Oral Maxillofacial Pathology

1. Allergies and Immunologic diseases

Behcet’s Syndrome
- Old description: Ocular, Oral, Genital lesions (Triad lesion)
o New Description: It is actually a multi-system disorder (Systemic Vasculitis)
- Immunologic basis: Associated with certain HLA types
- High frequency in eastern Mediterranean & Japan (Silk Road route)
- Clinical features
o Oral lesions are similar to aphthous stomatitis
o Oral involvement at some point in 99% of cases
o Ocular involvement in 70% - 85% of cases

Sarcoidosis
- Multi-granulomatous disorder
- Non-caseating granulomas
- Diagnosis: Through EXCLUSION because cause is UNKNOWN ***
o Kveim test: Skin test – It is not used much anymore
- Clinical features:
o North America: Blacks are affected 10x – 17 x more than Whites
o 4% - 10% die of pulmonary, cardiac, or CNS complications
- Histopathologic and Radiographic feature:
o Granulomatous inflammation = Chronic inflammatory, response characterized by histiocytes and
multinucleated giant cells
o Radiograph shows the presence of pulmonary granuloma
Oral Granulomatosis
- Most common site of Involvement is the lips, called “Cheilitis Granulomatosis”
- Clinical Features:
o Melkersson-Rosenthal syndrome: Combined signs of the following:
 Cheilitis granulomatosa
 Fissured tongue
 Facial paralysis
- Histopathologic Features:
o Presence of Multi-nucleated giant cells, Histiocytes
- Diagnosis
o Rule out Granulomatous inflammation cause by:
 Fungal infection
 TB
 Sarcoidosis (Chest X-rays)
 Chron’s disease
 Chronic granulomatous disease
 Foreign material
 Allergy
- Treatment
o Discover the cause and eliminate it
o Most cases: Treat with Intralesional steroid injections

Wegner’s Granulomatosis
- Necrotizing Granulomatous lesions of Unknown cause
 o Respiratory tract
o Kidney (Failure => Death)
o Systemic vasculitis
- Recognize it, don’t need to treat it!
- Most common oral lesion is “Strawberry gingivitis”
- Non-specific oral ulceration is also possible
- Diagnosis: Finding Necrotizing and Granulomatous vasculitis

Allergic mucosal reactions to systemic Drug administration

- Stomatitis medicamentosa
o Various forms
 Angioedema
 Lichenoid drug reaction: Looks just like Lichen planus
 Erythema multiforme: Usually idiopathic, but can be caused by drugs

Allergic Contact Stomatitis

- Stomatitis venenata
o Angioedema
o Toothpaste
o Cinnamon
o Amalgam (Lichen planus)
o Other metal

Angioedema
- Other names:
o Angioneurotic edema
o Quincke’s disease
- Causes
o Mast cell degranulation
 Most common cause
 Degranulation leads to histamine release and typical IgE Hypersensitivity reaction
o ACE inhibitors (Drug)
 Not mediated by IgE
- Hereditary angioedema
o Complement pathway => Inflammatory response
o Lack of, or dysfunction of the inhibitor of transformation of C1 to C1 esterase – this starts the complement
cascade
- Clinical features:
o Rapid onset of soft, non-tender tissue swelling
 Face, lips, tongue, pharynx and larynx
- Treatment:
o Oral antihistamines
 If this doesn’t work or if there’s laryngeal involvement, use Intramuscular epinephrine
Dentrifice Stomatitis
- Superficial epithelial sloughing
- Clinical Features:
o No pain
o No bleeding
o Reaction to detergent in toothpaste (Sodium Lauryl Sulfate)
- Treatment:
o Switch to toothpaste without Sodium Lauryl Sulfate (i.e. biotene)
 No Sodium Lauryl Sulfate => No/Low Foaming
 Inform patients that there won’t be bubbles & foam
 Expensive

Contact Stomatitis from Artificial Cinnamon Flavoring

- Concentrations of artificial flavoring are up to 100x that in the natural spice
- Most common in: Chewing gum, Candy, Toothpaste
- Clinical Features:
o White vertical red line – Caused by candy
- Histopathologic Features:
o Cinnamon irritation => Perivascular infiltrates of plasma cells
o Heavy inflammatory cell infiltrate that consists predominantly of lymphocytes that may be intermixed with
Plasma Cells, histiocytes, or eosinophils

2. Fungus – Candidiasis

Candidiasis
 - Synonyms
o Thrush (DON’T USE!)
o Angular Chelitis
o Median Rhomboid Glossitis
o Denture Sore mouth
o Yeast infection
o Candidal leukoplakia (Already know what it is, don’t need “leukoplakia”)
o Antibiotic stomatitis
o Monoliasis

Candidiasis Classification
- Acute
o Pseudomembranous
o Erythematous
- Chronic
o Erythematous
o Hyperplastic
- Mucocutaneous
o Localized (Oral, face, scalp, nails)
o Familial
o Syndrome-associated

Pseudomembranous Candidiasis
- Can be wiped off
- May leave a “bleeding area”
o Usually, at least looks Red & Inflamed
- White lesion can be placed on a glass slide, fixed with alcohol or hair spray and sent to the lab to look for Candida
organisms
Erythematous
- Denture sore mouth
- Etiology: Candida and/or Ill-fitting denture

