Oral Lesions and SCC 8/25

Question 1

Aphthous Stomatitis

Answer 1

“canker sores”

etiology:

• precise etiology unknown and pathogenesis unclear; may be manifestation of underlying systemic condition (Crohn’s, Celiac, Bechcet’s Syndrome)
• higher rate in HIV+ and immunosuppression
• can be stand alone condition
• lower prevalence in smokers

trigger:

• smoking cessation
• could be in response to meds, foods,oral bacteria

O/PE findings/characteristics:

• recurring, painful (pain out of proportion to lesion size) solitary or multiple ulcers covered by white to yellow pseudomembrane that can be removed surrounded by erythematous halo

subtypes:

• minor = well circumscribed, single or multiple, usually <1cm in diameter, rounded
  
  • most common on labial mucosa, buccal mucosa, ventral side of tongue
  • typically heal w/o scarring in 10-14 days
  • majority of pts do not require tx
• major = onset after puberty
  
  • lesions usually 1-3 cm and deeper
  • # of lesions varies b/n 1-10
  • last up to 2-6 weeks, heal with scarring
  • most common on labial mucosa, soft palate, tonsillar fauces
• Herpetiform = onset is adulthood
  
  • small, 1-3mm lesions wih multiple ulcerations that may coalesce
  • typically heal in 7-10 days
  • may affect any oral surface
  • can be confused with HSV but key is thta lesions are not vesicles here, they have pseudomembrane; to distinguish, can do wet mount after removing pseudomembrane to look for herpes virus

A:

• dx from history and PE
• bx only useful in eliminating other DDX (w/ atypical presentation)

P/TX:

• tx are predominantly for symptoms
• topical corticosteroids (decrease inflammation)
  
  • Fluocinonide 0.05% gel (Lidex)
  • Triamcinolone Acetonide w/ Carboxymethylcellulose paste 0.1% (Kenalog in Orabase)
    
    • apply 1cm of paste 2-3 times per day x 5-7 days over lesion (can taper when less sx-min of 3 days up to 10 days)
    • these are mid strength
• Chlorhexidine gluconate (Peridex) mouthwash (more for pain and stinging symptoms, doesn’t contribute to healing)
  
  • rinse twice per day w/ 15 ml of undiluted soln for 30 sec
  • do not swallow, swish and spit
• Amlexanox 5% paste (Aphthasol) = apply 1/4 inch paste QID after brushing for up to 10 days
• could do systemic corticosteroid tx if lasting

Question 2

Oral Herpes Simplex Virus

Answer 2

etiology:

• caused by Herpes Simplex Virus (HSV) (HSV I is usually oral and HSV II usually genital but both can be both)
• primary infection (asx or sx), virus then remains latent in cells, can be reactivated causing recurrent infections virus shed in saliva or active perioral lesions (when asx or sx)
  
  • primary infection = usually occurs at young age and often asx; virus taken up by sensory nerves and remains latent in ganglion (trigeminal); virus may spread to other sensory ganglia to create an infection at different site
  • secondary/recurrent infection = virus travels along axon of sensory neuron into peripheral skin or mucosa resulting in reactivation; most common site of recurrence of HSV I is vermilion border and adjacent perioral area (Herpes Labialis)

triggers: (of recurrent)

• UV light, trauma, fatigue, stress, menstruation, older age, heat/cold exposures, pregnancy

PE findings/characteristics of Herpes Labilais:

• vermilion border of lips, perioral area
• prodromal symptoms = pain, burning, itching may occur 6 to 24 hours before lesions
• multiple, small, erythematous papules which progress to clusters of vesicles (can coalesce into larger lesions); vesicle rupture and crust w/n 1-2 days
• healing usually occurs w/n 7-10 days

Characteristics and PE findings of Acute Herpetic Gingivostomatitis:

• most cases occur b/n 6 mo and 5 years (rare before 6 mo b/c child still protected by mom’s antibodies)
• abrupt onset
• self inoculation of fingers, eyes, and genitals (Herpetic Whitlow - lesions on fingertips and thumb from touching infected lesions)
• ass sxs: cervical lymphadenopathy, fever up to 103-105, chills, N, anorexia, irritability
• lesions may extend from labial mucosa to lips and vermillion border and perioral area as well as distal tongue; from external to internal
• start with pinhead vesicles rapidly enlarge & develop central ulcerations w/ erythematous bases
• gingiva is enlarged and painful and erythematous
• ALWAYS involvement of gingiva (how distinguish from Herpes Labialis)
• base very erythematous when take off hood
• mild cases resolve w/n 5-7 days and severe may extend for 1-2 weeks
• think about dehydration especially with fluids

