T lymphocyte -Kaposi’s sarcoma in 15-20% (HHV8) urine, breast milk, ear -Decrease in T helper cells + loss immune function -Non-Hodgkin’s lymphoma is the 2nd most common secretions, and vaginal -Initial exposure (acute self-limited viral syndrome) à malignancy secretions asymptomatic stage (averages 8-10 years) à final -Routes of transmission: sexual symptomatic stage contact, parenteral exposure to -Asymptomatic period variable and affected by nature of virus, blood, or mother to fetus host immune reaction -Saliva is NOT a significant source of transmission Clinical features  -Acute viral syndrome 1-6 weeks after exposure. Classic sign of acute viral syndrome = persistent generalized lymphadenopathy -Generalized lymphadenopathy, sore throat, fever, rash, headache, myalgia, etc. -AIDS related complex (ARC): chronic fever, weight loss, diarrhea, oral candidiasis, herpes zoster, oral hairy leukoplakia -In 50%, pneumocystis carinii pneumonia is the presenting condition when diagnosis is made -HIV related -Classic sign of acute viral -Enlargement fluctuates, usually > 1 cm -1/3 have AIDS within 5 years persistent syndrome -Axillary involvement, followed by post cervical enlargement generalized -Head and neck initial location lymphadenopathy most common -HIV related -Most common intraoral -Chronic multifocal involvement common -Often the presenting sign leading to diagnosis Candidiasis manifestation -Unusual candida presentation because there is a -Systemic medication indicated dysfunctional immune system Atypical oral candidiasis -HIV associated -4 patterns: gingivitis, -Linear gingival erythema: distinct red border along free -Not responsive to improved plaque Periodontal periodontitis, necrotizing gingival margin across the entire dentition. Extends 2-3mm control/conventional periodontal therapy Disease stomatitis of periodontal origin, apically. If you see this, ask your patient to get tested for HIV! -Debridement, antimicrobial therapy, follow-up care, and acute necrotizing ulcerative -Necrotizing periodontitis: severe deep pain, gingival long-term maintenance gingivitis (ANUG) hemorrhage, soft tissue necrosis, and rapid loss of support. -Chlorhexidine mouth rinses Deep pocketing is NOT typical. More than 90% of support/bone may be lost in a few weeks. Defects are usually X2 localized (unlike periodontitis) -HIV related -Herpes Simplex in HIV patients -Affects both attached and unattached mucosa (Recall, -Persistence of HSV infection for more than 1 month HSV is more wide-spread and has an Recurrent HSV only affected attached mucosa) in an HIV+ patient = definitive AIDS atypical pattern -May persist for months -HIV related EBV -Causes oral hairy leukoplakia -Oral hairy leukoplakia ranges from faint white vertical lines to -Differential diagnosis: tongue chewing and on lateral tongue thickened and furrowed areas of leukoplakia idiopathic leukoplakia -Often superadded candida infection -Need biopsy Karposi’s Sarcoma -Multifocal neoplasm of vascular -Multiple lesions of the skin or oral mucosa -Biopsy required endothelial cell origin -Oral lesion in 50% à hard palate and gingiva. Begin as flat, -Tx: chemo -Trunk, arms, head, and neck brown or reddish-purple zones develop into plaques or -Progressive malignancy that nodules may disseminate widely to lymph nodes and various organ systems LESS COMMON -Lesions clinically similar to ORAL aphthous ulcers MANIFESTATIONS -Human -Oral lesions usually multiple Papillomavirus (HPV) -Histoplasmosis -Most common respiratory -Oral lesions not uncommon fungal infection in the US -Most common oral lesion à chronic, indurated ulcer with a -Disseminated in ~5% raised border -HIV associated -Common in children -Bilateral parotid involvement in 60% salivary gland disease -Rare -Plasmablastic lymphoma very -Non-nodal locations, e.g. CNS most common site -Dx: viral culture or HIV antibodies or antigens, ELISA Lymphoma in specific to the oral cavity -Oral lesions à soft tissue enlargement of palate/gingiva (can be false positive/negative or cross-reactions), HIV/AIDS -Almost exclusively in HIV/AIDS -Aggressive 600, there is no increased risk. lymphoma You can perform extractions, etc. -Probably related to EBV -If patient has CD4+ < 200, severe immune depression, major opportunistic infections, poor prognosis  L13-15: PHYSCIAL AND CHEMICAL INJURIES PATHOLOGY DEFINITION/PREVALENCE CAUSE/EFFECT FUN FACTZ Linea Alba - “White line” – common alteration -Associated with pressure, frictional irritation, or sucking -Present in 13% of young people of buccal mucosa seen at the same trauma -Nothing to be concerned about level of occlusal plane -Usually bilateral and scalloped -Tx: none Mursicatio Buccarum -Chronic cheek chewing -Seen in stress or psychologic conditions -2x more likely in females -Most frequently on buccal mucosa, -Bilateral on buccal mucosa -3x more likely after age 35 but also labial mucosa and lateral -Thickened, shredded white areas (keratin) -Differential Dx: oral hairy leukoplakia borders of tongue -May be able to remove shreds of white material -Tx: none. Soft splint may be fabricated -On the tongue, clinically resembles oral hairy -Most important is clinical recognition and leukoplakia association picture Traumatic ulcerations -Aka Traumatic granuloma -Due to acute or chronic trauma -Differential Dx: clinically resembles SCCa. Take a ~ -Histologically unique à traumatic -May be present for long periods of time biopsy. Probably not cancer if the ulcer is recent granuloma, deep “pseudoinvasive” & -Areas of redness, surrounding a central removable (cancer is slow growing) or if the lesion is on the inflammatory reaction and slow to yellow membrane dorsum on the tongue (cancer is rare in this area) resolve -May have a rolled white border of hyperkeratosis -Tx: If no healing, biopsy is indicated -Most often