Hyperplastic Candidiasis
- Clinical features:
o Looks like Hyperkeratosis
o White, doesn’t wipe off; Looks like leukoplakia clinically
- Diagnosis: Biopsy & Stain with Silver/PAS stain
o Contains pseudohyphae
- Not a deep infection
Angular Cheilitis
- Denture leads to bilateral lesion
- Most common condition: Diminished VDO => Smaller opening of the mouth => Candidiasis growth

Median Rhomboid Glossitis

- Can be a double lesion

5 D’s of Candidiasis
- Drugs (Corticosteroids, antibiotics)
- Dentures (Ill-fitting)
- Diabetes
- Debilitation (Condition)
- Dryness (Older age, dryer)

Candidiasis: Predisposing Factors (Debilitation)

- Immunodeficiency
- Immunologic immaturity of infancy
- Acquired immunosuppression
- Endocrine disturbances
- Diabetes mellitus
- Hypoparathyroidism
- Pregnancy
- Hypoadrenalism (Addison Disease)
- Corticosteroid therapy, topical (Systemic)
- Systemic antibiotic therapy
- Malignancies and their therapies
- Xerostomia
5 D’s of Candidiasis
- Oral Pseudomembraneous Candidiasis: Can form a variation of morphology – Red circle in the center, but can still be
wiped off
- Median Rhomboid Glossitis – Can be bilateral
- Type 1 Diabetes can be unknown and can’t be seen clinically, so angular cheilitis can signify Candidiasis
- AIDS with Dentures are more susceptible to Candidiasis

Treatment for Candidiasis

- Diflucan (Fluconazole)
- Nizoral (Ketoconazole) *** NOT Recommended
- Topical
o Vaginal tablets (Hard to find)
o Cariogenic (Sugar component)
 Mycelex (Clotrimazole) Troches
 Nystatin Suspension
Nizoral (Ketoconazole)
- 1st Systemic antifungal
- Main side effect: Liver damage
- Needs Acidic environment to work
- Can Interact with several drugs and cause cardiac arrhythmias
- NOT RECOMMENDED for first treatment for oral candidiasis at this time because of possibility of liver damage

Case:
- Clinically: Actinic Cheilitis
- Exclude SCC through biopsy => Result was negative for SCC
- Result: Presence of Candida => Treated with Nizoral
Diflucan (Fluconazole)
- 1 time per day
- Acidic environment is NOT necessary
- Effective
o i.e. Candidiasis, Cryptococcal meningitis
- Expensive
- Interacts with Dilantin, Warfarin, Anticoagulants, and Oral hypoglycemic
- Case: AIDS patient with Median Rhomboid Glossitis – Usually symmetrical
o Result after 2 days of Diflucan treatment (Effective)

Anti-fungal therapy result

- If anti-fungal therapy fails to produce complete resolution, then the remaining abnormal tissue should be biopsied to
rule out premalignant change or malignancy

Treatment of Denture Candidiasis

- Underlying cause (5 Ds besides dentures)
- Change denture habit
- Disinfect denture
- Anti-fungal therapy
- Use Nystatin cream

Treatment for Angular Cheilitis

- Primary: Rx: Nystatin CREAM!!!
o Dispense: 15 g tube
o Sig: Apply to corners of mouth qid
- Others (Contain corticosteroids – Risk of Candidiasis)
o Vytone
 Cream-Iodoquinol 1% and Hydrocortisone 1%
o Mycolog II
o Nystatin and Triamcinalone 0.1% (Hydrocortisone)

Angular cheilitis
- In children: Caused by Staphylococcus; so it is BACTERIAL, NOT FUNGAL infection
- In adults: Does not clear quickly with anti-fungal
o Treat with OTC – Triple antibiotic ointment

Vaseline & Candidiasis

- Most people with angular cheilitis will have used Vaseline
- DO NOT TREAT WITH VASELINE
- Warm and Moist environment: Worse conditions for the patient
o Increases colonization of Yeast
- Therefore, use medication that is a CREAM (Water-based) will dry and leave residual medication
o Ointment is Oil-based (Vaseline)
 - 2 Most common presentations of Candidiasis
o Angular Chielitis
o Pseudomembraneous Candidiasis

Histoplasmosis
- Histoplasma capsulatum
o Most common systemic fungal disease in the US
- Dimorphic
o Mold (Body temperature): Fungus that grows in the form of multicellular filaments called Hyphae
o Yeast (Environment): Fungi that can adopt a single-celled growth habit
- Expression of disease depends on:
o Amount of spores Inhaled
o Immune status of the host
- Differential diagnosis:
o SCC => Do biopsy
 Histopathologic feature: Inflammatory; so it’s not cancer
o Silver stain for Fungi

Blastomycosis
- Range includes MN and WI
- Inhalation
- Locations: Oral mucosal and Skin lesions
- Fastest diagnosis: Biopsy or Scraping
Coccidoidomycosis
- “San Jauquin valley fever”
- Western US
o Counterpart of Histoplasmosis
o Travel negates geographical isolation
- Important in immunosuppression
 - Facial lesions more common than Oral
Paracoccidioidmycosis (South American Blastomycosis)
- Deep fungal infection
- South America and immigrants
- Oral lesions frequent, Mulberry-like