DX:

• made by history and PE findings
• viral cx = most reliable when vesicles intact; may take up to 2 weeks for results; PCR on specimen to detect HSV antigens
• cytologic smear = giant multinucleate epithelial cells (doesn’t tell what type of HSV)
• serologic tests for HSV antibodies are positive 4-8 days after exposure bx may be required from chronic ulcers (last resort)

TX:

• Antivirals: most effective in prodromal phase, decrease development of number of new lesions, decrease viral shedding period from active lesions
  
  • oral Acyclovir (Zovirax), Valacyclovir (Valtrex) & Famciclovir (Famvir)
    
    • primary infections:
      
      • Acyclovir = 400mg PO 5x/day
        
        • Ped Herpetic Gingivostomatitis: 15mg/kg PO 5x/day x7 days
      • Valacyclovir = 2g PO every 12 hours (2 doses) (10 day supply but can taper as sxs improve); not usually covered by insurance unless have tried Acyclovir with no relief
    • recurrent infections:
      
      • Famciclovir = 1500mg PO single dose
      • Acyclovir = 200mg PO 1-2x/day
  • topical = 1% Penciclovir Cream (Denavir) apply every 2 hours x4 days; antiviral; only shortens sxs by 1 day
• Symptomatic relief
  
  • Viscous Lidocaine (for adults only; can be absorbed and in kids can cause seizures) = 15-20ml swish and spit every 4 hours
  • Oral NSAIDS Prognosis: - most cases of oral herpes resolve w/o complications and recurrences are sporadic
  • long-term suppression is reserved for pt w/ greater than 6 infections per year and for some immunocompromised pts

Question 3

Oral Candidiasis

Answer 3

_etiology _

• *Candida Albicans *is most common oral fungal infection in humans
• risk factors that favor its overgrowth:
  
  • age (young and elderly)
  • dentures, xerostomia
  • use of broad spectrum abx, steroid inhalers, and oral corticosteroids
  • HIV, Leukemia, Endocrine disorders (esp DM), organ transplant pts
  • radiation therapy, chemotherapy

Clinical forms:

• Pseudomembranous (Thrush)
  
  • PE findings/chracteristics
    
    • adherent white plqs; “curdled milk” or “classic cottage cheese” presentation
    • most common on buccal mucosa, palate, and dorsal tongue
    • plqs can be removed with scraping and underlying mucosa may be NL or erythematous
    • may be ass w/ burning sensation of foul taste
• Erythematous
  
  • lacks white component; red macular ares due to loss of filiform papillae
  • usually with burning sensation
  • common sites = hard palate, buccal mucosa, dorsal tongue (midline)
  • more frequent in xerostomia pts
• Angular Chelitis
  
  • scaling erythematous fissures at corners of mouth, typically b/l
  • lesions may be co-infected with Staph aureus
  • usually in older pts
  • if chronic think Vit B or iron deficiency

_DX: _

• based on history and PE typically
• KOH 10-20% Prep
• specimen cx allows for definitive dx

_TX: _

• Polyene Agents
  
  • Nystatin (Mycostatin)
    
    • Adults = 4 to 0 ml PO swish and swallow (effectiveness based on contact, poor absorption in GI tract, so prolonged contact) QID or 1-2 troches 4-5x/day
    • can use in adults and kids (2 ml dose with plungers)
    • avoid in pts with xerostomia b/c contains sucrose and could cause cavities
• Imidazole Agents
  
  • Clotrimazole (Mycelex Troche)
    
    • Adults = 1 troche PO 5x/day for 14 days
  • Oral Ketoconazole (Nizoral)
    
    • Adults: 200-400mg PO/ day
    • not first line of defense; reserve for severe infection or underlying immunosuppressant b/c can cause hepatotoxicity-would have to check LFTs
    • can cause drug-dug interactions
    • needs acidic environ to be effective so don’t give to pt taking antacids
• Triazoles
  
  • Oral Fluconazole (Diflucan)
    
    • adults and kids
    • Adults: 200mg PO day 1, then 100mg PO daily x 2 weeks
    • kids: based on mg/kg x 2 weeks
    • will interfere with pts on Dilantin or Warfarin
  • Oral Itraconazole (Sporanox)
    
    • do not use for kids
    • Adults = 200mg PO daily x 2 weeks
    • not first line agent, associated with hepatotoxicity so would check LFTs
    • can lead to prolonged QT interval