on tongue, lips, and -May last 1 week to 8 months -If there is rapid healing after a biopsy, it was buccal mucosa -Traumatic granulomas à extend into deeper tissues and likely to be a traumatic granuloma (biopsy/injury exhibit sheets of benign histiocytes intermixed with promotes angiogenesis and healing) eosinophils Electrical/ Thermal -Fairly common; ~5% of all burn -Result from chewing or biting through a live wire -Pizza is the most common cause of thermal burn Burns admissions to hospitals (electrical) or ingestion of hot foods/beverages (thermal) -Occur in children younger than 4 -Lips most frequently affected -With a bad electrical burn, be careful of contracture of -Commissure is commonly involved mouth opening à significant microstomia can develop -Thermal food burns à usually on palate or posterior buccal mucosa Chemical injuries of -Due to many medications such as -Aspirin pH is very acidic (below 4). It dissolves fast and -Can be caused by too much mouthwash oral mucosa aspirin gives pain relief, but can cause severe burns in the oral -Can be caused by E-cigarette liquids (propylene -Silver nitrate, formoscresol, sodium cavity glycol, vegetable glycerin, or natural flavorings. hypochlorite, paraformaldehyde, -Reaction to Arm and Hammer Tartar Control dental cavity varnishes, and acid-etch Toothpaste materials -Tx: prevention of exposure -Hydrogen peroxides of 3% or greater Viadent Induced -Aka Sanguinaria induced leukoplakia -Leukoplakia of maxillary vestibule in 84.1% of patients -Tx: none Leukoplakia -Sanguinaria extract is derived from -Also affects the attached gingiva and vestibular mucosa -Initial biopsy mandatory the common bloodroot plant and has -Usually distinct and sharply demarcated -If histopathological Dx of dysplasia, treat like been in oral rinses and toothpastes -Prolonged retention of product in these areas due to potential premalignant since 1982 à effective against distance from major salivary ducts -Complete discontinuation plaque/gingivitis and carcinogenic -Significant keratosis with a verrucoid pattern -Careful clinical follow up with biopsy of any -Minimal atypical changes recurrent or worsening lesion Oral complications of -The mouth is a common site for -Clinical features include mucositis and hemorrhage cancer therapy complications related to cancer -Following outcomes possible: xerostomia, loss of taste therapy (hypogeusia), osteoradionecrosis, trismus, chronic dermatitis, and developmental abnormalities -Hemorrhage -Secondary to thrombocytopenia (low platelets) -Mucositis -Inflammation of oral cavity -Caused by radiation or chemotherapy -Slowly resolves in 2-3 weeks after cessations of -Develops a few days after radiation -Whitish discoloration followed by ulceration treatment mucositis -Pain, burning, and discomfort when eating -Tx: topical anesthetics, analgesics, coating agents -Xerostomia -Common complication of cancer -Loss of saliva is progressive, persistent, and irreversible -Salivary glands are very sensitive therapy -Dramatic decrease in saliva in first 6 weeks of treatment -Tx: sugarless candies/chewing gum, systemic -Increase in cervical caries index cholinergic drug (pilocarpine), and daily topical fluoride in fluoride trays -Osteoradionecrosis -Serious complication of radiation -Mandible – most frequently due to diminished blood -Prior to radiation, all questionable teeth should -Permanent damage to the supply be extracted or restored to avoid osteocytes and microvasculature -Radiation dose is the main factor osteoradionecrosis -Post radiation dental extractions avoided -Tx: hyperbaric oxygen ($$$), in combination with antibiotics and local debridement -Trismus -Difficulty in opening due to effects -Extensive difficulties for hygiene and dental treatment of radiation on muscles of mastication  TQ: What causes petechiae? all of the above thrombocytopenia, vomiting, coughing, hand foot mouth, herpangina, infectious mono Submucosal -Petechiae: minute hemorrhages -Etiology: repeated or prolonged increased intrathoracic -Ill-fitting dentures or rubber dams may cause hemorrhage into skin/mucosa & pressures due to repeated coughing, convulsions, giving ecchymosis -Purpura: slightly larger area - birth, vomiting, etc. -Biting the cheek very hard may cause hematoma -Ecchymosis: measuring > 2 cm -Other causes: thrombocytopenia and DIC viral infections -Hematoma: accumulation of blood (infectious mono and measles) within tissue with mass formation Amalgam Tattoo -Implantation of amalgam à areas -Appear black, blue, or grey -Really common of mucosal abrasion, broken -Well defined borders but may be diffused -PA x-rays are negative amalgam into extraction sites, or -Most common sites: gingiva, alveolar mucosa, and -May be confused with melanoma, especially in endodontic retrofill procedures buccal mucosa (near teeth) large areas of pigmentation -Mercury is released from dental -May necessitate biopsy if in an unusual location amalgams à no well documented Most common oral mucosa pigmentation adverse health effects Systemic -Most wide-spread in the US – Oral manifestations Metallic/Lead plumbism -Ulcerative stomatitis Intoxication -Water pipes, lead based paint -Gingival lead line: bluish line alone the marginal gingiva SEVERAL teeth action of bacteria H2S on Pb – lead sulfide -Excessive salivation, a metallic taste Smoker’s melanosis -Significantly increased in heavy -Affects the anterior labial mucosa (ant. Mandibular) -Melanin has a protective response against toxins smokers -Pipe smokers – commissure and buccal mucosa -More often in females, and probably due to -21.5% of smokers vs. 3% in female sex hormones exert a synergistic effect nonsmokers TQ: select all that apply casestudypicture X2 combined with smoking ~ Drug related -Number of medications implicated -Diffuse melanosis of the skin and