Cryptococcus
- Devastating in immunosuppressed patients
- Important cause of death in AIDs
- Cryptococcal meningitis important in AIDS
- Extremely difficult to treat
Mucormycosis (Zygomycosis)
- Very important for Dentists
o Maxillary sinus infection
 Intraoral swelling of alveolus or palate
 Pain
 Ulceration – Black necrotic surface
- Insulin-dependent diabetics
- Diagnose fast enough to save life is Biopsy, NOT culture
Aspergillosis
- Common in uncontrolled diabetics
- AIDS
- Immunosuppression for transplants
- Fungal Ball: Maxillary sinus lesion can be radiopaque
Toxoplasmosis
- Protozoa
- Cats, Cat feces
- Encephalitis
- Myocarditis
Leishmaniasis
- Sand fly
- Dogs

3. Physical Injuries

ASA (Acetyl Salicylic Acid/Asprin) & Peroxide

- Chemical burns; Peroxide is the most common etiology
- Morphology: “Shaggy” or “Ragged” Surface
- Treatment: Mouth-guard
 - Histopathologic feature:
o Indication of burn with fluid and inflammation

Cotton Roll Injury

- Cotton roll is held in shape by “Sizing”, A starch-like material
o When Starch gets wet it forms a paste
o Dries and stick to mucosa
- Cotton roll is pulled off and takes the layer of the epithelium
- Prevention: Wet cotton roll before removal

Riga-Fede Disease
- Traumatic Ulcerations

Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE)

- Clinical-Pathologic-Correlation (CPC)
o Helps correlate the symptoms and patient’s medical history, and pathological results to determine a
diagnosis
- Case history
o 45 y/o female
o Medical history: Healthy (Unremarkable)
o CC: “I have a sore on the side of my tongue. It has been there for a couple of months but does not hurt.”
o Differential Diagnosis
 SCC
 Traumatic Granuloma
  Deep Fungal Infections
o Histopathologic Features:
 Lots of inflammation, Eosinophils (Red cells)
o Diagnosis:
 Traumatic ulcerative granuloma with Stromal eosinophilia (TUGSE)
 Benign reactive lesion
 Characterized by an intense mixed inflammatory infiltrate (predominantly histiocytes,
with lymphocytes, neutrophils, and scattered eosinophils)
 May clinically mimic neoplasia.
 Chronic inflammatory condition
 Self-limiting

- Case 2
o 45 y/o black male with 3-4 weeks history of ulcerative mass anterior ventral tongue
o Histopathologic Features:
 General Eosinophilic granuloma
 Looks like Langerhans cell Histiocytosis

4. Physical Injuries continued

2 weeks ->
Maxillary Torus

Bed Sores (Chronic Ulcer)

- In this case, lesion has danger signals: Location, Ulcer, Sharp white border
o Differential diagnosis: SCC => Do biopsy; Result: Bed sores
- Diagnosis is the Treatment: Excisional Biopsy
Post-anesthetic Chewing Lip
- Inform the parent & patient

Anterior Papillitis
- Due to pushing or rubbing anterior tongue against anterior teeth
- Treatment: Thick mouth-guard

Munchausen by proxy syndrome

- Munchausen: Injury of self to gain attention
- Proxy Munchausen: Other person causes injury for attention
o Usually parent injures child (Child abuse; Because of mental issue)

Erosion
- Clinical Features:
o Cupping: Concave of the tooth that is lost
  Enamel is lost
o Smooth (Non-carious Dentin)
o Can create sharp teeth
- Etiology (Acid)
o Lemon-sucking
o Gastric regurgitation
o Vitamin C (Ascorbic acid)
- Treatment: Remove etiology

Bulimia
- Eating disorder; self-induced vomiting

Toothbrush Trauma
- First thought: Recurrent intraoral herpes simplex
- Non-specific Gingival ulcer(s)
o Linear, Horizontal appearance
o Factitial injury

Water Pik injury

Oral Sex Trauma
- Patalatal Hemorrhage: Female/Gay males
- Lingual Frenum injury: Males/Gay females

Molten Metal Injury

- Patient couldn’t get partial denture off because molten metal stuck on RPD

Linea Alba
- Injury from pressure, friction, or sucking trauma
Radiation-induced Injury
- Types
o Ionizing radiation
o Radiation-induced xerostomia
- Telangectasia: Radiation-induced Skin damage
- Radiation-induced Hair loss
- Radiation-induced Mucositis
- Radiation-induced Xerostomia – Leads to “Radiation caries”