Prognosis:

• most resolve with antifungal tx
  
  • topical or systemic
• consider underlying immunosuppression if recurrent infections (ex: DM)

Question 4

Hairy Tongue

Answer 4

etiology:
* often result of inadequate desquamation or increased keritinization of papillae
epidemiology:

• more common in heavy smokers and ppl with poor oral hygeine, h/o radiation to head and neck
• may be associated with increased prevalence of *C. albicans *infections

S:

• halitosis and/or metallic taste

O:

• elongation and hypertrophy of filiform papillae on dorsal surface of tongue
• most commonly affects midline and may be associated with brown/black or yellow discoloration
• dx usually made by history and PE

P/TX:

• most cases improve w/ improvement in oral hygeine including tongue brushing and decreased smoking
• do not confuse with Oral Hairy Leukoplakia = malignant lesion on lateral sides of tongue, can be unilateral or b/l, usually associated with underlying HIV, caused by Epstein-Barr virus, bx if see this b/c associated w/ oral SCC

Question 5

Leukoplakia

Answer 5

epidemiology:

• risk factors =
  
  • smoking
  • UV radiation
  • Sanguinaria - herbal extract found in toothpastes and mouthwashes
  • Tertiary Syphilis
  • HPV, subtypes 16&18
• usually affects ppl over the age of 40

etiology:

• most common premalignant oral cancer lesion (will see the most but has lowest transformation rate into SCC)
• only about 1/4 are associated with dysplasia

O:

• white patch does not scrape off
• most common locations of lesions= lip vermilion, buccal mucosa, gingiva
• lesions of tongue, lip vermilion and oral floor have higher incidence of dysplasia and carcinoma
• early or mild lesions appear elevatedm gray to white plqs, may appear translucent, fissured, or wrinkled (sometimes like sunburned peeling skin)
• may remain unchanged for years, slowly extend or disappear completely
• no erythematous halo
• thickened keratin layer (hyperkeratosis) of the surface epithelium or a thickened spinous layer (acanthosis)
• Proliferative Verrucous Leukoplakia (PVL)
  
  • female predilection, not associated with tobacco use
  • development of multiple keratotic plqs w/ rough surface projections (cauliflower-like appearance)
  • usually transform into SCC w/n 8 yrs of dx (bx these!)

A:

• DX made by biopsy

P/TX:

• Leukoplakia not exhibiting dysplasia can be followed by clinical evaluation every 6 months
• smoking cessation recommended
• leukoplakia demonstrating moderate epithelial dysplasia or worse requires complete excision
• approx 4% of leukoplakias transform into SCC
  
  • factors that increase risk of transformation
    
    • occurence in female pts
    • occurence in nonsmokers
    • occurence on the oral floor or ventral tongue

Question 6

Erythroplakia

Answer 6

etiology:
* less common than Leukoplakia but more likely to be dysplastic and to become malignant
epidemiology:
* peak prevalence in adults b/n ages of 65-74

O:

• most common sites include floor of mouth, tongue, soft palate
• multiple lesions are frequent
• well-demarcated erythematous asx macule or plq w/ soft velvety texture

A:

• bx required for definitive DX

P:

• tx guided by degree of dysplasia
• long term f/u is required (will transform at higher rate than leukoplakia)
• can have combo erythroleukoplakia (combo has higher rate of progression to SCC than leuko)
  
  • make sure to bx from different sites

Question 7

Oral Cancer and Oral Squamous Cell Carcinoma (SCC)

Answer 7

epidemiology:

• cancer of oral cavity and oropharynx is 9th most common cancer
• accounts for 3% of malignancies in men and 2% in women
• approx 90% are SCC in origin
• principle risk factors =
  
  • tobacco use and heavy ETOH consumption
    
    • 80% dx w/ SCC are smokers
    • 15x more likely to have oral cancer with someone who drinks and smokes
• risk factors for Oral SCC =
  
  • age, race, gender
    
    • >40 yo
    • more prevalent in African Americans
  • tobacco smoking
    
    • pipe and cigar smoking carry a greater oral cancer risk than cigarette (>2 packs per day)
  • smokeless tobacco use (50% of cancers show up where hold tobacco)
  • alcohol (dose and time dependent) (1/3 are heavy alcohol users)
  • Phenolic Agents
    
    • increase risk for wood workers exposed by phenoxyacetic acid
  • UV light
  • Radiation exposure
  • Betel Quid
  • iron deficiency
    