mucosal surfaces -Females affected more discolorations -Most common offender is all the -Long term use of minocycline à in discoloration of quinines (chloroquine, bone and developing teeth · hydrochloroquine, quinidine, quinacrine, chlorpromazine, etc.) -AIDS patients – azaothioprine, clofazimine, or ketoconazole ~ Cysts of sinuses -Antral pseudocyst -Common finding on panoramic -Dome shaped, faintly radiopaque lesions arising from -May show a possible source of odontogenic radiographs floor of the maxillary sinus infection ↓ -Not a true cyst -Inflammatory exudate – accumulated under sinus -Pseudocysts are asymptomatic and don’t need -Floor of sinus filling with fluid mucosa with sessile elevation treatment -Retention cyst -Partial blockage of a duct of the -Located around the ostium or within antral polyps seromucous glands or from an -Majority are small and not evident clinically invagination of the respiratory epithelium -Mucin is surrounded by epithelium -Sinus mucoceles -True sinus mucoceles, -Obstruction of sinus ostium, blocking normal drainage. accumulations of mucin completely -Enlarge in size as intraluminal pressure increases. encased by epithelium -Distend walls of sinus and erode through bone, often -Trauma or surgery to sinus – mimicking a malignancy of antral origin surgical ciliated cyst or -Very serious condition postoperative maxillary cyst Cervicofacial -Introduction of air into o -May follow the use of compressed air by clinical (high -90% develop during surgery or within the first emphysema subcutaneous or facial spaces of the speed handpieces) after difficult or prolonged postoperative hour ~ face and neck extractions -Usually resolves on its own -Forced air may spread through -As a result of increased intraoral pressure (e.g. sneezing, spaces to retropharyngeal and blowing) following oral surgery mediastinal areas -Unknown etiology -Soft tissue enlargement picture -Minimal pain -Crepitus detected on palpitation aka crinkling Myospherulosis -Foreign body reaction -Exploration: black, greasy, tar-like material -Treated by surgical removal of the foreign -Adding topical antibiotic petrolatum -Collections of spherules resembles a “bag of marbles.” material base (Neosporin) into surgical site -Spherules represent red blood cells that have been -Within bone at previous extraction altered by the medication sites (especially third molars)  L15 MEDICATION RELATED OSTEONECROSIS OF JAWS (MRONJ) MRONJ: current or previous treatment with antiresorptive or antiangiogenic agents. Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for more than 8 weeks. No history of radiation therapy or obvious metastatic disease Indication of infection: pain Bisphosphonates share a common PCP backbone exposure present 6-8 wks o R1 chain influences pharmacokinetics no response to tx o R2 chain determines chemical properties such as potency. Adding nitrogen to R2 chain = thousands of times more potent Monoclonal antibody (MAB): denosumab, bevacizumab, rituximab, and adalimumab Small molecular inhibitor, typically kinase (NIB): Sunitinib (gleevac), imatinib, and dabrafenib Risk factors for MRONJ o Medication related: cancer/osteoporosis patients § Cancer patients exposed to zolendronate had a 50-100 times higher risk of ONJ. Denosumab has a comparable risk o Local factors: surgery, anatomic factors, concomitant oral disease § Dentoalveolar surgery is a MAJOR risk factor § Tooth extraction is a common predisposing event § More likely in mandible than maxilla § Pre-existing inflammatory disease (perio/PA pathology) is a well-known risk factor o Demographic and systemic factors KNOW What is osteonecrosis? § More common in females What are the class of drugs that can cause osteonecrosis? § Steroid therapy is a major comorbid factor Difference between oral and IV bisphosphate New groups of drug (bid phosphate vs densumab) § Antiangiogenic + antiresorptive = increased risk Antigenic § Diabetes Stages of osteonecrosis o Genetic factors Periodontal cleanings and minimizing dental alveolar surgery help minimize ONJ risk Stages of MRONJ o At risk: no exposed necrotic bone in patients who have been treated with oral/IV BP o Stage 0/Pre-MRONJ: osteosclerosis above the canal, widened PDL bone (alveolar sclerosis) o Stage 1: exposed necrotic bone in patients who are asymptomatic and have no evidence of infection. No pus o Stage 2: exposed necrotic bone with infection, pain, erythema without purulent discharge o Stage 3: exposed necrotic bone in patients with pain, infection, and one of more of the following à pathologic fracture, extraoral fistula, or osteolysis extending to inferior border. Pus present, abscess, complete destruction Medication Indications Effect Examples IV Bisphophonates -Manage cancer related -Inhibit OC formation and induce OC Aredia (pamidronate) conditions: apoptosis à decreased bone resorption Zometa (zoledronic acid) -Hypercalcemia of malignancy, -Inhibit angiogenesis and decrease VEGF skeletal events associated with -Bind to bone and slow OC function bone metastasis such as in -Significant positive effect on quality of life in breast, prostate, and lung cancer advanced cancer involving the skeleton -Management of lytic lesions -Risk of ONJ higher compared to oral BP such as multiple myeloma Oral Bisphosphonates -Osteoporosis, osteopenia, and -Inhibit OC formation and induce OC less common conditions such as apoptosis à decreased bone resorption 113 Long term oral Paget’s disease of bones an osteogenesis imperfecta -Inhibit angiogenesis and decrease VEGF -Bind to bone and slow OC function bisphoponates, -Risk ONJ increased when treated over 4 0.1% become ONJ. years with oral BP (3-5 yrs) RANK L Inhibitors -Osteoporosis and cancer -Fully humanized antibody against RANK-L à Denosumab – fully humanized antibody inhibits osteoclast function