Osteoradionecrosis
- Most severe, bad effect from therapeutic radiation
- Underlying change is the radiation damage to the blood vessels
o Microorganisms that gain access to the bone are unlikely to be controlled by normal
inflammation => Susceptible to uncontrollable damage => osteonecrosis
 - Hyperbaric oxygen is the best adjunctive treatment to surgery (improves symptoms caused by
radiation injuries); Provides oxygen for healing
- Cobalt-60 irradiation damage
- Osteonecrosis => Denture sore => Pathological fracture
- Prevention is the KEY
o Good exam prior to irradiation
o All unsalvageable teeth must be extracted BEFORE irradiation
 Can’t extract teeth after radiation (Maybe Maxillary, but NOT Mandible)
o All restorative and perio done IMMEDIATELY
o Lifelong Prescription-level fluoride
o Frequent exams and prophys

Medication (Bisphosphonate)-Related Osteonecrosis of the Jaw (MRONJ/BRONJ)

- Definition and medications that cause MRONJ:
- Identify patients with and at risk for developing MRONJ:
- Understand the pathophysiology of MRONJ:
- Discuss Treatment Recommendations:
- Case 1:
o 44 y/o man
o MHx: Renal cell ca with lung and bone mets (humerus) and treatment with Zometa
o Presents with painful, non-healing exposed bone in the mandible following dental
extraction of teeth #30 and #31, one year after the dental treatment
o Co-morbid conditions: NIDDM, Hyperlipidemia, Hypertension
- Case 2:
o 70 y/o female
o MHx: Osteoporosis on Fosamax for 4 years and Boniva for 6 months
 Cardiovascular disease, Myocardial infarction, Hypertension, Asthma,
Hypothyroidism
o No history of smoking or alcohol
- MRONJ – AAOMS definition
o Current or previous treatment with antiresorptive or antiangiogenic agents
o Exposed bone or bone that can be probed through an intraoral or extraoral fistula(e) in
the maxillofacial region that has persisted for more than 8 weeks
 8 weeks is consistent with a time frame where most trauma, extractions, and
oral surgical procedures would have resulted in soft tissue closure, and exposed
bone would no longer be present
o No history of radiation therapy or obvious metastatic disease to the jaws
- Medications associated with ONJ development
o IV bisphosphonates (Zoledronate): Used to treat cancer-related skeletal events
 Multiple myeloma
 Solid tumors
 Breast, prostate, lung
 Reclast: (One/year) for osteoporosis
o Oral bisphosphonates: Treat Osteoporosis, other bone turnover disease (Paget’s disease)
and osteogenesis imperfecta
o Antiangiogenic medications (Suntinib and Bevacizumab): GI cancer, renal cell carcinoma
and neuroendocrine tumors
o RANK ligand inhibitor (denosumab): Osteoporosis and skeletal related events in
malignancy
- Clinical presentation
o Clinical presentations as painful, exposed bone in mandible and/or maxilla
o Symptoms resemble dental abscesses, “Tooth-aches”, denture sore spots and
osteomyelitis
o Diagnosis made with clinical examination and patient history
o Areas of exposed bone can remain asymptomatic for days, weeks, or even years
o Lesions become symptomatic when surrounding mucosa become inflamed or there is
clinical evidence of infection
o Signs and symptoms before exposed bone:
 Pain, tooth mobility, mucosal swelling, erythema, and ulceration
o Exposed bone can be seen in areas following dentoalveolar surgery or with no history of
trauma or in edentulous areas
o Mandible > Maxilla; more prevalent in areas with Thin mucosa such as overlying bony
prominences such as Tori, Exostoses and Mylohyoid ridge
o Size of exposed bone is variable from non-healing extraction sites to exposure and
necrosis of large sections of jawbone
o Intraoral and extra-oral fistulae in cases with secondary infection of the necrotic jaw
- ONJ-Risk Factors
o Drug-related
 Potency (Zometa > Aredia > Oral)
 IV Route
 Duration of therapy
o Local-DA Surgery
 Extractions
 Dental implant placement
 Periapical surgery
 Periodontal surgery (Osseous)
 o Local-Anatomic
 Exostoses and prominent mylohyoid ridge
o Concomitant Oral disease
 Periodontal and dental abscess
o Demographic/Systemic
 Age
 Cancer type
 Dose of BP
 Duration of BP
o Other Risk Factor
 Corticosteroid Tx
 Chemotherapy Tx
 Smoking
 Diabetes
 Alcohol use
 Poor oral hygiene
- Radiographic identification of BRONJ
o CT is superior compared to panoramic
o CT findings showed a consistent associated with clinical severity
- Why the Jaw?
o Anatomy of the alveolar bone
 Covered by a thin layer of periosteum and epithelium with an attenuated layer
of connective tissue
o Unique stresses in the oral cavity
 Physiologic (Mastication)
 Iatrogenic (Dental procedures)
 Inflammatory (Periodontal disease, Caries)
o Combination of Anatomy and stress
 Predisposes the thin mucosa to trauma leads to exposure of bone, but likely
demands an increase in metabolic compensation including bone remodeling
o Complex microbial microflora
 Many are pathogenic organisms
 Intimate relation between teeth to the jaws allows a portal of entry for microbes
and other inflammatory products to the underlying bone (not seen in any other
part of the body).
 Identification of Actinomyces in ONJ
 Not clear whether actinomycotic colonization is a primary or a
secondary event
- Pathophysiology
o Inhibition of Osteoclastic bone resorption and remodeling
- Treatment strategy for MRONJ
o Patient on BP for < 4 years and with NO clinical risk factors:
 No alteration or delay in planned surgery or dental procedures
 For dental implants: obtain informed consent for possible long-term failure and
low-risk of MRONJ
o Patients on oral BP for < 4 years and also on corticosteroids/antiangiogenic drugs:
  Contact MD to consider discontinuation of oral BP for at least 2 months prior to
oral surgery and not restarted until osseous healing has occurred
o Patients on oral BP for > 4 years with or without concomitant medical therapy:
 Contact MD to consider discontinuation of oral BP for at least 2 months prior to
oral surgery and not restarted until osseous healing has occurred