    • Plummer Vinson Syndrome associated with higher risk (due to turnover of esophageal epithelium (dysphagia); improves if tx underlying anemia
  • Vitamin A Deficiency
    
    • produces excessive keratinization of the skin and mucous membranes
  • Syphillis (Tertiary Disease)
    
    • ass w/ increased risk of tongue cancer
  • HPV (see more at base of tongue in oropharynx and in female nonsmokers)
  • immunosuppression

S:

• warning signs:
  
  • lesion in mouth that does not heal w/n 14 days (think abt bx)
  • pain in mouth that does not resolve (even after various txs/can’t see a lesion but having pain)
  • lump or thickening in cheek
  • difficulty chewing or swallowing
  • otalgia
  • difficulty moving jaw or tongue
  • voice changes
  • numbness of tongue or other areas of mouth
  • swelling of oral cavity
  • repeated bleeding from mouth or throat
  • red or white lesions of mouth or lips
  • persistent halitosis

O:

• most common locations are = tongue, floor of mouth, vermilion border of lip

A:

• DDX for a malignant lesion should also include bacterial or viral infection, trauma, leukoplakia or erythroplakia, eosinophilic granuloma, fibroma, giant cell tumor, pyogenic granuloma, papilloma, and verruciform xanthoma

P/TX:

• SCC of the oral cavity are primarily treated surgically, while those of the oropharynx are primarily treated with definitive radiotherapy (RT).
• In general, early-stage lesions are treated by surgery or radiation alone, whereas locally advanced disease necessitates a multimodal approach:
  
  • surgery and postoperative radiotherapy (PORT) ± chemotherapy in the oral cavity and definitive RT with concurrent chemotherapy in the oropharynx

Question 8

Lip Vermilion Carcinoma

Answer 8

epidemiology:
* typically in light-skinned individuals with h/o sun exposure

O:

• majority of found on lower lip is particularly where a cigarette, cigar, or pipe is held
• lesion appears crusted, nontender, oozing with ulceration and typically <1cm in size but size can vary
• usually slow growing lesion with late metastasis

P/TX:

• surgery is preferred modality for primary tx
• Postop RT +/- chemotherapy indicated in resected pts with high-risk features
• due to low incidence of regional metastasis, region al LNs not usually treated for early-stage cancers of lip

Question 9

Intraoral SCC

Answer 9

etiology:

• carcinoma of oral floor most likely to arise from preexisting leukoplakia or erythroplakia
• gingival carcinoma most often destorys the underlying bone and is least ass w/ tobacco smoking and has greater predilection for females (pt c/o pain in jaw or with chewing)
• posterior oropharyngeal carcinoma is often associated with more advanced lesions; pts wait to come in normally

S:

• usually ass w/ minimal pain during early growth phase
  
  • leukoplakia, erythroplakia, erythroleukoplakia
  • exophytic lesions
  • endophytic lesions
• lesions may be accompanied by underlying bone destruction
• pt’s w/ oropharyngeal cacers don’t normally come in until having obstructive sxs

O:

• tongue is most common site, usually on the posterior lateral and ventral surfaces
• majority appear as painless indurated masses or ulcers
• exophytic lesions:
  
  • typically ass w/ a surface growth pattern that is either mass-like, fungating, papillary or verruciform
  • color may vary; normal, white, red
  • tumor usually feels hard
  • surface ulceration may be evident
• endophytic lesions:
  
  • typically ass w/ a depressed surface growth pattern
  • central ulcer formation with rolling borders (somewhat smooth)
  • color may vary: normal, white, red
• metastatic spread is usually to ipsilateral cervical LNs
• approximately 2% of pts have spread below thee clavicles at time of dx
• most common metastatic sites are lungs, liver, and bone

A:

• Bx of all suspected lesions should be performed
• direct laryngoscopy, bronchoscopy and esophagoscopy performed to exclude a simultaneous second primary cancer
• head and neck CT
• Chest X-ray or CT
• Tumor-Node-Metastasis (TNM) system
  
  • T: size of primary tumor
    
    • Graded I, II, III, IV
  • N: involvement of local LNs
  • M: distant spread

P/TX:

• tumor size and metastatic spread are the best indicators of a pt’s prognosis
• tumor stage guides tx
• tx options include surgical excision, radiation therapy (RT), or combo radiation and chemotherapy
• overall 5 r survival is 50-55%
• pt’s who survive first oral cancer have a 20x higher risk of developing a second cancer
• early DX and prevention are essential for improving pt outcomes
• see CURRENTS ch.23 for