and bone against RANKL. Prolia (every 6 months to resorption decrease vertebral and hip fractures) and -Do not bind to bone (unlike BP) Xgeva (monthly to reduce metastasis from -Do not inhibit angiogenesis solid tumors) -Not indicated for multiple myeloma (MAB = monoclonal antibody) Angiogenesis -Mostly cancer -Interfere with formation of new blood Bevacizum – Avastin Inhibitors vessels by binding to various signaling Sunitinib – Sutent (Suppresses VEGF) molecules disrupting angiogenesis-signaling cascades (NIB = small molecule inhibitor, typically -Sunitinib is a tyrosine kinase inhibitor tyrosine kinase)  L16, 17 ALLERGIC AND IMMUNOLOGICAL DISEASES PATHOLOGY DEFINITION/PREVALENCE CAUSE/EFFECT FUN FACTZ Recurrent -Aka Canker Sores -Etiology: allergies, genetic predisposition, hematologic -Prevalence 5-66% (mean 20%) ~ Aphthous -Super common abnormalities, hormones, infectious agents, nutritional -Increased percentages of CD8+ cytotoxic cells seen Stomatitis -Primary immunodysregulation, imbalances, and stress on biopsy, reduction CD4+ T lymphocytes certain HLA antigens in patients -Tobacco products increase keratinization of oral mucosa and -Increased frequency and severity in AIDS patients with aphthous ulcers decrease frequency of aphthae -Recurrence rate is variable TQ: A lady -Mostly affects the buccal and -An antigenic stimulus primary initiating factor in immune- -Dx: based on clinical presentation and exclusion of showed up for a labial mucosa (Non-keratinized) 8 mediated cytotoxic destruction of mucosa in many patients other ulcerative diseases prophylaxis and then developed -3 clinical variations à minor, -Ulcers are 3-10 mm, heal without scarring in 7-14 days -Biopsy not useful, nonspecific histologic features ulcer on the major, and herpetiform… -1 to 5 lesions each episode -Tx for all forms of aphthous stomatitis = topical mandibular (Recall, recurrent herpes -Pain out of proportion for size corticosteroids. Treat with 0.05% Clobetasol gel. vestibule? keratinized/outer lips and canker Apply sparingly twice a day ~ sores are on non-keratinized!) & -Minor -Most common form, affects up -Ulcers almost exclusively on non-keratinized mucosa Aphthous ulcers to 80% of individuals with -Ulcer covered by yellow-white, fibrinopurulent membrane with aphthous stomatitis erythematous halo ⑧ -Major -Aka Sutton’s disease or -Larger than minor aphthae and longest duration -Tx: Prednisone 40 mg/day for 5 days Aphthous periadenitis mucosa necrotica -Ulcers measure 1-3 cm and take 2-6 weeks to heal & -Also apply topical steroids and continue until ulcerations recurrens (PMNR) -Usually just 1 lesion, but can be up to ??10 healed completely -Affects 10% of patients with -Most common on labial mucosa, soft palate, and tonsillar -Taper if over 2 weeks on systemic steroids aphthous stomatitis fauces -Can cause permanent scarring -Colbetasol gel 0.05%, dispense a total of 15 or 30 grams. Apply sparingly twice a day -Cover with a methylcellulose film (Zilactin B) ~ -Not in children! -Omega-3, 1 gram 3x/day for 6 months -Reduced # and duration of ulcers and pain -Herpetiform -Considered to be a form of -Greatest number of lesions, most frequent recurrences -Pregnancy may reduce the incidence & Aphthous erythema multiforme -Individual lesions are small (1-3mm) and 100 may be present in -Almost constantly effected for years ulcerations a single recurrence -Female predominance, onset in adulthood -Non-keratinized movable mucosa predominates, but any surface may be involved -Red background and swelling with overlying ulcers later developing erythema multiforme Behcet’s -Chronic ocular inflammation and -Oral lesions in 99% of patients, typically precedes other sites of -Ocular involvement is more frequent and severe in Syndrome oro-genital ulcerations involvement males -GOES à Genital ulcers, Oral -Lesions demonstrate the same duration and frequency as -Dx: must have oral ulcers that have recurred at ulcers, Eye ulcers, and Skin aphthous ulcers least 3 times in 1 year. In addition, must have 2 of -Primary immunodysregulation or -Involve soft palate and oropharynx (infrequent sites for the following secondary to one or more aphthae) 1. Recurrent genital ulceration triggers -Lesions vary in size, ragged borders surrounded by diffuse 2. Appropriate ocular lesions -Oral involvement is the 1st erythema 3. Appropriate cutaneous lesions manifestation in 25-75% of cases -Genital ulcers are like oral (75% of patients) -Tx: oral lesions can be treated with topical steroids -“Pathergy” 1-2 days after injection of inert substance à or topical tacrolimus tuberculin like skin reaction or sterile pustule develops -Prognosis is generally good in the absence of CNS -Ocular involvement in 90% of cases involvement -Arthritis is a common minor manifestation that is usually self- limiting and non-deforming -10-25% of patients demonstrate CNS involvement (paralysis, severe dementia, etc.) Sarcoidosis -Common multisystem -Nature of antigen unknown, many different antigens may be -In North America, blacks are affected 10 times & granulomatous disease responsible more frequently than whites & -Hypersensitivity reaction -Clinical Sx: dyspnea, dry cough, chest pain, malaise, fatigue, -Arises between 20-40 years of age -Improper degradation of arthralgia, and weight loss -Elevated serum ACE (angiotensin converting antigenic material with the -20% of patients have no symptoms, discovered on routine enzyme) levels and pulmonary involvement formation of non-caseating O chest x-ray strongly support the diagnosis granulomatous inflammation à -Frequently present with bilateral hilar lymphadenopathy on -60% of patients with sarcoidosis symptoms resolve hard tubercule chest radiographs spontaneously within 2 years without treatment -Predominant sites: lungs, lymph nodes, skin, eyes, and salivary