5. Oral Manifestation of HIV & AIDS

HIV/AIDS Introduction
- Human Immunodeficiency Virus
- Acquired Immunodeficiency Syndrome
- Practice universal precaution: Avoid all bodily fluids of infected patients
- Clinically difficult to see who is infected, so we do lab tests
o Lab test: HIV uses CD4+ to enter cell
o T4:T8 (Helper:Supressor) ratio deteriorates; T4 depletes with time
 Normal is 2:1
 AIDS: T4 cells/mm^3 < 200
 o Death within 10 years w/o treatment
- Global summary of the AIDS epidemic, December 2007
o Number of people living with HIV in 2007
 Total: 33.2 million
 Adults: 30 million
 Women: 15 million
 Children < 15: 2.1 million
o People newly infected with HIV in 2007
 Total: 2.5 million
 Adults: 2.1 million
 Children < 15: 420 thousand
o AIDS death in 2007
 Total: 2.1 million
 Adults: 1.7 million
 Children <15: 290 thousand

Clinical Manifestation of AIDS

- Neurological
o Toxoplasmosis
o Cryptococcal meningitis
o CMV
o Progressive multiple leukoencephalopathy
o Esophagitis
o Candidiasis
o Herpes simplex
o CMV
- Neoplasms
o Kaposi’s Sarcoma
o Lymphomas/Hodgkins
o Multiple basal cell carcinomas

Common oral Manifestation of AIDS

- Candidiasis
- Oral “Hairy” Leukoplakia
- HSV, VZV
- Kaposi sarcoma
- Non-Hodgkin’s lymphoma
- HIV gingivitis and periodontitis
- Acute non-specific Ulcers
- Chronic ulcers (Deep fungal, CMV, HSV)

Oral Manifestations of HIV (+) Pre-AIDS patients

- Acute pseudomembranous candidiasis
- Oral “Hairy” Leukoplakia
- HSV diffuse
- Gingivitis and periodontitis
- Acute Non-specific Ulcers
 - VZV lesions

Persistent Generalized Lymphadenopathy (PGL)

- Early sign in up to 70% of patients
- > 3 months
- 2 or more Extrainguinal sites
- Initial site: Head and neck
- Differential diagnosis (DD): Lymphoma, Florid follicular hyperplasia
- PGL leads to AIDS

Candidiasis in HIV/AIDS
- Most common intraoral manifestation ***
- Predictive but NOT diagnosis for AIDS
- Other mucosae affected (epiglottic, laryngeal, esophageal, nasopharyngeal)
- Pseudomembranous (Thrush), erythematous, hyperplastic, angular cheilitis
- Antifungals produce transient (short-term) responses
- Histopathological feature: Formation of Hyphae

HIV-associated Periodontal Disease

- HIV-related gingivitis
o Linear erythema of the free gingiva; presence of candida; NOT responsive to plaque
control
- “Skip” lesions
 - HIV-associated periodontitis
o Necrotizing process, rapid loss of periodontal support, PAIN, not deep pockets
- ANUG & Necrotizing stomatitis

Deep Fungal Infections

- Histoplasmosis: Respiratory Infection
- Cryptococcosis: Respiratory, CNS
- Oral Involvement: Manifestation of WIDESPREAD disease

Herpes Simplex Virus

- Recurrent HSV rates are the same as immune-competent patients
- Lesions more widespread and persistent
- Atypical presentation intraorally (Recurrent, not just on fixed mucosa; Large single lesions)

Varicella Zoster Virus

- Fairly common in HIV-infected patients
- More severe; Morbidity and mortality
- Younger patients
- Lesions last longer than usual
 - Cutaneous dissemination – Visceral involvement

Epstein-Barr Virus
- Hairy Leukoplakia (OHL)
o Distinctive lesion, but NOT diagnostic
o Lateral borders of tongue, also other sites
o Hairy leukoplakia can lead to AIDS in 2 years
o Occurs in Immunocompromised, immunocompetent patients, transplantation patients,
patients with immunologic instabilities, otherwise healthy individuals
 This means that OHL is NOT a marker for HIV/AIDS
o It is an opportunistic infection for AIDS
 EBV detected, HIV/HPV NOT detected
o Responds dramatically but temporarily to acyclovir
- Histopathological feature: In situ hybridization for EBV