glands Histopathology: -Microscopic: classic picture of granulomatous inflammation -Another 20% can be treated with corticosteroids -Usual course of Tx is to watch patient for 3-12 months and treat only the progressive forms or V -Granulomas often contain laminated basophilic calcifications those with significant lesions that fail to respond to (Schaumann bodies) or stellate inclusions (asteroid bodies) topical therapy 0 -Heerfordt’s Syndrome (uveoparotid fever): parotid Lip swelling (slow) enlargement, anterior uveitis of the eye, facial paralysis, and fever -Bony involvement is rare and can mimic periodontal disease  ~ Orofacial -Presence of granulomatous -Systemic processes with oral granulomatous inflammation -Dx of exclusion Granulomatosis inflammation in oral and facial include chronic granulomatous disease of childhood, Crohn’s -Most patients are adults but can occur at all ages regions disease, mycobacterial infection, and sarcoidosis -For patients under 30, many have inflammatory -Most frequently affects the lips -Labial tissues demonstrate non-tender, persistent swelling of bowel disease different from Crohn’s one or both lips -2 tiers of therapy à searching for cause and -When combined with facial paralysis and fissured tongue à treating the lesion Melkersson-Rosenthal syndrome -Tx with diet elimination of cinnamon and benzoate -Only lip involvement à cheilitis granulomatosa with good results -Currently, systemic and intralesional corticosteroids are administered successfully to Lip swelling (long term) control progression of this disease -Lesions often resolve spontaneously with or without therapy ~ Granulomatosis -Aka Wegener’s Granulomatosis & -Characterized by necrotizing granulomas of respiratory tract, -If untreated, limited and superficial types can with Polyangiitis -Well-recognized uncommon necrotizing glomerulonephritis, and systemic vasculitis of small progress to become generalized L disease of unknown cause arteries and veins -Dx: characteristic clinical features, serum -Abnormal immune reaction to a -Initially present with involvement of upper respiratory tract, antibodies directed against cytoplasmic nonspecific infection or aberrant often renal involvement develops components of neutrophils (c-ANCA) hypersensitivity to an inhaled -Sometimes, lesions on skin and mucosa -Biopsy shows necrotizing and granulomatous antigen -Oral lesions in 6% of patients vasculitis -3 flavors… & -Strawberry gingivitis is an early manifestation and distinctive -Mean survival untreated is 5 months. 80% dead at 1. Generalized: initial upper and feature of this disease 1 year. 90% dead at 2 years lower respiratory tract and rapid -Gingiva exhibits a florid and granular hyperplasia -Drugs of choice are cyclophosphamide and oral renal involvement most lethal -Non-specific oral ulcers on any mucosal surface prednisone 2. Limited: respiratory tract without rapid kidney involvement 3. Superficial: lesions primarily skin and mucosa. Systemic involvement develops slowly Allergic mucosal -Allergic reaction of oral mucosa Besides erythema multiforme, many patterns can be seen… -Very difficult Dx reactions to to the systemic administration of -Anaphylactic stomatitis -Tx: withdraw/substitute drugs with medical systemic drugs a medication is called stomatitis -Intraoral fixed drug eruptions consult medicamentosa -Lichenoid drug reactions (white lines) -Localized acute reactions resolve with topical -Involve any mucosa surface, -Lupus erythematosus like eruptions (rash) corticosteroids but this is ineffective is medicine is most often à posterior buccal -Pemphigus like drug reactions (blisters) continued mucosa and lateral borders of -Nonspecific vesiculoulcerative lesions (most common) -If the patient cannot discontinue meds, palliative tongue care can be provided -Presents as localized areas of erythema and edema that may ~ develop into vesiculoerosive lesions (aphthous like ulcers) located most frequently on labial mucosa -Lichenoid, lupus like, and pemphigus like drug reactions resemble their namesakes -Bilateral and symmetric lesions common & -Fixed drug eruptions: inflammatory alterations of mucosa or skin recur at same site after taking drug Allergic contact -Allergic reaction due to foods, -Allergic contact stomatitis can be acute or chronic -Oral mucosa much less sensitive than the skin stomatitis chewing gum, dentifrices, -With acute à burning is the most frequent symptom because the period of contact is often brief and the mouthwash, topical anesthetics, -Mild erythema to brilliantly erythematous lesion with or saliva dilutes and removes many antigens and restorative materials without edema may be seen -Both acute and chronic have a distinct female -Cinnamon and amalgam TQ: Time of exposure is the cause predominance demonstrate unique clinical and for allergies to nickel and amalgam. histopathological patterns… -Contact -Concentrations of cinnamon -Clinically may resembles plasma cell gingivitis -Tx: signs and symptoms disappear within 1 week Stomatitis from flavoring is about 100x more than -Clinical presentation varies after discontinuation of cinnamon product Cinnamon the natural spice -Toothpaste results in more diffuse pattern (mostly gingiva) Flavoring -Most lesions on lateral tongue -Candy and gum are more localized (buccal mucosa and lateral and cheek borders of the tongue) -Acute à red, ulcerated -Pain and burning are common symptoms in all cases -Chronic à white plaques, -Diffuse lesions associated with “soft” cinnamon hyperkeratosis, or erythematous -Characteristic histopathology à lichenoid or psoriasiform with prominent perivasculitis (inflammatory cells around blood vessels) ~ -Contact -With hypersensitivity reactions, -Lesions similar clinically/microscopically to lichen planus. * - Have been called “galvanic” lesions