Cytomegalovirus
- Infects Salivary gland epithelium, endothelial cells
- Disseminated infection constitutes criterion for AIDS
- Parotid Gland swelling
- Reduction in salivary flow lead to xerostomia
- Occasionally affects newborns
Human Papilloma Virus
- Oral lesions
o Condyloma Acuminatum
o Heck’s Disease-like
 Can be infected with HPV 13 & 32
- Premalignant potential, Cervical – Oral?
- Dysplasia in oral HPV lesions is not necessarily associated with progression to oral cancer
- Anogenital lesions

Aphthous Stomatitis
- Increased frequency in HIV patients
o Worse clinical feature with HIV; Looks like Major Aphthous Stomatitis
- Atypical presentation
- Crater-like
- Sharp or Thickened edges
- Etiology, Immunologic basis: NOT an infection
o Decrease of Ratio of T-helper cells (CD4+) to T-Suppressor cells (CD8+)
o CD8+ predominate in lesions
o Increased TNF-alpha
o Tendency to be “Familial”: Associated with certain HLA types
Kaposi Sarcoma (KS)
- Before AIDS: KS was a rare neoplasm, seen on the Legs of old men of Mediterranean ethnicity
- Etiology: HHV8; Skin and oral mucosa
- Clinical features: Flat lesions, Plaques and nodules
o Red, purple and brown; Bleeding, Pain
o Early lesion looks like Bruise
o Esthetics problem, doesn’t kill people but may mean AIDS (bad)

Other Malignancies
- Lymphoma
o Maybe Most common or Second-most common malignancy
o Non-Hodgkin vs Kaposi Sarcoma
 cART is diminishing Kaposi’s number, while NHL is NOT decreasing as fast; So
Non-Hodgkin Lymphoma is becoming #1 cancer
- Oral squamous cell carcinoma
o Can be unusual appearance and location
Foreign Body Reaction to Dermal Filler
- Case: 64 y/o female with yellowish mass in lower lip/vestibule. Denies any injections in the area
- Clinical features: Firm submucosal mass, asymptomatic slowly enlarging, odd consistency on
biopsy, seemed to be diving into the muscle
- Clinical impression: Cholesterol or protein deposit vs neoplasm
- Picture: Appearance of the intraoral Radiesse granuloma; Yellow plaque of the lower lip
associated with calcium hydroxylapatite injection
- Histopathologic feature: Muscle with shattered cells
- Radiesse cosmetic filler
o Claims no need for allergy test because it is comprised of a substance naturally found in
the body: Calcium hydroxylapatite
o Also claims that the microspheres stimulate natural collagen growth
o Research on oral lesions and hydroxyapatite injection:
 Oral foreign body granuloma associated with the dermal filler
 It induced nodules occur more often in older women, most commonly in the lips
and the mandibular labial vestibule
 Conclusion: Nodules will increase in time, parallel to the aging population
 Dermal filler can be distant from the site of injection, which means that it can
migrate
Oral Pigmentation Related to Chemotherapeutic Agent
- Case:65 y/o female with Gray/Blue pigmented macule, bilateral hard palate, asymptomatic.
History of (H/o) leukemia and chemo (now in remission)
- Mucosal Pigmentation caused by Imatinib (Chemotherapy)
- Imatinib mesylate, Gleevec
o Tyrosine Kinase Inhibitor
o First-line medication for treating Chronic Myeloid Leukemia (CML)
- Clinical studies revealed very good hematological responses without significant side effects.
However, imatinib may lead to mucosal pigmentation
- Imatinib-induced pigmentation is similar to that caused by other medications such as
minocycline and anti-malarial medications, namely the deposition of a drug metabolite
containing melanin and iron
- Imatinib also blocks the binding of ligands to c-kit receptors on melanocytes
o This reduces the activity of melanocytes and leading to Hypopigmentation
o It may also lead to Hyperpigmentation of the skin or mucosa and it likely does this
through a drug metabolite chelated to iron and melanin, in a similar mechanism to
minocycline and anti-malarial drugs
Focal Melanotic Pigmentation
- Differential diagnosis
o Oral/Labial melanotic macule
o Post-inflammatory hypermelanosis
o Melanoacanthosis
o Nevo-melanocytic lesions
- Causes of Diffuse Melanotic Pigmentation
o Physiologic pigmentation
o Post-inflammatory hypermelanosis
o Pigmentation associated with Systemic Diseases
o Medication-related pigmentation
o Melanoma
Medication-associated pigmentation of the oral cavity
 - Cause:
o Pigmented breakdown produced of the drug itself
o Drug metabolites chelated with iron
o Drugs that are able to induce melanin formation
- Oral pigmentation from anti-malarial medication, minocyclines, and imatinib ALWAYS involves
the mucosa of the hard palate
o It is unclear why this mucosa and not others are particularly susceptible
- The corollary to this is that oral pigmentation associated with other medications, that occurs on
non-palate sites more susceptible to trauma, are more likely to be post-inflammatory
hypermelanosis