suggesting relations to the most frequent antigen is -Contact lichenoid reaction to amalgam (not true lichen planus) that changes develop from electrical currents Dental Amalgam mercury -Lesions involve only mucosa in contact with amalgams developed between restorative metals -Most commonly posterior -Lesions resolve rapidly after removal of adjacent amalgams -Tx: improved oral hygiene, buccal mucosa and -Gingival cuffs adjacent to subgingival amalgam margins may smoothing/polishing/recontouring should be ventral/lateral borders of tongue also be involved attempted. -Lesions maybe white or erythematous and periodic erosion -Biopsy should be done if the lesion does not may be noted resolve after removal of amalgam  ~ Angioedema -Aka Angioneurotic edema -Diffuse edematous swelling of soft tissues -Attacks precipitated by dental procedures have -IgE mediated hypersensitivity -May affect gastrointestinal or respiratory tract, occasionally been reported in long term users of ACE inhibitors reactions due to drugs, food, with fatal results -Tx: oral antihistamines. If not controlled or plants, dust, and inhalants -Mast cell degranulation can result from physical stimuli laryngeal involvement, IM epinephrine -Produce mast cell degranulation including heat, cold, exercise, emotional stress, and solar and are fairly common exposure -Most commonly subcutaneous -Clinically, relatively rapid onset on soft, nontender tissue and submucosal connective tissue swelling -Itching is common and erythema may be present. Pain unusual TQ: 3 things with lip swelling Unlike orofacial -Enlargement resolves in 24-72 hours sarcoidosis granulomatous -Centers around upper airway (pharynx and larynx) and is orofacial granulomatosis (longer time) potentially life-threatening from closure of airway angioedema (painless) -Hoarseness and difficulty in swallowing or breathing being Lip swelling (fast) important signs -Perioral and periorbital involvement is typical of allergic angioedema  L18 EPITHELIAL PATHOLOGY PART 1 PATHOLOGY DEFINITION/PREVALENCE CAUSE/EFFECT FUN FACTZ Oral Squamous -Benign proliferation of stratified squamous -White, slightly red, or normal color -Being infected by HPV doesn’t necessarily Papilloma epithelium, induced by human papilloma -Soft, painless, pedunculated (on a stalk) mean you’ll get the disease, mostly affects virus (HPV) -Exophytic with numerous finger-like projections, immunocompromised -150+ known HPV subtypes “cauliflower” appearance -Mostly 30-50 years old -HPV 2, 6, 11 are 50% of oral papillomas -Solitary, enlarge rapidly to 0.5 cm -Males = Females -Commonly affects the tongue and soft -Difficult to distinguish from verruca palate (dorsal) vulgaris or condyloma -Tx: conservative surgical excision, most common benign skin lesion including the base of the lesion Condyloma -Aka Venereal Wart -Oral lesions on labial mucosa, soft palate, and lingual -Affects immunocompromised Acuminatum -Papillary epithelial proliferation of genitalia, frenum -Teenagers and young adults anus, larynx, and mouth -Multiple and clustered -May be extensive, but usually self-limiting -HPV 6, 11, 16, 18 (cause cancer) -KEY: blunt, fat, fleshy, “stuck on” -Patients can self-infect, must be removed -STD lesions develop at site of sexual contact -Compared to papillomas, these are larger, more infective, -Tx: treat surgically, but often recur. Should -20% of all STD’s and more likely to come back be removed because they are contagious -1% US, 10% Scandinavia -Average size 1.0 – 1.5 cm -Not very keratotic/white. More red/fleshy/pink Verruca Vulgaris -Benign, virus-induced, focal hyperplasia of -Uncommon on oral mucosa, but extremely common on -Frequent in children, skin and hands are stratified squamous epithelium skin the usual site -HPV 2, 4, 6, 40 -Commonly affects the vermillion, labial mucosa, or anterior -Contagious and spread by autoinoculation tongue -2/3 disappear within 2 years, especially in children Seborrheic -Does not occur in the mouth -Cause unknown, positive correlation with chronic sun -Becomes more prevalent with each Keratosis -Arise on skin of face, trunk, and extremities exposure passing decade during fourth decade -Multiple, begin as small tan to brown macules become -Hereditary (autosomal dominant) papillary raised tendency -Appear “stuck on” and usually less than 2 cm common skin lesion of older people Oral Melanotic -Benign solitary uniform tan to dark brown, -Unknown etiology, focal increase in melanin (not an -2:1 female predilection Macule round or oval macule & flat increase in melanocytes) -Tx: usually none required -NOT related to sun exposure -Vermillion border > buccal mucosa > gingiva > palate -All oral pigmented lesions should be -Less than 7 mm biopsied to rule out melanomas -Lesions do not enlarge Acquired -“Nevus” congenital or developmental -Not common intraorally -White adults 10-40 cutaneous nevi Melanocytic Nevus malformations, skin (and mucosa) -Head and neck regions are common sites -Most are present before age 35 (Mole) -Most common acquired melanocytic nevus, -Evolve through several clinical stages, with specific -2/3 intraoral nevi in females or mole histopathologic features. -Average age 35 -Benign, localized proliferation of neural -Earliest presentation is sharply demarcated, brown or black -Tx: none for cutaneous nevi crest cells, “nevus cells.” macule, < 6 mm (Junctional Nevus) -Most common “tumor” -Nevus cells proliferate, slightly elevated, becomes papillomatous, and brown-tan papule (Compound Nevus) -Gradually loses pigmentation, hairs grow from center (Intradermal Nevus) -Remains less than 6 mm -Intraoral melanocytic nevi are uncommon, but mostly occur on the palate or gingiva ABCDE Rule for pigmented lesions A = Asymmetry B = Irregular Borders C = Color Variation D = Diameter larger than 6 mm E = Evolving change