6. Salivary Glands

Mucocele
- Mucus Extravasation (Escape) Phenomenon
- Morphology: round, smooth, elevated, feels fluctuant
- Size: Usually “Small” because it affects only minor salivary gland
o If it’s “Big” and affects major salivary gland, it is a Ranula
- Color: May be consistent color or bluish
o Bluish color is formed because too much fluid (Saliva)
- Location: Lower lip (By far the most common location)
o Can also occur at the posterior hard palate
o NEVER the upper lip
 If there’s something like the mucocele on the upper lip, it is a Minor Salivary
Gland Tumor
- Cut open: Gel-like consistency
 o The duct is affected, so popping it will just recur if you don’t remove the etiologic factor:
The salivary duct
o If it does recur within 2 weeks, it won’t go away by itself
o If it’s firm, instead of being fluctuant, it is a fibroma
- “Mucus”: The good stuff
- “Mucous”: Adjective – Secretion process
- Other info:
o Duct is severed
o Mucus leaks out
o Brisk inflammatory reaction
o Macrophages come in to clean it up
o Replacement by granulation tissue
o Organization and fibrosis yields fibrous tissue (fibroma)
- Histopathologic feature:
o Space with NO lining of epithelium; Therefore it is NOT a cyst
o Salivary duct, granulation tissue, granular-like, protein stains
o Engorged macrophages
- Diagnostic
o Patient has a lesion in an area of minor salivary glands
o Becomes bigger/smaller in size
 Because of salivary secretion when gland is active => Bigger
 This does NOT happen in tumors

Ranula
- Cause:
o Virtually ALWAYS blockage of Major Salivary Gland Duct
 Very difficult to sever major duct and cause leakage of saliva into surrounding
tissue
o This is a mucus retention cyst rather than mucus extravasation
o Should x-ray the area to see if a stone is visible
- Morphology: the “Bigger” version of Mucocele
Salivary Duct Cyst/Mucus Retention Cyst
- Cannot tell clinically from a mucocele
- Much LESS common than mucocele (< 5%)
- Usually due to duct obstruction and dilatation
- Histological feature:
o Looks like a true cyst (Has epithelial lining)
o Sectioning dilated duct results in an epithelial lined space that looks like a cyst
o Presence of Nyhus => Accumulation
 Forms concentric layers, looks like stones
- Radiographic Feature
o Stones found in major salivary gland location (Submandibular/parotid area)
- Treatment
o The affected major salivary gland is often removed with the ranula
 Acinar cells are extremely sensitive to any injury
 The major salivary gland is often fibrotic and non-functional at the time of
discovery of the ranula

Cysts of Blandin-Nuhn
 - Looks like mucocele
- Location: Anterior, inferior tongue (Ventral)
- Very high recurrence rate
- Minor salivary glands are WITHIN the tongue MUSCLE
- To prevent recurrence, affected glands (IN THE MUSCLE) must be removed

Sialadenitis (Acute sialadenitis – parotitis)

- Bacterial sialadenitis almost always due to xerostomia or blockage
- Typical precipitating factor – Abdominal surgery
- Retrograde infection
- Chronic sialadenitis usually due to obstruction
- Rx: Stones, bilateral parotid area
o If pressed on => Pus can flow out and sore feeling (Acute inflammation)

Xerostomia
- SUBJECTIVE sensation of a dry mouth
- May or may not associated with function of salivary glands (Ageing decreases salivary gland
function)
- Many Causes
o Most common cause is medication - AMOUNT of meds more important than specific
meds
- Radiation-induced xerostomia leads to rampant caries which can lead to osteoradionecrosis
- Treatment: Biotene stuff (Alcohol-free)

7. Salivary Glands cont. Part 2

Antral Pseudocyst
- Tips
o NOT Sinus Mucocele / Retention Cyst of the sinus
o On floor of Mx sinus
 o Due to accumulation of inflammatory exudate (So not mucin)
o No need for CT
- Treatment
o No treatment needed IF:
 Inferiorly-based
 Smooth, dome-shaped rounded surface
 No bone destruction
 No significant symptoms (i.e. bleeding/breathing problems)
o Periodic pan x-rays for a couple of years
- Differential diagnosis
o Other Mx cysts or neoplasms

Benign Lymphoepithelial Lesion

- Sjogren syndrome/Non-Sjogren
o Most in parotid gland
o Firm, diffuse swelling
o Diagnosis by biopsy
o Increased risk for Malignant lymphoma – 40x higher risk ***
o Many are early lymphomas (MALT type)
o Treatment = Removal of involved gland

Sjogren Syndrome
- Chronic, Systemic, Autoimmune disorder
- Principally affects salivary and lacrimal glands
o Xerostomia
o Xerophthalmia
- If both conditions present = Sicca syndrome
o Primary: Sicca syndrome with NO other autoimmune disease
o Secondary: Sicca syndrome in ADDITION to another associated autoimmune disease
- Familial tendency, virus cause speculative
- Histopathologic feature:
o Replacement of acini by lymphocytes ****
o Parotid glands are shown with lymphocytes
o Epimyoepithelial islands
 Ductal epithelium persists
- Lab results
o Increased erythrocyte sedimentation rate
o High serum immunoglobulin levels
o Positive rheumatoid factor
 o Anti-nuclear antibodies
 Anti-Ro
 Anti-La
- Dentist can help with Diagnosis with Lip biopsy
o 1 cm horizontal incision on mucosal surface of lower lip lateral to midline
o “Pop out” AT LEAST 5 minor salivary glands
o Submit for Biopsy with top differential: Sjogren disease (Or rule out SD)

Necrotizing Sialometaplasia
- Most common in hard palate
o Low-risk area for cancer
- Treatment is excision/biopsy
o Cancer would recur
- Locally destructive inflammatory condition of minor salivary glands
- Probable cause is ischemia (Very frequently associated with smoking)
- Biggest problem is Misdiagnosis of Squamous Cell Carcinoma
o Clinically AND Histologically looks like SCC!!!!***

Benign Salivary Gland Tumors

- Pleomorphic Adenoma “Mixed Tumor”
- Monomorphic adenoma
o Canalicular adenoma
o Basal Cell adenoma
- Papillary cystadenoma Lymphomatosum “Warthin Tumor”
o Hallmark: Looks like Pleomorphic adenoma in the parotid but VERY FREQUENTLY
BILATERAL
- Differential Diagnosis
o Minor salivary gland tumor (There are a lot of different types of minor salivary glands, so
don’t need to specify specific)
 o Malignany lymphoma
o Kaposi’s sarcoma
o Other mesenchymal tumor (Connective tissue – Bumpy)

Pleomorphic adenoma (Mixed Tumor) ***

- A Bump in the parotid gland is a Mixed Tumor UNTIL PROVEN OTHERWISE
- Histopathologic Feature
o First thing to look at is the border and ask: Is it benign/malignant?
o Presence of pseudocapsule
 Tumor does NOT violate the border (Capsule) – Benign
 Tumor areas look like cartilage
- Differentiated from salivary gland hyperplasia
o ONLY by BIOPSY

Salivary Gland tumors to know***

- Benign
o Pleomorphic Adenoma “Mixed”
o Monomorphic Adenoma
 Canalicular adenoma
 Basal cell adenoma
o Papillary cystadenoma lymphomatosum “Warthin Tumor”
- Malignant
o Mucoepidermoid carcinoma
o Acinic Cell adenocarcinoma
o Malignant mixed tumors
o Adenoid cystic carcinoma
o Polymorphous low-grade adenocarcinoma
- Excision of minor salivary gland tumors
o “Your first shot is your best shot”
 Do excision to remove

8. Salivary Gland cont. Part 3

Pleomorphic Adenoma (Benign Mixed Tumor)

- Most common tumor in the parotid gland

- Most common Benign Minor Salivary gland tumor
- Not truly a “Mixed” tumor from more than one germ layer
- Derived from Glandular epithelium and Myoepithelial cells
- Mixed tumor: Often a mesenchymal stroma that can look like cartilage or bone
- Check for symmetry
- Very high recurrence rate of pleomorphic adenomas in the Parotid Gland
o Facial nerve is present in the parotid gland
o Preserving the facial nerve often results in leaving tumor behind => Recurrence
- *** A Bump in the parotid gland is a Mixed tumor UNTIL PROVEN OTHERWISE
- Minor salivary gland tumors have 50% Malignancy rate ***

Malignant Salivary Gland tumors you should know

- Mucoepidermoid carcinoma
- Acinic cell adenocarcinoma
- Malignant mixed tumors/carcinoma ex pleomorphic adenoma
- Adenoid cystic carcinoma
- Polymorphous low-grade adenocarcinoma

Mucoepidermoid carcinoma

- Most common Malignant salivary gland neoplasm

- Most common one to be found in bone (Intrabony)
- Wide age range; Most commonly seen in young people beginning 2nd Decade ***
- 3 Grades of Malignancy
o Low, Intermediate, High
- Histopathologic feature:
 o Lower Grade: More Mucous, & Cyst
o Higher Grade: More Squamous cell Differentiation

Acinic Cell Adenocarcinoma

- Most occur in parotid gland

- Cells show acinar differentiation

Malignant Mixed Tumor

- Most common type: Carcinoma ex pleomorphic adenoma

- Malignant transformation of benign pleomorphic adenoma

Adenoid Cystic Carcinoma

- 50% in Minor salivary glands

- Location: Palate most common
- Histopathologic Feature: Perineural invasion (Signature lesion) ***
- Relentless tumor, poor overall prognosis
o 5 year survival: 70%
o 20 year survival: 20%
- Excise, get out as much as possible “First shot is the best shot”
- Distant metastases
o Occur between 5 & 10 years after initial treatment
o Influenced by perineural invasion (Metastases follows nerve)
o NOT influenced by local tumor control
o Most important factor on survival are:
 Tumor site
 Clinical stage
 Histologic type
o Late onset of distant metastases, REGARDLESS of local control
 This supports hypothesis of a potential to develop distant metastases in the very
early phases of tumor growth
Polymorphous Low-Grade Adenocarcinoma (PLGA)

- Almost Exclusively in minor glands

- Location: Most common in Hard/Soft Palate
- Prognosis: Fairly good prognosis without radical treatment
o Certain ones metastasize and cause serious complications or death
 At this time, we can’t predict which ones will be bad actors
- First Identified in 1983 – Now recognized as one of the most common minor SG tumors
- Remember: A bump in the UPPER LIP is NOT a mucocele

9. Pigmentation