in size, shape, color, symptom bleeding, picture itching or crusting Biopsy needed These are all red flags! Leukoplakia -Predominantly white patch or plaque that -Oral leukoplakia carries an increased risk of cancer -Must rule out lichen planus, cheek biting, cannot be characterized clinically or development and is associated with smoking, drinking, frictional keratosis, tobacco pouch pathologically as any other disease and/or high risk HPV keratosis, nicotine stomatitis, candidiasis, -Leukoplakia is a clinical term, does not -Color results from thickened keratin layer (white when leukoedema, and white sponge nevus imply specific histopathology wet) or thickened spinous layer masks vascularity (redness) -Transformation rate greatly related to -Leukoplakia is pre-malignant of underlying CT clinical appearance and location -Tongue, lip vermillion, and oral floor is -Early lesions are flat, slightly elevated, translucent, -Biopsy mandatory. Tissue sample the more than 90% of dysplasia or carcinoma fissured, or wrinkled gray-white plaques most severe areas -2/3 thin leukoplakias extend laterally, thicken and become -Moderate epithelial dysplasia or worse Leukoplakia transformation by location distinctly white à homogenous or thick leukoplakias warrant complete removal -Tongue (ventral/lateral) – 25% -Exophytic with multiple projections à verrucous -Floor of mouth – 15% leukoplakia (not benign) Histologic diagnosis -Buccal mucosa (up to 63% leukoplakia) – 4% -Hyperkeratosis/benign – 80% -True leukoplakia of buccal mucosa much -Homogenous leukoplakia (thin/flat) = 4-5% -Epithelial dysplasia or ca-in-situ – 17% lower – 18% -Heterozygous (verrucal, nodular, erythroplakic speckled) = -Squamous cell carcinoma – 3% -6x more likely to transform if involves more 15% à more likely to be malignant than 1 anatomic structure -Floor of mouth and ventral tongue are the Other factors affecting transformation worst locations L -Size > 200 mm = 20 cm = 8 inches -High risk HPV (16,18) also causes leukoplakia -HPV found in 10% of normal tissue -15% HPV+ lesions associated with invasive cancer -Primarily found on ventral tongue and floor of mouth -Tobacco smoking is closely associated with leukoplakia, more than 80% of leukoplakia patients smoke -Heavier smokers à more and bigger lesions -Stopping smoking à lesions disappear or becomes smaller within 1 year -Alcohol has a strong synergistic effect with tobacco -Alcohol alone not associated with leukoplakia -UV Radiation is an etiologic factor for vermillion lesions -Dysplastic changes begin in the basilar portions of epithelium -More severe dysplasia, atypical changes extend to higher levels of epithelium -Mild epithelial dysplasia à limited to basal and parabasal layers -Moderate epithelial dysplasia à basal layer to midportion of spinous layer -Severe epithelial dysplasia à alterations from basal layer to level above midpoint -Carcinoma-in-situ: entire thickness of epithelium involved (intraepithelial carcinoma). Dysplastic cells extend from basal layer to surface (“top to bottom”). No invasion, but atypical epithelial cells like squamous cell carcinoma -Proliferative -Involve multiple sites/multifocal -Extensive white plaques -Recur after excision verrucous -40 to 50% progression to cancer -Transform into carcinoma -Females 4:1 leukoplakia (PVL) -Can look like it’s growing out of the mouth -Erythroplakia -Red patches that cannot be -Almost all trye erythroplakias demonstrate significant Histologic Spectrum clinically/pathologically diagnosed as any dysplasia, carcinoma in situ, or invasive squamous cell -Benign keratosis – 0% other condition carcinoma -Mild dysplasia – 10% -Immature epithelial cells produce no -In other words, true erythroplakia = cancer L -Severe dysplasia or ca-in-situ – 40% keratin -Invasive carcinoma – 50% 1001dysplasiaandcancer  19, 20 EPITHELIAL PATHOLOGY PART 2 Squamous Cell Carcinoma STAGING System à Tumor Node Metastasis (TMN) System. Know the characteristics of Stage I, II, III, and IV!!! Tumor size and extent of metastatic spread are the best indicators of prognosis T: tumor size cm o T1: 2 cm or less o T2: between 2-4 cm o T3: greater than 4 cm o T4: massive tumor N: presence and type of spread to local lymph nodes I o N1: palpable cervical non-fixed nodes on same side o N2: palpable non-fixed contralateral or bilateral nodes o N3: clinically palpable nodes which are fixed Metastasis M: presence or absence of distant metastasis is the worst o M: no metastasis prognosis o M1: metastasis to sites other than cervical lymph nodes Squamous Cell Carcinoma GRADING System Grading: degree tumors resemble parent tissue (squamous epithelium) and produces normal product (keratin) Grading does not decide the management protocol Low-grade (I) or well-differentiated tumor closely resemble tissue of origin, grow slower and metastasize later High-grade (III/IV), poorly differentiated, or anaplastic tumor very pleomorphic cells, little or no keratin, difficult to identify, enlarge rapidly, metastasizes early Clinical staging correlates much better than grading with prognosis in most cases!!! PATHOLOGY DEFINITION/PREVALENCE CAUSE/EFFECT FUN FACTZ Tobacco Pouch -Aka Snuff Pouch -Due to smokeless tobacco or spit tobacco use; -6% adult men use spit tobacco Keratosis -Chewing tobacco leaves or holding correlates with duration and quantity of use -Started early (9-15) and rarely initiated after 20 finely ground tobacco (snuff) in cheek -Alterations found in chronic users -Epithelial dysplasia uncommon in tobacco pouch keratosis -Usually in the back of the mouth and -Painless gingival “recession” and facial bone (almost never cancer) thick destruction (area of tobacco contact) -Habit cessation leads to normal mucosa within 1-2 weeks -White lesion becomes thickened leathery or -Lesions that remain after 1 month should be considered true nodular leukoplakias and biopsied -Hyperkeratosis and acanthosis may be present -Edema in keratin layer Squamous Cell -Oral cancer is 3% of all US cancers -SCC of the lip (extra-oral) behaves completely -Risk increases with age Carcinoma -Oral cancers are 90% SCC differently than intra-oral. Extra-oral SCC related -Male to Female 3:1 -21 new cases diagnosed annually to sun exposure and is less aggressive than intra- -Heredity does NOT play a major etiologic role in oral -6000 Americans die each year oral. carcinoma -Head, neck, and throat cancer in -Extrinsic factors: tobacco, smoking, alcohol, -Relative risk is dose dependent for cigarette smokers 225% (1988-2004). sunlight (vermillion cancers only). Pipe and cigar -Intraoral cancer minus 50% -Throat cancer has surpassed cervical smoking carries a greater risk than cigarette. cancer -Intrinsic factors: systemic or generalized -Changes in sexual behavior causing immunodeficiency status, malnutrition, or iron- increase in oral cancer deficiency anemia HPV and Oral Population Specifics for HPV cancers -Oncogenic viruses play a major role -10-fold risk acquiring persistent oral HPV if spouse has had Cancer -Often seen in patients with no risk -HPV strongly implicated (45-90%) in oral HPV infection. Quickly transfers between people factors oropharyngeal cancers but less proven (2-5%) in -10% male, 3.6% female -Typically, younger (BUT only 3-5 the oral cavity -Men 45-60 years old are 2-3x more likely to get oro- years) -HIV increased risk oral cancer, Kaposi sarcoma, pharyngeal cancers -Associated with sexual behaviors and lymphoma -Peak incidence: 30-34 years 7.37%, 60-64 – 11.45%!!! such as premarital sex, multiple sex -HPV subtypes 16, 18, 31, and 33 associated with partners, oral sex, # of lifetime dysplasia and SCC. -90% of HPV clears within 2 years, but can recur. tongue kissing partners -HPV 16 in non-smokers have high oral cancer risk -85% of women will acquire an HPV infection within their -60% of sexually active US adults are -Oncogenic HPV’s code for 2 proteins: E6 lifetime HPV+ degrades a tumor suppressor gene product p53, -Oral HPV most commonly found in 60-64 age group -Prevalence in HPV US population is and E7 which degrades pRb (retinoplastoma 7% protein), also a tumor suppressor -FDA approved an HPV vaccine (Gardasil 9) which can -HPV driven oropharyngeal cancer is -Especially troubling increase in non-smoking prevent pre-cancers and cancers caused by HPV 16 and 18 the most common head and neck younger males with oropharyngeal cancers and also condylomas/genital warts caused by HPV 6 and 11 cancer -Preventative vaccination indications for men as -HPV 16 incidence is 1% (2.13 million -Sx: lump in neck, change in voice, trismus, sore oropharyngeal and oral cancer prevention. Male people) but only 15,000 cases of throat, feeling mass in throat, ear pain, and oropharyngeal cancers are as numerous as female cervical oropharyngeal cancer per year difficulty swallowing cancers. -HPV vaccine: minimum age 9. Ideally administer a 2 or 3 -Fortunately, HPV associated cancers have a dose series through ages 9-11 through 12 (97% vaccine better prognosis because HPV+HNSCC have less efficiency). base of tongue, tonsillar chromosomal mutations (compared to -Should be vaccinated before sexual habits start! area and oro-pharynx smoking/drinking/risk factor associated tumors) -Catch up vaccines ages 13-18 -Side effects of vaccine: #1 fainting (from the large needle! prognosis and location Not the vaccine!), headache, arm soreness More HPV infections in the cervix Intraoral -90% of intraoral cancers are -Minimal pain during early stages -Mostly affects older men Squamous Cell squamous cell carcinoma -Usually not aware of lesion until its 4-8 months -Metastasis usually spread the lymphatics à ipsilateral Carcinoma -Most common sites: ventral/lateral later cervical lymph nodes. Malignant cells perforate nodal capsule tongue >>> floor of mouth > soft -Leukoplakic and erythroplakic early cases don’t and nodes become “fixed.” palate > gingiva > buccal mucosa > have mass or ulceration. These can be exophytic -2% have distant (below clavicles) metastases at diagnosis labial mucosa > hard palate or endophytic -Single treatment modality for smaller carcinomas -Every part of the oral cavity that -Exophytic: irregular or papillary surface normal to -Larger lesions or lesions with palpable lymph nodes require comes in contact with pooled saliva red to white color. Surface ulcerated and hard combined therapy including either a modified or radial neck is a high-risk site (indurated) dissection -Most oral cancer is on the floor of -Endophytic: depressed, irregularly shaped, mouth and lateral/ventral tongue ulcerated. Central area with surrounding “rolled” (especially posterior) and lingual (raised) border frenum -Lip vermillion -Usually related to chronic UV -Vermillion carcinoma crusted, nontender, -Intraoral carcinoma 4x more frequent that vermillion carcinoma radiation and sun exposure, indurated ulceration carcinoma -Many have outdoor occupations -Slow growing, late to metastasize -SCC of the lip (extra-oral) behaves completely differently -90% on the lower lip than intra-oral. Extra-oral SCC related to sun exposure and is less aggressive than intra-oral. -Lip SCC similar to sun exposed skin SCC -SCC Tongue -Carcinoma of tongue is greater than -2/3 on posterior lateral border 50% of oral cancer -20% anterior lateral or ventral -Only 4% on dorsum -SCC Oral floor -Oral floor is the next most common -Most common site is midline near the frenum location for oral cancer (35% intra oral cancer) -SCC Gingival -Gingival and alveolar carcinomas are -Mimics benign inflammatory changes and -May become clinically evident after tooth extraction and alveolar painless and involve keratinized re